FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chou, JW Zhou, T Kaufmann, WK Paules, RS Bushel, PR AF Chou, Jeff W. Zhou, Tong Kaufmann, William K. Paules, Richard S. Bushel, Pierre R. TI Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes SO BMC BIOINFORMATICS LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; CHECKPOINT; PROFILES; CANCER AB Background: A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results: Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and LI starvation in C. elegans and after ultraviolet (UV) or ionizing radiation (IR)-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying biological processes affected by IR-and/or UV-induced DNA damage. Conclusion: EPIG competed with CLICK and performed better than CAST in extracting patterns from simulated data. EPIG extracted more biological informative patterns and co-expressed genes from both C. elegans and IR/UV-treated human fibroblasts. Using Gene Ontology analysis of the genes in the patterns extracted by EPIG, several key biological categories related to p53-dependent cell cycle control were revealed from the IR/UV data. Among them were mitotic cell cycle, DNA replication, DNA repair, cell cycle checkpoint, and G(0)-like status transition. EPIG can be applied to data sets from a variety of experimental designs. C1 [Chou, Jeff W.; Paules, Richard S.; Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC 27709 USA. [Zhou, Tong; Kaufmann, William K.] Univ N Carolina, Ctr Environm Hlth & Susceptibil, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Zhou, Tong; Kaufmann, William K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Bushel, PR (reprint author), Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC 27709 USA. EM chou@niehs.nih.gov; tzhou@email.unc.edu; bill_kaufmann@med.unc.edu; paules@niehs.nih.gov; bushel@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [U19 ES011391] NR 30 TC 22 Z9 25 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 2 PY 2007 VL 8 AR 427 DI 10.1186/1471-2105-8-427 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 253XJ UT WOS:000252550600001 PM 17980031 ER PT J AU Sherman, BT Huang, DW Tan, QN Guo, YJ Bour, S Liu, D Stephens, R Baseler, MW Lane, HC Lempicki, RA AF Sherman, Brad T. Huang, Da Wei Tan, Qina Guo, Yongjian Bour, Stephan Liu, David Stephens, Robert Baseler, Michael W. Lane, H. Clifford Lempicki, Richard A. TI DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis SO BMC BIOINFORMATICS LA English DT Article ID PROTEIN INFORMATION; EXPRESSION DATA; TOOL; ONTOLOGIES; UNIPROT; NCBI AB Background: Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description: The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion: The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/. C1 [Sherman, Brad T.; Huang, Da Wei; Tan, Qina; Baseler, Michael W.; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Liu, David; Stephens, Robert] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. [Guo, Yongjian; Bour, Stephan] NIAID, Bioinformat & Sci IT Program, NIAID Off Technol Informat Syst, NIH, Bethesda, MD 20892 USA. RP Lempicki, RA (reprint author), NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM bsherman@mail.nih.gov; huangdawei@mail.nih.gov; tanq@mail.nih.gov; guoyo@niaid.nih.gov; sbou@niaid.nih.gov; dliu@ncifcrf.gov; bobs@ncifcrf.gov; mbaseler@mail.nih.gov; clane@niaid.nih.gov; rlempicki@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N0I-CO-56000] NR 21 TC 203 Z9 215 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 2 PY 2007 VL 8 AR 426 DI 10.1186/1471-2105-8-426 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 249KC UT WOS:000252225800001 PM 17980028 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI 25 years of HIV/AIDS science: Reaching the poor with research advances SO CELL LA English DT Editorial Material ID GLOBAL HEALTH; HIV; AIDS; COUNTRIES AB Last year marked the 25th anniversary of the recognition of what we now call AIDS. The AIDS pandemic has claimed more than 25 million lives, the majority of them in the developing world, and has exacerbated poverty and slowed human development. Although much has been accomplished in HIV/AIDS research, much remains to be done, especially regarding delivery of HIV/AIDS therapies and care and prevention interventions to the poorest countries that need them most. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 15 TC 12 Z9 12 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2007 VL 131 IS 3 BP 429 EP 432 DI 10.1016/j.cell.2007.10.019 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WF UT WOS:000250618500006 PM 17981106 ER PT J AU Hayashi, T Su, TP AF Hayashi, Teruo Su, Tsung-Ping TI Sigma-1 receptor chaperones at the ER-Mitochondrion interface regulate Ca2+ signaling and cell survival SO CELL LA English DT Article ID INOSITOL TRISPHOSPHATE RECEPTORS; UNFOLDED PROTEIN RESPONSE; SIGMA(1) BINDING-SITES; ENDOPLASMIC-RETICULUM; CALCIUM OSCILLATIONS; MEMBRANE-FRACTION; DYNAMICS; CHANNEL; MICRODOMAINS; AGONISTS AB Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca2+ directly to mitochondria via inositol 1,4,5- trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca2+- sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca2+ depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca2+ signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca2+ concentrations, regulates ER-mitochondrial interorganellar Ca2+ signaling and cell survival. C1 NIDA, Cellular Pathobiol Unit, Plast & Dev Sect, Cellular Neurobiol Res Branch,Intramural Res Prog, Baltimore, MD 21224 USA. RP Hayashi, T (reprint author), NIDA, Cellular Pathobiol Unit, Plast & Dev Sect, Cellular Neurobiol Res Branch,Intramural Res Prog, Room 3418,Room 3304,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM thayashi@intra.nida.nih.gov; tsu@intra.nida.nih.gov RI Hayashi, Teruo/A-9690-2008 FU Intramural NIH HHS NR 38 TC 587 Z9 601 U1 6 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2007 VL 131 IS 3 BP 596 EP 610 DI 10.1016/j.cell.2007.08.036 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WF UT WOS:000250618500025 PM 17981125 ER PT J AU Blanco, C Harford, TC Nunes, E Grant, B Hasin, D AF Blanco, Carlos Harford, Thomas C. Nunes, Edward Grant, Bridget Hasin, Deborah TI The latent structure of marijuana and cocaine use disorders: Results from the National Longitudinal Alcohol Epidemiologic Survey (NLAES) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; marijuana; factor analysis; nosology ID INTERVIEW SCHEDULE AUDADIS; ENVIRONMENTAL RISK-FACTORS; GENERAL-POPULATION SAMPLE; DSM-IV; UNITED-STATES; DRUG MODULES; CANNABIS DEPENDENCE; MAJOR DEPRESSION; ABUSE; RELIABILITY AB To better understand the underlying concepts of substance dependence and abuse, the present study examines the factor structure of DSM-IV lifetime criteria for cannabis and cocaine use disorders. Data for this study were drawn from the National Longitudinal Alcohol Epidemiologic Survey (NLAES), a large nationally representative U.S. sample aged 18 years and older. Exploratory factor analysis (EFA) examined the factor structure for each substance and the factors were related to background covariates using latent variable modeling techniques. Separate analyses were conducted for lifetime marijuana and cocaine users. A two-factor solution was identified for each substance and was similar to DSM-IV abuse and dependence. The factors were highly correlated for both cannabis (r = 0.73) and cocaine (r = 0.77). Background variables accounted only for a modest amount of factor variance. In conjunction with the findings in alcohol use disorders, these results support the use of consistent criteria across substances in DSM-IV and ICD-10, and suggest that the consistent finding of two correlated factors across substances needs to be better understood. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Portsmouth, NH 03801 USA. NIH, NIAAA, Div Intramral Clin & Biol Res, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY 10032 USA. RP Blanco, C (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA. EM cb255@columbia.edu RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU NIAAA NIH HHS [K05-AA014223, K05 AA014223]; NIDA NIH HHS [K02 DA023200, K23 DA000482, K23 DA000482-04, K23 DA00482, R01 DA 18652, R01 DA018652, R01 DA019606, R01 DA019606-01A2, R01 DA020783, R01 DA020783-01A1, R03 DA015559, R03 DA015559-02] NR 39 TC 19 Z9 19 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 2 PY 2007 VL 91 IS 1 BP 91 EP 96 DI 10.1016/j.drugalcdep.2007.04.003 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 219TS UT WOS:000250111700011 PM 17512682 ER PT J AU Jacobs, A Quraishi, O Huang, XC Bousquet-Gagnon, N Nault, G Francella, N Alvord, WG Pham, N Soucy, C Robitaille, M Bridon, D Blumenthal, R AF Jacobs, Amy Quraishi, Omar Huang, Xicai Bousquet-Gagnon, Nathalie Nault, Genevieve Francella, Nicholas Alvord, W. Gregory Pham, Nga Soucy, Chantal Robitaille, Martin Bridon, Dominique Blumenthal, Robert TI A covalent inhibitor targeting an intermediate conformation of the fusogenic subunit of the HIV-1 envelope complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-CELL FUSION; 6-HELIX BUNDLE; PEPTIDE INHIBITOR; POTENT INHIBITORS; SYNTHETIC PEPTIDE; ATOMIC-STRUCTURE; MEMBRANE-FUSION; COILED-COIL; SOLUBLE CD4 AB Peptide inhibitors corresponding to sequences in the six helix bundle structure of the fusogenic portion (gp41) of the HIV envelope glycoprotein have been successfully implemented in preventing HIV entry. These peptides bind to regions in HIV gp41 transiently exposed during the fusion reaction. In an effort to improve upon these entry inhibitors, we have successfully designed and tested peptide analogs composed of chemical spacers and reactive moieties positioned strategically to facilitate covalent attachment. Using a temperature-arrested state prime wash in vitro assay we show evidence for the trapping of a pre-six helix bundle fusion intermediate by a covalent reaction with the specific anti-HIV-1 peptide. This is the first demonstration of the trapping of an intermediate conformation of a viral envelope glycoprotein during the fusion process that occurs in live cells. The permanent specific attachment of the covalent inhibitor is projected to improve the pharmacokinetics of administration in vivo and thereby improve the long-term sustainability of peptide entry inhibitor therapy and help to expand its applicability beyond salvage therapy. C1 Conjuchem Biotechnol Inc, Montreal, PQ H2X 3Y8, Canada. NCI, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. Data Management Serv Inc, NCI, NIH, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), Conjuchem Biotechnol Inc, 225 President Kennedy Ave,Ste PK-3950, Montreal, PQ H2X 3Y8, Canada. EM blumenthalr@mail.nih.gov FU Intramural NIH HHS NR 50 TC 15 Z9 15 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 NOV 2 PY 2007 VL 282 IS 44 BP 32406 EP 32413 DI 10.1074/jbc.M705577200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224WY UT WOS:000250480300063 PM 17726011 ER PT J AU Wang, L Zhang, ZG Gregg, SR Zhang, RL Jiao, ZX LeTourneau, Y Liu, XS Feng, YF Gerwien, J Torup, L Leist, M Noguchi, CT Chen, ZY Chopp, M AF Wang, Lei Zhang, Zheng Gang Gregg, Sara R. Zhang, Rui Lan Jiao, Zhongxian LeTourneau, Yvonne Liu, Xianshuang Feng, Yifan Gerwien, Jens Torup, Lars Leist, Marcel Noguchi, Constance Tom Chen, Zhi-Yong Chopp, Michael TI The sonic hedgehog pathway mediates carbamylated erythropoietin-enhanced proliferation and differentiation of adult neural progenitor cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEM-CELLS; MAMMALIAN FOREBRAIN; SUBVENTRICULAR ZONE; IN-VIVO; SUBEPENDYMAL CELLS; PRECURSOR CELLS; CREST CELLS; NEUROGENESIS; STROKE; RAT AB Carbamylated erythropoietin (CEPO), a well characterized erythropoietin (EPO) derivative, does not bind to the classical EPO receptor and does not stimulate erythropoiesis. Using neural progenitor cells derived from the subventricular zone of the adult mouse, we investigated the effect of CEPO on neurogenesis and the associated signaling pathways in vitro. We found that CEPO significantly increased neural progenitor cell proliferation and promoted neural progenitor cell differentiation into neurons, which was associated with up-regulation of Sonic hedgehog (Shh), its receptor ptc, and mammalian achaete-scute homolog 1 (Mash1), a pro-neuron basic helix-loop-helix protein transcription factor. Blockage of the Shh signaling pathway with a pharmacological inhibitor, cyclopamine, abolished the CEPO-induced neurogenesis. Attenuation of endogenous Mash1 expression by short-interfering RNA blocked CEPO-promoted neuronal differentiation. In addition, recombinant mouse Shh up-regulated Mash1 expression in neural progenitor cells. These results demonstrate that the Shh signaling pathway mediates CEPO-enhanced neurogenesis and Mash1 is a downstream target of the Shh signaling pathway that regulates CEPO-enhanced neuronal differentiation. C1 Henry Ford Hosp, Dept Neurol, Henry Ford Hlth Sci Ctr, Detroit, MI 48202 USA. Oakland Univ, Dept Phys, Rochester, MI 48309 USA. H Lundbeck & Co AS, Drug Metab, DK-2500 Valby, Denmark. H Lundbeck & Co AS, Neurophamacol, DK-2500 Valby, Denmark. Univ Konstanz, Dept Biol, D-78457 Constance, Germany. NIDDK, Mol Cell Biol Sect, Biol Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zhang, ZG (reprint author), Henry Ford Hosp, Dept Neurol, Henry Ford Hlth Sci Ctr, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM zhazh@neuro.hfh.edu RI Leist, Marcel/D-2133-2010 OI Leist, Marcel/0000-0002-3778-8693 FU NHLBI NIH HHS [R01HL64766]; NINDS NIH HHS [P01 NS23393, P01 NS42345, R01NS43324] NR 44 TC 77 Z9 80 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 NOV 2 PY 2007 VL 282 IS 44 BP 32462 EP 32470 DI 10.1074/jbc.M706880200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224WY UT WOS:000250480300069 PM 17804404 ER PT J AU Tycko, R AF Tycko, Robert TI Stochastic dipolar recoupling in nuclear magnetic resonance of solids SO PHYSICAL REVIEW LETTERS LA English DT Article ID STATE NMR; ROTATING SOLIDS; SPECTROSCOPY; COUPLINGS AB I describe a nuclear magnetic resonance (NMR) technique, called stochastic dipolar recoupling (SDR), that permits continuous experimental control of the character of spin dynamics between coherent and incoherent limits in a system of magnetic dipole-coupled nuclei. In the fully incoherent limit of SDR, spin polarization transfers occur at distance-dependent rates without the quantum mechanical interferences among pairwise dipole-dipole couplings that often limit the feasibility or precision of structural studies of solids by NMR. In addition to facilitating structural studies, SDR represents a possible route to experimental studies of effects of decoherence on the dynamics of quantum many-body systems. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS [Z01 DK029029-11] NR 20 TC 21 Z9 21 U1 1 U2 12 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 2 PY 2007 VL 99 IS 18 AR 187601 DI 10.1103/PhysRevLett.99.187601 PG 4 WC Physics, Multidisciplinary SC Physics GA 227GA UT WOS:000250644000056 PM 17995438 ER PT J AU Linguraru, MG Kabla, A Marx, GR del Nido, PJ Howe, RD AF Linguraru, Marius George Kabla, Alexandre Marx, Gerald R. del Nido, Pedro J. Howe, Robert D. TI Real-time tracking and shape analysis of atrial septal defects in 3D echocardiography SO ACADEMIC RADIOLOGY LA English DT Article DE echocardiography; real time; atrial septal defect; tracking; segmentation; dynamic morphology ID BEATING-HEART-SURGERY; 3-DIMENSIONAL ULTRASOUND; CARDIOPULMONARY BYPASS; VELOCITY ESTIMATION; CLOSURE; SEGMENTATION; IMAGES; FEASIBILITY; MODEL AB beating heart procedures. Our application assists pediatric atrial septal defect (ASD) closure techniques using real-time 3D US guidance and rigid instruments. ASD tracking is also an important tool for facilitating systematic clinical studies of the dynamic behavior of the intra-atrial communication. One major image processing challenge is associated with the required processing of information at high frame rate, especially given the low image quality. Materials and Methods. We present an optimization scheme for a block flow technique, which combines the probability-based velocity computation for an entire block (a 3D volume centered on the ASD) with cyclic template matching. The adapted similarity imposes constraints both locally (from frame to frame) to conserve energy, and globally (from a reference template) to minimize cumulative errors. The algorithm is optimized for fast and reliable results. For tests, we use three intra-operational 4D ultrasound sequences of clinical infant beating hearts with ASD. Results. Computing velocity at the block level with an optimized scheme, our technique tracks ASD motion at a frequency of 60 frames/s on clinical 4D datasets. Results are stable and accurate for changes in resolution and block size. In particular, we show robust real-time tracking and preliminary segmentation results of the ASD shape, size and orientation as a function of time. Conclusions. We present an optimized block flow technique for real-time tracking of ASD to assist in minimally invasive beating heart surgery. Our method proposes the standard use of references for processing repetitive data. This paper represents, to our knowledge, the first study on the dynamic morphology of ASD that takes into account the angular effect introduced by the slanted position of the intra-atrial communication with respect to the US probe. C1 Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. NIH, Diagnost Radiol Dept, Bethesda, MD 20892 USA. Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England. Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiac Surg, Boston, MA USA. RP Linguraru, MG (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM lingurarum@mail.nih.gov OI Kabla, Alexandre/0000-0002-0280-3531 FU NHLBI NIH HHS [R01 HL073647-01, R01 HL073647] NR 29 TC 6 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2007 VL 14 IS 11 BP 1298 EP 1309 DI 10.1016/j.acra.2007.07.011 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229PR UT WOS:000250817000003 PM 17964455 ER PT J AU Armato, SG McNitt-Gray, MF Reeves, AP Meyer, CR McLennan, G Aberle, DR Kazerooni, EA MacMahon, H van Beek, EJR Yankelevitz, D Hoffman, EA Henschke, CI Roberts, RY Brown, MS Engelmann, RM Pais, RC Piker, CW Qing, D Kocherginsky, M Croft, BY Clarke, LP AF Armato, Samuel G., III McNitt-Gray, Michael F. Reeves, Anthony P. Meyer, Charles R. McLennan, Geoffrey Aberle, Denise R. Kazerooni, Ella A. MacMahon, Heber van Beek, Edwin J. R. Yankelevitz, David Hoffman, Eric A. Henschke, Claudia I. Roberts, Rachael Y. Brown, Matthew S. Engelmann, Roger M. Pais, Richard C. Piker, Christopher W. Qing, David Kocherginsky, Masha Croft, Barbara Y. Clarke, Laurence P. TI The Lung Image Database Consortium (LIDC): An evaluation of radiologist variability in the identification of lung nodules on CT scans SO ACADEMIC RADIOLOGY LA English DT Article DE lung nodule; computed tomography (CT); thoracic imaging; interobserver variability; computer-aided diagnosis (CAD) ID COMPUTER-AIDED DIAGNOSIS; PULMONARY NODULES; PERFORMANCE; TOMOGRAPHY; RESOURCE; SYSTEM; MDCT AB Rationale and Objectives: The purpose of this study was to analyze the variability of experienced thoracic radiologists in the identification of lung nodules on computed tomography (CT) scans and thereby to investigate variability in the establishment of the "truth" against which nodule-based studies are measured. Materials and Methods: Thirty CT scans were reviewed twice by four thoracic radiologists through a two-phase image annotation process. During the initial "blinded read" phase, radiologists independently marked lesions they identified as "nodule 3 rum (diameter)," "nodule < 3 mm," or "non-nodule. 3 mm." During the subsequent "unblinded read" phase, the blinded read results of all four radiologists were revealed to each radiologist, who then independently reviewed their marks along with the anonymous marks of their colleagues; a radiologist's own marks then could be deleted, added, or left unchanged. This approach was developed to identify, as completely as possible, all nodules in a scan without requiring forced consensus. Results: After the initial blinded read phase, 71 lesions received "nodule >= 3 mm" marks from at least one radiologist; however, all four radiologists assigned such marks to only 24 (33.8%) of these lesions. After the unblinded reads, a total of 59 lesions were marked as "nodule >= 3 mm" by at least one radiologist. Twenty-seven (45.8%) of these lesions received such marks from all four radiologists, three (5.1%) were identified as such by three radiologists, 12 (20.3%) were identified by two radiologists, and 17 (28.8%) were identified by only a single radiologist. Conclusion: The two-phase image annotation process yields improved agreement among radiologists in the interpretation of nodules >= 3 mm. Nevertheless, substantial variabilty remains across radiologists in the task of lung nodule identification. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Cornell Univ, Ithaca, NY 14853 USA. Univ Iowa, Iowa City, IA 52242 USA. NCI, Bethesda, MD 20892 USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, MC 2026,5841 S Maryland Ave, Chicago, IL 60637 USA. EM s-armato@uchicago.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU NCI NIH HHS [U01CA091085, U01 CA091085, U01 CA091090, U01 CA091090-01, U01 CA091090-02, U01 CA091090-03, U01 CA091090-04, U01 CA091090-05, U01 CA091090-05S1, U01 CA091099, U01 CA091100, U01 CA091103, U01CA091090, U01CA091099, U01CA091100, U01CA091103] NR 24 TC 53 Z9 54 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2007 VL 14 IS 11 BP 1409 EP 1421 DI 10.1016/j.acra.2007.07.008 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229PR UT WOS:000250817000012 PM 17964464 ER PT J AU Kobayashi, H Koyama, Y Barrett, T Hama, Y Regino, CAS Shin, IS Jang, BS Le, N Paik, CH Choyke, PL Urano, Y AF Kobayashi, Hisataka Koyama, Yoshinori Barrett, Tristan Hama, Yukihiro Regino, Celeste A. S. Shin, In Soo Jang, Beom-Su Le, Nhat Paik, Chang H. Choyke, Peter L. Urano, Yasuteru TI Multimodal nanoprobes for radionuclide and five-color near-infrared optical lymphatic imaging SO ACS NANO LA English DT Article DE dendrimer; scintigraphy; near-infrared; fluorescence imaging; multiple modalities; multiple colors; lymphatic imaging ID MAGNETIC RESONANCE LYMPHANGIOGRAPHY; NODE BIOPSY; BREAST-CANCER; QUANTUM DOTS; CONTRAST AGENT; IN-VIVO; MICE; SCINTIGRAPHY; ANGIOGRAPHY; MELANOMA AB Current contrast agents generally have one function and (an only be imaged in monochrome; therefore, the majority of imaging methods can only impart uniparametric information. A single nanoparticle has the potential to be loaded with multiple payloads. Such multimodality probes have the ability to be imaged by more than one imaging technique, which could compensate for the weakness or even combine the advantages of each individual modality. Furthermore, optical imaging using different optical probes enables us to achieve multicolor in vivo imaging, wherein multiple parameters can be read from a single image. To allow differentiation of multiple optical signals in vivo, each probe should have a close but different near-infrared emission. To this end, we synthesized nanoprobes with multimodal and multicolor potential, which employed a polyamidoamine dendrimer platform linked to both radionuclides and optical probes, permitting dual-modality scintigraphic and five-color near-infrared optical lymphatic imaging using a multiple-excitation spectrally resolved fluorescence imaging technique. C1 [Kobayashi, Hisataka; Koyama, Yoshinori; Barrett, Tristan; Hama, Yukihiro; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Regino, Celeste A. S.] NCI, Radiat Oncol Branch, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA. [Shin, In Soo; Jang, Beom-Su; Le, Nhat; Paik, Chang H.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Urano, Yasuteru] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS [Z01 BC010654-03, Z99 CA999999] NR 33 TC 128 Z9 131 U1 5 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD NOV PY 2007 VL 1 IS 4 BP 258 EP 264 DI 10.1021/nn700062z PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 249YP UT WOS:000252267200008 PM 19079788 ER PT J AU Blaszczyk, J Li, Y Cherry, S Alexandratos, J Wu, Y Shaw, G Tropea, JE Waugh, DS Yan, HG Ji, XH AF Blaszczyk, Jaroslaw Li, Yue Cherry, Scott Alexandratos, Jerry Wu, Yan Shaw, Gary Tropea, Joseph E. Waugh, David S. Yan, Honggao Ji, Xinhua TI Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; CONFORMATIONAL-CHANGES; TRANSFERABLE PLASMID; ARGININE RESIDUE-82; PROTEIN; ROLES; CRYSTALLOGRAPHY; INTERFACES AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate-biosynthetic pathway and is essential for microorganisms but absent from mammals. HPPK catalyzes Mg2+-dependent pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). Previously, three-dimensional structures of Escherichia coli HPPK (EcHPPK) have been determined at almost every stage of its catalytic cycle and the reaction mechanism has been established. Here, the crystal structure of Yersinia pestis HPPK (YpHPPK) in complex with HP and an ATP analog is presented together with thermodynamic and kinetic characterizations. The two HPPK molecules differ significantly in a helix-loop area (alpha 2-Lp3). YpHPPK has lower affinities than EcHPPK for both nucleotides and HP, but its rate constants for the mechanistic steps of both chemical transformation and product release are comparable with those of EcHPPK. Y. pestis, which causes plague, is a category A select agent according to the Centers for Disease Control and Prevention (CDC). Therefore, these structural and biochemical data are valuable for the design of novel medical countermeasures against plague. C1 Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Yan, HG (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM yanh@msu.edu; jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU Intramural NIH HHS; NIGMS NIH HHS [GM51901] NR 37 TC 10 Z9 10 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV PY 2007 VL 63 BP 1169 EP 1177 DI 10.1107/S0907444907047452 PN 11 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 232OU UT WOS:000251029800006 PM 18007032 ER PT J AU Hirai, H Hu, YF Notkins, AL Tzioufas, AG Lernmark, A Ivarsson, SA AF Hirai, H. Hu, Y. F. Notkins, A. L. Tzioufas, A. G. Lernmark, A. Ivarsson, S. -A. TI Selective screening of secretory vesicle-associated proteins for autoantibodies to type 1 diabetes SO ACTA DIABETOLOGICA LA English DT Meeting Abstract C1 [Hirai, H.; Hu, Y. F.; Notkins, A. L.; Tzioufas, A. G.] NIH, NIDCR, Bethesda, MD 20892 USA. [Lernmark, A.] Univ Washington, Seattle, WA 98195 USA. [Ivarsson, S. -A.] Lund Univ, Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD NOV PY 2007 VL 44 SU 1 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WD UT WOS:000251618000069 ER PT J AU Koczwara, K Franks, AK Harlan, DM Pechhold, K AF Koczwara, K. Franks, A. K. Harlan, D. M. Pechhold, K. TI In vivo assay for candidate cytotoxic T cell epitopes associated with autoimmune diabtes SO ACTA DIABETOLOGICA LA English DT Meeting Abstract C1 [Koczwara, K.; Franks, A. K.; Harlan, D. M.; Pechhold, K.] Natl Inst Hlth, NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD NOV PY 2007 VL 44 SU 1 BP S28 EP S28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WD UT WOS:000251618000090 ER PT J AU Pechhold, K Zhu, X Lee, J Liu, E Koczwara, K Harlan, DM AF Pechhold, K. Zhu, X. Lee, J. Liu, E. Koczwara, K. Harlan, D. M. TI Increased proliferation of insulin-producing B cells and diminished other-than-B endocrine islet cell frequencies coincide with development of autoimmune diabetes SO ACTA DIABETOLOGICA LA English DT Meeting Abstract C1 [Pechhold, K.; Zhu, X.; Lee, J.; Liu, E.; Koczwara, K.; Harlan, D. M.] Natl Inst Hlth, NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD NOV PY 2007 VL 44 SU 1 BP S39 EP S40 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WD UT WOS:000251618000129 ER PT J AU Heilig, M AF Heilig, Markus TI IMAGEN: Implications for addiction science and science policy SO ADDICTION LA English DT Editorial Material ID OPIOID RECEPTOR GENE; CORTICOTROPIN-RELEASING-FACTOR; ALCOHOL DEPENDENCE; FUNCTIONAL POLYMORPHISM; ANIMAL-MODELS; CRHR1; ASSOCIATION; SENSITIVITY; CONSUMPTION; RISK C1 NIAAA, Bethesda, MD 20892 USA. RP Heilig, M (reprint author), NIAAA, 10 Ctr Dr,10-1-5334, Bethesda, MD 20892 USA. EM mheilig@mail.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2007 VL 102 IS 11 BP 1699 EP 1700 DI 10.1111/j.1360-0443.2007.02004.x PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 220GD UT WOS:000250144300005 PM 17935578 ER PT J AU Lang, IA Rice, NE Wallace, RB Guralnik, JM Melzer, D AF Lang, Iain A. Rice, Neil E. Wallace, Robert B. Guralnik, Jack M. Melzer, David TI Smoking cessation and transition into retirement: analyses from the English Longitudinal Study of Ageing SO AGE AND AGEING LA English DT Article ID CORONARY HEART-DISEASE; OLDER-ADULTS; HEALTH; WOMEN; INTERVENTION; AMERICANS; DECLINE; TRIAL; RISK; MEN AB Background transitions such as retirement may represent points at which changes in health behaviour occur. Objective to assess whether transition into retirement is associated with increased rates of smoking cessation. Design population-based prospective cohort study in England. Setting and Participants one thousand seven hundred and twelve smokers aged 50years and over, followed up for 5 to 6years. Measurements work status (working/retired) and smoking status (non-smoker/smoker) at baseline and follow-up. Results at baseline, 381 (22.2%) of our respondents had retired, 444 (25.9%) were working and remained in work at follow-up, and 167 (9.8%) transitioned from work to retirement. Seven hundred and twenty (42.1%) had some other status (e.g. unpaid work/unemployment). A total of 42.5% (95% CI 34.950.1) of those who retired quit smoking; for those remaining in employment this figure was 29.3% (95% CI 25.033.6), and for those already retired it was 30.2% (95% CI 25.534.9). In adjusted regression analyses, those aged 5570 who retired were more than twice as likely (fully adjusted odds ratio 2.50 (95% CI 1.354.62)) to quit smoking as those who continued to work. Results were robust when those who retired for reasons of ill-health were excluded. Conclusions our results suggest individuals who undergo the transition into retirement are more likely to quit smoking than those who do not. Interventions should be developed to specifically target those who are retiring, or soon to retire, and those who are due to retire should be helped to incorporate smoking cessation into their retirement planning. C1 Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. NIH, Natl Inst Aging, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. RP Lang, IA (reprint author), Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. EM iain.lang@pms.ac.uk RI Lang, Iain/B-8255-2008; OI Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838 NR 22 TC 16 Z9 16 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD NOV PY 2007 VL 36 IS 6 BP 638 EP 643 DI 10.1093/ageing/afm119 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 239FZ UT WOS:000251505500008 PM 17906305 ER PT J AU Lutalo, T Gray, RH Wawer, M Sewankambo, N Serwadda, D Laeyendecker, O Kiwanuka, N Nalugoda, F Kigozi, G Ndyanabo, A Bwanika, JB Reynolds, SJ Quinn, T Opendi, P AF Lutalo, Tom Gray, Ronald H. Wawer, Maria Sewankambo, Nelson Serwadda, David Laeyendecker, Oliver Kiwanuka, Noah Nalugoda, Fred Kigozi, Godfrey Ndyanabo, Anthony Bwanika, John Baptist Reynolds, Steven J. Quinn, Tom Opendi, Pius TI Survival of HIV-infected treatment-naive individuals with documented dates of seroconversion in Rakai, Uganda SO AIDS LA English DT Article DE HIV survival; subtype; Uganda ID DISEASE PROGRESSION; TYPE-1 INFECTION; NATURAL-HISTORY; FOLLOW-UP; AFRICA; COHORT; SUBTYPES; MORTALITY; TANZANIA; WOMEN AB Objective: To estimate the survival time from HIV infection to death. Methods: A community cohort in Rakai district, Uganda, identified 837 seroconverters followed annually between 1995 and 2003 until they died, were censored by out-migration or truncated on 31 December 2003 because antiretroviral treatment became available. HIV-1 subtype was determined by multiple hybridization assay for 396 seroconverters. The median interval from infection to death was estimated by Kaplan-Meier survival analyses and Weibull models. Hazard ratios (HR) and their 95% confidence intervals (Cl) associated with survival were estimated using Cox proportional hazards modeling Results: There were 122 deaths over 2330 person-years (py), an average mortality of 5.2/100 py. The median survival time was 8.7 years (95% Cl 8.1-9.3), and did not differ by sex, place of residence or time period of seroconversion. Survival time decreased significantly with older age at infection (P = 0.01). Survival was shorter with subtypes D, AD recombinant or multiple infections compared with subtype A (log rank P = 0.04), but this was of borderline significance after adjustment (adjusted HR 3.47, 95% Cl 0.89-15.44, P = 0.07). Non-A subtypes constituted 84.6% of all identifiable infections and had a median survival time of 7.5 years (95% Cl 6.4-8.5), whereas over 90% of those infected with subtype A were still alive 7 years post-infection. Conclusion: The median survival time in Rakai was shorter than reported in other African populations, and we hypothesize that this may be a result of the predominance of non-A subtypes with faster disease progression in this population. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Gray, Ronald H.; Wawer, Maria] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21215 USA. [Lutalo, Tom; Kiwanuka, Noah; Nalugoda, Fred; Kigozi, Godfrey; Ndyanabo, Anthony; Bwanika, John Baptist; Opendi, Pius] Rakai Hlth Sci Program, Entebbe, Uganda. [Sewankambo, Nelson] Makerere Univ, Dept Med, Kampala, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Laeyendecker, Oliver; Reynolds, Steven J.; Quinn, Tom] Natl Inst Hlth, Bethesda, MD USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Suite E4132, 615N Wolfe St, Baltimore, MD 21215 USA. EM rgray@jhsph.edu RI Laeyendecker, Oliver/B-9331-2009 FU FIC NIH HHS [5D43TW00010]; NICHD NIH HHS [5P30HD06826]; PHS HHS [R01 A134265, R01 A134826] NR 25 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV PY 2007 VL 21 SU 6 BP S15 EP S19 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 243KC UT WOS:000251794200003 PM 18032934 ER PT J AU Nussenblatt, V McLaughlin, M Rehm, CA Lempicki, RA Brann, T Yang, J Proschan, M Highbarger, HC Dewar, RL Imamichi, T Koratich, C Neumann, AU Masur, H Polis, MA Kottilil, S AF Nussenblatt, Veronique McLaughlin, Mary Rehm, Catherine A. Lempicki, Richard A. Brann, Terry Yang, Jun Proschan, Michael Highbarger, Helene C. Dewar, Robin L. Imamichi, Tom Koratich, Chad Neumann, Avidan U. Masur, Henry Polis, Michael A. Kottilil, Shyam TI Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CHRONIC HEPATITIS-C; ALPHA-2A PLUS RIBAVIRIN; INFECTED PATIENTS; VIRUS-INFECTION; PEGYLATED INTERFERON-ALPHA-2B; PEGINTERFERON; ANTIBODIES AB Viral breakthroughs (VB), defined as having detectable HCV VL while on anti-HCV therapy after achieving maximal suppression, have not yet been characterized with the use of PEG-IFN in HIV/HCV-coinfected patients. We evaluated possible mechanisms for VB among HIV/HCV-coinfected patients receiving PEG-IFN/RBV. Thirty HIV/HCV coinfected patients were treated with PEG-IFN (1.5 mu g/kg sc qwk) and RBV (1-1.2 g daily) for 48 weeks. Liver chemistry, HCV VL, genotyping, DNA microarray, and sequencing of HCV E-2 envelope were performed before and during treatment. VB had lower baseline HCV VL but higher ALT and AST than relapsers (ETR) (p < 0.05) and lower CD4(+) T lymphocytes (%) than patients with sustained virological responses (SVR), but similar first and second phase HCV viral kinetics (vs. ETR and SVR; p > 0.05). HCV genotypes and envelope sequences were similar for patients with VB pretreatment and at breakthrough. VB had higher levels of interferon-induced gene (IFIG) expression pretreatment than patients with ETR ( p < 0.01). HIV/HCV-coinfected patients have a high rate of VB on PEG-IFN/RBV therapy characterized by higher levels of IFIG expression, immunodeficiency, and hepatic inflammation. Novel strategies are required for the treatment of persons with VB. C1 NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH,US Dept HHS, Bethesda, MD 20892 USA. SAIC Frederick Natl Canc Inst, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIDDK, Lab Biol Modeling, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, US Dept HHS, Bethesda, MD 20892 USA. RP Kottilil, S (reprint author), NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH,US Dept HHS, Bldg 10,Rm 11N204, Bethesda, MD 20892 USA. EM skottilil@niaid.nih.gov RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Polis, Michael/0000-0002-9151-2268 NR 19 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2007 VL 23 IS 11 BP 1354 EP 1359 DI 10.1089/aid.2007.0091 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 239SU UT WOS:000251538800007 PM 18184077 ER PT J AU Bakshi, RP Hamzeh, F Frank, I Eron, JJ Bosch, RJ Rosenkranz, SL Cramer, YS Ussery, M Flexner, C AF Bakshi, Rahul P. Hamzeh, Fayez Frank, Ian Eron, Joseph J., Jr. Bosch, Ronald J. Rosenkranz, Susan L. Cramer, Yoninah S. Ussery, Michael Flexner, Charles TI Effect of hydroxyurea and dideoxyinosine on intracellular 3 '-deoxyadenosine-5 '-triphosphate concentrations in HIV-infected patients SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-TRIALS; DIDANOSINE; SAFETY; PHARMACOKINETICS; REPLICATION; COMBINATION; EFFICACY; DRUG AB Hydroxyurea (HU) significantly enhances the antiretroviral effects of the adenosine analog reverse transcriptase inhibitor dideoxyinosine (ddI). This is believed to be due to a reduction in intracellular deoxyadenosine triphosphate (dATP) concentrations resulting from HU-mediated inhibition of ribonucleotide reductase (RnR). The effect of combined HU-ddI treatment on intracellular dATP pools in vivo has not been examined. We measured intracellular dATP concentrations in peripheral blood mononuclear cells (PBMCs) from 69 HIV-infected patients receiving 1000 or 1500 mg HU daily for 14 days, 200 mg ddI twice daily for 14 days, or a combination of the two drugs. Median intracellular dATP concentrations decreased from baseline to day 14 by 46% in the ddI + 1000 mg HU arm and by 62% in the ddI + 1500 mg HU arm. When compared to the HU monotherapy arms, these changes proved statistically significant (p = 0.018; stratified Wilcoxon rank-sum test). These findings support reduced intracellular dATP as the mechanism of ddI-HU synergistic activity, and indicate that changes in intracellular nucleotides contribute to HU activity and toxicity in patients. Since a significant reduction in dATP was measurable only when ddI was combined with HU, the antiretroviral activity of ddI may be more complex than previously assumed. C1 Johns Hopkins Univ, Dept Med, Div Clin Pharmacol, Baltimore, MD 21287 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. RP Flexner, C (reprint author), Johns Hopkins Univ, Dept Med, Div Clin Pharmacol, Osler 527,600 N Wolfe St, Baltimore, MD 21287 USA. EM flex@jhmi.edu OI Bakshi, Rahul/0000-0003-1478-1031 FU NCRR NIH HHS [RR-00046, RR-00052]; NIAID NIH HHS [U01 AI025868, AI-25868, AI-27668, U01 AI069423, AI-38858, AI-38855] NR 22 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2007 VL 23 IS 11 BP 1360 EP 1365 DI 10.1089/aid.2007.0078 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 239SU UT WOS:000251538800008 PM 18184078 ER PT J AU Gao, X Chen, HL Fung, TT Logroscino, G Schwarzschild, MA Hu, FB Ascherio, A AF Gao, Xiang Chen, Honglei Fung, Teresa T. Logroscino, Giancarlo Schwarzschild, Michael A. Hu, Frank B. Ascherio, Alberto TI Prospective study of dietary pattern and risk of Parkinson disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE Parkinson disease; dietary pattern; prospective study; dietary index; principal components analysis ID CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; HEALTHY LIFE-STYLE; URIC-ACID LEVELS; METHYLENETETRAHYDROFOLATE REDUCTASE; NEURODEGENERATIVE DISEASES; ENDOTHELIAL DYSFUNCTION; PLASMA-CONCENTRATIONS; MEDITERRANEAN DIET AB Background: Several studies have shown associations between Parkinson Disease (PD) risk and individual foods and nutrients with inconsistent results. Objective: We examined associations between dietary patterns and risk of PD in the Health Professionals Follow-Up Study (19862002) and the Nurses' Health Study (1984-2000). Design: We included 49 692 men and 81676 women free of PD at baseline and used principal components analysis to identify major dietary patterns and the Alternate Healthy Eating Index (AHEI) and the alternate Mediterranean Diet Score (aMed) to assess diet quality. Relative risks (RRs) were computed by using Cox proportional hazards models within each cohort and were pooled by using a random-effects model. Results: We documented 508 new PD cases after 16 y of follow-up. The principal components analysis identified 2 dietary patterns: prudent and Western. The prudent dietary pattern, characterized by high intakes of fruit, vegetables, and fish, was inversely associated with PD risk. but the Western pattern was not. The pooled multivariate-adjusted RR for the top compared with the bottom quintiles of the prudent score was 0.78 (95% Cl: 0.56. 1.07; P for trend = 0.04). For the AHEI, the pooled multivariate-adjusted RR for the top compared with the bottom quintile was 0.70 (95% Cl: 0.51. 0.94; P for trend 0.01) and for aMED was 0.75 (95% Cl: 0.57. 1.00; P for trend 0.07). Conclusions: Dietary patterns with a high intake of fruit, vegetables, legumes, whole grains, nuts, fish, and poultry and a low intake of saturated fat and a moderate intake of alcohol may protect against PD. Benefits of a plant-based dietary pattern including fish to PD merit further investigation. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Simmons Coll, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gao, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM xgao@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2, R01 NS048517-03] NR 49 TC 95 Z9 96 U1 2 U2 13 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2007 VL 86 IS 5 BP 1486 EP 1494 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 231HE UT WOS:000250936500032 PM 17991663 ER PT J AU Li, TY Zhang, C Asselbergs, FW Qi, L Rimm, E Hunter, DI Hu, FB AF Li, Tricia Y. Zhang, Cuilin Asselbergs, Folkert W. Qi, Lu Rimm, Eric Hunter, David I. Hu, Frank B. TI Interaction between dietary fat intake and the cholesterol ester transfer protein TaqlB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cholesterol ester transfer protein; CETP; genetics; polymorphism; dietary fat; HDL cholesterol; diabetes ID HIGH-DENSITY-LIPOPROTEIN; CETP GENE; HEPATIC LIPASE; ALCOHOL-CONSUMPTION; MELLITUS; ACID; METABOLISM; RISK; MICE; ACYLTRANSFERASE AB Background: A low plasma HDL-cholesterol concentration is a major characteristic of diabetic dyslipidemia. HDL concentrations are determined by both environmental factors and genetic factors. Cholesterol ester transfer protein (CETP) plays an important role in the regulation of HDL metabolism, and the TaqIB polymorphism of the CETP gene has been associated with elevated HDL concentrations. Objective: We examined the association between the CETP TaqIB polymorphism and plasma HDL concentrations and evaluated whether this association was modified by dietary fat intake Design: We followed 780 diabetic men aged 40-75 y who participated in the Health Professionals Follow-Up Study since its initiation in 1986. The participants had confirmed type 2 diabetes and were free of cardiovascular disease at the time blood was drawn. Results: After adjustment for age, smoking, alcohol consumption, fasting status, hemoglobin A(1C), physical activity, total energy intake and body mass index, HDL concentrations were significantly higher in men with the B2B2 or B1B2 genotype than in those with the B1B1 genotype (adjusted (x) over bar +/- SE: 37.9 +/- 0.02, 40.3 +/- 0.01, and 42.6 +/- 0.02 mg/dL for B1B1. B1B2, and B2B2, respectively P for trend 0.0004). This inverse association of the B1 allele with plasma HDL concentrations existed for those with a high consumption of animal fat (P for interaction = 0.02), saturated fat (P for interaction = 0.02) and monounsaturated fat (P for interaction = 0.04). Conclusion: These data confirmed a significant effect of the CETP Taq1 gene on HDL concentrations and suggested a potential interaction between the CETP Taq1B polymorphism and intake of dietary fat on plasma HDL concentration. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD 20892 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. EM nhbfh@channing.harvard.edu FU NHLBI NIH HHS [HL 35464, HL 65582] NR 34 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2007 VL 86 IS 5 BP 1524 EP 1529 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 231HE UT WOS:000250936500037 PM 17991668 ER PT J AU Stoler, M Castle, P Solomon, D Schiffman, M AF Stoler, Mark Castle, Philip Solomon, Diane Schiffman, Mark TI Expanded use of human papillomavirus testing in gynecologic practice - Reply SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ATYPICAL SQUAMOUS-CELLS; HYBRID CAPTURE 2; UNDETERMINED SIGNIFICANCE; COSTA-RICA; WOMEN; TRIAGE; CANCER; CARCINOGENICITY; SMEARS C1 NCI, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, Charlottesville, VA USA. RP Stoler, M (reprint author), Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, Charlottesville, VA USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 2007 VL 128 IS 5 BP 884 EP 886 PG 3 WC Pathology SC Pathology GA 222PS UT WOS:000250310000024 ER PT J AU Stoler, M Solomon, D Schiffman, M AF Stoler, Mark Solomon, Diane Schiffman, Mark TI Expanded use of human Papillomavirus testing in gynecologic practice - The authors' reply SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter ID MANAGEMENT; WOMEN C1 NCI, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, Charlottesville, VA USA. RP Stoler, M (reprint author), Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, Charlottesville, VA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 2007 VL 128 IS 5 BP 888 EP 890 PG 3 WC Pathology SC Pathology GA 222PS UT WOS:000250310000026 ER PT J AU Bonner, MR Coble, J Blair, A Freeman, LEB Hoppin, JA Sandler, DP Alavanja, MCR AF Bonner, Matthew R. Coble, Joseph Blair, Aaron Freeman, Laura E. Beane Hoppin, Jane A. Sandler, Dale P. Alavanja, Michael C. R. TI Malathion exposure and the incidence of cancer in the agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE malathion; neoplasms; pesticides ID NON-HODGKINS-LYMPHOMA; ORGANOPHOSPHORUS INSECTICIDE MALATHION; CHROMOSOMAL-ABERRATIONS; PESTICIDE APPLICATORS; IN-VITRO; MICRONUCLEUS ASSAY; OXIDATIVE STRESS; PROSTATE-CANCER; RISK-FACTORS; WORKERS AB Malathion is the most common organophosphate insecticide applied in the United States, and while some studies suggest that it may be clastogenic, its carcinogenicity has not been demonstrated in rodents. However, malathion has been associated with non-Hodgkin's lymphoma in several epidemiologic studies. The authors investigated associations between malathion exposure and cancer among 19,717 pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Information on lifetime years and days per year of use and intensity of malathion exposure was obtained with self-administered questionnaires prior to the onset of any cancer. The average follow-up time was 7.5 years (1993-2002). Rate ratios and 95% confidence intervals were calculated using Poisson regression, adjusting for potential confounders. Overall, lifetime days of malathion use (top tertile of exposure, >39 days) was not associated with all cancers combined (rate ratio = 0.97, 95% confidence interval: 0.81, 1.15). The risk of non-Hodgkin's lymphoma was not associated with malathion use, although the number of cases was small. The risk of melanoma with more than 39 lifetime exposure-days was 0.39 (95% confidence interval: 0.14, 1.03). In summary, malathion exposure was not clearly associated with cancer at any of the sites examined. Although the rate ratios for melanoma were reduced, small numbers and lack of experimental evidence suggest that the observed reductions may have arisen by chance. C1 NCI, Natl Inst Hlth, US Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Hlth, Natl Inst Environm Hlth Sci, US Dept Hlth & Human Serv, Epidemiol Branch, Res Triangle Pk, NC 20892 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, 2160 Executive Blvd, Bethesda, MD USA. EM alavanjm@exchange.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 62 TC 40 Z9 44 U1 2 U2 13 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 NOV 1 PY 2007 VL 166 IS 9 BP 1023 EP 1034 DI 10.1093/aje/kwm182 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223VN UT WOS:000250400700006 PM 17720683 ER PT J AU Hahn, KME Bondy, ML Selvan, M Lund, MJ Liff, JM Flagg, EW Brinton, LA Porter, P Eley, JW Coates, RJ AF Hahn, Karin M. E. Bondy, Melissa L. Selvan, Mano Lund, Mary Jo Liff, Jonathan M. Flagg, Elaine W. Brinton, Louise A. Porter, Peggy Eley, J. William Coates, Ralph J. TI Factors associated with advanced disease stage at diagnosis in a population-based study of patients with newly diagnosed breast cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; breast neoplasms; demography; ethnic groups; socioeconomic factors ID HORMONE-RECEPTOR STATUS; AFRICAN-AMERICAN; WHITE WOMEN; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; RACIAL-DIFFERENCES; ADIPOSE-TISSUE; TUMOR CHARACTERISTICS; HEALTH-INSURANCE; CERVICAL-CANCER AB Breast cancer is diagnosed at a younger age and a more advanced stage in African-American women than in White women. The authors investigated the effects of several factors, including race, on stage of breast cancer in women aged 20-54 years living in Atlanta, Georgia, and diagnosed between 1990 and 1992. A total of 251 African-American and 580 White women were interviewed and their medical records reviewed. By use of polytomous logistic regression, factors possibly influencing stage and racial differences in stage were studied. In African-American women, the odds of stage III/IV breast cancer at diagnosis were almost four times the odds in White women (odds ratio = 3.79, 95% confidence interval: 2.45, 5.89) and approximately two and one-half times for stage IIA or stage IIB disease (odds ratio = 2.57, 95% confidence interval: 1.66, 3.99; odds ratio = 1.94, 95% confidence interval: 1.31, 2.86, respectively). These racial differences appeared to be largely explained by insurance status, poverty, history of mammography, method of tumor detection, and obesity. Interventions targeting these factors could potentially lower the stage at diagnosis for African-American breast cancer patients and, in doing so, improve their survival and other outcomes. C1 Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol & Epidemiol, Houston, TX 77230 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77230 USA. Univ Texas, MD Anderson Canc Ctr, Dept Qual Improvement, Houston, TX 77230 USA. Emory Univ, Winship Canc Inst, Atlanta, GA USA. Emory Univ, Rollins Sch Public Hlth, Dept Epidemiol, Atlanta, GA USA. Natl Ctr HIV,STD & TB Prevent, Ctr Dis Control & Prevent, Div Std HIV Prevent, Atlanta, GA USA. Natl Canc Inst, Hormonal & Reproduct Epidemiol Branch, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. RP Hahn, KME (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol & Epidemiol, PO Box 301439, Houston, TX 77230 USA. EM khahn@mdanderson.org RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [R01-CA64292-01A2, N01-CP-95604, N01-PC-35135]; PHS HHS [U48 CCU0619515] NR 49 TC 69 Z9 69 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2007 VL 166 IS 9 BP 1035 EP 1044 DI 10.1093/aje/kwm177 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223VN UT WOS:000250400700007 PM 17690220 ER PT J AU Simons-Morton, B AF Simons-Morton, Bruce TI Growing and becoming: American academy of health behavior 2007 presidential welcome address SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Editorial Material C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd 7B13M, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gou NR 0 TC 0 Z9 0 U1 0 U2 0 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2007 VL 31 IS 6 BP 667 EP 669 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 233LG UT WOS:000251091800011 ER PT J AU Simons-Morton, B AF Simons-Morton, Bruce TI Social influences adolescent substance use SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE latent growth curve modeling; mediation; peer influence; parenting; selection; socialization ID GROWTH CURVE ANALYSES; PEER ALCOHOL-USE; PARENT INFLUENCES; DRUG-USE; SMOKING; SELECTION; CHILDREN; DRINKING; ONSET; PROGRESSION AB Objectives: To assess the over-time relationships between adolescent and peer substance use and parenting practices. Methods: Five times from sixth to ninth grade, students (n=2453) inn 7 middle schools reported smoking, drinking, and marijuana use; the number of substance-using friends; and parent practices. Relationships were assessed using latent growth curve modeling. Results: Adolescent substance use predicted the growth in substance-using friends, and substance-using friends predicted adolescent use, except for smoking. The negative over-time relationship between parenting practices and adolescent substance use was mediated by tine growth in tine number of substance-using friends. Conclusions: The results are consistent with both selection and socialization effects and provide evidence of the protective effects of positive parenting practices. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd 7B13M, Bethesda, MD 20892 USA. EM mortonb@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [N01-HD-4-3207] NR 45 TC 49 Z9 51 U1 4 U2 14 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2007 VL 31 IS 6 BP 672 EP 684 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 233LG UT WOS:000251091800013 PM 17691881 ER PT J AU Abou Jamra, R Fuerst, R Kaneva, R Diaz, GO Rivas, F Mayoral, F Gay, E Sans, S Gonzalez, MJ Gil, S Cabaleiro, F del Rio, F Perez, F Haro, J Auburger, G Milanova, V Kostov, C Chorbov, V Stoyanova, V Nikolova-Hill, A Onchev, G Kremensky, I Jablensky, A Schulze, TG Propping, P Rietschel, M Nothen, MM Cichon, S Wienker, TF Schumacher, J AF Abou Jamra, Rami Fuerst, Robert Kaneva, Radka Diaz, Guillermo Orozco Rivas, Fabio Mayoral, Fermin Gay, Eudoxia Sans, Sebastian Gonzalez, Maria Jose Gil, Susana Cabaleiro, Francisco del Rio, Francisco Perez, Fermin Haro, Jesus Auburger, Georg Milanova, Vihra Kostov, Christian Chorbov, Vesselin Stoyanova, Vessela Nikolova-Hill, Amelia Onchev, George Kremensky, Ivo Jablensky, Assen Schulze, Thomas G. Propping, Peter Rietschel, Marcella Noethen, Markus M. Cichon, Sven Wienker, Thomas F. Schumacher, Johannes TI The first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder: Strong evidence of epistatic effects between loci on chromosomes 2q and 6q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DYSBINDIN GENE DTNBP1; NF-KAPPA-B; SUSCEPTIBILITY LOCUS; WIDE SCAN; NATIONAL-INSTITUTE; INCREASE SUSCEPTIBILITY; PUTATIVE LOCI; I DISORDER; SCHIZOPHRENIA; PEDIGREES AB We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P < .0001 and P = .0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; and P = .0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies. C1 NIMH, Unit Genet Basis Mood & Anxiety Disorders, Natl Inst Hlth, Bethesda, MD 20892 USA. Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. Community Adolescent Team, Hunter New England Hlth, New Lambton, Australia. Pfalzklinikum, Klin Psychiat & Psychotherapie, Rockenhausen, Germany. Univ Frankfurt, Neurol Clin, D-6000 Frankfurt, Germany. Mental Hlth Care Ctr Algeciras Cadiz, Cadiz, Spain. Puerto Santamaria Cadiz, La Unidad Rehabil Area, Cadiz, Spain. Mental Hlth Care Ctr San Dionisio Jerez Frontera, Cadiz, Spain. Prov Hosp, Jaen, Spain. Mental Hlth Care Ctr Montoro, Cordoba, Spain. Mental Hlth Care Ctr Lucena, Cordoba, Spain. Univ Hosp Reina Sofia, Cordoba, Spain. Civil Hosp Carlos Haya, Malaga, Spain. Med Univ Sofia, Dept Psychiat, Sofia, Bulgaria. Med Univ Sofia, Natl Genet Lab, Sofia, Bulgaria. Med Univ Sofia, Mol Med Ctr, Sofia, Bulgaria. Univ Cologne, Cologne Ctr Genom, Cologne, Germany. Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany. Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany. Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. RP Schumacher, J (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, Natl Inst Hlth, 35 Convent Dr,1A-202, Bethesda, MD 20892 USA. EM schumacherj@mail.nih.gov RI mayoral, fermin/C-2652-2013; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Jablensky, Assen/H-5116-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Nothen, Markus/0000-0002-8770-2464 NR 45 TC 22 Z9 22 U1 2 U2 6 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 NOV PY 2007 VL 81 IS 5 BP 974 EP 986 DI 10.1086/521690 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 224XE UT WOS:000250480900009 PM 17924339 ER PT J AU Karkera, JD Lee, JS Roessler, E Banerjee-Basu, S Ouspenskaia, MV Mez, J Goldmuntz, E Bowers, P Towbin, J Belmont, JW Baxevanis, AD Schier, AF Muenke, M AF Karkera, J. D. Lee, J. S. Roessler, E. Banerjee-Basu, S. Ouspenskaia, M. V. Mez, J. Goldmuntz, E. Bowers, P. Towbin, J. Belmont, J. W. Baxevanis, A. D. Schier, A. F. Muenke, M. TI Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; NODAL SIGNALS; EXPRESSION; PROTEIN; XENOPUS; GENE; VG1; SPECIFICATION; ESTABLISHMENT AB Congenital heart defects (CHDs) are among the most common birth defects in humans (incidence 8-10 per 1,000 live births). Although their etiology is often poorly understood, most are considered to arise from multifactorial influences, including environmental and genetic components, as well as from less common syndromic forms. We hypothesized that disturbances in left-right patterning could contribute to the pathogenesis of selected cardiac defects by interfering with the extrinsic cues leading to the proper looping and vessel remodeling of the normally asymmetrically developed heart and vessels. Here, we show that heterozygous loss-of-function mutations in the human GDF1 gene contribute to cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries and that decreased TGF-beta signaling provides a framework for understanding their pathogenesis. These findings implicate perturbations of the TGF-beta signaling pathway in the causation of a major subclass of human CHDs. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Mol & Cellular Biol, Harvard Stem Cell Inst, Broat Inst, Cambridge, MA 02138 USA. Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Baylor Coll Med, Dept Pediat, Div Cardiol, Houston, TX 77030 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Belmont, John/0000-0001-7409-3578; Mez, Jesse/0000-0003-1438-5442 FU Intramural NIH HHS; PHS HHS [PSOHL74731] NR 42 TC 49 Z9 51 U1 1 U2 7 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 NOV PY 2007 VL 81 IS 5 BP 987 EP 994 DI 10.1086/522890 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 224XE UT WOS:000250480900010 PM 17924340 ER PT J AU Venugopal, B Browning, MF Curcio-Morelli, C Varro, A Michaud, N Nanthakumar, N Walkley, SU Pickel, J Slaugenhaupt, SA AF Venugopal, Bhuvarahamurthy Browning, Marsha F. Curcio-Morelli, Cyntia Varro, Andrea Michaud, Norman Nanthakumar, Nanda Walkley, Steven U. Pickel, James Slaugenhaupt, Susan A. TI Neurologic, gastric, and opthalmologic Pathologies in a murine model of Mucolipidosis type IV SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TARGETED DISRUPTION; LYSOSOMAL STORAGE; CATION CHANNEL; CULTURED FIBROBLASTS; ABNORMAL TRANSPORT; MEMBRANE-PROTEIN; ACID-SECRETION; MOUSE MODEL; GENE; DISEASE AB Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV. The Mcoln1(-/-) mice present with numerous dense inclusion bodies in all cell types in brain and particularly in neurons, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. Neurobehavioral assessments, including analysis of gait and clasping, confirm the presence of a neurological defect. Gait deficits progress to complete hind-limb paralysis and death at age similar to 8 mo. The Mcoln1(-/-) mice are born in Mendelian ratios, and both male and female Mcoln1(-/-) mice are fertile and can breed to produce progeny. The creation of the first murine model for human MLIV provides an excellent system for elucidating disease pathogenesis. In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Liverpool, Sch Biomed Sci, Physiol Labs, Liverpool L69 3BX, Merseyside, England. Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominck P Purpura Dept Neurosci, Bronx, NY 10467 USA. Natl Inst Mental Hlth Transgen Core, NIH, Bethesda, MD USA. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM susan_slaugenhaupt@chgr.mgh.harvard.edu RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NICHD NIH HHS [HD045561, R01 HD045561]; NIDDK NIH HHS [DK12437, DK40561, DK43351, DK57521, DK70260, P30 DK040561, P30 DK043351, P30 DK057521, R01 DK070260]; NIGMS NIH HHS [T32-GM077481-25]; NINDS NIH HHS [1F32NS052072-01A1, F32 NS052072, NS39995, R01 NS039995] NR 73 TC 56 Z9 57 U1 0 U2 1 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 NOV PY 2007 VL 81 IS 5 BP 1070 EP 1083 DI 10.1086/521954 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 224XE UT WOS:000250480900017 PM 17924347 ER PT J AU Grotto, I Huerta, M Grossman, E Sharabi, Y AF Grotto, Itamar Huerta, Michael Grossman, Ehud Sharabi, Yehonatan TI Relative impact of socioeconomic status on mood pressure - Lessons from a large-scale survey of young adults SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; socioeconomic status; epidemiology; young adults ID CARDIOVASCULAR-DISEASE RISK; BLOOD-PRESSURE; EDUCATIONAL-ATTAINMENT; LIFE-STYLE; JOB STRAIN; STRESS; HYPERTENSION; MEN; POSITION; ATHEROSCLEROSIS AB Background: Although several studies reported on the association between socioeconomic status (SES) and hypertension, the results are conflicting, the quantification is problematic, only a few focused on young adults, and the effects of various key determinants of SES, such as education and job type, need further clarification. We aimed to assess the influence of SES on blood pressure in a large population of young adults. Methods: We studied 11,053 male Israel Defense Force officers who underwent periodic medical evaluation during the years 1991 to 1999. Subjects completed a detailed medical questionnaire and underwent physical examination. We calculated mean systolic and diastolic blood pressure (SBP and DBP, respectively) by level of education, rank, and job type (as measures of SES), adjusting for demographic variables and body mass index (BMI). Results: Adjusted means of SBP and DBP were highest among low-ranking officers (SBP, 119 mm Hg, compared with 117 and 115 mm Hg among intermediate and high-ranking officers, respectively, P < .001; DBP, 77 mm Hg, compared with 76 mm Hg among intermediate and high-ranking officers, P = .001). No differences were observed for level of education, but the mean SBP was higher among office workers (117 turn Hg nu 116 mm Hg among physical workers, P = .038). The partial eta(2) for rank, age, and BMI was found to be 0.003, 0.008, and 0.066, respectively, for SBP, and 0.002, 0.026 and 0.054, respectively, for DBP. Conclusions: Low SES, as reflected by low rank, is associated with elevated blood pressure. However, as a whole, SES is a weak determinant of blood pressure compared with age and BMI. (C) 2007 American Journal of Hypertension, Ltd. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol, IL-84105 Beer Sheva, Israel. Israel Def Forces Med Corps, Tel Hashomer, Israel. Sheba Med Ctr, Hypertens Unit, Tel Hashomer, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Grotto, I (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol, PO Box 653, IL-84105 Beer Sheva, Israel. EM grotto@bgu.ac.il RI Grotto, Itamar/F-2028-2012 NR 30 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 2007 VL 20 IS 11 BP 1140 EP 1145 DI 10.1016/j.amjhyper.2007.06.004 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 231QK UT WOS:000250963900002 PM 17954358 ER PT J AU Hendler, I Andrews, WW Carey, CJ Klebanoff, MA Noble, WD Sibai, BM Hillier, SL Dudley, D Ernest, JM Leveno, KJ Wapner, R Iams, JD Varner, M Moawad, A Miodovnik, M O'Sullivan, MJ Van Dorsten, PJ AF Hendler, Israel Andrews, William W. Carey, Christopher J. Klebanoff, Mark A. Noble, William D. Sibai, Baha M. Hillier, Sharon L. Dudley, Donald Ernest, Joseph M. Leveno, Kenneth J. Wapner, Ronald Iams, Jay D. Varner, Michael Moawad, Atef Miodovnik, Menachem O'Sullivan, Mary J. Van Dorsten, Peter J. CA NICHHDMF Med Units Network TI The relationship between resolution of asymptomatic bacterial vaginosis and spontaneous preterm birth in fetal fibronectin-positive women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med DE antibiotic treatment; bacterial vaginosis; fetal fibronectin; preterm birth ID PREGNANT-WOMEN; METRONIDAZOLE; DELIVERY; INFECTION; PREVENTION; PREDICTION; ERYTHROMYCIN; TRIAL; RISK AB Objective: The purpose of this study was to determine the impact of persistent bacterial vaginosis (BV) on the occurrence of spontaneous preterm birth (SPB) in women who test positive for fetal fibronectin. Study design: This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7) and 25(6/7) weeks of gestation and who participated in randomized placebo controlled trials of antibiotic therapy. Nugent's criteria were used for the diagnosis of BV. Patients were reassessed for the presence of BV after treatment. The rate of SPB at <34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit. Results: The primary studies included a total of 3285 women. A subset of 215 women met the criteria for this analysis. Seventy-seven of 100 patients (77%) in the antibiotics group vs 33 of the 115 patients (28.7%) in the placebo group became BV negative (P = .0001). The rate of SPB at <34 weeks of gestation was lower for BV resolution compared with persistent BV (0 vs 5.7%, respectively; P = .01). Conclusion: In women who tested positive for fetal fibronectin and BV, resolution of BV is associated with less SPB before 34 weeks of gestation. C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. Univ Alabama, Med Sch Birmingham, Birmingham, AL USA. Univ Oklahoma, Coll Med, Oklahoma City, OK USA. Natl Inst Hlth, NICHHD, Bethesda, MD USA. George Washington Univ, Ctr Med, Washington, DC USA. Univ Tennessee, Hlth Sci Ctr, Coll Med, Dept Obstet & Gynecol, Memphis, TN USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Texas, Hlth Sci Ctr, Sch Med, San Antonio, TX USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA USA. Ohio State Univ, Coll Med, Columbus, OH USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Univ Chicago, Pritzker Sch Med, Chicago, IL USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. Med Univ S Carolina, Charleston, SC USA. RP Hendler, I (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3990 John R St, Detroit, MI 48201 USA. EM ihendler@med.wayne.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 NR 22 TC 2 Z9 2 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2007 VL 197 IS 5 AR 488.e5 DI 10.1016/j.ajog.2007.03.073 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 230ZN UT WOS:000250915500012 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI The birth of Caesar and the Cesarean Misnomer SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE cesarean birth; history of medicine; history of obstetrics; Julius Caesar; Ulysses grant AB Although cesarean section is one of the most ancient surgical procedures, the origin of its name remains obscure. The term, however, did not originate because of the birth of the Roman Emperor Julius Caesar through this route. In fact, historians are certain that Julius Caesar was not delivered by the dangerous cesarean section. The evidence for this comes from indirect inferences. Cesarean sections were rarely attempted on living women until the early 17th century, and Julius Caesar's mother was alive and wen through her son's adult life. Two other possible reasons for the origin of the term are discussed in this article. Mention is also made of the cesarean birth histories of some mythological characters and a few historical personalities. C1 NIH, NICHD, CDBPM, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NIH, NICHD, CDBPM, Pregnancy & Perinatol Branch, 6100 Execut Blvd, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2007 VL 24 IS 10 BP 567 EP 568 DI 10.1055/s-2007-986693 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 233KN UT WOS:000251089900001 PM 17893840 ER PT J AU Benjamin, IJ Guo, Y Srinivasan, S Boudina, S Taylor, RP Rajasekaran, NS Gottlieb, R Wawrousek, EF Abel, ED Bolli, R AF Benjamin, Ivor J. Guo, Yiru Srinivasan, Sathyanarayanan Boudina, Sihem Taylor, Ryan P. Rajasekaran, Namakkal S. Gottlieb, Roberta Wawrousek, Eric F. Abel, E. Dale Bolli, Roberto TI CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE small molecular weight heat shock protein; cardioprotection; aging; preconditioning; reperfusion injury ID ALPHA-B-CRYSTALLIN; SHOCK-PROTEIN FAMILY; INTRAMITOCHONDRIAL CA2+; ENERGY-METABOLISM; LATE-PHASE; PHOSPHORYLATION; MUSCLE; STRESS; CALCIUM; GENE AB The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched (similar to 5-9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion x 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 +/- 17.9 vs. 59.8 +/- 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges. C1 Univ Utah, Sch Med, Ctr Cardiovasc Translat Biomed, Salt Lake City, UT USA. Univ Louisville, Inst Mol Cardiol, Louisville, KY 40292 USA. Univ Utah, Program Human Mol Biol & Genet, Div Endocrinol & Metab, Salt Lake City, UT USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Benjamin, IJ (reprint author), 30 N 1900 E,Rm 4A100, Salt Lake City, UT 84112 USA. EM ivor.benjamin@hsc.utah.edu RI Wawrousek, Eric/A-4547-2008; Bolli, Roberto/A-6870-2010; Guo, Yiru/L-2618-2015 FU NHLBI NIH HHS [R01 HL043151, R01 HL055757, R01 HL063834, R01-HL-63834] NR 39 TC 32 Z9 32 U1 0 U2 3 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 NOV PY 2007 VL 293 IS 5 BP H3201 EP H3209 DI 10.1152/ajpheart.01363.2006 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TU UT WOS:000251400100071 PM 17873008 ER PT J AU Pagel-Langenickel, I Schwartz, DR Arena, RA Minerbi, DC Johnson, DT Waclawiw, MA Cannon, RO Balaban, RS Tripodi, DJ Sack, MN AF Pagel-Langenickel, Ines Schwartz, Daniel R. Arena, Ross A. Minerbi, Diane C. Johnson, D. Thor. Waclawiw, Myron A. Cannon, Richard O., III Balaban, Robert S. Tripodi, Dorothy J. Sack, Michael N. TI A discordance in rosiglitazone mediated insulin sensitization and skeletal muscle mitochondrial content/activity in Type 2 diabetes mellitus SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE exercise capacity; citrate synthase activity; peroxisome proliferator-activated receptor gamma-agonist ID IMPAIRED FASTING GLUCOSE; ADIPOSE-TISSUE; CARDIOVASCULAR RISK; EXERCISE CAPACITY; ENZYME-ACTIVITY; RESISTANCE; BIOGENESIS; METABOLISM; DYSFUNCTION; REDUCTION AB Skeletal muscle mitochondrial dysfunction is hypothesized to contribute to the pathophysiology of insulin resistance and Type 2 diabetes. Whether thiazolidinedione therapy enhances skeletal muscle mitochondrial function as a component of its insulin-sensitizing effect is unknown. To test this, we evaluated skeletal muscle mitochondria and exercise capacity in Type 2 diabetic subjects with otherwise normal cardiopulmonary function in response to rosiglitazone therapy. Twenty-three subjects were treated for 12 wk and underwent pre- and post-therapy metabolic stress testing and skeletal muscle biopsies. Rosiglitazone significantly ameliorated fasting glucose, insulin, and free fatty acid levels but did not augment the subjects' maximal oxygen consumption ( VO(2max)) or their skeletal muscle mitochondrial copy number. The baseline VO(2max) correlated strongly with muscle mitochondrial copy number ( r = 0.56, P = 0.018, n = 17) and inversely with the duration of diabetes ( r = - 0.67, P = 0.004, n = 23). Despite the global lack of effect of rosiglitazone-mediated insulin sensitization on skeletal muscle mitochondria, subjects with the most preserved functional capacity demonstrated some plasticity in their mitochondria biology as evidenced by an upregulation of electron transfer chain proteins and in citrate synthase activity. This study demonstrates that the augmentation of skeletal muscle mitochondrial electron transfer chain content and/or bioenergetics is not a prerequisite for rosiglitazone-mediated improved insulin sensitivity. Moreover, in diabetic subjects, VO(2max) reflects the duration of diabetes and skeletal muscle mitochondrial content. It remains to be determined whether longer-term insulin sensitization therapy with rosiglitazone will augment skeletal muscle mitochondrial bioenergetics in those diabetic subjects with relatively preserved basal aerobic capacity. C1 NHLBI, NIH, Cardiol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Office Biostat Res, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. Virginia Commonwealth Univ, Dept Physiol, Richmond, VA USA. Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA. RP Sack, MN (reprint author), NHLBI, NIH, Cardiol Branch, Bldg 10-CRC,Rm 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 FU Intramural NIH HHS NR 39 TC 12 Z9 12 U1 0 U2 2 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 NOV PY 2007 VL 293 IS 5 BP H2659 EP H2666 DI 10.1152/ajpheart.00782.2007 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TU UT WOS:000251400100009 PM 17890427 ER PT J AU Grenz, A Zhang, H Weingart, J Von Wietersheim, S Eckle, T Schnermann, J Kohle, C Kloor, D Gleiter, CH Vallon, V Eltzschig, HK Osswald, H AF Grenz, Almut Zhang, Hua Weingart, Jochen Von Wietersheim, Simone Eckle, Tobias Schnermann, Juergen Kohle, Christoph Kloor, Doris Gleiter, Christoph H. Vallon, Volker Eltzschig, Holger K. Osswald, Hartmut TI Lack of effect of extracellular adenosine generation and signaling on renal erythropoietin secretion during hypoxia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE adenosine receptors; ecto-5'-nucleotidase; CD73; carbon monoxide ID RAT-KIDNEY; TUBULOGLOMERULAR FEEDBACK; ECTO-5'-NUCLEOTIDASE CD73; MICE LACKING; MAJOR ROLE; RECEPTOR; THEOPHYLLINE; GENE; TRANSPLANTATION; ERYTHROCYTOSIS AB Previous studies have yielded conflicting results as to whether extracellular adenosine generation and signaling contributes to hypoxia-induced increases in renal erythropoietin (EPO) secretion. In this study, we combined pharmacological and genetic approaches to elucidate a potential contribution of extracellular adenosine to renal EPO release in mice. To stimulate EPO secretion, we used murine carbon monoxide exposure (400 and 750 parts per million CO, 4 h), ambient hypoxia (8% oxygen, 4 h), or arterial hemodilution. Because the ecto-5-nucleotidase (CD73, conversion of AMP to adenosine) is considered the pacemaker of extracellular adenosine generation, we first tested the effect of blocking extracellular adenosine generation with the specific CD73-inhibitor adenosine 5'-(alpha,beta- methylene) diphosphate (APCP) or by gene-targeted deletion of cd73. These studies showed that neither APCP-treatment nor targeted deletion of cd73 resulted in changes of stimulated EPO mRNA or serum levels, although the increases of adenosine levels in the kidney following CO exposure were attenuated in mice with APCP treatment or in cd73-/- mice. Moreover, pharmacological studies using specific inhibitors of individual adenosine receptors (A(1)AR, DPCPX; A(2A)AR, DMPX; A(2B)AR, PSB 1115; A(3)AR, MRS 1191) showed no effect on stimulated increases of EPO mRNA or serum levels. Finally, stimulated EPO secretion was not attenuated in gene-targeted mice lacking A(1)AR -/-, A(2A)AR -/-, A(2B)AR -/-, or A(3)AR -/-. Together, these studies combine genetic and pharmacological in vivo evidence that increases of EPO secretion during limited oxygen availability are not affected by extracellular adenosine generation or signaling. C1 Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol & Perioperat Med, Mucosal Inflammat Program, Denver, CO 80262 USA. Univ Tubingen Hosp, Dept Pharmacol & Toxicol, Tubingen, Germany. Univ Appl Sci, Albstadt Sigmaringen, Germany. Univ Tubingen Hosp, Dept Anesthesiol & Intens Care Med, Tubingen, Germany. NIDDK, Natl Inst Hlth, Bethesda, MD USA. Univ Calif San Diego, Dept Med & Pharmacol, San Diego, CA 92103 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Eltzschig, HK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Anesthesiol & Perioperat Med, Mucosal Inflammat Program, 4200 E 9th Ave,Campus Box B113, Denver, CO 80262 USA. EM holger.eltzschig@uchsc.edu; hartmut.osswald@uni-tuebingen.de NR 53 TC 17 Z9 18 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 NOV PY 2007 VL 293 IS 5 BP F1501 EP F1511 DI 10.1152/ajprenal.00243.2007 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 225WD UT WOS:000250548000010 PM 17855480 ER PT J AU Bukelis, I Porter, FD Zimmerman, AW Tierney, E AF Bukelis, Irena Porter, Forbes D. Zimmerman, Andrew W. Tierney, Elaine TI Smith-Lemli-Opitz syndrome and autism spectrum disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID CHOLESTEROL; MICRODOMAINS; INDIVIDUALS; DIAGNOSIS; PLASMA C1 Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Ctr Genet Disorders Cofnit & Behav,Dept Psychait, Baltimore, MD 21211 USA. NICHHD, NIH, Heritable Disorders Branch, Bethesda, MD 20892 USA. RP Tierney, E (reprint author), Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Ctr Genet Disorders Cofnit & Behav,Dept Psychait, 3901 Greenspring Ave, Baltimore, MD 21211 USA. EM tier-ney@kennedykrieger.org FU Intramural NIH HHS; NIMH NIH HHS [154MH066417] NR 22 TC 34 Z9 35 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2007 VL 164 IS 11 BP 1655 EP 1661 DI 10.1176/appi.ajp.2007.07020315 PG 7 WC Psychiatry SC Psychiatry GA 229NP UT WOS:000250811200009 PM 17974928 ER PT J AU Brogly, SB Franco, EL Watts, DH Van Dyke, R AF Brogly, Susan B. Franco, Eduardo L. Watts, D. Heather Van Dyke, Russell TI Brogly et al. respond SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID CHILDREN C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat, AIDS Res, Boston, MA 02115 USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. McGill Univ, Dept Oncol, Montreal, PQ, Canada. NICHD, Pediat Adolescent & Mat AIDS Branch, Rockville, MD USA. Tulane Univ, Dept Pediat, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Brogly, SB (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat, AIDS Res, 651 Huntington Ave,FXB-607, Boston, MA 02115 USA. EM sbrogly@sdac.harvard.edu NR 4 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 NOV PY 2007 VL 97 IS 11 BP 1930 EP 1930 DI 10.2105/AJPH.2007.119594 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 225AJ UT WOS:000250489200004 ER PT J AU Richardson, HS AF Richardson, Henry S. TI Gradations of researchers' obligation to provide ancillary care for HIV/AIDS in developing countries SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; MEDICAL RESEARCHERS; TRIAL PARTICIPANTS; CLINICAL CARE; RESPONSIBILITIES; AFRICA; ETHICS C1 Georgetown Univ, Dept Philosophy, Washington, DC 20057 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Richardson, HS (reprint author), Georgetown Univ, Dept Philosophy, Washington, DC 20057 USA. EM richardh@georgetown.edu NR 22 TC 27 Z9 27 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 NOV PY 2007 VL 97 IS 11 BP 1956 EP 1961 DI 10.2105/AJPH.2006.093658 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 225AJ UT WOS:000250489200014 PM 17901449 ER PT J AU Subramaniam, M Bausch, C Twomey, A Andreeva, S Yoder, BA Chang, LY Crapo, JD Pierce, RA Cuttitta, F Sunday, ME AF Subramaniam, Meera Bausch, Christine Twomey, Anne Andreeva, Svetlana Yoder, Bradley A. Chang, LingYi Crapo, James D. Pierce, Richard A. Cuttitta, Frank Sunday, Mary E. TI Bornbesin-like peptides modulate alveolarization and angiogenesis in bronchopulmonary dysplasia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE bombesin; gastrin-releasing peptide; mechanical ventilation; prematurity; antibody treatment ID HYALINE-MEMBRANE DISEASE; BOMBESIN-LIKE PEPTIDE; PULMONARY NEUROENDOCRINE CELLS; ENDOTHELIAL GROWTH-FACTOR; NEONATAL LUNG-DISEASE; GENE-EXPRESSION; BABOON MODEL; PREMATURE BABOONS; POTENTIAL ROLE; IN-VITRO AB Rationale: The incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, is paradoxically rising despite medical advances. We demonstrated elevated bombesin-like peptide levels in infants that later developed BPD. In the 140-day hyperoxic baboon model of BPD, anti-bombesin antibody 2A11 abrogated lung injury. Objectives: To test the hypothesis that bombesin-like peptides mediate BPD in extremely premature baboons (born at Gestational Day 125 and given oxygen pro re nata [PRN], called the 125-day PRN model), similar to "modern-day BPD." Methods: The 125-day animals were treated with 2A11 on Postnatal Day 1 (P1), P3, and P6. On P14 and P21, lungs were inflation-fixed for histopathologic analyses of alveolarization. Regulation of angiogenesis by bombesin was evaluated using cultured pulmonary microvascular endothelial cells. Measurements and Main Results: In 125-day PRN animals, urine bombesin-like peptide levels at P2-3 are directly correlated with impaired lung function at P14. Gastrin-releasing peptide (the major pulmonary bombesin-like peptide) mRNA was elevated eightfold at P1 and remained high thereafter. At P14, 2A11 reduced alveolar wall thickness and increased the percentage of secondary septa containing endothelial cells. At P21, 2A11-treated 125-day PRN animals had improved alveolarization according to mean linear intercepts and number of branch points per millimeter squared. Bombesin promoted tubulogenesis of cultured pulmonary microvascular endothelial cells, but cocultured fetal lung mesenchymal cells abrogated this effect. Conclusions: Early bombesin-like peptide overproduction in 125-day PRN animals predicted alveolarization defects weeks later. Bombesin-like peptide blockade improved septation, with the greatest effects at P21. This could have implications for preventing BPD in premature infants. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm,Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Pulm Med,Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Washington Univ, Med Ctr, St Louis, MO USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sunday, ME (reprint author), Duke Univ, Med Ctr, DUMC Box 3712, Durham, NC 27708 USA. EM mary.sunday@duke.edu RI Cuttitta, Frank/B-4758-2016 FU NCRR NIH HHS [P51RR1398]; NHLBI NIH HHS [UO1-HL52636, UO1-HL52638] NR 55 TC 28 Z9 30 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 NOV 1 PY 2007 VL 176 IS 9 BP 902 EP 912 DI 10.1164/rccm.200611-1734OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 225ON UT WOS:000250527300011 PM 17585105 ER PT J AU Zembowicz, A Knoepp, SM Bei, T Stergiopoulos, S Eng, C Mihm, MC Stratakis, CA AF Zembowicz, Artur Knoepp, Stewart M. Bei, Thalia Stergiopoulos, Sotirios Eng, Charis Mihm, Martin C. Stratakis, Constantine A. TI Loss of expression of protein kinase A regulatory subunit 1 alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pigmented epithelioid melanocytoma; nevus; melanoma; equine melanotic disease; epithelioid blue nevus; Carney complex; protein kinase A regulatory subunit 1 alpha ID ANIMAL-TYPE MELANOMA; CARNEY COMPLEX; BLUE NEVUS; REGULATORY SUBUNIT; MALIGNANT-MELANOMA; PRKAR1A GENE; MOUSE MODEL; I-ALPHA; TUMORS; MUTATIONS AB Pigmented epithelioid melanocytoma (PEM) is a recently described entity comprising most cases previously described as "animal-type melanoma" and epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory subunit type 1 alpha (R1 alpha) (coded by the PRKAR1A gene) are found in more than half of CNC patients. In this study, we investigated whether PEM and EBN are related at the molecular level, and whether changes in the PRKAR1A gene status and the expression of the R1 alpha protein may be involved in the pathogenesis of PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin-stained sections and immunohistochemistry (IHC) with R1 alpha antibody were performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86 melanomas of various types); in addition, 170 tissue microarray sections consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas, and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on preexisting pathologic reports and were confirmed for this study. DNA studies [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene sequencing] were performed on 60 melanomas and 7 PEMs. IHC showed that R I a was expressed in all but one core from tissue microarrays (169/170), and in all 127 melanocytic lesions evaluated in conventional sections. By contrast, R1 alpha was not expressed in the 8 EBN from patients with CNC and PRKAR1A mutations. Expression of R1 alpha was lost in 28 of 34 PEMs (82%). R1 alpha was expressed in the 5 equine melanomas studied. DNA studies correlated with IHC findings: there were no PRKAR1A mutations in any of the melanomas studied and the rate of LOH for 17q22-24 was less than 7%; 5 of the 7 PEMs showed extensive 17q22-24 LOH but no PRKAR1A mutations. The results support the concept that PEM is a distinct melanocytic tumor occurring in a sporadic setting and in the context of CNC. They also suggest that PEM differs from melanomas in equine melanotic disease, further arguing that the term animal-type melanoma may be a misnomer for this group of lesions. Loss of expression of R1 alpha offers a useful diagnostic test that helps to distinguish PEM from lesions that mimic it histologically. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. NICHHD, NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. Taussig Canc Ctr, Cleveland, OH USA. Cleveland Clin Fdn, Lerner Res Inst, Genome Med Inst, Cleveland, OH 44195 USA. RP Zembowicz, A (reprint author), Lahey Clin Fdn, Dept Pathol, 41 Mall Rd, Burlington, MA 01805 USA. EM dr.zembowicz@DermatopathologyConsultations.com FU Intramural NIH HHS NR 30 TC 50 Z9 51 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2007 VL 31 IS 11 BP 1764 EP 1775 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 225OL UT WOS:000250527100018 PM 18059235 ER PT J AU Kirk, AD Cherikh, WS Ring, M Burke, G Kaufman, D Knechtle, SJ Potdar, S Shapiro, R Dharnidharka, VR Kauffman, HM AF Kirk, A. D. Cherikh, W. S. Ring, M. Burke, G. Kaufman, D. Knechtle, S. J. Potdar, S. Shapiro, R. Dharnidharka, V. R. Kauffman, H. M. TI Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE depletion; induction therapy; kidney transplantation; posttransplant lymphoproliferative disease ID RENAL-ALLOGRAFT SURVIVAL; TRANSPLANTATION; CAMPATH-1H; IMMUNOSUPPRESSION; THERAPY; MONOTHERAPY; THYMOGLOBULIN; METAANALYSIS; SIROLIMUS; DISORDER AB Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk. C1 Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. United Network Organ Sharing, Res, Richmond, VA USA. NIDDK, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33152 USA. Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. Univ Wisconsin, Hlth Sci Ctr, Div Transplantat, Madison, WI USA. Geisinger Med Ctr, Dept Surg, Danville, PA 17822 USA. Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. Univ Florida, Div Pediat Nephrol, Gainesville, FL USA. RP Kirk, AD (reprint author), Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. EM allan.kirk@emoryhealthcare.org RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS [Z01 DK062007-06] NR 21 TC 112 Z9 115 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 NOV PY 2007 VL 7 IS 11 BP 2619 EP 2625 DI 10.1111/j.1600-6143.2007.01972.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 219IH UT WOS:000250077600025 PM 17868060 ER PT J AU Regis, DP Sedegah, M Mendoza-Silveiras, J Steinbeiss, V Reyes, S Epstein, JE Chuang, I Williams, F Levine, GL Bruder, JT King, CR Patterson, NB Limbach, K Soisson, L Diggs, C Doolan, DL Richie, T AF Regis, David P. Sedegah, Martha Mendoza-Silveiras, Jose Steinbeiss, Victoria Reyes, Sharina Epstein, Judith E. Chuang, Ilin Williams, Francis Levine, Gail L. Bruder, Joseph T. King, C. Richter Patterson, Noelle B. Limbach, Keith Soisson, Lorraine Diggs, Carter Doolan, Denise L. Richie, Thomas TI Safety and tolerability of a multi-stage, multi-antigen adenovirus-vectored Plasmodium Falciparum malaria vaccine, in healthy, malaria-naive adults SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Regis, David P.; Sedegah, Martha; Mendoza-Silveiras, Jose; Steinbeiss, Victoria; Reyes, Sharina; Epstein, Judith E.; Chuang, Ilin; Williams, Francis; Patterson, Noelle B.; Limbach, Keith; Doolan, Denise L.; Richie, Thomas] Naval Med Res Ctr, Silver Spring, MD USA. [Levine, Gail L.] Fdn Natl Inst Hlth, Bethesda, MD USA. [King, C. Richter] GenVec Inc, Gaithersburg, MD USA. [Soisson, Lorraine; Diggs, Carter] US Agcy Int Dev, Malaria Vaccine Program, Washington, DC USA. RI Doolan, Denise/F-1969-2015 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 11 BP 3 EP 3 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200012 ER PT J AU Miura, K Zhou, H Mullen, G Moretz, S Diouf, A Diemert, D Dicko, A Miller, L Doumbo, O Long, C AF Miura, Kazutoyo Zhou, Hong Mullen, Gregory Moretz, Samuel Diouf, Ababacar Diemert, David Dicko, Alassane Miller, Louis Doumbo, Ogobara Long, Carole TI Purified IGGS from unvaccinated malians interfere with the biological activity of apical membrane antigen 1-specific IGGS as judged by the in vitro growth inhibition assay SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Miura, Kazutoyo; Zhou, Hong; Mullen, Gregory; Moretz, Samuel; Diouf, Ababacar; Diemert, David; Miller, Louis; Long, Carole] NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD USA. [Dicko, Alassane; Doumbo, Ogobara] Univ Bamako, Malaria Res & Training Ctr, Dept Haematol & Parasitol, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 13 BP 4 EP 4 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200014 ER PT J AU Gupta, L Kumar, S Barillas-Mury, C AF Gupta, Lalita Kumar, Sanjeev Barillas-Mury, Carolina TI Anopheles gambiae STAT pathway participates in mosquito immunity SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Gupta, Lalita; Kumar, Sanjeev; Barillas-Mury, Carolina] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 39 BP 12 EP 12 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200040 ER PT J AU Martin, LB Long, CA Zhou, H Medina, S Newland, J Moretz, SE Lambert, LE Mullen, GE Saul, A MiLer, LH AF Martin, Laura B. Long, Carole A. Zhou, Hong Medina, Sarimar Newland, Joseph Moretz, Samuel E. Lambert, Lynn E. Mullen, Gregory E. Saul, Allan Miler, Louis H. TI Animal immunogenicity studies of a blood-stage malaria vaccine based on a combination of AMA1 and MSP1(42) SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Martin, Laura B.; Long, Carole A.; Zhou, Hong; Medina, Sarimar; Newland, Joseph; Moretz, Samuel E.; Lambert, Lynn E.; Mullen, Gregory E.; Saul, Allan; Miler, Louis H.] Natl Inst Hlth, NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. RI Martin, Laura/N-1789-2013; OI Martin, Laura/0000-0002-4431-4381; Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 47 BP 14 EP 15 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200048 ER PT J AU Avrill, M Kulasekara, B Gose, S Rowe, C Dahlback, M Salanti, A Misher, L Narum, DL Smith, JD AF Avrill, Marion Kulasekara, Bridget Gose, Severin Rowe, Chris Dahlbaeck, Madeleine Salanti, Ali Misher, Lynda Narum, David L. Smith, Joe D. TI Induction of antibodies in rabbits against the pregnancy malaria vaccine candidate VAR2CSA using Pichia pastoris yeast and plasmid DNA immunization SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Avrill, Marion; Kulasekara, Bridget; Gose, Severin; Misher, Lynda; Smith, Joe D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Rowe, Chris; Narum, David L.] Natl Inst Hlth, NIAID, Rockville, MD USA. [Dahlbaeck, Madeleine; Salanti, Ali] Ctr Med Parasitol, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 49 BP 15 EP 15 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200050 ER PT J AU Patterson, NB Bruder, JT Limbach, K McGrath, A Enright, B King, CR Butman, BT Gowda, K Chen, P Konovalova, S Moretz, SE Zhou, H Diouf, A Richie, TL Li, S Soisson, L Diggs, C Locke, E Brandt, W Long, CA Doolan, DL AF Patterson, Noelle B. Bruder, Joseph T. Limbach, Keith McGrath, Andrew Enright, Bill King, C. Richter Butman, Bryan T. Gowda, Kalpana Chen, Ping Konovalova, Svetlana Moretz, Samuel E. Zhou, Hong Diouf, Ababacar Richie, Thomas L. Li, Sheng Soisson, Lorraine Diggs, Carter Locke, Emily Brandt, Walter Long, Carole A. Doolan, Denise L. TI Monovalent and bivalent adenovectored vaccines expressing the Plasmodium falciparum antigens AMA-1 and MSP1-42 (3D7) elicit functional antibodies in NZW rabbits SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Patterson, Noelle B.; Limbach, Keith; Gowda, Kalpana; Richie, Thomas L.; Doolan, Denise L.] Naval Med Res Ctr, Silver Spring, MD USA. [Bruder, Joseph T.; McGrath, Andrew; Enright, Bill; King, C. Richter; Butman, Bryan T.; Chen, Ping; Konovalova, Svetlana] GenVic Inc, Rockville, MD USA. [Moretz, Samuel E.; Zhou, Hong; Diouf, Ababacar; Long, Carole A.] Natl Inst Hlth, NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [Li, Sheng; Locke, Emily; Brandt, Walter] PATH Malaria Vaccine Initiative, Bethesda, MD USA. [Soisson, Lorraine; Diggs, Carter] United States Agcy Int Dev, Malaria Vaccine Dev Program, Washington, DC USA. RI Doolan, Denise/F-1969-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 48 BP 15 EP 15 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200049 ER PT J AU Ramalho-Ortigao, M Coutinho-Abreu, IV Stayback, G Wadsworth, M Fawaz, E El-Hossary, S Hanafi, H Hoel, D Abo-Shehada, M Valenzuela, J Kamhawi, S Mukbel, R McDowell, MA AF Ramalho-Ortigao, Marcelo Coutinho-Abreu, Iliano V. Stayback, Gwen Wadsworth, Marina Fawaz, Emad El-Hossary, Shaaban Hanafi, Hanafi Hoel, David Abo-Shehada, Mahmoud Valenzuela, Jesus Kamhawi, Shaden Mukbel, Rami McDowell, Mary Ann TI Differential expression of salivary gland CDNAS in laboratory and field populations of Phlebotomus papatasi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Ramalho-Ortigao, Marcelo; Coutinho-Abreu, Iliano V.; Stayback, Gwen; Wadsworth, Marina; Mukbel, Rami; McDowell, Mary Ann] Univ Notre Dame, Notre Dame, IN 46556 USA. [Fawaz, Emad; El-Hossary, Shaaban; Hanafi, Hanafi; Hoel, David] Naval Med Res Unit 3, Cairo, Egypt. [Abo-Shehada, Mahmoud] Jordan Univ Sci & Technol, Irbid, Jordan. [Valenzuela, Jesus; Kamhawi, Shaden] NIH, Rockville, MD USA. RI Ramalho-Ortigao, Marcelo/E-8225-2011; Coutinho-Abreu, Iliano/C-6548-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 64 BP 19 EP 20 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200065 ER PT J AU Teixeira, CR Kamhawi, S Gomes, RB Oliveira, LF Elnaiem, DE Valenzuela, JG AF Teixeira, Clarissa R. Kamhawi, Shaden Gomes, Regis B. Oliveira, Luiz F. Elnaiem, Dia-eldin Valenzuela, Jesus G. TI Evaluation of early inflammatory response expression in response to Phlebotomus duboscqi bites SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Teixeira, Clarissa R.; Kamhawi, Shaden; Gomes, Regis B.; Oliveira, Luiz F.; Elnaiem, Dia-eldin; Valenzuela, Jesus G.] NIH, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 69 BP 21 EP 21 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200070 ER PT J AU Mills, LA Blank, LR Kagaayi, J Aluma, S Shott, J Bwanika, JB Wawer, MJ Serwadda, D Quinn, TC Reynolds, SJ Gray, RL AF Mills, Lisa A. Blank, Lydia R. Kagaayi, Joseph Aluma, Simon Shott, Joseph Bwanika, John B. Wawer, Maria J. Serwadda, David Quinn, Thomas C. Reynolds, Steven J. Gray, Ronald L. TI Performance of a malaria rapid diagnostic test versus traditional microscopy among rural Ugandan outpatients SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Mills, Lisa A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Blank, Lydia R.] Becton Dickinson Diagnost Syst, Cockeysville, MD USA. [Kagaayi, Joseph; Aluma, Simon; Bwanika, John B.; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda. [Shott, Joseph; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Bethesda, MD USA. [Wawer, Maria J.; Gray, Ronald L.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 96 BP 28 EP 29 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200097 ER PT J AU Blaney, J Wlazlo, A Speicher, J Sathe, N Hanson, C Murphy, B Whitehead, S Pletnev, A AF Blaney, Joseph Wlazlo, Anthony Speicher, James Sathe, Neeraj Hanson, Christopher Murphy, Brian Whitehead, Stephen Pletnev, Alexander TI Characterization of antigenic chimeric St. Louis encephalitis virus/dengue virus type 4 recombinant viruses in mice and monkeys SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Blaney, Joseph; Wlazlo, Anthony; Speicher, James; Sathe, Neeraj; Hanson, Christopher; Murphy, Brian; Whitehead, Stephen; Pletnev, Alexander] Natl Inst Hlth, NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 124 BP 37 EP 37 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200125 ER PT J AU Ramanathan, R Burbelo, PB Laclarola, MJ Neva, FA Nutman, TB AF Ramanathan, Roshan Burbelo, Peter B. Laclarola, Michael J. Neva, Franklin A. Nutman, Thomas B. TI Development of a rapid and specific immunodiagnostic assay for Strongyloides infection using a luciferase immunoprecipitation system SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Ramanathan, Roshan; Burbelo, Peter B.; Laclarola, Michael J.; Neva, Franklin A.; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 137 BP 40 EP 40 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200136 ER PT J AU Nicoll, WS Sacci, JB Rodolfo, C DiGiacomo, G Piacentini, M Hollingdale, MR Lanar, DE AF Nicoll, William S. Sacci, John B. Rodolfo, Carlo DiGiacomo, Giuseppina Piacentini, Mauro Hollingdale, Michael R. Lanar, David E. TI Plasmodium falciparum liver stage Antigen-1 is crosslinked by tissue transglutaminase SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Nicoll, William S.; Sacci, John B.; Lanar, David E.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Sacci, John B.] Univ Maryland, Sch Med, Baltimore, MD USA. [DiGiacomo, Giuseppina; Piacentini, Mauro] Univ Roma Tor Vergata, Rome, Italy. [Hollingdale, Michael R.] Natl Inst Hlth, Rockville, MD USA. RI Lanar, David/B-3560-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 158 BP 46 EP 46 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200158 ER PT J AU Martin, LB Shaffer, D Ellis, RD Long, CA Miura, K Narum, DL Zhu, D Mullen, GE Mahanty, S Malkin, E Miller, LH Saul, A Durbin, AP AF Martin, Laura B. Shaffer, Donna Ellis, Ruth D. Long, Carole A. Miura, Kazutoyo Narum, David L. Zhu, Darning Mullen, Gregory E. Mahanty, Siddhartha Malkin, Elissa Miller, Louis H. Saul, Allan Durbin, Anna P. TI Phase 1 safety and immunogenicity trial of blood-stage malaria vaccines MSP1(42)-C1/alhydrogel with and without the addition of CPG 7909 in US adults SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Martin, Laura B.; Ellis, Ruth D.; Long, Carole A.; Miura, Kazutoyo; Narum, David L.; Zhu, Darning; Mullen, Gregory E.; Mahanty, Siddhartha; Malkin, Elissa; Miller, Louis H.; Saul, Allan] Natl Inst Hlth, NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. [Shaffer, Donna; Durbin, Anna P.] Johns Hopkins Sch Publ Hlth, Ctr Immunizat Res, Washington, DC USA. RI Martin, Laura/N-1789-2013; OI Martin, Laura/0000-0002-4431-4381; Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 213 BP 62 EP 62 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200213 ER PT J AU Tozan, Y Saclasivaiah, S Breman, JG AF Tozan, Yesim Saclasivaiah, Shobha Breman, Joel G. TI Dichlorodiphenyltrichloroethane (DDT) for indoor residual spraying in africa: How can it be used for malaria control? SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Tozan, Yesim] Columbia Univ, Earth Inst, New York, NY USA. [Tozan, Yesim; Saclasivaiah, Shobha; Breman, Joel G.] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA. [Saclasivaiah, Shobha] Cornell Univ, Weill Cornell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 224 BP 65 EP 65 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200224 ER PT J AU Hume, J Lehmann, T AF Hume, Jen Lehmann, Tovi TI Development of Plasmodium falciparum in Culex mosquitoes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Hume, Jen; Lehmann, Tovi] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 226 BP 66 EP 66 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200226 ER PT J AU Barillas-Mury, C Gupta, L Molina-Cruz, A Kumar, S AF Barillas-Mury, Carolina Gupta, Lalita Molina-Cruz, Alvaro Kumar, Sanjeev TI The STAT pathway limits Plasmodium infection in Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Barillas-Mury, Carolina; Gupta, Lalita; Molina-Cruz, Alvaro; Kumar, Sanjeev] Natl Inst Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 243 BP 70 EP 70 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200243 ER PT J AU Piriou, E Chelimo, K Kimmel, R Dutta, S Long, C Lanar, DE Middeldorp, JM Moormann, AM Rochford, R AF Piriou, Erwan Chelimo, Kiprotich Kimmel, Rhonda Dutta, Sheetij Long, Carole Lanar, David E. Middeldorp, Jaap M. Moormann, Ann M. Rochford, Rosemary TI Multiplexed measurement of epstein barr virus, cytomegalovirus and Plasmodium falciparum-specific antibodies using the luminex system SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Piriou, Erwan; Chelimo, Kiprotich] Kenya Govt Med Res Ctr, Ctr Vector Biol & Control Res, Kisumu, Kenya. [Kimmel, Rhonda; Moormann, Ann M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Dutta, Sheetij; Lanar, David E.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Long, Carole] NIH, NIAID, Rockville, MD USA. [Middeldorp, Jaap M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Rochford, Rosemary] SUNY Upstate Med Univ, Syracuse, NY USA. RI Lanar, David/B-3560-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 303 BP 86 EP 86 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200302 ER PT J AU Lamb, EW Crow, ET Pesce, JT Wynn, TA Schaefer, BC Davies, SJ AF Lamb, Erika W. Crow, Emily T. Pesce, John T. Wynn, Thomas A. Schaefer, Brian C. Davies, Stephen J. TI Blood fluke exploitation of innate-adaptive immune interactions to facilitate parasite development SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Lamb, Erika W.; Crow, Emily T.; Schaefer, Brian C.; Davies, Stephen J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Pesce, John T.; Wynn, Thomas A.] NIH, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 309 BP 88 EP 88 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200308 ER PT J AU Durbin, AR McArthur, JH Marron, J Wanionek, K Thumar, B Blaney, JE Murphy, BR Whitehead, SS AF Durbin, Anna R. McArthur, Julie H. Marron, Jennifer Wanionek, Kimberli Thumar, Bhavin Blaney, Joseph E. Murphy, Brian R. Whitehead, Stephen S. TI Phase I study of the safety and immunogenicity of rDEN4 Delta 30-200,201 a live attenuated virus vaccine candidate for dengue serotype 4 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Durbin, Anna R.; McArthur, Julie H.; Marron, Jennifer; Wanionek, Kimberli; Thumar, Bhavin] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Blaney, Joseph E.; Murphy, Brian R.; Whitehead, Stephen S.] Natl Inst Hlth, Infect Dis Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 347 BP 100 EP 100 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200346 ER PT J AU Mohammed, H Stramer, S Tomashek, K Munoz, J Linnen, J Petersen, L AF Mohammed, Hamish Stramer, Susan Tomashek, Kay Munoz, Jorge Linnen, Jeff Petersen, Lyle TI Prevalence of dengue virus nucleic acid in blood products donated in Puerto Rico SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Mohammed, Hamish; Stramer, Susan; Tomashek, Kay; Munoz, Jorge; Linnen, Jeff] Johns Hopkins Univ, Bloomberg Sch Public Hlth, Baltimore, MD 21218 USA. [Petersen, Lyle] NIH, Infect Dis Lab, Bethesda, MD USA. [Mohammed, Hamish; Tomashek, Kay; Munoz, Jorge] Dengue Branch, San Juan, PR USA. [Stramer, Susan] Amer Red Cross, Gaithersburg, MD USA. [Linnen, Jeff] Gen Probe Inc, San Diego, CA USA. [Petersen, Lyle] Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 348 BP 100 EP 100 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200347 ER PT J AU Klion, AD Talaat, K White, S Rosenberg, H Nutman, TB AF Klion, Amy D. Talaat, Kawsar White, Sandy Rosenberg, Helene Nutman, Thomas B. TI Eosinophils are not required for DEC-mediated clearance of microfilaremia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Klion, Amy D.; Talaat, Kawsar; White, Sandy; Rosenberg, Helene; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 390 BP 112 EP 113 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200389 ER PT J AU Gomes, RB Collin, N Teixeira, C Jochinn, R Elnaiem, DE Volf, P Costa, C Valenzuela, JG AF Gomes, Regis B. Collin, Nicolas Teixeira, Clarissa Jochinn, Ryan Elnaiem, Dia-Eldin Volf, Peter Costa, Carlos Valenzuela, Jesus G. TI Lutzomyia longipalpis salivary recombinant proteins recognized by human, dog and fox antibodies SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Gomes, Regis B.; Collin, Nicolas; Teixeira, Clarissa; Jochinn, Ryan; Elnaiem, Dia-Eldin; Valenzuela, Jesus G.] NIAID, NIH, Rockville, MD USA. [Volf, Peter] Charles Univ Prague, Prague, Czech Republic. [Costa, Carlos] Univ Fed Piaui, Teresina, Brazil. RI Volf, Petr/C-4300-2012 OI Volf, Petr/0000-0003-1790-1123 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 391 BP 113 EP 113 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200390 ER PT J AU Elnaiern, DEA Oliveira, LF Gomes, RE Toxeira, C Subrahmanyam, S Kamhawi, S Lawyer, PG Ward, JM Valenzuela, JG AF Elnaiern, Dia-Eldin A. Oliveira, Luiz F. Gomes, Regis E. Toxeira, Clarissa Subrahmanyam, Sreenath Kamhawi, Shaden Lawyer, Phillip G. Ward, Jerrold M. Valenzuela, Jesus G. TI Molecular basis of specificity and cross reactivity in delayed-type-hypersensitivity reactions to bites of sand flies and implication for protection against Leishmania infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Elnaiern, Dia-Eldin A.; Oliveira, Luiz F.; Gomes, Regis E.; Toxeira, Clarissa; Subrahmanyam, Sreenath; Kamhawi, Shaden; Lawyer, Phillip G.; Ward, Jerrold M.; Valenzuela, Jesus G.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 396 BP 114 EP 114 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200395 ER PT J AU Mukbell, RM Wortmann, G Lesho, E Tripathi, V Wadsworth, M Stayback, G Oliveira, F Kamhawi, S Valenzuela, J Ramalho-Ortigao, M McDowell, MA AF Mukbell, Rami M. Wortmann, Glenn Lesho, Emil Tripathi, Vinita Wadsworth, Marina Stayback, Gwen Oliveira, Fabiano Kamhawi, Shaden Valenzuela, Jesus Ramalho-Ortigao, Marcelo McDowell, Mary Ann TI Human immune responses against Phlebotomus papatasi saliva SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Mukbell, Rami M.; Tripathi, Vinita; Wadsworth, Marina; Stayback, Gwen; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann] Univ Notre Dame, Notre Dame, IN 46556 USA. [Wortmann, Glenn; Lesho, Emil] Walter Reed Army Med Ctr, Washington, DC USA. [Oliveira, Fabiano; Kamhawi, Shaden; Valenzuela, Jesus] Natl Inst Hlth, Rockville, MD USA. RI Ramalho-Ortigao, Marcelo/E-8225-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 395 BP 114 EP 114 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200394 ER PT J AU Ramalho-Ortigao, M Balbino, VQ Coutinho-Abreu, IV Mukbel, R Fawaz, E El-Hossary, S Hanafi, H Hoel, D Abo-Shehada, M Valenzuela, J Kamhawi, S McDowell, MA AF Ramalho-Ortigao, Marcelo Balbino, Valdir Q. Coutinho-Abreu, Iliano V. Mukbel, Rami Fawaz, Emad El-Hossary, Shaaban Hanafi, Hanafi Hoel, David Abo-Shehada, Mahmoud Valenzuela, Jesus Kamhawi, Shaden McDowell, Mary Ann TI Phlebotomus papatasi salivary gland sequence variability and impact on defining vaccine candidates SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Ramalho-Ortigao, Marcelo; Balbino, Valdir Q.; Coutinho-Abreu, Iliano V.; Mukbel, Rami; McDowell, Mary Ann] Univ Notre Dame, Notre Dame, IN 46556 USA. [Fawaz, Emad; El-Hossary, Shaaban; Hanafi, Hanafi] Naval Med Res Unit, Cairo, Egypt. [Abo-Shehada, Mahmoud] Jordan Univ Sci & Technol, Irbid, Jordan. [Valenzuela, Jesus; Kamhawi, Shaden] Natl Inst Hlth, Rockville, MD USA. RI Balbino, Valdir/B-1410-2008; Ramalho-Ortigao, Marcelo/E-8225-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 397 BP 114 EP 115 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200396 ER PT J AU Arvay, M Terp, S Armah, G Wontuo, P Curns, A Widdowson, MA Parashar, U Glass, RI Binka, F AF Arvay, Melissa Terp, Sophia Armah, George Wontuo, Peter Curns, Aaron Widdowson, Marc-Alain Parashar, Umesh Glass, Roger I. Binka, Fred TI Assessing the potential impact of vaccination on prevention of rotavirus deaths among children in rural Ghana SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Arvay, Melissa; Curns, Aaron; Widdowson, Marc-Alain; Parashar, Umesh] Ctr Dis Control & Prevent, Atlanta, GA USA. [Terp, Sophia] Ctr Dis Control Fdn, Atlanta, GA USA. [Armah, George] Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana. [Wontuo, Peter] Navrongo Hlth Res Ctr, Navrongo, Ghana. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Binka, Fred] Univ Ghana, Sch Publ Hlth, Legon, Ghana. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 439 BP 126 EP 126 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200438 ER PT J AU Rodrigo, WWSI Goncalvez, AP Jin, X Rose, RC Lai, CJ Schlesinger, JJ AF Rodrigo, W. W. Shanaka I. Goncalvez, Ana P. Jin, Xia Rose, Robert C. Lai, Ching-Juh Schlesinger, Jacob J. TI Dengue virus cross-reactive mouse or humanized chimpanzee monoclonal antibodies favor enhanced dengue virus immune complex infectivity in engineered human FC gamma receptor CD64 or CD32 expressing cells SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Rodrigo, W. W. Shanaka I.; Jin, Xia; Rose, Robert C.; Schlesinger, Jacob J.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Goncalvez, Ana P.; Lai, Ching-Juh] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 457 BP 131 EP 131 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200455 ER PT J AU Jiang, L Duriseti, S Sun, P Miller, LH AF Jiang, Lubin Duriseti, Sai Sun, Peter Miller, Louis H. TI Molecular basis of Plasmodium falciparum receptor BAEBL for binding to erythrocyte ligand glycophorin C SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Jiang, Lubin; Duriseti, Sai; Sun, Peter; Miller, Louis H.] NIH, Natl Inst Allergy & Inf Dis, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 488 BP 140 EP 140 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200486 ER PT J AU Ostera, GR Tokumasu, F Teixeira, C Oliveira, F Dvorak, JA AF Ostera, Graciela R. Tokumasu, Fuyuki Teixeira, Clarissa Oliveira, Fabiano Dvorak, James A. TI Nitric oxide in intraerythrocytic Plasmodium falciparum may be produced in the food vacuole by an arginine-independent mechanism SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Ostera, Graciela R.; Tokumasu, Fuyuki; Teixeira, Clarissa; Oliveira, Fabiano; Dvorak, James A.] NIH, Rockville, MD USA. RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 487 BP 140 EP 140 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200485 ER PT J AU Smith, DL Boni, M Klein, E Laxminarayan, R AF Smith, David L. Boni, Maciej Klein, Eili Laxminarayan, Ramanan TI A two-stage model of malaria transmission and its impact on the spread of resistance SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Boni, Maciej; Klein, Eili; Laxminarayan, Ramanan] Resources Water Future, Washington, DC USA. RI Klein, Eili/C-3745-2012; Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 532 BP 153 EP 153 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200529 ER PT J AU Tozan, Y Breman, JG AF Tozan, Yesim Breman, Joel G. TI A decision tree model for estimating the cost-effectiveness of rectal artesunate treatment for severe childhood malaria at the community level SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Tozan, Yesim] Columbia Univ, Inst Earth, New York, NY 10027 USA. [Tozan, Yesim; Breman, Joel G.] Fogarty Int Ctr, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 534 BP 153 EP 153 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200531 ER PT J AU Raj, DK AF Raj, Dipak K. TI Disruption of a putative ABC transporter in Plasmodium falciparum alters parasite growth and responses to antimalarial drugs SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Raj, Dipak K.] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 562 BP 162 EP 162 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201024 ER PT J AU Qian, F Reiter, K Zhang, Y Shimp, RL Nguyen, V Lebowitz, J Lambert, L Mullen, GE Martin, LB Miller, LH Narum, DL AF Qian, Feng Reiter, Karine Zhang, Yanling Shimp, Richard L., Jr. Nguyen, Vu Lebowitz, Jacob Lambert, Lynn Mullen, Gregory E. Martin, Laura B. Miller, Louis H. Narum, David L. TI A platform for generating conjugated malarial vaccines to Pseudomonas aeruginosa Exoprotein A SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Qian, Feng; Reiter, Karine; Zhang, Yanling; Shimp, Richard L., Jr.; Nguyen, Vu; Lambert, Lynn; Mullen, Gregory E.; Martin, Laura B.; Miller, Louis H.; Narum, David L.] Natl Inst Hlth, Rockville, MD USA. [Lebowitz, Jacob] Natl Inst Hlth, Bethesda, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 576 BP 165 EP 166 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201038 ER PT J AU Zhu, D Gebregeorgis, EM McClellan, HA Huang, S Miller, LH Martin, LB AF Zhu, Daming Gebregeorgis, Elizabeth M. McClellan, Holly A. Huang, Shuhui Miller, Louis H. Martin, Laura B. TI Effect of CPG on stability of BSAM-1/Alhydrogel formulation SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Zhu, Daming; Gebregeorgis, Elizabeth M.; McClellan, Holly A.; Huang, Shuhui; Miller, Louis H.; Martin, Laura B.] Natl Inst Hlth, NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 573 BP 165 EP 165 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201035 ER PT J AU Manoukis, NC Diabate, A Dao, A Tokumasu, F Lehmann, T AF Manoukis, Nicholas C. Diabate, Abdoulaye Dao, Adama Tokumasu, Fuyuki Lehmann, Tovi TI Lights, camera, action: A method to study male Anopheles gambiae mating behavior in the field SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Manoukis, Nicholas C.; Diabate, Abdoulaye; Tokumasu, Fuyuki; Lehmann, Tovi] Natl Inst Hlth, NIAID, Bethesda, MD USA. [Dao, Adama] MRTC FMPOS, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 588 BP 169 EP 169 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201050 ER PT J AU Bennuru, S Semnani, R Ribeiro, JMC Meng, Z Veenstra, TD Nutman, TB AF Bennuru, Sasisekhar Semnani, Roshanak Ribeiro, Jose M. C. Meng, Zhaojing Veenstra, Timothy D. Nutman, Thomas B. TI Abundance of immunomodulatory proteins revealed by analysis of the excretory-secretory (E/S) proteome of Brugia malayi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Bennuru, Sasisekhar; Semnani, Roshanak; Nutman, Thomas B.] NIAID, Natl Inst Hlth, Parasit Dis Lab, Bethesda, MD USA. [Ribeiro, Jose M. C.] NIAID, Natl Inst Hlth, Lab Malaria & Vector Res, Bethesda, MD USA. [Meng, Zhaojing; Veenstra, Timothy D.] SAIC Frederick Inc, Natl Canc Inst, Lab Proteom & Analyt Technol, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 665 BP 190 EP 191 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201126 ER PT J AU Babu, S Jayantasri, V Rukmani, S Kumaran, P Gopi, PG Sadacharam, K Kumaraswami, V Nutman, TB AF Babu, Subash Jayantasri, V. Rukmani, S. Kumaran, Paul Gopi, P. G. Sadacharam, K. Kumaraswami, V. Nutman, Thomas B. TI Coexistent filarial infections downregulate antigen-specific Th1 and Th17 responses in latent tuberculosis: association with enhanced expression of CTLA-4 and PD-1 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Babu, Subash; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. [Jayantasri, V.; Rukmani, S.; Kumaran, Paul; Gopi, P. G.; Sadacharam, K.; Kumaraswami, V.] Tuberculosis Res Ctr, Madras, Tamil Nadu, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 666 BP 191 EP 191 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201127 ER PT J AU Talaat, KR Feng, CG Scanga, CA Mentink-Kane, MM White, S Nutman, TB AF Talaat, Kawsar R. Feng, Carl G. Scanga, Charles A. Mentink-Kane, Margaret M. White, Sandy Nutman, Thomas B. TI Brugia malayi microfilariae inhibit IFN gamma and TNF-alpha in response to Mycobacterium tuberculosis infection in a murine coinfection model SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Talaat, Kawsar R.; Feng, Carl G.; Mentink-Kane, Margaret M.; White, Sandy; Nutman, Thomas B.] NIAID, Bethesda, MD 20892 USA. [Scanga, Charles A.] Aeras, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 667 BP 191 EP 191 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201128 ER PT J AU May, K Malhotra, I Grube, M Long, C Mandaliya, K Fusch, C Schneider, H King, CL AF May, Karen Malhotra, Inclu Grube, Marcus Long, Carole Mandaliya, Kishor Fusch, Christoph Schneider, Henning King, Christopher L. TI Transplacental transfer of MSP1(42) using the in vitro placental perfusion model SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [May, Karen; Grube, Marcus; Fusch, Christoph] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Malhotra, Inclu; King, Christopher L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Long, Carole] Natl Inst Hlth, Bethesda, MD USA. [Mandaliya, Kishor] Minist Hlth, Pathol Serv Kenyan, Mombasa, Kenya. [Schneider, Henning] Univ Bern, CH-3012 Bern, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 803 BP 230 EP 231 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201262 ER PT J AU Toure, MB Manoukis, N Guindo, B Sissoko, IM Traore, SF Doumbia, S Taylor, CE AF Toure, Maharnoudou B. Manoukis, Nickolas Guindo, Boubacar Sissoko, Ibrahim M. Traore, Sekou F. Doumbia, Seydou Taylor, Charles E. TI Density and species composition of Anopheles gambiae SL in Banambani, Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Toure, Maharnoudou B.; Taylor, Charles E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Manoukis, Nickolas] Natl Inst Hlth, Washington, DC USA. [Guindo, Boubacar; Sissoko, Ibrahim M.; Traore, Sekou F.; Doumbia, Seydou] MRTC FMPOS, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 868 BP 248 EP 249 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201327 ER PT J AU Gonzalez-Cerdas, R Riehle, MM Vernick, KD Hume, J Ribeiro, J Lehmann, T AF Gonzalez-Cerdas, Rodrigo Riehle, Michelle M. Vernick, Kenneth D. Hume, Jen Ribeiro, Jose Lehmann, Tovi TI Polymorphism in the gene encoding Gambicin and Plasmodium falciparum infection susceptibility in Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Gonzalez-Cerdas, Rodrigo; Hume, Jen; Ribeiro, Jose; Lehmann, Tovi] Natl Inst Hlth, NIAID, Bethesda, MD USA. [Riehle, Michelle M.; Vernick, Kenneth D.] Univ Minnesota, Ctr Microbial & Plant Genom, Dept Microbiol, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 876 BP 251 EP 251 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201335 ER PT J AU Rodrigues, J Barillas-Mury, C AF Rodrigues, Janneth Barillas-Mury, Carolina TI Immune responsive serine protease from Anopheles gambiae promotes Plasmodium falciparum development SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Rodrigues, Janneth; Barillas-Mury, Carolina] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 885 BP 253 EP 253 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201344 ER PT J AU Kumar, S Gupta, L Barillas-Mury, C AF Kumar, Sanjeev Gupta, Lalita Barillas-Mury, Carolina TI A secreted Anopheles midgut peroxidase regulates Plasmodium falciparum development SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Kumar, Sanjeev; Gupta, Lalita; Barillas-Mury, Carolina] Natl Inst Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 941 BP 269 EP 269 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201400 ER PT J AU Subramanian, RA Lehmann, T Atkinson, PA O'Brochta, DA AF Subramanian, Ramanand Arun Lehmann, Tovi Atkinson, Peter A. O'Brochta, David A. TI The Herves transposable element in Anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Subramanian, Ramanand Arun; O'Brochta, David A.] UMBI, Rockville, MD USA. [Lehmann, Tovi] Natl Inst Hlth, Natl Inst Allergy & Infect, Rockville, MD USA. [Atkinson, Peter A.] Univ Calif Riverside, Riverside, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S BP 270 EP 270 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201404 ER PT J AU Steel, C Nutman, TB AF Steel, Cathy Nutman, Thomas B. TI Microfilaria positivity modulates the expression of FC epsilon R1-alpha on monocytes in filaria-infected patients SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Steel, Cathy; Nutman, Thomas B.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S BP 271 EP 271 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201409 ER PT J AU Dembele, B Kole, A Diallo, A Metenou, S Konate, S Coulibaly, Y Dolo, H Coulibaly, ME Soumaoro, L Nutman, TB Klion, A Traore, C Mahanty, S AF Dembele, Benoit Kole, Abhisake Diallo, Abdallah Metenou, Simon Konate, Siaka Coulibaly, Yaya Dolo, Husseini Coulibaly, Michel E. Soumaoro, Lamine Nutman, Thomas B. Klion, Amy Traore, Cheick Mahanty, Siddhartha TI Cytokine responses to malarial antigens and activation of toll-like receptor (TLR) mediated pathways in human co-infections with filarial parasites and malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Dembele, Benoit; Diallo, Abdallah; Konate, Siaka; Coulibaly, Yaya; Dolo, Husseini; Coulibaly, Michel E.; Soumaoro, Lamine; Traore, Cheick] Univ Bamako, Malaria Res & Training Ctr, Filariaris Unit, Bamako, Mali. [Kole, Abhisake; Metenou, Simon; Nutman, Thomas B.; Klion, Amy; Mahanty, Siddhartha] NIAID, Lab Parasit Dis, Bethesda, MD USA. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S BP 272 EP 272 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201410 ER PT J AU Glass, GE Holt, RD Gardner-Santana, LC Chen, J Norris, DE Klein, SL Roy, M Purcell, RH AF Glass, Gregory E. Holt, Robert D. Gardner-Santana, Lynne C. Chen, Jessica Norris, Douglas E. Klein, Sabra L. Roy, Manojit Purcell, Robert H. TI The role of predators in reducing parasites in prey populations: An example in urban USA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Glass, Gregory E.; Gardner-Santana, Lynne C.; Norris, Douglas E.; Klein, Sabra L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Holt, Robert D.; Roy, Manojit] Univ Florida, Dept Zool, Gainesville, FL 32611 USA. [Chen, Jessica] Johns Hopkins Univ, Dept Psychol, Baltimore, MD USA. [Purcell, Robert H.] Natl Inst Hlth, NIAID, Infect Dis Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S BP 274 EP 274 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201417 ER PT J AU Duggal, P Peterson, K Haque, R Mondal, D Sher, A Ricklefs, SM Porcella, S Petri, WA AF Duggal, Priya Peterson, Kristine Haque, Rashidul Mondal, Dinesh Sher, Alan Ricklefs, Stacy M. Porcella, Steve Petri, William A. TI The study of associations between Entamoeba histolytica infection and disease with single nucleotide polymorphisms (SNPS) in immune response genes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Duggal, Priya] Natl Inst Hlth, Natl Human Genome Res Ctr, Baltimore, MD USA. [Peterson, Kristine; Petri, William A.] Univ Virginia, Charlottesville, VA 22903 USA. [Haque, Rashidul; Mondal, Dinesh] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Sher, Alan] Natl Inst Hlth, NIAID, Bethesda, MD USA. [Ricklefs, Stacy M.; Porcella, Steve] Natl Inst Hlth, NIAID, Rocky Mt Lab, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S BP 275 EP 276 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201422 ER PT J AU Collin, N Karnhavvi, S Gonnes, RB Teixeira, C Elnaiem, DE Valenzuela, JG AF Collin, Nicolas Karnhavvi, Shaden Gonnes, Regis B. Teixeira, Clarissa Elnaiem, Dia-Eldin Valenzuela, Jesus G. TI Towards a vaccine against canine visceral leishmaniasis based on vector salivary antigens SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Collin, Nicolas; Karnhavvi, Shaden; Gonnes, Regis B.; Teixeira, Clarissa; Elnaiem, Dia-Eldin; Valenzuela, Jesus G.] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 981 BP 280 EP 280 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201439 ER PT J AU Oakley, M Faucette, L Majam, V Zheng, H Mahajan, B Erexson, C Ward, J McCutchan, T Kumar, S AF Oakley, Miranda Faucette, Laurence Majam, Victoria Zheng, Hong Mahajan, Babita Erexson, Cindy Ward, Jerrold McCutchan, Thomas Kumar, Sanjai TI Molecular markers of the pathogenesis of cerebral malaria in the murine malaria Plasmodium berghei SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Oakley, Miranda; Faucette, Laurence; Erexson, Cindy; Ward, Jerrold; McCutchan, Thomas] NIAID, Rockville, MD USA. [Majam, Victoria; Zheng, Hong; Mahajan, Babita; Kumar, Sanjai] US FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1017 BP 291 EP 291 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201475 ER PT J AU Diabate, A Dao, A Yaro, AS Alpha, A Traore, SC Gonzalez, R Gwadz, B Lehmann, T AF Diabate, Abdoullaye Dao, Adama Yaro, Alpha S. Alpha, Adamou Traore, S. Cheick Gonzalez, Rodrigo Gwadz, Bob Lehmann, Tovi TI Swarm segregation is the main mechanism that prevents mating between sympatric molecular forms of anopheles gambiae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Diabate, Abdoullaye; Gonzalez, Rodrigo; Gwadz, Bob; Lehmann, Tovi] NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD USA. [Dao, Adama; Yaro, Alpha S.; Alpha, Adamou; Traore, S. Cheick] MRTC, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1022 BP 292 EP 293 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201480 ER PT J AU Molina-Cruz, A Leszczynski, S Gupta, L Kumar, S DeJong, R Ndikuyeze, G Barillas-Mury, C AF Molina-Cruz, Alvaro Leszczynski, Sara Gupta, Lalita Kumar, Sanjeev DeJong, Randall Ndikuyeze, Georges Barillas-Mury, Carolina TI Anopheles gambiae gut flora dinamics and microarray analysis of gut gene expression in response to bacteria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Molina-Cruz, Alvaro; Leszczynski, Sara; Gupta, Lalita; Kumar, Sanjeev; DeJong, Randall; Ndikuyeze, Georges; Barillas-Mury, Carolina] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1037 BP 297 EP 297 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201495 ER PT J AU Jochim, RC Teixeira, CR Gomes, RB Laughinghouse, A Elnaiem, DE Mu, J Oliveira, LF Valenzuela, JG AF Jochim, Ryan C. Teixeira, Clarissa R. Gomes, Regis B. Laughinghouse, Andre Elnaiem, Dia-Eldin Mu, Jianbing Oliveira, Luiz F. Valenzuela, Jesus G. TI Transcriptomic analysis and temporal expression profiling of the midgut of the sand fly lutzomyia longipalpis in blood feeding and infection with Leishmania chagasi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Jochim, Ryan C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Teixeira, Clarissa R.; Gomes, Regis B.; Laughinghouse, Andre; Elnaiem, Dia-Eldin; Mu, Jianbing; Oliveira, Luiz F.; Valenzuela, Jesus G.] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1039 BP 298 EP 298 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201497 ER PT J AU Oliveira, LF Gomes, RB Kamhawi, S Teixeira, C Elnaiem, DE Valenzuela, JG AF Oliveira, Luiz F. Gomes, Regis B. Kamhawi, Shaden Teixeira, Clarissa Elnaiem, Dia-eldin Valenzuela, Jesus G. TI A DNA vaccine encoding a sand fly salivary yellow related protein (UM11) confers protection against challenge with Leishmania major in the presence of Lutzomyia longipalpis salivary gland homogenate SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Oliveira, Luiz F.; Gomes, Regis B.; Kamhawi, Shaden; Teixeira, Clarissa; Elnaiem, Dia-eldin; Valenzuela, Jesus G.] Natl Inst Hlth, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1052 BP 302 EP 302 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201510 ER PT J AU Anderson, JM Miller, NJ Mather, TN Ward, JM Valenzuela, JG AF Anderson, Jennifer M. Miller, Nathan J. Mather, Thomas N. Ward, Jerrold M. Valenzuela, Jesus G. TI Immunity to saliva at the tick-host interface: Identification of Ixodes scapularis salivary proteins eliciting a cellular immune response SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Anderson, Jennifer M.; Ward, Jerrold M.; Valenzuela, Jesus G.] Natl Inst Hlth, Rockville, MD USA. [Miller, Nathan J.; Mather, Thomas N.] Univ Rhode Isl, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1061 BP 304 EP 305 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201519 ER PT J AU Baker, SG Kramer, BS AF Baker, Stuart G. Kramer, Barnett S. TI Peirce, Youden, and receiver operating characteristic curves SO AMERICAN STATISTICIAN LA English DT Article DE diagnostic tests; screening tests ID MARKERS; CANCER AB In 1884 Charles Sanders Peirce introduced two measures for evaluating predictions of a binary outcome, "the science of the method" and the "utility of the method." In modern terminology, the former corresponds to the Youden index and the latter corresponds to the expected utility. The maximum of each measure is a commonly used criterion for the optimal point on a receiver operating characteristic curve that summarizes performance when predictions of a binary outcome are based on a continuous result. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 11 TC 31 Z9 32 U1 2 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD NOV PY 2007 VL 61 IS 4 BP 343 EP 346 DI 10.1198/000313007X247643 PG 4 WC Statistics & Probability SC Mathematics GA 226QX UT WOS:000250604700013 ER PT J AU Mayne, ST Wright, ME Albanes, D AF Mayne, Susan T. Wright, Margaret E. Albanes, Demetrius TI Re: Hypothesis: Oxidative stress score as a combined measure of pro-oxidant and antioxidant exposures SO ANNALS OF EPIDEMIOLOGY LA English DT Letter C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Illinois, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. RP Mayne, ST (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA. RI Albanes, Demetrius/B-9749-2015 NR 2 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2007 VL 17 IS 11 BP 930 EP 930 DI 10.1016/j.annepidem.2007.06.012 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 231IE UT WOS:000250939300016 PM 17855113 ER PT J AU Ward, MM AF Ward, Michael M. TI Interpreting measurements of physical function in clinical trials SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 9th International Symposium on Advances in Targeted Therapies CY APR 18-22, 2007 CL Athens, GREECE ID PRELIMINARY CORE SET; RHEUMATOID-ARTHRITIS; DISEASE-ACTIVITY; OUTCOME MEASURES; DAMAGE; DISABILITY AB Improving physical functioning is one of the major goals of anti-rheumatic treatment. However, functional limitations can have several different causes, which may differ in their capacity to respond to a given treatment. Functional limitations due to pain or other acute symptoms or signs may be readily reversible with efficacious treatment, while those due to chronic structural changes may be relatively irreversible in the short term. Because measures of physical function characterise the degree of limitation without regard to cause, patients with the same apparent degree of functional limitation may differ greatly in their ability to demonstrate response to treatment. Structural damage accumulates over the course of disease, so measures of functional limitations tend to be less responsive among patients with more longstanding disease. This decreased responsiveness leads to a decreased ability to discriminate between treatments in patients with more longstanding arthritis. In addition, the criteria for minimal clinically important improvement may be underestimated when patients with irreversible functional limitations are included as test subjects, because judgments of improvement may be associated with smaller measured changes in physical functioning. The interpretation of measurements of physical function in clinical trials should consider the composition of the study sample, with attention to the stage of disease and the heterogeneity in disease duration or structural damage among subjects. C1 NIAMS, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 17 TC 2 Z9 3 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2007 VL 66 SU 3 BP 32 EP 34 DI 10.1136/ard.2007.079806 PG 3 WC Rheumatology SC Rheumatology GA 225IE UT WOS:000250509500005 ER PT J AU Singh-Grewal, D Chaitow, J Aksentijevich, I Christodoulou, J AF Singh-Grewal, Davinder Chaitow, Jeffrey Aksentijevich, Ivona Christodoulou, John TI Coexistent MEFV and CIAS1 mutations manifesting as familial Mediterranean fever plus deafness SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Letter ID MICE C1 Childrens Hosp, Dept Rheumatol, Sydney, NSW, Australia. Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia. NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. Childrens Hosp, Western Sydney Genet Program, Sydney, NSW, Australia. RP Singh-Grewal, D (reprint author), Childrens Hosp, Dept Paediat, Locked Bag 4001, Westmead, NSW 2145, Australia. EM davindes@chw.edu.au RI Christodoulou, John/E-5866-2015 NR 7 TC 21 Z9 21 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2007 VL 66 IS 11 BP 1541 EP 1541 DI 10.1136/ard.2007.075655 PG 1 WC Rheumatology SC Rheumatology GA 220HN UT WOS:000250147900025 PM 17934081 ER PT J AU Hou, L Grillo, P Zhu, ZZ Lissowska, J Yeager, M Zatonski, W Zhu, G Baccarelli, A Chanock, SJ Fraumeni, JF Chow, WH AF Hou, Lifang Grillo, Paolo Zhu, Zhong-Zheng Lissowska, Jola Yeager, Meredith Zatonski, Witold Zhu, Guanshan Baccarelli, Andrea Chanock, Stephen J. Fraumeni, Joseph F., Jr. Chow, Wong-Ho TI COX1 and COX2 polymorphisms and gastric cancer risk in a Polish population SO ANTICANCER RESEARCH LA English DT Article DE polymorphisms; COX1; COX2; gastric cancer ID LUNG-CANCER; CYCLOOXYGENASE-2 GENE; COMMON POLYMORPHISM; STOMACH-CANCER; CARCINOMA; ASSOCIATION; EXPRESSION; VARIANTS; INVASION; WARSAW AB Background: Although a number of studies on the polymorphisms in COX1 and COX2 genes in association with risks for a number of cancers have been conducted, their relation to gastric cancer has not been well studied. Patients and Methods: Genotypes of several variants in both COX1 (Ex7+31 C>A and Ex10-4 G>A) and COX2 (-765 G>C, Ex.10+837 T>C, Ex10-90 C>T, IVS5-275 T>G, and TVS7+111 T>C) were identified by TaqMan(TM) assays in 305 gastric cancer cases and 427 age- and gender-matched controls in a high-risk Polish population. Odds ratios for gastric cancer and 95% confidence intervals from unconditional logistic regression models were used to evaluate relative risks. Results: We found no statistically significant evidence that the polymorphisms tested in COX1 and COX2 are associated with gastric cancer risk. Conclusion: These results suggest that the polymorphisms examined in COX1 and COX2 do not affect the risk of gastric cancer. C1 [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Grillo, Paolo; Baccarelli, Andrea] IRCCS, Osped Maggiore, Dept Occupat Clin & Prevent Med, Epidemiol Unit, I-20122 Milan, Italy. [Zhu, Zhong-Zheng] Hosp Peoples Liberat Army, Dept Pathol, Ningbo 315040, Peoples R China. [Lissowska, Jola; Zatonski, Witold] Canc Ctr, M Sklodowska Curie Inst Oncol, Div Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Yeager, Meredith; Chanock, Stephen J.] Natl Canc Inst, Ctr Adv Technol, Core Genotyping Facil, Gaithersburg, MD 20892 USA. [Zhu, Guanshan] Shanghai GeneCore Biotechnol Co Ltd, Shanghai 201203, Peoples R China. [Baccarelli, Andrea] Univ Milan, EPOCA Res Ctr Clin, Dept Occupat Med, I-20122 Milan, Italy. [Chanock, Stephen J.; Fraumeni, Joseph F., Jr.; Chow, Wong-Ho] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. RP Hou, L (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr, Chicago, IL 60611 USA. EM l-hou@northwestern.edu OI Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 31 TC 24 Z9 29 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2007 VL 27 IS 6C BP 4243 EP 4247 PG 5 WC Oncology SC Oncology GA 244YS UT WOS:000251902000001 PM 18214026 ER PT J AU Caughey, WS Priola, SA Kocisko, DA Raymond, LD Ward, A Caughey, B AF Caughey, Winslow S. Priola, Suzette A. Kocisko, David A. Raymond, Lynne D. Ward, Anne Caughey, Byron TI Cyclic tetrapyrrole sulforlation, metals, and oligomerization in antiprion activity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PRION PROTEIN-FORMATION; PHTHALOCYANINE TETRASULFONATE; SHEEP SCRAPIE; IN-VITRO; PORPHYRINS; INFECTION; METALLOPORPHYRINS; AGGREGATION; INHIBITION; MICE AB Cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (TSEs; or prion diseases). Here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. Their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of TSE-infected cell cultures. In addition, prophylactic antiscrapie activities were determined in scrapie-infected mice. The activity of phthalocyanine was relatively insensitive to the number of peripheral sulfonate groups but varied with the type of metal bound at the center of the molecule. The tendency of the various phthalocyanine sulfortates to oligomerize (i.e., stack) correlated with anti-TSE activity. Notably, aluminum(III) phthalocyanine tetrasulfonate was both the poorest anti-TSE compound and the least prone to oligomerization in aqueous media. Similar comparisons of iron- and manganese-bound porphyrin sulfortates confirmed that stacking ability correlates with anti-TSE activity among cyclic tetrapyrroles. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 4th St, Hamilton, MT 59840 USA. EM bcaughey@niaid.nih.gov FU Intramural NIH HHS NR 24 TC 18 Z9 22 U1 1 U2 2 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 NOV PY 2007 VL 51 IS 11 BP 3887 EP 3894 DI 10.1128/AAC.01599-06 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 226UB UT WOS:000250612900015 PM 17709470 ER PT J AU Feld, JJ Colledge, D Sozzi, V Edwards, R Littlejohn, M Locarnini, SA AF Feld, J. J. Colledge, D. Sozzi, V. Edwards, R. Littlejohn, M. Locarnini, S. A. TI The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging SO ANTIVIRAL RESEARCH LA English DT Article DE hepatitis B virus; drug resistance; phenylpropenamide; viral RNA packaging ID HEPATITIS-B-VIRUS; ADEFOVIR DIPIVOXIL THERAPY; IN-VITRO; DNA SYNTHESIS; CORE PROTEIN; WILD-TYPE; LAMIVUDINE; RESISTANT; INFECTION; INHIBITION AB Nucleos(t)ide analogue antiviral therapy for chronic hepatitis B has proven to be effective in the short term but the frequent development of resistance limits its clinical utility. Agents targeting other stages of viral replication are needed in order to develop improved combination therapies. The phenylpropenamide derivatives AT-61 and AT-130 have been shown to inhibit HBV replication in vitro, but the mechanism of action of these compounds remains undefined. The aim of this study was to determine the mechanism of action of AT-130, a non-nucleoside inhibitor of HBV in several in vitro models of replication. These studies found that AT-130 inhibited HBV DNA replication in hepatoma cells but had no effect on viral DNNA polymerase activity or core protein translation. Total HBV RNA production was also unaffected in the presence of the drug whilst the amount of encapsidated RNA was significantly reduced, thereby inhibiting subsequent viral reverse transcription. These studies have established that the inhibition of HBV genome replication by a non-nucleoside analogue acting at the level of viral encapsidation and packaging is a potentially useful strategy for future therapeutic drug development in the management of chronic hepatitis B. (C) 2007 Elsevier B.V. All rights reserved. C1 Victorian Infectious Dis Reference Lab, Melbourne, Vic 3051, Australia. Univ Toronto, Dept Med, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. RP Locarnini, SA (reprint author), Victorian Infectious Dis Reference Lab, 10 Wreckyn St N, Melbourne, Vic 3051, Australia. EM Stephen.Locarnini@mh.org.au OI Littlejohn, Margaret/0000-0002-8206-2664 NR 44 TC 66 Z9 67 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2007 VL 76 IS 2 BP 168 EP 177 DI 10.1016/j.antiviral.2007.06.014 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 220TD UT WOS:000250179300009 PM 17709147 ER PT J AU Duffy, S Holmes, EC AF Duffy, Siobain Holmes, Edward C. TI Multiple introductions of the old world Begomovirus Tomato yellow leaf curl virus into the new world SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID 1ST REPORT; GEMINIVIRUSES; IDENTIFICATION; RECOMBINATION; DISEASE; CLASSIFICATION; SEQUENCE; MEXICO; CUBA; POPULATION AB A phylogenetic analysis of three genomic regions revealed that Tomato yellow leaf curl virus (TYLCV) from western North America is distinct from TYLCV isolated in eastern North America and the Caribbean. This analysis supports a second introduction of this Old World begomovirus into the New World, most likely from Asia. C1 Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Duffy, S (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM smd16@psu.edu RI Duffy, Siobain/A-9104-2009; OI Duffy, Siobain/0000-0003-0753-223X; Holmes, Edward/0000-0001-9596-3552 NR 48 TC 37 Z9 38 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2007 VL 73 IS 21 BP 7114 EP 7117 DI 10.1128/AEM.01150-07 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 228AZ UT WOS:000250700600051 PM 17827315 ER PT J AU Rosenheck, RA Leslie, DL Sindelar, JL Miller, EA Tariot, PN Dagerman, KS Davis, SM Lebowitz, BD Rabins, P Hsiao, JK Lieberman, JA Schneider, LS AF Rosenheck, Robert A. Leslie, Douglas L. Sindelar, Jody L. Miller, Edward A. Tariot, Peter N. Dagerman, Karen S. Davis, Sonia M. Lebowitz, Barry D. Rabins, Peter Hsiao, John K. Lieberman, Jeffery A. Schneider, Lon S. CA CATIE AD Invetigators TI Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC-CRITERIA; TARDIVE-DYSKINESIA; HEALTH UTILITIES; CLINICAL-TRIALS; PRIMARY-CARE; RISK-FACTORS; DEMENTIA; DEPRESSION; DRUGS; METAANALYSIS AB Context: Second-generation antipsychotics (SGAs) are prescribed for psychosis, aggression, and agitation in Alzheimer disease (AD). Objective: To conduct a cost-benefit analysis of SGAs and placebo (taken to represent a '' watchful waiting '' treatment strategy) for psychosis and aggression in outpatients with AD. Design: Randomized placebo-controlled trial of alternative SGA initiation strategies. Setting: Forty-two outpatient clinics. Participants: Outpatients with AD and psychosis, aggression, or agitation (N= 421). Intervention: Participants were randomly assigned to treatment with olanzapine, quetiapine fumarate, risperidone, or placebo with the option of double-blind rerandomization to another antipsychotic or citalopram hydrobromide or open treatment over 9 months. Main Outcome Measures: Monthly interviews documented health service use and costs. The economic perspective addressed total health care and medication costs. Costs of study drugs were estimated from wholesale prices with adjustment for discounts and rebates. Quality-adjusted life-years (QALYs) were assessed with the Health Utilities Index Mark 3 and were supplemented with measures of functioning, activities of daily living, and quality of life. Primary analyses were conducted using all available data. Secondary analyses excluded observations after the first medication change (ie, phase 1 only). Cost-benefit analysis was conducted using the net health benefits approach in a sensitivity analysis in which QALYs were valued at $50 000 per year and $100 000 per year. Results: Average total health costs, including medications, were significantly lower for placebo than for SGAs, by $50 to $100 per month. There were no differences between treatments in QALYs or other measures of function. Phase 1-only analyses were broadly similar. Net-benefit analysis showed greater net health benefits for placebo as compared with other treatments, with probabilities ranging from 50% to 90%. Conclusions: There were no differences in measures of effectiveness between initiation of active treatments or placebo (which represented watchful waiting) but the placebo group had significantly lower health care costs. C1 VA Connecticut Hlth Care Syst, Program Evaluat Ctr 182, West Haven, CT 06516 USA. Yale Univ, New Haven, CT USA. Univ Arizona, Phoenix, AZ USA. Univ So Calif, Dept Psychiat, Los Angeles, CA USA. Univ So Calif, Dept Neurol, Los Angeles, CA USA. Univ So Calif, Dept Gerontol, Los Angeles, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ N Carolina, Chapel Hill, NC USA. NIMH, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. RP Rosenheck, RA (reprint author), VA Connecticut Hlth Care Syst, Program Evaluat Ctr 182, 950 Campbell Ave, West Haven, CT 06516 USA. EM rosenheck@yale.edu OI Adler, Lawrence/0000-0002-6619-2493 FU NIMH NIH HHS [N01 MH9001] NR 59 TC 28 Z9 31 U1 2 U2 3 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 NOV PY 2007 VL 64 IS 11 BP 1259 EP 1268 DI 10.1001/archpsyc.64.11.1259 PG 10 WC Psychiatry SC Psychiatry GA 228BK UT WOS:000250701700006 PM 17984395 ER PT J AU Volkow, ND Fowler, JS Wang, GJ Swanson, JM Telang, F AF Volkow, Nora D. Fowler, Joanna S. Wang, Gene-Jack Swanson, James M. Telang, Frank TI Dopamine in drug abuse and addiction - Results of imaging studies and treatment implications SO ARCHIVES OF NEUROLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; COCAINE DEPENDENCE; ALCOHOL DEPENDENCE; SMOKING-CESSATION; OPIOID DEPENDENCE; RECEPTORS; STRIATUM; INVOLVEMENT; TOPIRAMATE AB Imaging studies have provided new insights on the role of dopamine (DA) in drug abuse and addiction in the human brain. These studies have shown that the reinforcing effects of drugs of abuse in human beings are contingent not just on DA increases per se in the striatum (including the nucleus accumbens) but on the rate of DA increases. The faster the increases, the more intense the reinforcing effects. They have also shown that elevated levels of DA in the dorsal striatum are involved in the motivation to procure the drug when the addicted subject is exposed to stimuli associated with the drug (conditioned stimuli). In contrast, long-term drug use seems to be associated with decreased DA function, as evidenced by reductions in D2 DA receptors and DA release in the striatum in addicted subjects. Moreover, the reductions in D2 DA receptors in the striatum are associated with reduced activity of the orbitofrontal cortex (region involved with salience attribution and motivation and with compulsive behaviors) and of the cingulate gyrus (region involved with inhibitory control and impulsivity), which implicates deregulation of frontal regions by DA in the loss of control and compulsive drug intake that characterizes addiction. Because DA cells fire in response to salient stimuli and facilitate conditioned learning, their activation by drugs will be experienced as highly salient, driving the motivation to take the drug and further strengthening conditioned learning and producing automatic behaviors (compulsions and habits). C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Intramural NIH HHS; NIAAA NIH HHS [AA 09481]; NIDA NIH HHS [DA 06891, DA 06278, DA 09490] NR 32 TC 253 Z9 262 U1 5 U2 26 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 NOV PY 2007 VL 64 IS 11 BP 1575 EP 1579 DI 10.1001/archneur.64.11.1575 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 229YZ UT WOS:000250843800003 PM 17998440 ER PT J AU Celnik, P Hummel, F Harris-Love, M Wolk, R Cohen, LG AF Celnik, Pablo Hummel, Friedhelm Harris-Love, Michelle Wolk, Rebecca Cohen, Leonardo G. TI Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE electric stimulation; motor skills; rehabilitation; stroke ID HUMAN MOTOR CORTEX; PERIPHERAL-NERVE STIMULATION; PAIRED ASSOCIATIVE STIMULATION; HUMAN SENSORIMOTOR CORTEX; CORTICAL REORGANIZATION; ELECTRICAL-STIMULATION; MAGNETIC STIMULATION; CLINICAL-APPLICATION; PLASTICITY; REHABILITATION AB Celnik P, Hummel F, Harris-Love M, Wolk R, Cohen LG. Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. Arch Phys Med Rehabil 2007;88:1369-76. Objective: To test the hypothesis that somatosensory stimulation would enhance the effects of training functional hand tasks immediately after practice and I day later in chronic subcortical stroke patients. Design: Single-blinded and randomized, crossover study. Setting: Human research laboratory. Participants: Nine chronic subcortical stroke patients. Interventions: Three separate sessions of motor training preceded by (1) synchronous peripheral nerve stimulation (PNS), (2) no stimulation, or (3) asynchronous PNS. Main Outcome Measures: Time to complete the Jebsen-Taylor Hand Function Test (JTHFT time) and corticomotor excitability tested with transcranial magnetic stimulation. Results: After familiarization practice, during which all patients reached a performance plateau, training under the effects of PNS reduced JTHFT time by 10% beyond the post-familiarization plateau. This behavioral gain was accompanied by a specific reduction in GABAergically mediated intracortical inhibition in the motor cortex. These findings were not observed after similar practice under the influence of no stimulation or asynchronous PNS sessions. Conclusions: Somatosensory stimulation may enhance the training of functional hand tasks in patients with chronic stroke, possibly through modulation of intracortical GABAergic pathways. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. Natl Inst Neurol Disorders & Stroke, Stroke Rehabil Clin, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Univ Hamburg, Ctr Med, Dept Neurol, Hamburg, Germany. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Harris-Love, Michelle/J-1388-2014 OI Harris-Love, Michelle/0000-0001-5571-3858 FU Intramural NIH HHS; NICHD NIH HHS [5K12HD001097] NR 55 TC 74 Z9 80 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2007 VL 88 IS 11 BP 1369 EP 1376 DI 10.1016/j.apmr.2007.08.001 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 229AT UT WOS:000250774400001 PM 17964875 ER PT J AU Chan, L AF Chan, Leighton TI The state-of-the-science: Challenges in designing postacute care payment policy SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE health policy; outcome and process assessment (health care); outcomes research; rehabilitation ID TRAUMATIC BRAIN-INJURY; INPATIENT REHABILITATION; CASE-MIX; SYSTEM; IMPACT; OUTCOMES; FACILITIES; HOSPITALS; PROVIDERS AB Chan L. The state-of-the-science: challenges in designing postacute care payment policy, Arch Phys Med Rehabil 2007;88:1522-5. This report describes Medicare's postacute care (PAC) payment systems and their incentives, as well as global changes in capacity, quality, and utilization over time. It assesses the payment systems' impact on PAC services, referencing relevant works in progress. Suggestions are made for future research. C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Chan, L (reprint author), Bldg 10,CRC,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM chanle@cc.nih.gov NR 28 TC 23 Z9 23 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2007 VL 88 IS 11 BP 1522 EP 1525 DI 10.1016/j.apmr.2007.05.032 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 229AT UT WOS:000250774400025 PM 17964899 ER PT J AU Horvath, A Stratakis, C AF Horvath, Anelia Stratakis, Constantine TI Primary pigmented nodular adrenocortical disease and Cushing's syndrome SO ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA LA English DT Article DE PPNAD; Cushing's syndrome; adrenocortical hyperplasia; Carney complex; PRKAR1A; PDE11A ID PROTEIN-KINASE-A; SPOTTY SKIN PIGMENTATION; SCHWANNOMAS CARNEY COMPLEX; ALPHA REGULATORY SUBUNIT; ENDOCRINE OVERACTIVITY; PRKAR1A GENE; PHOSPHODIESTERASE 11A; ADRENAL-HYPERPLASIA; HUMAN TISSUES; MUTATIONS AB Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with corticotrophin (ACTH)-independent Cushing's syndrome (CS) and is characterized by small to normal-sized adrenal glands containing multiple small cortical pigmented nodules (1,2). PPNAD may occur in an isolated form or associated with a multiple neoplasia syndrome, the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, or Carney complex, in which Cushing's syndrome is the most common endocrine manifestation (3). Molecular studies have led to the identification of several genes, defects in which may predispose PPNAD formation; all of these molecules play important role for the cAMP signaling pathway. This review intends to present the most recent knowledge of the pathology and molecular genetics of the benign bilateral adrenocortical lesions, as well as to discuss the modern tools for diagnostics and treatment of this condition. C1 [Horvath, Anelia; Stratakis, Constantine] NICHHD, Head Sect Endocrinol & Genet SEGEN DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, C (reprint author), NICHHD, Head Sect Endocrinol & Genet SEGEN DEB, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mall.nih.gov NR 42 TC 11 Z9 13 U1 0 U2 0 PU SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA PI RIO DE JANEIRO, RJ PA RUA HUMAITA, 85 CJ 501, RIO DE JANEIRO, RJ, 22261-000, BRAZIL SN 0004-2730 EI 1677-9487 J9 ARQ BRAS ENDOCRINOL JI Arq. Bras. Endocrinol. Metabol. PD NOV PY 2007 VL 51 IS 8 BP 1238 EP 1244 DI 10.1590/S0004-27302007000800009 PG 7 GA 307UP UT WOS:000256344300009 PM 18209861 ER PT J AU Sabatine, MS Morrow, DA O'Donoghue, M Jablonksi, KA Rice, MM Solomon, S Rosenberg, Y Domanski, MJ Hsia, J AF Sabatine, Marc S. Morrow, David A. O'Donoghue, Michelle Jablonksi, Kathleen A. Rice, Madeline Murguia Solomon, Scott Rosenberg, Yves Domanski, Michael J. Hsia, Judith CA The PEACE Investigators TI Prognostic utility of lipoprotein-associated phospholipase A(2) for cardiovascular outcomes in patients with stable coronary artery disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary disease; lipoprotein-associated phospholipase A(2); C-reactive protein ID C-REACTIVE PROTEIN; ACTIVATING-FACTOR ACETYLHYDROLASE; MIDDLE-AGED MEN; HEART-DISEASE; RISK-FACTORS; FOLLOW-UP; ATHEROSCLEROSIS; EVENTS; INFLAMMATION; LYSOPHOSPHATIDYLCHOLINE AB Objective-To determine the prognostic utility of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) for specific adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD), independent of traditional risk factors and high-sensitivity C-reactive protein (hs-CRP). Methods and Results-We measured Lp-PLA(2) in 3766 patients with stable CAD from the PEACE trial. Patients were followed for a median of 4.8 years for adverse cardiovascular events including death, myocardial infarction (MI), coronary revascularization, hospitalization for unstable angina (UA), and stroke. Multivariable Cox regression was used to adjust for traditional cardiovascular risk factors and to conduct multimarker analyses that included hs-CRP. After adjustment for baseline characteristics, patients in higher quartiles of Lp-PLA(2) remained at significantly greater risk for the composite of cardiovascular death, MI, coronary revascularization, UA, or stroke (P<0.001 for trend, adj HR 1.41, 95% CI 1.17 to 1.70, for patients in 4th versus 1st quartile). The association was consistent regardless of a patient's sex, cholesterol levels, or use of lipid-lowering therapy. When analyzed together, both hs-CRP and Lp-PLA(2) were highly significant predictors of acute coronary syndromes (cardiovascular death, MI, or UA) (P for trend < 0.001 for hs-CRP and 0.005 for Lp-PLA(2)), whereas only Lp-PLA(2) was a significant predictor of coronary revascularization (P = 0.01 for trend). Conclusions-In stable CAD, an elevated level of Lp-PLA(2) was a significant predictor of nonfatal adverse cardiovascular outcomes independent of traditional clinical risk factors and hs-CRP. Further investigation will be needed to establish whether therapies that lower Lp-PLA(2) reduce cardiovascular risk. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. George Washington Univ, Rockville, MD USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NHLBI NIH HHS [N01 HC065149, N01HC65149, U01 HL083-1341] NR 26 TC 80 Z9 84 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2007 VL 27 IS 11 BP 2463 EP 2469 DI 10.1161/ATVBAHA.107.151670 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 224CZ UT WOS:000250424700028 PM 17766330 ER PT J AU Raben, N Takikita, S Pittis, MG Bembi, B Marie, SKN Roberts, A Page, L Kishnani, PS Schoser, BGH Chien, YH Ralston, E Nagaraju, K Plotz, PH AF Raben, Nina Takikita, Shoichi Pittis, Maria G. Bembi, Bruno Marie, Suely K. N. Roberts, Ashley Page, Laura Kishnani, Priya S. Schoser, Benedikt G. H. Chien, Yin-Hsiu Ralston, Evelyn Nagaraju, Kanneboyina Plotz, Paul H. TI Deconstructing Pompe disease by analyzing single muscle fibers SO AUTOPHAGY LA English DT Article DE autophagosome; lysosome; skeletal muscle; myopathy; glycogen storage; metabolic disorder; lysosomal storage disorder ID LYSOSOMAL STORAGE DISEASE; ACID MALTASE DEFICIENCY; MOLECULAR MACHINERY; GLYCOGEN AUTOPHAGY; ALPHA-GLUCOSIDASE; SKELETAL-MUSCLE; CELLS; PATHWAYS; STRESS; MARKER AB Autophagy is a major pathway for delivery of proteins and organelles to lysosomes where they are degraded and recycled. We have previously shown excessive autophagy in a mouse model of Pompe disease (glycogen storage disease type II), a devastating myopathy caused by a deficiency of the glycogen-degrading lysosomal enzyme acid a-glucosidase. The autophagic buildup constituted a major pathological component in skeletal muscle and interfered with delivery of the therapeutic enzyme. To assess the role, of autophagy in the pathogenesis of the human disease, we have analyzed vesicles of the lysosomal-degradative pathway in isolated single muscle fibers from Pompe patients. Human myofibers showed abundant autophagosome formation and areas of autophagic buildup of a wide range of sizes. In patients, as in the mouse model, the enormous autophagic buildup causes greater skeletal muscle damage than the enlarged, glycogenfilled lysosomes outside the autophagic regions. Clearing or preventing autophagic buildup seems, therefore, a necessary target of Pompe disease therapy. C1 NIAMSD, Arthrit & Rheumatism Branch, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. NIAMSD, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Pediat Hosp Burlo Garofolo, Trieste, Italy. Univ San Paolo, Sch Med, San Paola, Brazil. Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. Univ Munich, Dept Neurol, Friedrich Baur Inst, D-8000 Munich, Germany. Natl Taiwan Univ Hosp, Dept Pediat & Med Genet, Taipei, Taiwan. Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. RP Raben, N (reprint author), NIAMSD, Arthrit & Rheumatism Branch, Off Sci & Technol, NIH, 9000 Rockville Pike,Clin Ctr Bld 10-9N244, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov RI Marie, Suely/D-1870-2012 FU Intramural NIH HHS NR 40 TC 63 Z9 66 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 NOV-DEC PY 2007 VL 3 IS 6 BP 546 EP 552 PG 7 WC Cell Biology SC Cell Biology GA 229IR UT WOS:000250797000003 PM 17592248 ER PT J AU Gregory, AM Rijsdijk, FV Lau, J Napolitano, M McGuffin, P Eley, TC AF Gregory, Alice. M. Rijsdijk, Fruhling V. Lau, Jennifer Napolitano, Maria McGuffin, Peter Eley, Thalia C. TI Interpersonal cognitions and associations with depressive symptoms in 8 year-old twins SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 37th Annual Meeting of the Behavior-Genetics-Association CY JUN 03-08, 2007 CL Amsterdam, NETHERLANDS SP Behav Genet Assoc C1 [Gregory, Alice. M.] Univ London, Univ London Goldsmiths Coll, Dept Psychol, London WC1E 7HU, England. [Rijsdijk, Fruhling V.; Napolitano, Maria; McGuffin, Peter; Eley, Thalia C.] Inst Psychiat, London, England. NIMH, Bethesda, MD 20892 USA. EM a.gregory@gold.ac.uk RI Eley, Thalia/D-4811-2011; Rijsdijk, Fruhling/B-4191-2011; McGuffin, Peter/A-1565-2012 OI McGuffin, Peter/0000-0002-9888-2907 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2007 VL 37 IS 6 BP 757 EP 757 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 231VK UT WOS:000250977100060 ER PT J AU Neiderhiser, JM Lau, J Spotts, EL Haddad, S Ganiban, J Reiss, D Lichtenstein, P AF Neiderhiser, Jenae M. Lau, Jennifer Spotts, Erica L. Haddad, Suzanne Ganiban, Jody Reiss, David Lichtenstein, Paul TI The impact of parenting on adolescent depressive symptoms: Using children of twins to estimate parenting as a moderator of genetic and environmental influences SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 37th Annual Meeting of the Behavior-Genetics-Association CY JUN 03-08, 2007 CL Amsterdam, NETHERLANDS SP Behav Genet Assoc C1 [Neiderhiser, Jenae M.; Haddad, Suzanne; Ganiban, Jody; Reiss, David] George Washington Univ, Washington, DC 20052 USA. [Lau, Jennifer] NIMH, Bethesda, MD 20892 USA. [Spotts, Erica L.] Natl Inst Aging & Geo, Bethesda, MD 20892 USA. [Lichtenstein, Paul] Karolinska Inst, S-10401 Stockholm, Sweden. EM cfrjmn@gwumc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2007 VL 37 IS 6 BP 779 EP 780 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 231VK UT WOS:000250977100113 ER PT J AU Page, WF Sutin, AR Costa, PT AF Page, William F. Sutin, Angelina R. Costa, Paul T. TI Genetic influences on personality in old age SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 37th Annual Meeting of the Behavior-Genetics-Association CY JUN 03-08, 2007 CL Amsterdam, NETHERLANDS SP Behav Genet Assoc C1 [Page, William F.] Inst Med, Washington, DC USA. [Sutin, Angelina R.; Costa, Paul T.] Natl Inst Aging, Baltimore, MD USA. EM wpaage@nas.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2007 VL 37 IS 6 BP 783 EP 783 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 231VK UT WOS:000250977100121 ER PT J AU Schmitt, JE Lenroot, R Wallace, GL Giedd, JN Neale, MC AF Schmitt, J. Eric Lenroot, Rhoshel Wallace, Gregory L. Giedd, Jay N. Neale, Michael C. TI The genetics of neurodevelopment: Methods and results from the NIMH pediatric twin study SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 37th Annual Meeting of the Behavior-Genetics-Association CY JUN 03-08, 2007 CL Amsterdam, NETHERLANDS SP Behav Genet Assoc C1 [Schmitt, J. Eric; Neale, Michael C.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Lenroot, Rhoshel; Wallace, Gregory L.; Giedd, Jay N.] NIMH, Bethesda, MD 20892 USA. EM schmittje@vcu.edu RI Neale, Michael/B-1418-2008; 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 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2007 VL 37 IS 6 BP 793 EP 793 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 231VK UT WOS:000250977100141 ER PT J AU Kodama, S Moore, R Yamamoto, Y Negishi, M AF Kodama, Susumu Moore, Rick Yamamoto, Yukio Negishi, Masahiko TI Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene SO BIOCHEMICAL JOURNAL LA English DT Article DE cAMP-response element-binding protein (CREB); glucagon; gluconeogenesis; glucose-6-phosphatase (G6Pase); insulin; pregnane X receptor (PXR) ID CONSTITUTIVE ANDROSTANE RECEPTOR; ELEMENT-BINDING PROTEIN; HEPATIC GLUCONEOGENESIS; RESPONSE ELEMENT; MOUSE-LIVER; CYCLIC-AMP; COACTIVATOR PGC-1; ENHANCER MODULE; TRANSCRIPTION; CAR AB The nuclear PXR (pregnane X receptor) was originally characterized as a key transcription factor that activated hepatic genes encoding drug-metabolizing enzymes. We have now demonstrated that PXR also represses glucagon-activated transcription of the G6Pase (glucose-6-phosphatase) gene by directly binding to CREB [CRE (CAMP-response element)-binding protein]. Adenoviral-mediated expression of human PXR (hPXR) and its activation by rifampicin strongly repressed cAMP-dependent induction of the endogenous G6Pase gene in Huh7 cells. Using the - 259 by G6Pase promoter construct in cell-based transcription assays, repression by hPXR of PKA (CAMP-dependent protein kinase)-mediated promoter activation was delineated to CRE sites. GST (glutathione transferase) pull-down and immunoprecipitation assays were employed to show that PXR binds directly to CREB, while gel-shift assays were used to demonstrate that this binding prevents CREB interaction with the CRE. These results are consistent with the hypothesis that PXR represses the transcription of the G6Pase gene by inhibiting the DNA-binding ability of CREB. In support of this hypothesis, treatment with the mouse PXR activator PCN (pregnenolone 16 alpha-carbonitrile) repressed CAMP-dependent induction of the G6Pase gene in primary hepatocytes prepared from wild-type, but not from PXR-knockout, mice, and also in the liver of fasting wildtype, but not PXR-knockout, mice. Moreover, ChIP (chromatin immunoprecipitation) assays were performed to show a decreased CREB binding to the G6Pase promoter in fasting wild-type mice after PCN treatment. Thus drug activation of PXR can repress the transcriptional activity of CREB, down-regulating gluconeogenesis. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 55 Z9 61 U1 1 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2007 VL 407 BP 373 EP 381 DI 10.1042/BJ20070481 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226TX UT WOS:000250612500006 PM 17635106 ER PT J AU Block, ML Hong, JS AF Block, M. L. Hong, J. -S. TI Chronic microglial activation and progressive dopaminergic neurotoxicity SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Focus Topic at Life Sciences 2007 Conference CY JUL 09-12, 2007 CL Glasgow, SCOTLAND DE dopaminergic neuron; microglia; NADPH oxidase; neuroinflammation; Parkinson's disease; reactive oxygen species ID ROTENONE-INDUCED DEGENERATION; ALZHEIMERS-DISEASE BRAINS; NECROSIS-FACTOR-ALPHA; PARKINSONS-DISEASE; NADPH OXIDASE; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; INFLAMMOGEN LIPOPOLYSACCHARIDE; MATRIX METALLOPROTEINASE-3; REACTIVE MICROGLIOSIS AB PD (Parkinson's disease) is characterized by the selective and progressive loss of DA neurons (dopaminergic neurons) in the substantia nigra. inflammation and activation of microglia, the resident innate immune cell in the brain, have been strongly linked to neurodegenerative diseases, such as PD. Microglia can respond to immunological stimuli and neuronal death to produce a host of toxic factors, including cytokines and ROS (reactive oxygen species). Microglia can also become persistently activated after a single stimulus and maintain the elevated production of both cytokines and ROS, long after the instigating stimulus is gone. current reports suggest that this chronic microglial activation may be fuelled by either dying/damaged neurons or autocrine and paracrine signals from local glial cells, such as cytokines. Here, we review proposed mechanisms responsible for chronic neuroinflammation and explain the interconnected relationship between deleterious microglial activation, DA neuron damage and neurodegenerative disease. C1 NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. RP Block, ML (reprint author), NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. EM mblock@vcu.edu FU Intramural NIH HHS; NIEHS NIH HHS [1K99ES01549-01, K99 ES015409, K99 ES015409-01] NR 61 TC 135 Z9 154 U1 0 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 2007 VL 35 BP 1127 EP 1132 PN 5 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236CE UT WOS:000251279800066 PM 17956294 ER PT J AU Ramakrishnan, B Boeggeman, E Qasba, PK AF Ramakrishnan, Boopathy Boeggeman, Elizabeth Qasba, Pradman K. TI Novel method for in vitro O-glycosylation of proteins: Application for bioconjugation SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SITE-SPECIFIC CONJUGATION; MONOCLONAL-ANTIBODIES; OLIGOSACCHARIDE MOIETIES; CANCER THERAPEUTICS; DOMAINS; IMMUNOGLOBULINS; RESIDUES; DESIGN; DRUGS AB Here, we describe a new method for the bioconjugation of a nonglycoprotein with biomolecules. Using polypeptide-alpha-N-acetyl gal actosaminyltransferase II (ppGalNAc-T2), we transfer a C2-modified galactose that has a chemical handle, such as ketone or azide, from its respective UDP-sugars to the Ser/Thr residue(s) of an acceptor polypeptide fused to the nonglycoprotein. The protein with the modified galactose is then coupled to a biomolecule that carries an orthogonal reactive group. As a model system for the nonglycoprotein, we engineered glutathione-S-transferase (GST) protein with a 17-amino-acid-long fusion peptide at the C-terminal end that was expressed as a soluble protein in E. coli. The ppGalNAc-T2 protein, the catalytic domain with the C-terminal lectin domain, was expressed as inclusion bodies in E. coli, and an in vitro folding method was developed to produce milligram quantities of the active enzyme from a liter of bacterial culture. This ppGalNAc-T2 enzyme transfers from the UDP-sugars not only GalNAc but also C2-modified galactose with a chemical handle to the Ser/Thr residue(s) in the fusion peptide. The chemical handle at the C2 of galactose is used for conjugation and assembly of bionanoparticles and preparation of immumo-liposomes for a targeted drug delivery system. This novel method enables one to glycosylate, using ppGalNAc-T2, the important biological nonglycoproteins, such as single-chain antibodies, growth factors, or bacterial toxins, with an engineered 17-residue peptide sequence at the C-terminus of the molecule, for conjugation and coupling. C1 NCI, Ctr Canc Res, Ctr Canc Res Nanobiol Program, Struct Glycobiol Sect,SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Ctr Canc Res Nanobiol Program, Basic Res Program,SAIC Frederick Inc, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Ctr Canc Res, Ctr Canc Res Nanobiol Program, Struct Glycobiol Sect,SAIC Frederick Inc, Bldg 469,Room 221, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01 CO12400] NR 30 TC 21 Z9 21 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 2007 VL 18 IS 6 BP 1912 EP 1918 DI 10.1021/bc7002346 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 234LU UT WOS:000251166400030 PM 17953440 ER PT J AU Shiryev, SA Papadopoulos, JS Schaffer, AA Agarwala, R AF Shiryev, Sergey A. Papadopoulos, Jason S. Schaeffer, Alejandro A. Agarwala, Richa TI Improved BLAST searches using longer words for protein seeding SO BIOINFORMATICS LA English DT Article ID ACID SUBSTITUTION MATRICES; DATABASE SEARCHES AB Motivation: The blastp and tblastn modules of BLAST are widely used methods for searching protein queries against protein and nucleotide databases, respectively. One heuristic used in BLAST is to consider only database sequences that contain a high-scoring match of length at most 5 to the query. We implemented the capability to use words of length 6 or 7. We demonstrate an improved trade-off between running time and retrieval accuracy, controlled by the score threshold used for short word matches. For example, the running time can be reduced by 20-30 while achieving ROC (receiver operator characteristic) scores similar to those obtained with current default parameters. C1 NIH, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Agarwala, R (reprint author), NIH, Dept Hlth & Human Serv, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. EM richa@helix.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 12 TC 10 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2007 VL 23 IS 21 BP 2949 EP 2951 DI 10.1093/bioinformatics/btm479 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 234XL UT WOS:000251197700022 PM 17921491 ER PT J AU Vitorino, R Calheiros-Lobo, MJ Williams, J Ferrer-Correia, AJ Tomer, KB Duarte, JA Domingues, PM Amado, FM AF Vitorino, Rui Calheiros-Lobo, Maria Joao Williams, Jason Ferrer-Correia, Antonio J. Tomer, Kenneth B. Duarte, Jose A. Domingues, Pedro M. Amado, Francisco M. TI Peptidomic analysis of human acquired enamel pellicle SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article DE acquired enamel pellicle; whole saliva; LC-MS/MS; salivary peptides; proteolytic activity ID PROLINE-RICH PROTEINS; MASS-SPECTROMETRY; IN-VITRO; SALIVARY PEPTIDES; CROSS-LINKING; HYDROXYAPATITE; ADSORPTION; STATHERIN; IDENTIFICATION; HISTATINS AB Human acquired enamel pellicle is the result of a selective interaction of salivary proteins and peptides with the tooth surface. In the present work, the characterization of the peptides as well as the type of interactions established with the enamel surface was performed. Peptides from in vivo bovine enamel implants in the human oral cavity were sequentially extracted using guanidine and trifluoroacetic acid solutions and the fractions obtained were analysed by LC-MS and LC-MS/MS. Based on the LC-MS data, six phosphorylated peptides were identified in an intact form, strongly adsorbed to the enamel surface. Data from the LC-MS/MS analyses allowed us to identified 30 fragment peptides non-covalently bonded to enamel [basic proline-rich proteins, histatins (I and 3) and acidic proline-rich protein classes]. The tandem mass spectrometry experiments showed the existence of a pattern of amide bond cleavage for the different identified peptide classes suggesting a selective proteolytic activity. For histatins, a predominance of cleavage at Arg, Lys and His residues was observed, while for basic proline-rich proteins, cleavage at Arg and Pro residues prevailed. In the case of acidic proline-rich proteins, a clearly predominance of cleavage of the Gln-Gly amide bond was evident. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Univ Aveiro, Dept Chem, P-3810193 Aveiro, Portugal. Univ Porto, Fac Sport, CIAFEL, P-4100 Oporto, Portugal. Natl Inst Environm Hlth Sci, NIH, DHHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Amado, FM (reprint author), Univ Aveiro, Dept Chem, P-3810193 Aveiro, Portugal. EM famado@dq.ua.pt RI Tomer, Kenneth/E-8018-2013; Domingues, Pedro/E-5202-2010; Duarte, Jose/F-1443-2013; PTMS, RNEM/C-1589-2014; Vitorino, Rui/G-7356-2014; Amado, Francisco/M-5337-2015 OI Domingues, Pedro/0000-0002-8060-7675; Duarte, Jose/0000-0003-4756-5917; Vitorino, Rui/0000-0003-3636-5805; CALHEIROS-LOBO, MARIA JOAO/0000-0003-1692-9108; Amado, Francisco/0000-0001-8256-1749 FU Intramural NIH HHS NR 45 TC 21 Z9 21 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD NOV PY 2007 VL 21 IS 11 BP 1107 EP 1117 DI 10.1002/bmc.830 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 237FE UT WOS:000251358800001 PM 17516463 ER PT J AU Shiotani, K Li, TY Miyazaki, A Tsuda, Y Yokoia, T Ambo, A Sasaki, Y Bryant, SD Lazarus, LH Okada, Y AF Shiotani, Kirnitaka Li, Tingyou Miyazaki, Anna Tsuda, Yuko Yokoia, Toshio Ambo, Akihiro Sasaki, Yusuke Bryant, Sharon D. Lazarus, Lawrence H. Okada, Yoshio TI Design and synthesis of opioidmimetics containing 2 ',6 '-dimethyl-L-tyrosine and a pyrazinone-ring platform SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE 2',6'-Dimethyl-L-tyrosine; Pyrazinone; mu-Selective opioid ligand; mu-Agonist/delta-antagonist; mu-Antagonist/delta-aiitagonist ID OPIOID RECEPTOR AGONISTS; AMPHIBIAN SKIN; HIGH-AFFINITY; ENDOGENOUS AGONIST; MEDIATED ANALGESIA; PEPTIDE; POTENT; SELECTIVITY; DERMORPHIN; ANALOGS AB Twelve 2 ',6 '-dimethyl-L-tyrosine (Dmt) analogues linked to a pyrazinone platform were synthesized as 3- or 6-[H-Dmt-NH(CH2)(n)],3- or 6-R-2(1H)-pyrazinone (n = 1-4). 3-[H-Dmt-NH-(CH2)(4)]-6-beta-phenethyl-5-methyl-2(1H)-pyrazinone 11 bound to mu-opioid receptors with high affinity (K-i mu = 0.13 nM; Ki delta/K-i mu = 447) with mu-agonism (GPI IC50 = 15.9 nM) and weak delta-antagonism (MVD pA(2) = 6.35), Key factors affecting opioid affinity and functional bioactivity are the length of the aminoalkyl chain linked to Dmt and the nature of the R residue. These data present a simplified method for the formation of pyrazinone opioidmimetics and new lead compounds. (c) 2007 Elsevier Ltd. All rights reserved. C1 Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Aoba Ku, Sendai, Miyagi 9818558, Japan. NIEHS, Pharmacol Lab & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS [Z99 ES999999, Z01 ES090053-20, Z01 ES100472-06] NR 28 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2007 VL 17 IS 21 BP 5768 EP 5771 DI 10.1016/j.bmcl.2007.08.058 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 222HU UT WOS:000250287800007 PM 17826995 ER PT J AU Huang, WW Zheng, W Urban, DJ Inglese, J Sidransky, E Austin, CP Thomas, CJ AF Huang, Wenwei Zheng, Wei Urban, Daniel J. Inglese, James Sidransky, Ellen Austin, Christopher P. Thomas, Craig J. TI N-4-Phenyl modifications N-2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE triazine; Gaucher disease; glucocerebrosidase; chemical chaperone ID LYSOSOMAL STORAGE DISORDERS; DERIVATIVES; STRATEGIES AB A series of 1,3,5-triazine-2,4,6-triamines were prepared and analyzed as inhibitors of glucocerebrosidase. Synthesis, structure activity relationships and the selectivity of chosen analogues against related Sugar hydrolases enzymes are described. Published by Elsevier Ltd. C1 NIH, NIH Chem Genome Ctr, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIH, NIH Chem Genome Ctr, Natl Human Genome Res Inst, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov; craigt@mail.nih.gov RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS [Z99 HG999999] NR 16 TC 20 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2007 VL 17 IS 21 BP 5783 EP 5789 DI 10.1016/j.bmcl.2007.08.050 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 222HU UT WOS:000250287800010 PM 17827006 ER PT J AU Toyooka, N Kobayashi, S Zhoti, D Tsuneki, H Wada, T Sakai, H Nemoto, H Sasaoka, T Garraffo, HM Spande, TF Daly, JW AF Toyooka, Naoki Kobayashi, Soushi Zhoti, Dejun Tsuneki, Hiroshi Wada, Tsutomu Sakai, Hideki Nemoto, Hideo Sasaoka, Toshiyasu Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE poison-frog alkaloids; neuronal nicotinic acetylcholine receptors; 1-epi-2071; 233A; 235U; 251AA ID INDOLIZIDINE; (-)-217A; 207I AB We previously reported that the synthetic quinolizidine 1-epi-2071 is a relatively selective blocker of 0 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked alpha 7 and alpha 4 beta 2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of a7 and alpha 4 beta 2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-2071 reduce alpha 7-potency without affecting alpha 4 beta 2-potency. (c) 2007 Elsevier Ltd. All rights reserved. C1 Natl Inst Hlth, DHHS, NIDDK, Lab Bioorgan Chem, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Sugitani 2630, Sugitani, Toyama 9300194, Japan. EM toyooka@pha.u-toyama.ac.jp FU Intramural NIH HHS NR 24 TC 16 Z9 16 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2007 VL 17 IS 21 BP 5872 EP 5875 DI 10.1016/j.bmcl.2007.08.045 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 222HU UT WOS:000250287800025 PM 17827002 ER PT J AU Zheng, J Jang, H Ma, B Tsai, CJ Nussinov, R AF Zheng, Jie Jang, Hyunbum Ma, Buyong Tsai, Chung-Jun Nussinov, Ruth TI Modeling the Alzheimer A beta(17-42) fibril architecture: Tight intermolecular sheet-sheet association and intramolecular hydrated cavities SO BIOPHYSICAL JOURNAL LA English DT Article ID SOLID-STATE NMR; AMYLOID-BETA-PROTEIN; MOLECULAR-DYNAMICS SIMULATIONS; EXPERIMENTAL CONSTRAINTS; ATOMIC STRUCTURES; COMMON MECHANISM; 3D STRUCTURE; PEPTIDE; DISEASE; OLIGOMERS AB We investigate A beta(17- 42) protofibril structures in solution using molecular dynamics simulations. Recently, NMR and computations modeled the A beta protofibril as a longitudinal stack of U-shaped molecules, creating an in-parallel beta-sheet and loop spine. Here we study the molecular architecture of the fibril formed by spine-spine association. We model in-register intermolecular beta-sheet-beta-sheet associations and study the consequences of Alzheimer's mutations (E22G, E22Q, E22K, and M35A) on the organization. We assess the structural stability and association force of A beta oligomers with different sheet-sheet interfaces. Double-layered oligomers associating through the C-terminal-C-terminal interface are energetically more favorable than those with the N-terminal-N-terminal interface, although both interfaces exhibit high structural stability. The C-terminal-C-terminal interface is essentially stabilized by hydrophobic and van der Waals ( shape complementarity via M35-M35 contacts) intermolecular interactions, whereas the N-terminal-N-terminal interface is stabilized by hydrophobic and electrostatic interactions. Hence, shape complementarity, or the "steric zipper'' motif plays an important role in amyloid formation. On the other hand, the intramolecular A beta beta-strand-loop-beta-strand U-shaped motif creates a hydrophobic cavity with a diameter of 6 - 7 angstrom, allowing water molecules and ions to conduct through. The hydrated hydrophobic cavities may allow optimization of the sheet association and constitute a typical feature of fibrils, in addition to the tight sheet-sheet association. Thus, we propose that A beta fiber architecture consists of alternating layers of tight packing and hydrated cavities running along the fibrillar axis, which might be possibly detected by high-resolution imaging. C1 NCI, Basic Res Program, SAIC Frederick Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Zheng, Jie/B-5057-2013 OI Ma, Buyong/0000-0002-7383-719X; Zheng, Jie/0000-0003-1547-3612 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 58 TC 117 Z9 117 U1 5 U2 31 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2007 VL 93 IS 9 BP 3046 EP 3057 DI 10.1529/biophysj.107.110700 PG 12 WC Biophysics SC Biophysics GA 221AR UT WOS:000250199300010 PM 17675353 ER PT J AU Li, P Jiang, S Pero, SC Oligino, L Krag, DN Michejda, CJ Roller, PP AF Li, Peng Jiang, Sheng Pero, Stephanie C. Oligino, Lyn Krag, David N. Michejda, Christopher J. Roller, Peter P. TI Design and synthesis of paclitaxel conjugated with an ErbB2-Recognizing pepticle, EC-1 SO BIOPOLYMERS LA English DT Article DE paclitaxel; erbB2; conjugate; cyclic peptide; EC-1; disulfide ID TARGETED DRUG-DELIVERY; BIOLOGICAL EVALUATION; THERAPY; TAXOL; CELLS; PEPTIDES; RECEPTOR; AGENTS; TUMORS; MODEL AB The selective delivery of therapeutic agents to receptors overexpressed in cancer cells without harming the rest of the body is a major challenge in clinical oncology today. In this study, we report the design and synthesis of paclitaxel (PTX) conjugated with an erbB2- recognizing peptide (EC-1). The cyclic peptide EC-1 specifically binds to the extracellular domain of ErbB2 and selectively inhibits proliferation of breast cancer cells overexpressing ErbB2. PTX is a potent antitumor agent commonly used in the treatment of advanced metastatic breast cancer, yet patients have to suffer some side effects caused by its systemic toxicity. The aim of our conjugate is to specifically deliver antitumor agent PTX to breast cancer cells that overexpress oncogenic ErbB2 with the purpose to reduce toxicity and enhance selective killing of cancer cells. In this study, a concise and efficient synthetic route for the preparation of the PTX-EC-1 conjugate has been developed in 69,6 overall yield. This synthetic approach provides a general method for conjugating a highly functionalized and disulfide-bridge containing cyclopeptide to Taxol or other antitumor agents. (c) 2007 Wiley Periodicals. C1 NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21701 USA. NCI, NIH, Struct Biophys Lab, Mol Aspects Drug Design Sect, Frederick, MD USA. Univ Vermont, Vermont Canc Ctr, Sch Med, Dept Surg, Burlington, VT 05405 USA. RP Roller, PP (reprint author), Intra Cellular Therapies Inc, New York, NY 10032 USA. EM proll@helix.nih.gov NR 32 TC 7 Z9 7 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD NOV PY 2007 VL 87 IS 4 BP 225 EP 230 DI 10.1002/bip.20828 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 221ER UT WOS:000250210700003 PM 17879382 ER PT J AU Dickstein, DP Roberson-Nay, R Berghorst, L Vinton, D Pine, DS Leibenluft, E AF Dickstein, Daniel P. Roberson-Nay, Roxann Berghorst, Lisa Vinton, Deborah Pine, Daniel S. Leibenluft, Ellen TI Neural activation during encoding of emotional faces in pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE adolescent; bipolar disorder; child; emotion; magnetic resonance imaging; memory ID TEMPORAL-LOBE STRUCTURES; VOXEL-BASED MORPHOMETRY; FACIAL EXPRESSIONS; NEUROCOGNITIVE FUNCTION; SPECTRUM DISORDERS; RESPONSE-REVERSAL; MAJOR DEPRESSION; SOCIAL COGNITION; BRAIN ENGAGEMENT; JUVENILE MANIA AB Objective: Neurobiological understanding of bipolar disorder (BD) is limited by a paucity of functional magnetic resonance imaging (fMRI) research examining correlates of psychological processes. To begin to address these limitations, the current study tests the hypothesis that pediatric BD (PBD) subjects exhibit altered neural activation during encoding of emotional faces compared to typically developing controls. Methods: Pediatric BD subjects (n = 23; mean age = 14.2 +/- 3.1 years) and controls (n = 22; mean age = 14.7 +/- 2.3 years) were matched on age, gender, and IQ. In this event-related fMRI study, subjects were scanned while viewing emotional faces and given a surprise recognition memory test 30 min postscan. Our main outcome measure was between-group differences in neural activation during successful versus unsuccessful face encoding. Results: Pediatric BD youth exhibited reduced memory for emotional faces, relative to healthy comparisons, particularly on fearful faces. Event-related fMRI analyses controlling for this behavioral difference showed that PBD subjects, compared to controls, had increased neural activation in the striatum and anterior cingulate cortex when successfully encoding happy faces and in the orbitofrontal cortex when successfully encoding angry faces. There were no between-group differences in neural activation during fearful face encoding. Conclusions: Our results extend what is known about memory and face emotion processing impairments in PBD subjects by showing increased fronto-striatal activation during encoding of emotional faces. Further work is required to determine the impact of mood state, medication, and comorbid illnesses on these findings. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Div Intramural Res Program, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Coll Med, Richmond, VA USA. RP Dickstein, DP (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Div Intramural Res Program, 9000 Rockville Pike MSC 2670,Bldg 15K,Room 204, Bethesda, MD 20892 USA. EM dicksted@mail.nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 FU NIMH NIH HHS [K22 MH074945-02, K22 MH074945-02S1, K22 MH074945] NR 88 TC 55 Z9 55 U1 5 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2007 VL 9 IS 7 BP 679 EP 692 DI 10.1111/j.1399-5618.2007.00418.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 227GD UT WOS:000250644300002 PM 17988357 ER PT J AU Sublette, ME Bosetti, F Demar, JC Ma, KZ Bell, JM Fagin-Jones, S Russ, MJ Rapoport, SI AF Sublette, M. Elizabeth Bosetti, Francesca Demar, James C. Ma, Kaizong Bell, Jane M. Fagin-Jones, Stephanie Russ, Mark J. Rapoport, Stanley I. TI Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute mania SO BIPOLAR DISORDERS LA English DT Article DE arachidonic acid; bipolar disorder; mania; polyunsaturated fatty acids; prostaglandins ID PLACEBO-CONTROLLED TRIAL; PRELIMINARY DOUBLE-BLIND; BLOOD-CELL MEMBRANES; DOCOSAHEXAENOIC ACID; RAT-BRAIN; POSTPARTUM DEPRESSION; SEAFOOD CONSUMPTION; BIPOLAR DEPRESSION; MAJOR DEPRESSION; ARACHIDONIC-ACID AB Objectives: Nutritionally essential polyunsaturated fatty acids (PUFAs) have been implicated as potentially important factors in mood disorders. For instance, n-3 PUFA supplementation is reported to improve outcomes in major depressive disorder and bipolar disorder. However, the role of PUFAs in acute mania has been minimally investigated. We performed a pilot study to compare plasma levels of free (non-esterified) and esterified PUFAs between patients in an acute manic episode and healthy volunteers, and to explore associations between symptom severity and levels of fatty acids and of the arachidonic acid metabolite, prostaglandin E-2 (PGE(2)). Methods: Patients (n = 10) who were medication-free for at least two weeks and seeking inpatient admission for an acute manic episode were compared with healthy volunteers (n = 10). Symptom severity was assessed at admission and after six weeks of naturalistic treatment. Fasting baseline free and esterified plasma levels of docosahexaneoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3), arachidonic acid (AA,20:4n-6) and the AA metabolite PGE(2) were determined, and PGE(2) levels were tested again at six weeks. Results: No between-group differences were found in levels of individual or total fatty acids, or of PGE(2). Among subjects, manic symptom severity correlated negatively with levels of free AA and free EPA, and positively with the free AA:EPA ratio. PGE(2) levels did not differ between groups or in subjects pre- and post-treatment. Conclusions: Our preliminary results suggest that, in susceptible persons, low plasma levels of free EPA compared with AA are related to the severity of mania. C1 Columbia Univ, New York State Psychiat Inst, Dept Neurosci, New York, NY 10032 USA. Columbia Univ, New York State Psychiat Inst, Dept Child Psychiat, New York, NY 10032 USA. NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NIAAA, NIH, Lab Membrane Biochem & Biophys, Bethesda, MD USA. Columbia Univ, Teachers Coll, Dept Clin & Counselling Psychol, New York, NY 10027 USA. Zucker Hillside Hosp, Dept Psychiat, N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. RP Sublette, ME (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Neurosci, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA. EM es2316@columbia.edu RI Sublette, M/A-8391-2009 OI Sublette, M/0000-0001-7378-4262 FU Intramural NIH HHS [Z01 AG000422-04] NR 49 TC 39 Z9 40 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2007 VL 9 IS 7 BP 759 EP 765 DI 10.1111/j.1399-5618.2007.00387.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 227GD UT WOS:000250644300012 PM 17988367 ER PT J AU Silverstein, RL Bauer, KA Cushman, M Esmon, CT Ershler, WB Tracy, RP AF Silverstein, Roy L. Bauer, Kenneth A. Cushman, Mary Esmon, Charles T. Ershler, William B. Tracy, Russell P. TI Venous thrombosis in the elderly: more questions than answers SO BLOOD LA English DT Article ID DEEP-VEIN THROMBOSIS; QUALITY-OF-LIFE; FACTOR-V-LEIDEN; PULMONARY-EMBOLISM; RISK-FACTORS; D-DIMER; THROMBOEMBOLISM ETIOLOGY; POSTTHROMBOTIC SYNDROME; CARDIOVASCULAR RISK; IN-VIVO C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. Vet Adm VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. NIA, Baltimore, MD 21224 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Silverstein, RL (reprint author), Cleveland Clin, Lerner Res Inst, Dept Cell Biol, NC10,9500 Euclid Ave, Cleveland, OH 44195 USA. EM silverr2@ccf.org NR 51 TC 38 Z9 39 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2007 VL 110 IS 9 BP 3097 EP 3101 DI 10.1182/blood-2007-06-096545 PG 5 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200009 PM 17684155 ER PT J AU Litzinger, MT Fernando, R Curiel, TJ Grosenbach, DW Schlom, J Palena, C AF Litzinger, Mary T. Fernando, Romaine Curiel, Tyler J. Grosenbach, Douglas W. Schlom, Jeffrey Palena, Claudia TI IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity SO BLOOD LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; ANTITUMOR-ACTIVITY; PERIPHERAL-BLOOD; BONE-MARROW; MONOCLONAL-ANTIBODY; CD25 EXPRESSION; CANCER-PATIENTS; FUSION-PROTEIN; TUMOR-IMMUNITY; OVARIAN-CANCER AB CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB(389)IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigenspecific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox I day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, San Antonio Canc Inst, San Antonio, TX USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Rm 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov FU FDA HHS [R01 FD003118]; Intramural NIH HHS; NCI NIH HHS [R01 CA100425, CA 100425, CA 105207, R01 CA105207] NR 43 TC 107 Z9 110 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2007 VL 110 IS 9 BP 3192 EP 3201 DI 10.1182/blood-2007-06-094615 PG 10 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200021 PM 17616639 ER PT J AU Sellick, GS Goldin, LR Wild, RW Slager, SL Ressenti, L Strom, SS Dyer, MJS Mauro, FR Marti, GE Fuller, S Lyttelton, M Kipps, TJ Keating, MJ Call, TG Catovsky, D Caporaso, N Houlston, RS AF Sellick, Gabrielle S. Goldin, Lynn R. Wild, Ruth W. Slager, Susan L. Ressenti, Laura Strom, Sara S. Dyer, Martin J. S. Mauro, Francesca R. Marti, Gerald E. Fuller, Stephen Lyttelton, Matthew Kipps, Thomas J. Keating, Michael J. Call, Timothy G. Catovsky, Daniel Caporaso, Neil Houlston, Richard S. TI A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia SO BLOOD LA English DT Article ID B-CELLS; CYTOGENETIC ABNORMALITIES; CHEMOKINE RECEPTORS; GROWTH ARREST; DISEQUILIBRIUM; APOPTOSIS; LYMPHOMA; PREDISPOSITION; EXPRESSION; GUIDELINES AB Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P =.001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P = 7.7 x 10(-5)), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P <.002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci. C1 Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biostat, Rochester, MN USA. Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Div Hematol, Rome, Italy. US FDA, Ctr Biol Evaluat & Res, Div Cell Therapy, Flow & Image Cytometry Sect, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Gene Therapy, Flow & Image Cytometry Sect, Bethesda, MD USA. Univ Sydney, Nepean Hosp, Dept Med, Penrith, Australia. Gen Hosp Kettering, Kettering, England. Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, San Diego, CA 92103 USA. Univ Texas, MD Anderson Canc Ctr, Div Hematol, Houston, TX 77030 USA. Mayo Clin, Coll Med, Dept Med, Div Hematol, Rochester, MN USA. Inst Canc Res, Sect Hematooncol, Sutton, Surrey, England. RP Sellick, GS (reprint author), Inst Canc Res, Sect Canc Genet, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. RI Slager, Susan/B-6756-2009; Fuller, Stephen/C-1200-2009; Dyer, Martin/F-2691-2014; OI Dyer, Martin/0000-0002-5033-2236; Houlston, Richard/0000-0002-5268-0242 FU Intramural NIH HHS; Medical Research Council [MC_U132670597]; NCI NIH HHS [CA 118444, U01 CA118444] NR 38 TC 45 Z9 45 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2007 VL 110 IS 9 BP 3326 EP 3333 DI 10.1182/blood-2007-05-091561 PG 8 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200036 PM 17687107 ER PT J AU Li, WJ Kezele, I Collins, DL Zijdenbos, A Keyak, J Kornak, J Koyama, A Saeed, I LeBlanc, A Harris, T Lu, Y Lang, T AF Li, Wenjun Kezele, Irina Collins, D. Louis Zijdenbos, Alex Keyak, Joyce Kornak, John Koyama, Alain Saeed, Isra LeBlanc, Adnian Harris, Tamara Lu, Ying Lang, Thomas TI Voxel-based modeling and quantification of the proximal femur using inter-subject registration of quantitative CT images SO BONE LA English DT Article DE image processing; image registration; modeling; quantitative computed tomography; proximal femur; bone mineral density; bone loss; spaceflight; osteoporosis ID FINITE-ELEMENT MODELS; COMPUTED-TOMOGRAPHY; PARATHYROID-HORMONE; OSTEOPOROSIS; SEGMENTATION; HIP; ALENDRONATE; VALIDATION; STRENGTH; FRACTURE AB We have developed a general framework which employs quantitative computed tomography (QCT) imaging and inter-subject image registration to model the three-dimensional structure of the hip, with the goal of quantifying changes in the spatial distribution of bone as it is affected by aging, drug treatment or mechanical unloading. We have adapted rigid and non-rigid inter-subject registration techniques to transform groups of hip QCT scans into a common reference space and to construct composite proximal femoral models. We have applied this technique to a longitudinal study of 16 astronauts who on average, incurred high losses of hip bone density during spaceflights of 4-6 months on the International Space Station (ISS). We compared the pre-flight and post-flight composite hip models, and observed the gradients of the bone loss distribution. We performed paired t-tests, on a voxel by voxel basis, corrected for multiple comparisons using false discovery rate (FDR), and observed regions inside the proximal femur that showed the most significant bone loss. To validate our registration algorithm, we selected the 16 pre-flight scans and manually marked 4 landmarks for each scan. After registration, the average distance between the mapped landmarks and the corresponding landmarks in the target scan was 2.56 mm. The average error due to manual landmark identification was 1.70 mm. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Montreal Neurol Inst Montreal, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Univ Calif Irvine, Dept Orthopaed Surg, Irvine, CA 92697 USA. Univ Space Res Assoc, Houston, TX 77058 USA. Baylor Coll Med, Houston, TX 77058 USA. Natl Inst Hlth, NIA, Lab Epidemiol Demog & Biomet, Bethesda, MD 20892 USA. RP Li, WJ (reprint author), Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. EM wenjun.li@radiology.ucsf.edu RI Lang, Thomas/B-2685-2012 OI Lang, Thomas/0000-0002-3720-8038 FU NIAMS NIH HHS [R42 AR045713, R42 AR045713-02A1, R42 AR45713] NR 18 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2007 VL 41 IS 5 BP 888 EP 895 DI 10.1016/j.bone.2007.07.006 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225PD UT WOS:000250528900018 PM 17707712 ER PT J AU Shaikh, AG Miura, K Optican, LM Ramat, S Leigh, RJ Zee, DS AF Shaikh, Aasef G. Miura, Kenichiro Optican, Lance M. Ramat, Stefano Leigh, R. John Zee, David S. TI A new familial disease of saccadic oscillations and limb tremor provides clues to mechanisms of common tremor disorders SO BRAIN LA English DT Article DE ion channels; saccade; tremor; computational simulation; oscillations ID THALAMIC RETICULAR NUCLEUS; ACTIVATED CATION CURRENT; BURST NEURONS; BRAIN-STEM; CHANNELS; ELECTROPHYSIOLOGY; MODULATION; GLYCINE; SYSTEM; RAT AB Tremor disorders pose fundamental questions about disease mechanisms, and challenges to successful neurotherapeutics: What causes motor circuits to oscillate in disorders in which the central nervous system otherwise seems normal? How does inheritance 'determine' the clinical phenotype in familial tremor disorders? Here, we address these questions. Analogies between the neural circuits controlling rapid eye movements (saccades) and those controlling limb movements allow us to translate the interpretations from the saccadic systems to the limb movement system. Moreover, the relatively well understood neurophysiology of the ocular motor system offers a unique opportunity to test specific hypotheses about normal and abnormal motor control of both eye and limb movements. We describe a new familial disorder-'micro-saccadic oscillations and limb tremor (mu SOLT)' - in a mother and daughter who had tiny saccadic oscillations of the eyes and tremor of the hands. This unique oscillatory movement disorder resembles other common tremor disorders (such as essential tremor) that occur in patients who have an otherwise normally functioning central nervous system. We hypothesize that mu SOLT is caused by an inherited abnormality that results in abnormal membrane properties causing reduced external inhibition in the premotor neurons that generate the high-frequency discharge (burst) for saccades and for ballistic limb movements. To test this hypothesis, we recorded hand tremor and eye movements in two patients with mu SOLT and particularly during natural circumstances when inhibition of the premotor saccadic burst neurons is removed (e. g. eye closure). We then simulated a conductance-based model for the premotor commands which included excitatory and reciprocally inhibitory burst neurons. The structure of this physiologically realistic model was based upon known cell types and anatomical connections in the brainstem (for saccades) and the thalamus (for limb movements). The physiological phenomenon of post-inhibitory rebound in premotor burst neurons makes the circuit inherently unstable and prone to oscillate unless prevented by external inhibition. Indeed, with simulated reduction of external inhibition (in this case glycinergic), saccadic oscillations and limb tremor were reproduced. Our results suggest that a single-inherited deficit can alter membrane properties, which impairs inhibition in an inherently unstable neural circuit causing the eye and limb oscillations in mu SOLT. This concept has broad implications for understanding the mechanism and designing rationale pharmacotherapy for abnormal oscillations and may be applicable to other common disorders in which there are no structural abnormalities in the brain such as essential tremor. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. NEI, NIH, Baltimore, MD 21287 USA. Univ Pavia, I-27100 Pavia, Italy. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Shaikh, AG (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St,Path 2-210, Baltimore, MD 21287 USA. EM ashaikh@dizzy.med.jhu.edu RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU Intramural NIH HHS NR 39 TC 30 Z9 30 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2007 VL 130 BP 3020 EP 3031 DI 10.1093/brain/awm240 PN 11 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227RJ UT WOS:000250675200027 PM 17921180 ER PT J AU Ikemoto, S AF Ikemoto, Satoshi TI Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex SO BRAIN RESEARCH REVIEWS LA English DT Review DE ventral striatum; ventral tegmental area; caudal linear nucleus; reinforcement; arousal; autoshaping ID CONDITIONED PLACE PREFERENCE; INTRACRANIAL SELF-STIMULATION; PAVLOVIAN APPROACH BEHAVIOR; VENTROMEDIAL MESENCEPHALIC TEGMENTUM; PHASEOLUS-VULGARIS LEUKOAGGLUTININ; CORTICOTROPIN-RELEASING-FACTOR; PRIMING-INDUCED REINSTATEMENT; MEDIODORSAL THALAMIC NUCLEUS; INTRAACCUMBENS D-AMPHETAMINE; COCAINE-SEEKING BEHAVIOR AB Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization. Published by Elsevier B.V. C1 NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@intra.nida.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 FU Intramural NIH HHS [Z01 DA000439-08, Z01 DA000480-03] NR 389 TC 591 Z9 605 U1 10 U2 84 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD NOV PY 2007 VL 56 IS 1 BP 27 EP 78 DI 10.1016/j.brainresrev.2007.05.004 PG 52 WC Neurosciences SC Neurosciences & Neurology GA 244MY UT WOS:000251871200002 PM 17574681 ER PT J AU Bowen, DJ Alfano, CM McGregor, BA Kuniyuki, A Bernstein, L Meeske, K Baumgartner, KB Fetherolf, J Reeve, BB Smith, AW Ganz, PA McTiernan, A Barbash, RB AF Bowen, Deborah J. Alfano, Catherine M. McGregor, Bonnie A. Kuniyuki, Alan Bernstein, Leslie Meeske, Kathy Baumgartner, Kathy B. Fetherolf, Josala Reeve, Bryce B. Smith, Ashley Wilder Ganz, Patricia A. McTiernan, Anne Barbash, Rachel Ballard TI Possible socioeconomic and ethnic disparities in quality of life in a cohort of breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer survivorship; fear of recurrence; race disparities; SES disparities ID CARCINOMA IN-SITU; LONG-TERM; HEALTH; IMPACT; RISK; WOMEN; FATIGUE AB This paper describes the ethnic and socioeconomic correlates of functioning in a cohort of long-term nonrecurring breast cancer survivors. Participants (n = 804) in this study were women from the Health, Eating, Activity, and Lifestyle (HEAL) Study, a population-based, multicenter, multiethnic, prospective study of women newly diagnosed with in situ or Stages I to IIIA breast cancer. Measurements occurred at three timepoints following diagnosis. Outcomes included standardized measures of functioning (MOS SF-36). Overall, these long-term survivors reported values on two physical function subscales of the SF-36 slightly lower than population norms. Black women reported statistically significantly lower physical functioning (PF) scores (P = 0.01), compared with White and Hispanic women, but higher mental health (MH) scores (P < 0.01) compared with White and Hispanic women. In the final adjusted model, race was significantly related to PF, with Black participants and participants in the "Other" ethnic category reporting poorer functioning compared to the White referent group (P < 0.01, 0.05). Not working outside the home, being retired or disabled and being unemployed (on leave, looking for work) were associated with poorer PF compared to currently working (both P < 0.01). These data indicate that race/ethnicity influences psychosocial functioning in breast cancer survivors and can be used to identify need for targeted interventions to improve functioning. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ New Mexico, Canc Res & Treatment Ctr, Dept Internal Med, Albuquerque, NM USA. DCCPS, ARP, Outcomes Res Branch, NCI, Bethesda, MD 20892 USA. NCI, Appl Res Program, Bethesda, MD USA. NCI, Div Canc Control & Populat Sci, Div Canc Prevent & Appl Res Program, Bethesda, MD USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM amctiern@fhcrc.org FU NCI NIH HHS [N01 PC067010, N01 CN005228, N01 PC035138-22, N01-CN-05228, N01-CN-75036-20, R25 CA092408, R25 CA92408] NR 24 TC 69 Z9 69 U1 0 U2 12 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 NOV PY 2007 VL 106 IS 1 BP 85 EP 95 DI 10.1007/s10549-006-9479-2 PG 11 WC Oncology SC Oncology GA 215MO UT WOS:000249813100010 PM 17260096 ER PT J AU Howard, RA Gilbert, ES Chen, BE Hall, P Storm, H Pukkala, E Langmark, F Kaijser, M Andersson, M Joensuu, H Fossa, SD Travis, LB AF Howard, Regan A. Gilbert, Ethel S. Chen, Bingshu E. Hall, Per Storm, Hans Pukkala, Eero Langmark, Froydis Kaijser, Magnus Andersson, Michael Joensuu, Heikki Fossa, Sophie D. Travis, Lois B. TI Leukemia following breast cancer: an international population-based study of 376,825 women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; excess absolute risk; leukemia; second primary cancer ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-TOPOISOMERASE-II; ADJUVANT CHEMOTHERAPY; YOUNG-WOMEN; MYELODYSPLASTIC SYNDROMES; CONSERVING THERAPY; INCREASED RISK; 2ND CANCERS; EXPERIENCE AB Purpose To quantify long-term temporal trends in the excess absolute risk (EAR) of secondary leukemia among breast cancer (BC) survivors, using multivariate analyses to evaluate the effects of subtype, age at BC diagnosis, attained age, and calendar year. Patients and methods We identified 376,825 1-year survivors of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark, Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were modeled using Poisson regression methods and cumulative risks calculated using a competing risk model. Results A total of 687 non-chronic lymphocytic leukemias (EAR = 9.05; 95% confidence interval (CI) = 7.5 - 10.7) was reported. Significantly elevated risks were observed for the first time for chronic myeloid leukemia (CML) (EAR = 2.06; 95% CI = 1.3 - 2.9) and acute lymphoblastic leukemia (ALL) (EAR = 0.62; 95% CI = 0.2 - 1.1), in addition to acute myeloid leukemia (AML) (EAR = 5.00; 95% CI = 3.9 - 6.2). Excesses of CML, ALL, AML and all leukemias combined persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and AML by calendar year of BC diagnosis depended on age at diagnosis. For women diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively. Conclusions Although secondary leukemia is a rare event, BC survivors experience statistically significant excesses for at least 25 years after diagnosis, including CML and ALL. Decreasing leukemia risks in recent calendar years likely reflect changes in treatment. C1 NIH, NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. Danish Canc Soc, Copenhagen, Denmark. Finnish Canc Registry, Helsinki, Finland. Canc Registry Norway, Oslo, Norway. Univ Helsinki, Cent Hosp, Helsinki, Finland. Norwegian Radium Hosp, Oslo, Norway. RP Howard, RA (reprint author), NIH, NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Plaza S,Suite 7091, Bethesda, MD 20892 USA. EM reganho@mail.nih.gov OI Chen, Bingshu/0000-0001-6139-0696; Storm, Hans/0000-0001-7223-8198; Joensuu, Heikki/0000-0003-0281-2507 NR 52 TC 25 Z9 27 U1 0 U2 0 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 NOV PY 2007 VL 105 IS 3 BP 359 EP 368 DI 10.1007/s10549-006-9460-0 PG 10 WC Oncology SC Oncology GA 215KC UT WOS:000249806200013 PM 17221155 ER PT J AU Alvord, WG Roayaei, JA Quinones, OA Schneider, KT AF Alvord, W. Gregory Roayaei, Jean A. Quinones, Octavio A. Schneider, Katherine T. TI A microarray analysis for differential gene expression in the soybean genome using Bioconductor and R SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE microarray; Affymetrix GeneChip (R); probe-level data preprocessing; quality control; differential gene expression analysis ID FALSE DISCOVERY RATE; PROBE LEVEL DATA; SUMMARIES; BIOLOGY AB This article describes specific procedures for conducting quality assessment of Affymetrix GeneChip soybean genome data and for performing analyses to determine differential gene expression using the open-source R programming environment in conjunction with the open-source Bioconductor software. We describe procedures for extracting those Affymetrix probe set IDs related specifically to the soybean genome on the Affymetrix soybean chip and demonstrate the use of exploratory plots including images of raw probe-level data, boxplots, density plots and M versus A plots. RNA degradation and recommended procedures from Affymetrix for quality control are discussed. An appropriate probe-level model provides an excellent quality assessment tool. To demonstrate this, we discuss and display chip pseudo-images of weights, residuals and signed residuals and additional probe-level modeling plots that may be used to identify aberrant chips. The Robust Multichip Averaging (RMA) procedure was used for background correction, normalization and summarization of the AffyBatch probe-level data to obtain expression level data and to discover differentially expressed genes. Examples of boxplots and MA plots are presented for the expression level data. Volcano plots and heatmaps are used to demonstrate the use of (log) fold changes in conjunction with ordinary and moderated t-statistics for determining interesting genes. We show, with real data, how implementation of functions in R and Bioconductor successfully identified differentially expressed genes that may play a role in soybean resistance to a fungal pathogen, Phakopsora pachyrhizi. Complete source code for performing all quality assessment and statistical procedures may be downloaded from our web source: http://css.ncifcrf.gov/services/download/MicroarraySoybean.zip" C1 NCI Frederick, Data Management Serv Inc, Stat Consulting Serv, Frederick, MD 21702 USA. N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. RP Alvord, WG (reprint author), NCI Frederick, Data Management Serv Inc, Stat Consulting Serv, POB B, Frederick, MD 21702 USA. EM gwa@css.ncifcrf.gov RI Moreira, Eder/B-2309-2010 NR 56 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD NOV PY 2007 VL 8 IS 6 BP 415 EP 431 DI 10.1093/bib/bbm043 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 234XK UT WOS:000251197600005 ER PT J AU Cowen, EW Liu, CW Steinberg, SM Kang, S Vonderheid, EC Kwak, HS Booher, S Petricoin, EF Liotta, LA Whiteley, G Hwang, ST AF Cowen, E. W. Liu, C-W. Steinberg, S. M. Kang, S. Vonderheid, E. C. Kwak, H. S. Booher, S. Petricoin, E. F. Liotta, L. A. Whiteley, G. Hwang, S. T. TI Differentiation of tumour-stage mycosis fungoides, psoriasis vulgaris and normal controls in a pilot study using serum proteomic analysis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE mycosis fungoides; proteomics; psoriasis ID T-CELL LYMPHOMA; MASS-SPECTROMETRY; PERIPHERAL-BLOOD; CANCER; CLASSIFICATION; PATTERNS AB Background Serum proteomic analysis is an analytical technique utilizing high-throughput mass spectrometry (MS) in order to assay thousands of serum proteins simultaneously. The resultant 'proteomic signature' has been used to differentiate benign and malignant diseases, enable disease prognosis, and monitor response to therapy. Objectives This pilot study was designed to determine if serum protein patterns could be used to distinguish patients with tumour-stage mycosis fungoides (MF) from patients with a benign inflammatory skin condition (psoriasis) and/or subjects with healthy skin. Methods Serum was analysed from 45 patients with tumour-stage MF, 56 patients with psoriasis, and 47 controls using two MS platforms of differing resolution. An artificial intelligence-based classification model was constructed to predict the presence of the disease state based on the serum proteomic signature. Results Based on data from an independent testing set (14-16 subjects in each group), MF was distinguished from psoriasis with 78.6% (or 78.6%) sensitivity and 86.7% (or 93.8%) specificity, while sera from patients with psoriasis were distinguished from those of nonaffected controls with 86.7% (or 93.8%) sensitivity and 75.0% (or 76.9%) specificity (depending on the MS platform used). MF was distinguished from unaffected controls with 61.5% (or 71.4%) sensitivity and 91.7% (or 92.9%) specificity. In addition, a secondary survival analysis using 11 MS peaks identified significant survival differences between two MF groups (all P-values < 0.05). Conclusions Serum proteomics should be further investigated for its potential to identify patients with neoplastic skin disease and its ability to determine disease prognosis. C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Clin Prote Reference Lab, Gaithersburg, MD USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Rockville, MD USA. Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI USA. Johns Hopkins Med Inst, Dept Dermatol, Baltimore, MD 21205 USA. George Mason Univ, Dept Mol Microbiol, Ctr Appl Prote & Mol Med, Manassas, VA USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural NIH HHS NR 21 TC 6 Z9 11 U1 0 U2 2 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 NOV PY 2007 VL 157 IS 5 BP 946 EP 953 DI 10.1111/j.1365-2133.2007.08185.x PG 8 WC Dermatology SC Dermatology GA 220GI UT WOS:000250144800015 PM 17854367 ER PT J AU Wu, CJ Gladwin, M Tisdale, J Hsieh, M Law, T Biernacki, M Rogers, S Wang, X Walters, M Zahrieh, D Antin, JH Ritz, J Krishnamurti, L AF Wu, Catherine J. Gladwin, Mark Tisdale, John Hsieh, Matthew Law, Terence Biernacki, Melinda Rogers, Shelby Wang, Xunde Walters, Mark Zahrieh, David Antin, Joseph H. Ritz, Jerome Krishnamurti, Lakshamanan TI Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE sickle cell disease; engraftment; transplantation ID PULMONARY-HYPERTENSION C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst Dept Med Div Hematol M, Boston, MA 02115 USA. NIH, NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, Bethesda, MD USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Oakland, CA 94609 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Childrens Hosp, Pittsburgh, PA 15213 USA. RP Wu, CJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst Dept Med Div Hematol M, Boston, MA 02115 USA. RI Krishnamurti, Lakshmanan/F-7637-2011 FU Intramural NIH HHS [Z01 DK027010-04]; NHLBI NIH HHS [HL070149-01, P01 HL070149]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 8 TC 21 Z9 21 U1 0 U2 1 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 NOV PY 2007 VL 139 IS 3 BP 504 EP 507 DI 10.1111/j.1365-2141.2007.06803.x PG 4 WC Hematology SC Hematology GA 216LY UT WOS:000249880700019 PM 17910640 ER PT J AU Zerhouni, EA AF Zerhouni, Elias A. TI Transforming medicine through discovery. Major trends in biomedical research SO BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE LA French DT Article DE biomedical research; public health; NIH AB The NIH, which originated from the Marine Hospital Laboratory of Hygiene (1887), was established as the national agency for medical research by President F D. Roosevelt in 1944. The NIH rests on its independent, world-class peer review process and its distinctive scientific and public advisory structure. The two-fold mission of NIH is to define research priorities based on public health needs and to allocate funding. Eighty-four percent of the budget supports 300,000 extramural scientists and research workers at more than 3,000 universities. Only 16% of the budget is spent within the NIH itself (on administration and the 27 institutes and centers, including some 10,000 intramural scientists, that make up NIH today). The ecosystem of science and biotechnology connects NIH, the public, Congress, universities, the FDA, industry, and investors. The budget, which in 2007 was $29 billion, is submitted to Congress by the Director The impact of biomedical research over the last 30 years is demonstrated by an increase in life expectancy and a decrease in death and disability from many diseases. Five evolving challenges in public health include acute conditions becoming chronic, the aging of the population, health disparities, emerging or re-emerging infectious diseases, and emerging non-communicable diseases (obesity, mental illness). Medical strategies must clearly be transformed for the 21(st) century. Molecular diagnosis of preclinical disease is the paradigm of the future : intervening before symptoms appear because the preclinical molecular events are known and because we have the ability to detect at-risk patients constitutes the "future paradigm of the 4 P's." Currently, the fundamental scientific barrier is our limited understanding of the complexity of biologic networks. New theoretical concepts are needed in this "hardware-to-software phase." Any roadmap for the acceleration of medical discovery will have to integrate new pathways, future research teams, and the restructuring of clinical research. C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 4 PU ACAD NATL MEDECINE PI PARIS 06 PA 16 RUE BONAPARTE, 75272 PARIS 06, FRANCE SN 0001-4079 J9 B ACAD NAT MED PARIS JI Bull. Acad. Natl. Med. PD NOV PY 2007 VL 191 IS 8 BP 1685 EP 1694 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 306CI UT WOS:000256225500039 PM 18666466 ER PT J AU Fisher, ER Costantino, JR Leon, ME Bandos, H Palekar, AS Fisher, B Wolmark, N AF Fisher, Edwin R. Costantino, Joseph R. Leon, Marino E. Bandos, Hanna Palekar, Alka S. Fisher, Bernard Wolmark, Norman TI Pathobiology of small invasive breast cancers without Metastases (T1a/b, N0, M0) - National surgical adjuvant breast and bowel project (NSABP) protocol B-21 SO CANCER LA English DT Article DE small breast cancers; pathobiology; pathology; treatment; national surgical adjuvant breast and bowel project (NSABP); protocol B-21 ID ONE CENTIMETER; FOLLOW-UP; CARCINOMA; RECURRENCE; PROGNOSIS; LESS; PREDICTORS; PATHOLOGY; THERAPY; LESIONS AB BACKGROUND. Uncertainties continue to exist concerning the outcomes and management of small (T1a/b N0 M0) invasive breast cancers. METHODS. A central pathology review was performed of 638 such lesions from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial B-21. RESULTS. Univariate analysis revealed a high risk for ipsilateral breast tumor recurrence with tumors exhibiting a ductal carcinoma in situ component or poor nuclear grade. The converse (protective effect) was found with tumors arising in radial scars, those of tubular histologic type, and those with moderate/marked tumor stroma. The correlations were generally similar for disease-free survival. However, only nuclear grade was found to be independently significant for both of these outcomes. Only lymphatic tumor extension was univariately and multivariately significant for overall survival. CONCLUSIONS. The long-term results of follow-up (median, 11.2 years) from the current trial continue to support the need for local breast irradiation and adjuvant therapy in the management of patients with these small cancers. C1 Allegheny Gen Hosp, Ctr Canc, W Penn Allegheny Hlth Syst, Dept Pathol,NSABP, Pittsburgh, PA 15212 USA. NSABP, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Biostat, NSABP, Dept Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. RP Fisher, ER (reprint author), Allegheny Gen Hosp, Ctr Canc, W Penn Allegheny Hlth Syst, Dept Pathol,NSABP, 5th Floor,320 E N Ave, Pittsburgh, PA 15212 USA. EM cgriffit@wpahs.org FU NCI NIH HHS [U24-CA 114732, U-10-CA 69651, U10-CA 12027] NR 26 TC 14 Z9 15 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 NOV 1 PY 2007 VL 110 IS 9 BP 1929 EP 1936 DI 10.1002/cncr.23011 PG 8 WC Oncology SC Oncology GA 224CE UT WOS:000250422500006 PM 17896781 ER PT J AU Kuebler, JP Colangelo, L O'Connell, MJ Smith, RE Yothers, G Begovic, M Robinson, B Seay, TE Wolmark, N AF Kuebler, J. Philip Colangelo, Linda O'Connell, Michael J. Smith, Roy E. Yothers, Greg Begovic, Mirsada Robinson, Bridget Seay, Thomas E. Wolmark, Norman TI Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin - A prospective analysis SO CANCER LA English DT Article DE enteropathy; diarrhea; chemotherapy; colon cancer; adjuvant therapy; oxaliplatin; fluorouracill; leucovorin ID CHEMOTHERAPY-INDUCED DIARRHEA; SMALL-BOWEL TOXICITY; COLORECTAL-CARCINOMA; MANIFESTATIONS; FLUOROURACIL; LEUCOVORIN; THERAPY AB BACKGROUND. Cases of severe gastrointestinal toxicity were monitored prospectively during NSABP C-07, a randomized clinical trial of adjuvant therapy for patients with stage II/III colon cancer. METHODS. Patients were treated with weekly bolus 5-fluorouracil (5-FU) and leucovorin (FL; "Roswell Park Regimen") or the same regimen plus oxaliplatin (FLOX). RESULTS. Of 1857 patients, 79 (4.3%) developed a syndrome of bowel wall injury (BWI, small or large) characterized by hospitalization for the management of severe diarrhea or dehydration and radiographic or endoscopic evidence of bowel wall thickening or ulceration. Fifty-one (64.6%) of these adverse events occurred in patients treated with FLOX and 28 (35.4%) in those treated with FL (P <.01). Enteric sepsis (ES), characterized by grade 3 or greater diarrhea and grade 4 neutropenia with or without proven bacteremia occurred in 22 patients treated with FLOX, versus 8 in those treated with FL (P =.01). Patients > 60 years were at higher risk for BWI after treatment with FLOX (6.7%) versus treatment with FL (2.9%, P <.01). Female patients had a higher incidence of BWI with FLOX (9.1%) than with FL (3.9%, P <.01). Severe gastrointestinal toxicity usually occurred during the third or fourth week on the first cycle of therapy, required hospitalization, and was managed with fluids, antidiarrheals, and antibiotics. There were 5 deaths (0.3%) due to enteropathy, 2 related to ES and 3 related to both BWI and ES. Seventy-one percent of patients resumed treatment with FL after recovery. CONCLUSIONS. Patients treated with adjuvant FL should be closely monitored for diarrhea and aggressively managed, especially if oxaliplatin has been added to the regimen. C1 NSABP, Allegheny Ctr 4, Ctr Biostat, Pittsburgh, PA USA. Community Clin Oncol Program, Columbus, OH USA. Univ Pittsburgh, Med Ctr, Shadyside Hosp, Pittsburgh, PA USA. Christchurch Hosp, Christchurch, New Zealand. Atlanta Canc Care, Atlanta, GA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP O'Connell, MJ (reprint author), NSABP, Allegheny Ctr 4, Ctr Biostat, 5th Floor, Pittsburgh, PA USA. EM michael.O'Gonnell@nsabp.org OI Yothers, Greg/0000-0002-7965-7333 FU NCI NIH HHS [U10-CA-37377, U10-CA-12027, U10-CA-69651, U10-CA-69974] NR 20 TC 22 Z9 22 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 NOV 1 PY 2007 VL 110 IS 9 BP 1945 EP 1950 DI 10.1002/cncr.23013 PG 6 WC Oncology SC Oncology GA 224CE UT WOS:000250422500008 PM 17853393 ER PT J AU Honda, H Pazin, MJ D'Souza, T Ji, HX Morin, PJ AF Honda, Hiroshi Pazin, Michael J. D'Souza, Theresa Ji, Hongxiu Morin, Patrice J. TI Regulation of the CLDN3 gene in ovarian cancer cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE ovarian cancer; claudin-3; promoter methylation; Sp1; histone acetylation ID CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; TIGHT JUNCTION PROTEINS; CLAUDIN-4 EXPRESSION; POTENTIAL MARKERS; PANCREATIC-CANCER; EPITHELIAL-CELLS; PROMOTER; SP1; IDENTIFICATION; DIAGNOSIS AB The claudin (CLDN) genes encode a family of proteins involved in the formation and function of tight junctions. CLDN gene expression is frequently altered in several human cancers, and in particular, CLDN3 and CLDN,4 are commonly overexpressed in ovarian cancer. However, the mechanisms leading to the deregulation of these genes in cancer remain unclear. In the present study, we have examined the CLDN3 promoter and have identified a minimal region containing an Sp1 site crucial for its activity. In addition, we find that the CLDN3 promoter is regulated through epigenetic processes. Cells that express high levels of CLDN3 exhibit low DNA methylation and high histone H3 acetylation of the critical CLDN3 promoter region, and the reverse is observed in cells that do not express this gene. CLDN3-negative cells can be induced to express CLDN3 through treatment with DNA methyltransferase or histone deacetylase inhibitors. Interestingly, in vitro binding experiments, as well as chip assays show that Sp1 binds the unmethylated promoter much more efficiently, providing a mechanism for CLDN3 silencing in non-expressing cells. Finally, siRNA-mediated knockdown of Sp1 led to a significant decrease of CLDN3 expression at both the mRNA and protein levels, demonstrating a crucial role for this transcription factor in the regulation of CLDN3. Our data provide a basis for CLDN3 expression in ovarian cancer cells, as well as a mechanism for the silencing of this promoter in tumors lacking expression of claudin-3. C1 [Honda, Hiroshi; Pazin, Michael J.; D'Souza, Theresa; Morin, Patrice J.] NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. [Ji, Hongxiu; Morin, Patrice J.] Johns Hopkins Univ, Inst Med, Dept Pathol, Baltimore, MD USA. RP Morin, PJ (reprint author), NIA, Lab Cellular & Mol Biol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM morinp@grc.nio.nih.gov OI Pazin, Michael/0000-0002-7561-3640 FU Intramural NIH HHS [ZIA AG000377-02] NR 38 TC 31 Z9 31 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2007 VL 6 IS 11 BP 1733 EP 1742 PG 10 WC Oncology SC Oncology GA 273PQ UT WOS:000253944600023 PM 17986852 ER PT J AU Purdue, MP Hartge, P Davis, S Cerhan, JR Colt, JS Cozen, W Severson, RK Li, Y Chanock, SJ Rothman, N Wang, SS AF Purdue, Mark P. Hartge, Patricia Davis, Scott Cerhan, James R. Colt, Joanne S. Cozen, Wendy Severson, Richard K. Li, Yan Chanock, Stephen J. Rothman, Nathaniel Wang, Sophia S. TI Sun exposure, vitamin D receptor gene polymorphisms and risk of non-Hodgkin lymphoma SO CANCER CAUSES & CONTROL LA English DT Article DE non-Hodgkin lymphoma; vitamin D; polymorphism; genetic; sunlight ID SINGLE NUCLEOTIDE POLYMORPHISMS; ULTRAVIOLET-RADIATION; UNITED-STATES; SUNLIGHT; MORTALITY; HEIGHT; QUESTIONNAIRE; POPULATIONS; VARIANTS; HEALTH AB Objective Recent findings suggest that ultraviolet (UV) radiation exposure may reduce risk of developing non-Hodgkin lymphoma (NHL), but the biologic basis for this relationship remains unclear. We analyzed data from our US population-based case-control study of NHL to investigate whether our previously reported inverse association with sun exposure was dependent upon variants in the vitamin D receptor gene (IVS10 + 283G > A (BsmI), Ex11 + 32T > C (TaqI)), and genes linked to UV-induced immune modulation (IL4, IL10, IL12A, IL12B, TNF). Methods UV exposure data was collected from an in-person interview with 551 cases and 462 controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for sun exposure measures for joint variant-exposure effects. Results The association with NHL risk for time in the midday sun within the last decade was dependent upon Ex11 + 32 T > C genotype. Compared to TT carriers who reported < 7 h/week of sun exposure, CC subjects with < 7 h/week of sun exposure had an increased risk of NHL (OR = 1.9, 95% CI 0.8-4.4, P-interaction = 0.16), while the relative risks for other CC carriers approached unity with increasing level of sun exposure. This pattern of effects was especially apparent for follicular lymphoma (for CC genotype and < 7 h/week of exposure: OR 6.3, 95% CI 1.9-22, P-interaction = 0.004), and was consistently observed across measures of reported sun exposure for different periods of life. As IVS10 + 283G > A is correlated with Ex11 + 32T > C in our population (r(2) stop = 0.95), results were equivalent for those with the IVS10 + 283 AA genotype. No evidence of interaction with cytokine gene variants was observed. Conclusions Our results suggest that the inverse association between UV exposure and NHL risk may be mediated by the vitamin D pathway. Further investigation of this finding in other studies is warranted. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Rockville, MD USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ So Calif, Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NCI, NCI Core Genotyping Facil, Dept Hlth & Human Serv, NIH, Gaithersburg, MD USA. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Exccut Blvd,EPS 8009, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS NR 47 TC 30 Z9 32 U1 1 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 NOV PY 2007 VL 18 IS 9 BP 989 EP 999 DI 10.1007/s10552-007-9039-z PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 201BE UT WOS:000248805700008 PM 17653830 ER PT J AU Terry, MB Gammon, MD Zhang, FF Vaughan, TL Chow, WH Risch, HA Schoenberg, JB Mayne, ST Stanford, JL West, AB Rotterdam, H Blot, WJ Fraumeni, JF Santella, RM AF Terry, Mary Beth Gammon, Marilie D. Zhang, Fang Fang Vaughan, Thomas L. Chow, Wong-Ho Risch, Harvey A. Schoenberg, Janet B. Mayne, Susan T. Stanford, Janet L. West, A. Brian Rotterdam, Heidi Blot, William J. Fraumeni, Joseph F., Jr. Santella, Regina M. TI Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; esophageal adenocarcinoma; alcohol dehydrogenase ID SQUAMOUS-CELL CARCINOMA; ALDEHYDE DEHYDROGENASE; ALCOHOL-DEHYDROGENASE; UNITED-STATES; GENETIC POLYMORPHISMS; SOCIOECONOMIC-FACTORS; MEDICAL CONDITIONS; CANCER; TOBACCO; CARDIA AB Objectives Alcohol increases esophageal squamous carcinoma risk but has been less consistently associated with esophageal adenocarcinoma. Alcohol dehydrogenase catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a carcinogen. The alcohol dehydrogenase gene has several polymorphisms which may lead to faster conversion of ethanol to acetaldehyde, which may increase cancer risk. Methods We undertook a study to examine whether a common polymorphism in the alcohol dehydrogenase 3 gene was associated with a higher risk of esophageal adenocarcinoma using data and biological samples collected for the Esophageal and Gastric Cancer Study (n = 114 esophageal and gastric cardia adenocarcinoma, n = 60 non-cardia gastric carcinoma, n = 23 cases of esophageal squamous cell carcinoma and 160 controls). Results Individuals homozygous for ADH(3)(1-1) had a higher risk of each tumor type compared to individuals who had ADH(3)(2-2) or ADH(3)(1-2) genotype (OR = 1.7, 95% CI = 1.0-2.9 for esophageal and gastric cardia adenocarcinomas; OR = 1.7, 95% CI = 0.7-4.3 for esophageal squamous cell carcinoma; and OR = 2.8, 95% CI = 1.5-5.1 for non-cardia gastric cancer). The elevation in risk from homozygosity of the ADH(3)(1) allele was seen in drinkers and nondrinkers, although the risk estimate was only significant for drinkers, particularly of liquor. Conclusions These data suggest ADH3 genotype may be associated with risk of esophageal and gastric cardia adenocarcinomas. C1 Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Fred Hutchinson Canc Res Ctr,Program Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Yale Canc Ctr, New Haven, CT 06510 USA. Ctr Canc Initiat, New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. AmeriPath New York Gastrointestinal Diagnost, Shelton, CT USA. Columbia Univ, Dept Pathol, New York, NY USA. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. RP Terry, MB (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St,Room 724A, New York, NY 10032 USA. EM mt146@columbia.edu FU NCI NIH HHS [U01-CA57983, U01-CA57949, U01-CA57923, N01-CN05230, N02-CP40501]; NIEHS NIH HHS [P30 ES009089, P30-ES10126, P30-ES09089] NR 30 TC 17 Z9 18 U1 1 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 NOV PY 2007 VL 18 IS 9 BP 1039 EP 1046 DI 10.1007/s10552-007-9046-0 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 201BE UT WOS:000248805700014 PM 17665311 ER PT J AU Yu, J Cao, Q Mehra, R Laxman, B Yu, J Tomlins, SA Creighton, CJ Dhanasekaran, SM Shen, R Chen, G Morris, DS Marquez, VE Shah, RB Ghosh, D Varambally, S Chinnaiyan, AM AF Yu, Jinclan Cao, Qi Mehra, Rohit Laxman, Bharathi Yu, Jianjun Tomlins, Scott A. Creighton, Chad J. Dhanasekaran, Saravana M. Shen, Ronglai Chen, Guoan Morris, David S. Marquez, Victor E. Shah, Rajal B. Ghosh, Debashis Varambally, Sooryanarayana Chinnaiyan, Arul M. TI Integrative genornics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer SO CANCER CELL LA English DT Article ID GROUP PROTEIN EZH2; AGGRESSIVE BREAST-CANCER; EMBRYONIC STEM-CELLS; GENE-EXPRESSION; ZESTE HOMOLOG-2; DEVELOPMENTAL REGULATORS; REPRESSIVE COMPLEX; TARGET GENES; ENHANCER; PROLIFERATION AB The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes. C1 Univ Michigan, Sch Med, Dept Pathol, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Bioinformat Program, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA. NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Cao, Qi/A-5517-2010 OI Cao, Qi/0000-0002-5140-3681 FU Intramural NIH HHS; NCI NIH HHS [P50 CA69568, R01 CA97063, U01 CA111275] NR 40 TC 121 Z9 123 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2007 VL 12 IS 5 BP 419 EP 431 DI 10.1016/j.ccr.2007.10.016 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 232GQ UT WOS:000251006900006 PM 17996646 ER PT J AU Cadieu, E Ostrander, EA AF Cadieu, Edouard Ostrander, Elaine A. TI Canine genetics offers new mechanisms for the study of human cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CARCINOMA IN-SITU; PROSTATIC INTRAEPITHELIAL NEOPLASIA; TRANSITIONAL-CELL CARCINOMA; BREAST-CANCER; ESTROGEN-RECEPTOR; URINARY-BLADDER; INCIDENCE RATES; DOMESTIC DOG; TUMORS; RISK C1 NHGRI, NIH, Ctr Genet Branch, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, Ctr Genet Branch, Bldg 50,Room 5351,50 S Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 43 TC 16 Z9 16 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2181 EP 2183 DI 10.1158/1055-9965.EPI-07-2667 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500002 PM 17982116 ER PT J AU Setiawan, VW Schumacher, FR Haiman, CA Stram, DO Albanes, D Altshuler, D Berglund, G Buring, J Calle, EE Clavel-Chapelon, F Cox, DG Gaziano, JM Hankinson, SE Hayes, RB Henderson, BE Hirschhorn, J Hoover, R Hunter, DJ Kaaks, R Kolonel, LN Kraft, P Ma, J Le Marchand, L Linseisen, J Lund, E Navarro, C Overvad, K Palli, D Peeters, PHM Pike, MC Riboli, E Stampfer, MJ Thun, MJ Travis, R Trichopoulos, D Yeager, M Ziegler, RG Feigelson, HS Chanock, SJ AF Setiawan, Veronica Wendy Schumacher, Fredrick R. Haiman, Christopher A. Stram, Daniel O. Albanes, Demetrius Altshuler, David Berglund, Gran Buring, Julie Calle, Eugenia E. Clavel-Chapelon, Francoise Cox, David G. Gaziano, J. Michael Hankinson, Susan E. Hayes, Richard B. Henderson, Brian E. Hirschhorn, Joel Hoover, Robert Hunter, David J. Kaaks, Rudolf Kolonel, Laurence N. Kraft, Peter Ma, Jing Le Marchand, Loic Linseisen, Jakob Lund, Eiliv Navarro, Carmen Overvad, Kim Palli, Domenico Peeters, Petra H. M. Pike, Malcolm C. Riboli, Elio Stampfer, Meir J. Thun, Michael J. Travis, Ruth Trichopoulos, Dimitrios Yeager, Meredith Ziegler, Regina G. Feigelson, Heather Spencer Chanock, Stephen J. TI CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ANDROGEN RECEPTOR GENE; POSTMENOPAUSAL WOMEN; HORMONE-LEVELS; MULTIETHNIC COHORT; BRAZILIAN PATIENTS; SERUM ANDROGENS; POLYMORPHISMS; ASSOCIATION; METAANALYSIS; DEFICIENCY AB CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Amer Canc Soc, Atlanta, GA 30329 USA. Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. VA Boston Healthcare Syst, Boston, MA USA. German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA. Univ Tromso, Inst Community Med, Tromso, Norway. Murcia Hlth Council, Dept Epidemiol, Murcia, Spain. Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark. SCPO Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Florence, Italy. Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Oxford, Canc Epidemiol Unit, Oxford, England. RP Setiawan, VW (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,Room 4425, Los Angeles, CA 90033 USA. EM vsetiawa@usc.edu RI Cox, David/A-2023-2009; Altshuler, David/A-4476-2009; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Albanes, Demetrius/B-9749-2015; OI Cox, David/0000-0002-2152-9259; Altshuler, David/0000-0002-7250-4107; Linseisen, Jakob/0000-0002-9386-382X; Hayes, Richard/0000-0002-0918-661X; PALLI, Domenico/0000-0002-5558-2437 FU Intramural NIH HHS; NCI NIH HHS [CA116543, R01 CA097193, UO1-CA98216, UO1-CA98233, UO1-CA98710, UO1-CA98758] NR 36 TC 40 Z9 41 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2237 EP 2246 DI 10.1158/1055-9965.EPI-07-0589 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500013 PM 18006912 ER PT J AU Garcia-Closas, M Troester, MA Qi, Y Langerod, A Yeager, M Lissowska, J Brinton, L Welch, R Peplonska, B Gerhard, DS Gram, IT Kristensen, V Borresen-Dale, AL Chanock, S Perou, CM AF Garcia-Closas, Montserrat Troester, Melissa A. Qi, Ying Langerod, Anita Yeager, Meredith Lissowska, Jolanta Brinton, Louise Welch, Robert Peplonska, Beata Gerhard, Daniela S. Gram, Inger Torhild Kristensen, Vessela Borresen-Dale, Anne-Lise Chanock, Stephen Perou, Charles M. TI Common genetic variation in GATA-Binding protein 3 and differential susceptibility to breast cancer by estrogen receptor alpha tumor status SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EXPRESSION PATTERNS; RISK-FACTORS; GATA-3; ASSOCIATION; CARCINOMAS; CELLS AB GATA-binding protein 3 (GATA3) is a transcription factor and a putative tumor suppressor that is highly expressed in normal breast luminal epithelium and estrogen receptor alpha (ER)-positive breast tumors. We hypothesized that common genetic variation in GATA3 could influence breast carcinogenesis. Four tag single-nucleotide polymorphisms (SNP) in GATA3 and its 3' flanking gene FLJ4598 were genotyped in two case control studies in Norway and Poland (2,726 cases and 3,420 controls). Analyses of pooled-data suggested a reduced risk of breast cancer associated with two intronic variants in GATA3 in linkage disequilibrium (rs3802604 in intron 3 and rs570613 in intron 4). Odds ratio (95% confidence interval) for rs570613 heterozygous and rare homozygous versus common homozygous were 0.85 (0.75-1.95) and 0.82 (0.62-0.96), respectively (P-trend = 0.004). Stronger associations were observed for subjects with ER-negative, than ER-positive, tumors (P-heterogeneity 0.01 for rs3802604; P-heterogeneity = 0.09 for rs570613). Although no individual SNPs were associated with ER-positive tumors, two haplotypes (GGTC in 2% of controls and AATT in 7% of controls) showed significant and consistent associations with increased risk for these tumors when compared with the common haplotype (GATT in 46% of controls): 1.71 (1.27-2.32) and 1.26 (1.03-1.54), respectively. In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status. These differential associations are consistent with markedly different levels of GATA3 protein by ER status. Additional epidemiologic studies are needed to clarify these intriguing relationships. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. NCI, Core Genotyping Facil Adv Technol Ctr, Gaithersburg, MD USA. Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Inst Canc Res,Dept Genet, Oslo, Norway. Univ Oslo, Fac Med, Oslo, Norway. Ctr Canc & M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. NCI, Off Canc Genom, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Tromso, Inst Community Med, Tromso, Norway. RP Garcia-Closas, M (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 7076,MSC 7234, Rockville, MD 20852 USA. EM montse@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; Perou, Charles/0000-0001-9827-2247 FU Intramural NIH HHS; NCI NIH HHS [R01-CA-101227-01, R25 CA57726, P50-CA58223] NR 31 TC 13 Z9 14 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 NOV PY 2007 VL 16 IS 11 BP 2269 EP 2275 DI 10.1153/1055-9965.EPI-07-0449 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500017 PM 18006915 ER PT J AU Fink, BN Steck, SE Wolff, MS Britton, JA Kabat, GC Gaudet, MM Abrahamson, PE Bell, P Schroeder, JC Teitelbaum, SL Neugut, AI Gammon, MD AF Fink, Brian N. Steck, Susan E. Wolff, Mary S. Britton, Julie A. Kabat, Geoffrey C. Gaudet, Mia M. Abrahamson, Page E. Bell, Paula Schroeder, Jane C. Teitelbaum, Susan L. Neugut, Alfred I. Gammon, Marilie D. TI Dietary flavonoid intake and breast cancer survival among women on long island SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; POSTMENOPAUSAL WOMEN; PHYTOESTROGEN INTAKE; GENISTEIN CONTENT; FOOD GROUPS; RISK; HEALTH; DAIDZEIN; FRUIT; VEGETABLES AB Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n = 1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n = 173 deaths) and breast cancer-specific mortality (n = 113 deaths) were determined through the National Death Index. Results: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer-specific mortality only. Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings. C1 Univ Toledo, Dept Publ Hlth & Homeland Secur, Toledo, OH 43614 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Fink, BN (reprint author), Univ Toledo, Dept Publ Hlth & Homeland Secur, Hlth Sci Campus,Mailstop 1027,3015 Arlington Ave, Toledo, OH 43614 USA. EM brian.fink2@utoledo.edu RI Steck, Susan/G-5736-2013 FU NCI NIH HHS [5T32CA009330-25, CA52283, UO1CA/ES66572, UO1CA66572]; NIEHS NIH HHS [P30ES10126] NR 54 TC 40 Z9 41 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2285 EP 2292 DI 10.1158/1055-9965.EPI-07-0245 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500019 PM 18006917 ER PT J AU Newcomb, PA Baron, J Cotterchio, M Gallinger, S Grove, J Haile, R Hall, D Hopper, JL Jass, J Le Marchand, L Limburg, P Lindor, N Potter, JD Templeton, AS Thibodeau, S Seminara, D AF Newcomb, Polly A. Baron, John Cotterchio, Michelle Gallinger, Steve Grove, John Haile, Robert Hall, David Hopper, John L. Jass, Jeremy Le Marchand, Loic Limburg, Paul Lindor, Noralane Potter, John D. Templeton, Allyson S. Thibodeau, Steve Seminara, Daniela CA Colon Canc Family Registry TI Colon cancer family registry: An international resource for studies of the genetic epidemiology of colon cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; ADENOMATOUS POLYPOSIS; GENOMIC DNA; MUTATIONS; INTERDISCIPLINARY; CHROMOSOME-5; POPULATION; MOUTHWASH; CARCINOMA AB Background: Family studies have served as a cornerstone of genetic research on colorectal cancer. Materials and Methods: The Colorectal Cancer Family Registry (Colon CFR) is an international consortium of six centers in North America and Australia formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Differences in design and sampling schemes ensures a resource that covers the continuum of disease risk. Two separate recruitment strategies identified colorectal cancer cases: population-based (incident case probands identified by cancer registries; all six centers) and clinic-based (families with multiple cases of colorectal cancer presenting at cancer family clinics; three centers). At this time, the Colon CFR is in year 10 with the second phase of enrollment nearly complete. In phase I recruitment (19982002), population-based sampling ranged from all incident cases of colorectal cancer to a subsample based on age at diagnosis and/or family cancer history. During phase 11 (2002-2007), population-based recruitment targeted cases diagnosed before the age of 50 years are more likely attributable to genetic factors. Standardized protocols were used to collect information regarding family cancer history and colorectal cancer risk factors, and biospecimens were obtained to assess microsatellite instability (MSI) status, expression of mismatch repair proteins, and other molecular and genetic processes. Results: Of the 8,369 case probands enrolled to date, 2,602 reported having one or more colorectal cancer- affected relatives and 799 met the Amsterdam I criteria for Lynch syndrome. A large number of affected (1,324) and unaffected (19,816) relatives were enrolled, as were population-based (4,108) and spouse (983) controls. To date, 91% of case probands provided blood (or, for a few, buccal cell) samples and 75% provided tumor tissue. For a selected sample of high-risk subjects, lymphocytes have been immortalized. Nearly 600 case probands had more than two affected colorectal cancer relatives, and 800 meeting the Amsterdam I criteria and 128, the Amsterdam II criteria. MSI testing for 10 markers was attempted on all obtained tumors. Of the 4,011 tumors collected in phase I that were successfully tested, 16% were MSI-high, 12% were MSI-Iow, and 72% were microsatellite stable. Tumor tissues from clinic-based cases were twice as likely as population-based cases to be MSI-high (34% versus 17%). Seventeen percent of phase I proband tumors and 24% of phase II proband tumors had some loss of mismatch repair protein, with the prevalence depending on sampling. Active follow-up to update personal and family histories, new neoplasms, and deaths in probands and relatives is nearly complete. Conclusions: The Colon CFR supports an evolving research program that is broad and interdisciplinary. The greater scientific community has access to this large and well-characterized resource for studies of colorectal cancer. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Res Program, Seattle, WA 98109 USA. Dartmouth Med Sch, Lebanon, NH USA. Canc Care Ontario, Toronto, ON, Canada. Univ Hawaii, Honolulu, HI 96822 USA. Univ So Calif, Los Angeles, CA USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ Melbourne, Carlton, Vic 3053, Australia. McGill Univ, Montreal, PQ, Canada. Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. RP Newcomb, PA (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Res Program, POB 10924,M4-B402, Seattle, WA 98109 USA. EM pnewcomb@fhcrc.org RI Gallinger, Steven/E-4575-2013; OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [RFA CA-95-011, U01 CA074783, U01 CA074794, U01 CA074799, U01 CA074800, U01 CA074806, U01 CA097735, UO1 CA074783, UO1 CA074794, UO1 CA074799, UO1 CA074800, UO1 CA074806, UO1 CA078296, UO1 CA097735] NR 31 TC 211 Z9 213 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 NOV PY 2007 VL 16 IS 11 BP 2331 EP 2343 DI 10.1158/1055-9965.EPI-07-0648 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500024 PM 17982118 ER PT J AU Zhang, YW Shu, XO Gao, YT Ji, BT Yang, G Li, HL Kilfoy, B Rothman, N Zheng, W Chow, WH AF Zhang, Yawei Shu, Xiao-Ou Gao, Yu-Tang Ji, Bu-Tian Yang, Gong Li, Hong Lan Kilfoy, Briseis Rothman, Nathaniel Zheng, Wei Chow, Wong-Ho TI Family history of cancer and risk of lung cancer among nonsmoking Chinese women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; RESPIRATORY-DISEASE; AGGREGATION; SMOKING; POPULATION; RELATIVES; PROBANDS AB The relationship between family cancer history in first-degree relatives and risk of lung cancer was evaluated among a population-based cohort of 71,392 female nonsmokers in Shanghai, China. A total of 179 newly diagnosed lung cancer patients were identified during 441,410 person-years of follow-up. Lung cancer risk was not elevated among those with a family history of lung cancer. However, risk of lung cancer was increased among subjects who had two or more first-degree relatives with any type of cancers {rate ratio [RR], 1.95 [95% confidence intervals (95% CI, 1.08-3.54] for two relatives with any cancers and RR, 3.17 [95% CI, 1.00-10.03] for three or more relatives with any cancer}. Having a family history of colorectal cancer (RR, 2.38; 95% CI, 1.21-4.70) and having siblings with stomach cancer (RR, 2.16; 95% CI, 1.01-4.65) and pancreatic cancer (RR, 4.19; 95% CI, 1.04-16.95) were also found to be associated with lung cancer risk. This cohort study indicated a moderate association of lung cancer risk with a family cancer history in general, but not with a family history of lung cancer specifically. The associations were stronger when a sibling, rather than a parent, was affected. The apparent link between lung cancer risk and a family history of colorectal, stomach, and pancreas cancers may be worth further investigation. C1 Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Zhang, YW (reprint author), Yale Univ, Sch Epidemiol & Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012 FU Intramural NIH HHS; NCI NIH HHS [N02 CP1101066, R01 CA70867] NR 34 TC 13 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 NOV PY 2007 VL 16 IS 11 BP 2432 EP 2435 DI 10.1158/1055-9965.EPI-07-0398 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500036 PM 18006933 ER PT J AU Yu, KJ Bashirova, A Madeleine, MM Cheng, J Johnson, LG Schwartz, SM Carrington, M Hildesheim, A AF Yu, Kelly J. Bashirova, Arman Madeleine, Margaret M. Cheng, Jie Johnson, Lisa G. Schwartz, Stephen M. Carrington, Mary Hildesheim, Allan TI Evaluation of the association with cervical cancer of polymorphisms in syndecan-1, a heparan sulfate proteoglycan involved with viral cell entry SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-PAPILLOMAVIRUS; HIV-1 INFECTION; NUCLEAR IMPORT; CAPSID PROTEIN; UNITED-STATES; RISK-FACTORS; CARCINOMAS; ADENOCARCINOMAS; EXPRESSION; RECEPTOR AB Infection with 1 of similar to 15 oncogenic human papilloma-viruses is known to be linked to the development of all histologic forms of cervical cancer. We evaluated whether polymorphisms in syndecan-1 (SDC-1), a gene whose protein product is believed to be involved in human papillomavirus entry into epithelial cells, were associated with histologic subtypes of cervical cancer. A total of 293 in situ/invasive adenocarcinoma cases, 260 in situ/invasive squamous cell carcinoma cases, and 478 controls from two studies conducted in the Eastern United States and Seattle area were evaluated. DNA from peripheral blood was used for testing. We sequenced 5 exons and 60 nucleotides upstream of the start codon for SDC-1 in a random subset of 50 cases and 50 controls from the Eastern U.S. Study and identified two polymorphisms (E84E, rs2230924 and Pro-27 C -> T, rs11544860). PCR-based testing was done to evaluate risk associated with these two polymorphisms. Polymorphisms of SDC-1 were not associated with risk of squamous cell carcinomas of the cervix. Similarly, there was no evidence for an association between SDC-1 exon 3 polymorphisms and risk of cervical adenocarcinomas. A marginally significant increase in risk of cervical adenocarcinoma was associated with the presence of the Pro-27 polymorphism (pooled odds ratios, 1.6; 95% confidence intervals, 0.99-2.6), an effect that was restricted to the Eastern U.S. Study. Our results indicate a lack of association between SDC-1 polymorphisms and risk of squamous cell carcinomas of the cervix. An association between SDC-1 Pro-27 polymorphism and cervical adenocarcinoma cannot be ruled out. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Sci Applicat Int Corp Frederick Inc, Lab Genom Divers, Frederick, MD 21701 USA. RP Yu, KJ (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA. EM yuke@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA112512, R01CA112512, R01 CA112512-05, R01 CA112512-04, P01CA042792, R01 CA112512-01, R01 CA112512-02, R01 CA112512-03, N01-CO-12400]; NIDA NIH HHS [DA 13324] NR 25 TC 0 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2504 EP 2508 DI 10.1158/1055-9965.EPI-07-0261 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500048 PM 18006945 ER PT J AU Fine, HA AF Fine, Howard A. TI Promising new therapies for malignant gliomas SO CANCER JOURNAL LA English DT Article DE glioma; angiogenesis; epidermal growth factor receptor; gliobastoma; bevacizumab ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; BRAIN-TUMORS; GLIOBLASTOMA; ANGIOGENESIS; IRINOTECAN; PATHWAY AB Since the publication of the 7th edition of Cancer, Principles & Practice of Oncology, there have been several potentially important advances in the treatment of patients with high-grade gliomas. These advances have occurred in the area of molecular targeting of the epidermal growth factor receptor and in attempts to inhibit glioma-associated angiogenesis. For the first time ever, drugs are being used that can cause reproducible and clinically meaningful tumor responses in patients with recurrent malignant gliomas. Unfortunately, the number of patients with long-term responses to these agents remains relatively low. Identification of biomarkers that will allow a more accurate prediction of which patients are likely to benefit from a specific treatment and new radiographic criteria of true drug-mediated antitumor effects will be increasingly important as new molecular targeted agents are evaluated in patients with primary brain tumors. C1 NCI, Natl Inst Neurol Disorders & Stroke, NIH, Neurooncol Branch, Bethesda, MD USA. RP Fine, HA (reprint author), NCI, Natl Inst Neurol Disorders & Stroke, NIH, Neurooncol Branch, 9030 Old Georgetown Rd,Room 235, Bethesda, MD USA. EM hfine@mail.nih.gov NR 33 TC 13 Z9 14 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2007 VL 13 IS 6 BP 349 EP 354 DI 10.1097/PPO.0b013e31815b18db PG 6 WC Oncology SC Oncology GA 233DW UT WOS:000251071600002 PM 18032970 ER PT J AU Gerstenblith, MR Goldstein, AM Tucker, MA Fraser, MC AF Gerstenblith, Meg R. Goldstein, Alisa M. Tucker, Margaret A. Fraser, Mary C. TI Genetic testing for melanoma predisposition - Current challenges SO CANCER NURSING LA English DT Article DE CDK4; CDKN2A; familial melanoma; genetic testing; melanoma susceptibility genes; multiple primary melanoma; risk assessment counseling ID POPULATION-BASED SAMPLE; CDKN2A MUTATIONS; PRONE FAMILIES; PANCREATIC-CANCER; DYSPLASTIC NEVI; CDK4 MUTATIONS; HEREDITARY MELANOMA; GERMLINE MUTATIONS; AMERICAN-SOCIETY; RISK C1 Natl Canc Inst, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP Fraser, MC (reprint author), Natl Canc Inst, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Execut Plaa S,Room 7118,6120 Execut Blvd,MSC 7236, Rockville, MD 20852 USA. EM fraserm@mail.nih.gov RI Tucker, Margaret/B-4297-2015 NR 54 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD NOV-DEC PY 2007 VL 30 IS 6 BP 454 EP 461 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 236CN UT WOS:000251280700006 ER PT J AU Castillo, A Morse, HC Godfrey, VL Naeem, R Justice, MJ AF Castillo, Andrew Morse, Herbert C., III Godfrey, Virginia L. Naeem, Rizwan Justice, Monica J. TI Overexpression of Eg5 causes genomic instability and tumor formation in mice SO CANCER RESEARCH LA English DT Article ID MITOTIC MOTOR PROTEIN; SPINDLE ASSEMBLY CHECKPOINT; KINESIN-RELATED PROTEIN; DROSOPHILA EMBRYOS; MICROTUBULE MOTOR; GENE MUTATION; CROSS-LINKS; CANCER; ANEUPLOIDY; EXPRESSION AB Proper chromosome segregation in eukaryotes is driven by a complex superstructure called the mitotic spindle. Assembly, maintenance, and function of the spindle depend on centrosome migration, organization of microtubule arrays, and force generation by microtubule motors. Spindle pole migration and elongation are controlled by the unique balance of forces generated by antagonistic molecular motors that act upon microtubules of the mitotic spindle. Defects in components of this complex structure have been shown to lead to chromosome missegregation and genomic instability. Here, we show that overexpression of Eg5, a member of the Bim-C class of kinesin-related proteins, leads to disruption of normal spindle development, as we observe both monopolar and multipolar spindles in Eg5 transgenic mice. Our findings show that perturbation of the mitotic spindle leads to chromosomal missegregation and the accumulation of tetraploid cells. Aging of these mice revealed a higher incidence of tumor formation with a mixed array of tumor types appearing in mice ages 3 to 30 months with the mean age of 20 months. Analysis of the tumors revealed widespread aneuploidy and genetic instability, both hallmarks of nearly all solid tumors. Together with previous findings, our results indicate that Eg5 overexpression disrupts the unique balance of forces associated with normal spindle assembly and function, and thereby leads to the development of spindle defects, genetic instability, and tumors. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Texas Childrens Canc Ctr, Houston, TX USA. NIAID, Immunopathol Lab, NIH, Rockville, MD USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. RP Justice, MJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA. EM mjustice@bcm.tmc.edu OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; NCI NIH HHS [P30-CA16086, R01 CA63229]; NCRR NIH HHS [U42 RR014817-06A1]; NICHD NIH HHS [U01 HD39372]; NIGMS NIH HHS [R25 GM56929] NR 50 TC 57 Z9 62 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2007 VL 67 IS 21 BP 10138 EP 10147 DI 10.1158/0008-5472.CAN-07-0326 PG 10 WC Oncology SC Oncology GA 228AV UT WOS:000250700200008 PM 17974955 ER PT J AU Salvatore, G Nappi, TC Salerno, P Jiang, Y Garbi, C Ugolini, C Miccoli, P Basolo, F Castellone, MD Cirafici, AM Melillo, RM Fusco, A Bittner, ML Santoro, M AF Salvatore, Giuliana Nappi, Tito Claudio Salerno, Paolo Jiang, Yuan Garbi, Corrado Ugolini, Clara Miccoli, Paolo Basolo, Fulvio Castellone, Maria Domenica Cirafici, Anna Maria Melillo, Rosa Marina Fusco, Alfredo Bittner, Michael L. Santoro, Massimo TI A cell proliferation and chromosomal instability signature in anaplastic thyroid carcinoma SO CANCER RESEARCH LA English DT Article ID CYCLE REGULATION; CANCER-CELLS; PIK3CA GENE; P53; EXPRESSION; MUTATION; TUMORS; CLASSIFICATION; PROGRESSION; APOPTOSIS AB Here, we show that the anaplastic thyroid carcinoma (ATC) features the up-regulation of a set of genes involved in the control of cell cycle progression and chromosome segregation. This phenotype differentiates ATC from normal tissue and from well-differentiated papillary thyroid carcinoma. Transcriptional promoters of the ATC up-regulated genes are characterized by a modular organization featuring binding sites for E2F and NF-Y transcription factors and cell cycle-dependent element (CDE)/cell cycle gene homology region (CHR) cis-regulatory elements. Two protein kinases involved in cell cycle regulation, namely, Polo-like kinase 1 (PLK1) and T cell tyrosine kinase (TTK), are part of the gene set that is up-regulated in ATC. Adoptive overexpression of p53, p21 (CIP1 /WAF1), and E2F4 down-regulated transcription from the PLK1 and TTK promoters in ATC cells, suggesting that these genes might be under the negative control of tumor suppressors of the p53 and pRB families. ATC, but not normal thyroid, cells depended on PLK1 for survival. RNAi-mediated PLK1 knockdown caused cell cycle arrest associated with 4N DNA content and massive mitotic cell death. Thus, thyroid cell anaplastic transformation is accompanied by the overexpression of a cell proliferation/genetic instability-related gene cluster that includes PLK1 kinase, which is a potential molecular target for ATC treatment. C1 Univ Parthenope, Dipartimento Studi Ist & Sistemi Terr, Naples, Italy. Univ Naples Federico 2, Consiglio Nazl Ric, Ist Endocrinol & Oncol Sperimentale, Dipartimento Biol & Patol Cellulare & Mol L Calif, Naples, Italy. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Pisa, Dipartimento Chirurg, Pisa, Italy. TGen, Phoenix, AZ USA. RP Santoro, M (reprint author), Dipartimento Biol & Patol Cellulare & Mol, Via S Pansini 5, I-80131 Naples, Italy. EM masantor@unina.it OI MELILLO, Rosa Marina/0000-0002-9233-5275; CASTELLONE, MARIADOMENICA/0000-0003-0507-8037; Fusco, Alfredo/0000-0003-3332-5197; BASOLO, FULVIO/0000-0003-1657-5020 NR 38 TC 84 Z9 89 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2007 VL 67 IS 21 BP 10148 EP 10158 DI 10.1158/0008-5472.CAN-07-1887 PG 11 WC Oncology SC Oncology GA 228AV UT WOS:000250700200009 PM 17981789 ER PT J AU Datta, S Hoenerhoff, MJ Bommi, P Sainger, R Guo, WP Dimri, M Band, H Band, V Green, JE Dimri, GP AF Datta, Sonal Hoenerhoff, Mark J. Bommi, Prashant Sainger, Rachana Guo, Wei-Pan Dimri, Manjari Band, Hamid Band, Vimla Green, Jeffrey E. Dimri, Goberdhan P. TI Bmi-1 cooperates with H-ras to transform human mammary epithelial cells via Dysregulation of multiple growth-regulatory pathways SO CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; SELF-RENEWAL; STEM-CELLS; INVASIVE PHENOTYPE; INDUCED SENESCENCE; GROUP PROTEINS; IN-VIVO; POLYCOMB; EXPRESSION; PROLIFERATION AB Elevated expression of Bmi-I is associated with many cancers, including breast cancer. Here, we examined the oncogenic potential of Bmi-1 in MCF10A cells, a spontaneously immortalized, nontransformed strain of human mammary epithelial cells (HMEC). Bmi-1 overexpression alone in MCF10A cells did not result in oncogenic transformation. However, Bmi-1 co-overexpression with activated H-Ras (RasG12V) resulted in efficient transformation of MCF10A cells in vitro. Although early-passage H-Ras-expressing MCF10A cells were not transformed, late-passage H-Ras-expressing cells exhibited features of transformation in vitro. Early- and late-passage H-Ras-expressing cells also differed in levels of expression of H-Ras and Ki-67, a marker of proliferation. Subsets of early-passage H-Ras-expressing cells exhibited high Ras expression and were negative for Ki-67, whereas most late-passage H-Ras-expressing cells expressed low levels of Ras and were Ki-67 positive. Injection of late-passage H-Ras-expressing cells in severe combined inummodeficient mice formed carcinomas with leiomatous, hemangiomatous, and mast cell components; these tumors were quite distinct from those induced by late-passage cells co-overexpressing Bmi-1 and H-Ras, which formed poorly differentiated carcinomas with spindle cell features. Bmi-1 and H-Ras co-overexpression in MCF10A cells also induced features of epithelial-to-mesenchymal transition. Importantly, Bmi-1 inhibited senescence and permitted proliferation of cells expressing high levels of Ras. Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes HMEC transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways by p16(INK4a)-independent mechanisms. C1 ENH Res Inst, Div Canc Biol, Evanston, IL 60201 USA. ENH Res Inst, Dept Med, Evanston, IL 60201 USA. Northwestern Univ, Feinberg Sch Med, Div Mol Oncol, Evanston, IL USA. Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Dimri, GP (reprint author), ENH Res Inst, Div Canc Biol, 1001 Univ Pl, Evanston, IL 60201 USA. EM jegireen@nih.gov FU NCI NIH HHS [R01CA094150, R01 CA094150, R01 CA094150-05] NR 51 TC 70 Z9 72 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2007 VL 67 IS 21 BP 10286 EP 10295 DI 10.1158/0008-5472.CAN-07-1636 PG 10 WC Oncology SC Oncology GA 228AV UT WOS:000250700200025 PM 17974970 ER PT J AU Antony, S Agama, KK Miao, ZH Takagi, K Wright, MH Robles, AI Varticovski, L Nagarajan, M Morrell, A Cushman, M Pommier, Y AF Antony, Smitha Agama, Keli K. Miao, Ze-Hong Takagi, Kazutaka Wright, Mollie H. Robles, Ana I. Varticovski, Lyuba Nagarajan, Muthukaman Morrell, Andrew Cushman, Mark Pommier, Yves TI Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topolsomerase I cleavage complexes and overcome multidrug resistance SO CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE-I; CAMPTOTHECIN DERIVATIVES; BIOLOGICAL EVALUATION; MJ-III-65 NSC-706744; ANTICANCER ACTIVITY; COVALENT COMPLEX; MAMMALIAN-CELLS; HISTONE H2AX; INHIBITORS; PROTEIN AB Camptothecin (CPT) derivatives are effective anticancer drugs, especially against solid tumors. As CPTs are chemically unstable and have clinical limitations, we have synthesized indenoisoquinolines as novel topoisomerase I (Top1) inhibitors. We presently report two indenoisoquinoline derivatives, NSC 725776 and NSC 724998, which have been selected for therapeutic development. Both are potent Top1 inhibitors and induce Top1. cleavage at unique genomic positions compared with CPT. Consistent with Top1. poisoning, protein-linked DNA breaks were detected in cells treated with NSC 725776 and NSC 724998 at nanomolar concentrations. Those drug-induced protein-linked DNA breaks persisted longer after drug removal than those produced by CPT. Studies in human cells in culture show that NSC 725776 and NSC 724998 exert antiproliferative activity at submicromolar concentrations. Furthermore, NSC 725776 and NSC 724998 show cross-resistance in cells deficient or silenced for Top1, which is consistent with their selective Top1 targeting. Similar to other known Top1 inhibitors, NSC 725776-treated and NSC 724998-treated cells show an arrest of cell cycle progression in both S and G(2)-M and a dependence on functional p53 for their cytotoxicity. Dose-dependent gamma-H2AX foci formation was readily observed in cells treated with NSC 725776 and NSC 724998. These gamma-H2AX foci were detectable at pharmacologically relevant doses for up to 24 It and thus could be used as biomarkers for clinical trials (phase 0). C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS; NCI NIH HHS [ST32 CA09634-12, N01-CO-56000, UO1 CA89566] NR 50 TC 86 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 NOV 1 PY 2007 VL 67 IS 21 BP 10397 EP 10405 DI 10.1158/0008-5472.CAN-07-0938 PG 9 WC Oncology SC Oncology GA 228AV UT WOS:000250700200038 PM 17974983 ER PT J AU Greeneltch, KM Schneider, M Steinberg, SM Liewehr, DJ Stewart, TJ Liu, K Abrams, SI AF Greeneltch, Kristy M. Schneider, Monika Steinberg, Seth M. Liewehr, David J. Stewart, Trina J. Liu, Kebin Abrams, Scott I. TI Host Immunosurveillance controls tumor growth via IFN regulatory factor-8-dependent mechanisms SO CANCER RESEARCH LA English DT Article ID SEQUENCE-BINDING-PROTEIN; CTL ADOPTIVE IMMUNOTHERAPY; LEUKEMIA-LIKE SYNDROME; RENAL-CANCER CELLS; FAS LIGAND; IN-VIVO; MYELOID CELLS; NK CELLS; GAMMA; APOPTOSIS AB IFN regulatory factor (IRF)-8 plays an important role in normal myelopoiesis. The loss of IRF-8 in myeloid cells results in a chronic myelogenous leukemia-like syndrome, suggesting that IRF-8 behaves as a tumor suppressor gene in certain hematopoietic malignancies. We have been investigating the molecular determinants of solid tumor progression, with an emphasis on apoptotic resistance. Recently, we showed that IRF-8 expression was directly correlated with Fas-mediated apoptosis, and inversely related to malignant phenotype. However, the functional role of IRF-8 in solid tumors is unresolved. We stably silenced IRF-8 expression via RNA interference in IRF-8-expressing mouse tumor cells, and evaluated them for changes in apoptotic phenotype and malignant behavior. Apoptosis induced by Fas engagement or irradiation was markedly reduced in IRF-8-deficient tumor cells, despite unaltered proliferation, cell surface Fas, or MHC class I expression. Moreover, in syngeneic immunocompetent mice, IRF-8-deficient tumor cells grew more aggressively than their control counterparts. However, in IFN-gamma- or Fas ligand-deficient mice, but not T cell-deficient mice, both control and IRF-8-deficient tumor populations grew. similarly. Furthermore, both tumor populations grew similarly in mice with defects in innate immunity. Although subsequent studies precluded a role for natural killer cells, immunohistochemical analysis supported the involvement of macrophages. Overall, our findings show that IRF-8 expression in solid tumor cells is important for efficient host immunosurveillance and response to apoptotic stimuli. Therefore, IRF-8 down-regulation may represent a previously unrecognized tumor escape mechanism that facilitates tumor progression. Conversely, strategies aimed at up-regulating or restoring IRF-8 expression in neoplastic cells may improve therapeutic efficacy. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. EM sa47z@nih.gov RI Stewart, Trina/F-5967-2012; OI Stewart, Trina/0000-0003-3220-9231; Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS NR 47 TC 14 Z9 14 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 NOV 1 PY 2007 VL 67 IS 21 BP 10406 EP 10416 DI 10.1158/0008-5472.CAN-07-1228 PG 11 WC Oncology SC Oncology GA 228AV UT WOS:000250700200039 PM 17974984 ER PT J AU Sankala, HM Hait, NC Paugh, SW Shida, D Lepine, S Elmore, LW Dent, P Milstien, S Spiegel, S AF Sankala, Heidi M. Hait, Nitai C. Paugh, Steven W. Shida, Dai Lepine, Sandrine Elmore, Lynne W. Dent, Paul Milstien, Sheldon Spiegel, Sarah TI Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; TUMOR-CELLS; KINASE TYPE-2; DNA-DAMAGE; DEPENDENT ACTIVATION; PLASMA-MEMBRANE; CARCINOMA-CELLS; GROWTH-FACTOR; APOPTOSIS; P53 AB Sphingosine-1-phosphate is a potent lipid mediator formed by phosphorylation of sphingosine, a metabolite of sphingolipids, catalyzed by two sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2. Expression of SphK2, which is enriched in the nucleus of MCF7 human breast cancer cells, increased expression of the cyclin-dependent kinase inhibitor p21 but had no effect on p53 or its phosphorylation. The anticancer drug doxorubicin is known to increase p21 via p53-dependent and p53-independent mechanisms. Down-regulation of endogenous SphK2 with small interfering RNA targeted to unique mRNA sequences decreased basal and doxorubicin-induced expression of p21 without affecting increased expression of p53. Down-regulation of SphK2 also decreased G(2)-M arrest and markedly enhanced apoptosis induced by doxorubicin. Moreover, siSphK2 reduced doxorubicin-induced p21 expression in p53-inactivated MCF7 cells. Likewise, in human wildtype p53- and p21-expressing HCT116 colon carcinoma cells, as well as in p53-null counterparts, down-regulation of SphK2 markedly reduced p21 induction by doxorubicin. Knockdown of SphK2 sensitized HCT116 cells to apoptosis induced by doxorubicin with concomitant cleavage of poly(ADP-ribose) polymerase. Collectively, our results show that endogenous SphK2 is important for p53-independent induction of p21 expression by doxorubicin and suggest that SphK2 may influence the balance between cytostasis and apoptosis of human cancer cells. C1 Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. NIMH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Paugh, Steven/A-7739-2008 OI Paugh, Steven/0000-0001-5697-9228 FU Intramural NIH HHS; NCI NIH HHS [P30 CA16059, R01CA61774]; NIAID NIH HHS [T32AI007407]; NIDDK NIH HHS [DK52825]; NIGMS NIH HHS [R 37 GM043880] NR 46 TC 81 Z9 87 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2007 VL 67 IS 21 BP 10466 EP 10474 DI 10.1158/0008-5472.CAN-07-2090 PG 9 WC Oncology SC Oncology GA 228AV UT WOS:000250700200045 PM 17974990 ER PT J AU Pacheco-Rodriguez, G Steagall, WK Crooks, DM Stevens, LA Hashimoto, H Li, S Wang, JA Darling, TN Moss, J AF Pacheco-Rodriguez, Gustavo Steagall, Wendy K. Crooks, Denise M. Stevens, Linda A. Hashimoto, Hiroshi Li, Shaowei Wang, Ji-An Darling, Thomas N. Moss, Joel TI TSC2 loss in Lymphangioleiomyomatosis cells correlated with expression of CD44v6, a molecular determinant of metastasis SO CANCER RESEARCH LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR GENE; SERUM RESPONSE FACTOR; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; INTRACELLULAR DOMAIN; CANCER PROGRESSION; OSTEOPONTIN; ADHESION; GROWTH; GLYCOPROTEIN AB Lymphangioleiomyomatosis (LAM), a rare multisystern disease found primarily in women of childbearing age, is characterized by the proliferation of abnormal smooth muscle-like cells, LAM cells, that form nodules in the pulmonary interstitium. Proliferation of LAM cells results, in part, from dysfunction in tuberous sclerosis complex (TSC) genes TSC1 (hamartin) and/or TSC2 (tuberin). Identification of LAM cells in donor lungs, their isolation from blood, and their presence in urine, chylous ascites, and pleural effusions are consistent with their ability to metastasize. Here, we investigated the presence on LAM cells of the hyaluronic acid receptor CD44 and its splice variants associated with metastasis. The heterogeneous populations of cells grown from lungs of 12 LAM patients contain cells expressing mRNA for the variant CD44v6. Histologically, CD44v6 was present in LAM lung nodules, but not in normal vascular smooth muscle cells. CD44v6-positive sorted cells showed loss of heterozygosity at the TSC2 locus; binding of CD44v6 antibody resulted in loss of cell viability. Levels of CD44 were higher in cultured Eker rat (Tsc2-/-) cells than in Tsc2+/+ cells, but unlike human LAM cells, the Tsc2-/- Eker rat cells did not contain CD44v6 splice variant mRNA. CD44 splicing and signaling is regulated by osteopontin. Plasma from LAM patients contained higher concentrations of osteopontin than plasma of healthy, age-, and sex-matched volunteers (P = 0.00003) and may be a biomarker for LAM. The cell surface receptor CD44 and its splice variant CD44v6 may contribute to the metastatic potential of LAM cells. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. RP Pacheco-Rodriguez, G (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10-Room 5N307,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pachecog@nhlbi.nih.gov OI Darling, Thomas/0000-0002-5161-1974 FU Intramural NIH HHS; NCI NIH HHS [R01 CA100907] NR 46 TC 33 Z9 35 U1 0 U2 4 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 NOV 1 PY 2007 VL 67 IS 21 BP 10573 EP 10581 DI 10.1158/0008-5472.CAN-07-1356 PG 9 WC Oncology SC Oncology GA 228AV UT WOS:000250700200057 PM 17975002 ER PT J AU Yang, XR Pfeiffer, RM Garcia-Closas, M Rimm, DL Lissowska, J Brinton, LA Peplonska, B Hewitt, SM Cartun, RW Mandich, D Sasano, H Evans, DB Sutter, TR Sherman, ME AF Yang, Xiaohong R. Pfeiffer, Ruth M. Garcia-Closas, Montserrat Rimm, David L. Lissowska, Jolanta Brinton, Louise A. Peplonska, Beata Hewitt, Stephen M. Cartun, Richard W. Mandich, Daniza Sasano, Hironobu Evans, Dean B. Sutter, Thomas R. Sherman, Mark E. TI Hormonal markers in breast cancer: Coexpression, relationship with pathologic characteristics, and risk factor associations in a population-based study SO CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-BETA; CLINICAL-IMPLICATIONS; TUMOR CHARACTERISTICS; AROMATASE-ACTIVITY; ER-BETA; EXPRESSION; CARCINOMA; SULFATASE; SUBTYPES; WOMEN AB The objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns (factors): "nuclear receptor factor" [estrogen receptor (ER)-alpha, progesterone receptor, androgen receptor, cyclin D1, and aromatase], "estrogen metabolism/ER-beta factor" (ER-beta, peroxisome proliferator-activated receptor-gamma, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), "HER2 factor" (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and "proliferation factor" (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-beta factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity 0.01), and older age at menopause (P heterogeneity 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity < 0.0001), and in contrast to the estrogen metabolism/ER-beta factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-beta and enzymes involved in hormone metabolism. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 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. Hartford Hosp, Dept Pathol, Hartford, CT 06115 USA. Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan. Novartis Inst BioMed Res Basel, Basel, Switzerland. Univ Memphis, W Harry Feinstone Ctr Genom Res, Memphis, TN 38152 USA. RP Yang, XR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7014, Bethesda, MD 20892 USA. EM royang@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; 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; Hewitt, Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799 NR 34 TC 38 Z9 39 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2007 VL 67 IS 21 BP 10608 EP 10617 DI 10.1158/0008-5472.CAN-07-2142 PG 10 WC Oncology SC Oncology GA 228AV UT WOS:000250700200061 PM 17968031 ER PT J AU Gunn, AJ Hama, Y Koyama, Y Kohn, EC Choyke, PL Kobayashi, H AF Gunn, Andrew J. Hama, Yukihiro Koyama, Yoshinori Kohn, Elise C. Choyke, Peter L. Kobayashi, Hisataka TI Targeted optical fluorescence imaging of human ovarian adenocarcinoma using a galactosyl serum albumin-conjugated fluorophore SO CANCER SCIENCE LA English DT Article ID PHOTODYNAMIC THERAPY; CANCER-CELLS; PHASE-I; SURGERY; AVIDIN AB Achieving maximal cytoreduction during surgery is a critical prognostic factor for women with advanced-stage ovarian cancer. Targeting optical imaging agents directly to ovarian cancer cells by attaching them to galactosyl (galactosamine-conjugated) serum albumin, whose sugar residues bind surface lectins that are expressed in certain ovarian adenocarcinomas, may improve metastatic tumor identification and resection. Thus, we sought to demonstrate that galactosyl serum albumin-conjugated fluorophores would be a robust mechanism through which to target ovarian cancer by evaluating its tumor-targeting capability in nine human ovarian adenocarcinoma cell lines. The optical fluorophore rhodamine green was conjugated to galactosyl serum albumin, a non-immunogenic targeting molecule. Galactosyl serum albumin-rhodamine green's ability to target nine human ovarian adenocarcinoma cell lines was evaluated by flow cytometry, fluorescence microscopy and in vivo optical fluorescence imaging using female athymic nu/nu mice. All nine cell lines tested bound galactosyl serum albumin-rhodamine green more effectively than non-glycosylated controls (P < 0.0001). Fluorescence microscopy demonstrated that galactosyl serum albumin-rhodamine green was internalized into each cell line in a galactosamine-dependent manner. In vivo optical fluorescence images of intraperitoneal tumor-bearing mice acquired 3 h after intraperitoneal injection of galactosyl serum albumin-rhodamine green successfully differentiated between tumor and normal tissue. This technique also allowed the visualization of submillimeter-sized ovarian tumor implants. These results indicate that galactosyl serum albumin-rhodamine green can selectively target a variety of human ovarian adenocarcinomas for optical fluorescence imaging and thus may improve intraoperative tumor detection and resection. C1 NIH, Natl Canc Inst, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. NIH, Natl Canc Inst, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NIH, Natl Canc Inst, Ctr Canc Res, Mol Imaging Program, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC010657-03, Z01 SC009163-20] NR 18 TC 24 Z9 24 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD NOV PY 2007 VL 98 IS 11 BP 1727 EP 1733 DI 10.1111/j.1349-7006.2007.00602.x PG 7 WC Oncology SC Oncology GA 213XI UT WOS:000249700200013 PM 17784874 ER PT J AU Idle, JR Gonzalez, FJ AF Idle, Jeffrey R. Gonzalez, Frank J. TI Metabolomics SO CELL METABOLISM LA English DT Article ID METABONOMICS; MICROBIOME; EXPRESSION AB Metabolomics is the systematic identification and quantitation of all metabolites in a given organism or biological sample. The enhanced resolution provided by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), along with powerful chemometric software, allows the simultaneous determination and comparison of thousands of chemical entities, which has lead to an expansion of small molecule biochemistry studies in bacteria, plants, and mammals. Continued development of these analytical platforms will accelerate the widespread use of metabolomics and allow further integration of small molecules into systems biology. Here, recent studies using metabolomics in xenobiotic metabolism and genetically modified mice are highlighted. C1 Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic. Natl Canc Inst, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20894 USA. RP Idle, JR (reprint author), Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic. EM jidle@lfl.cuni.cz; fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS [Z01 BC005562-19] NR 15 TC 57 Z9 59 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV PY 2007 VL 6 IS 5 BP 348 EP 351 DI 10.1016/j.cmet.2007.10.005 PG 4 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 229NC UT WOS:000250809700005 PM 17983580 ER PT J AU Freundt, EC Czapiga, M Lenardo, MJ AF Freundt, Eric C. Czapiga, Meggan Lenardo, Michael J. TI Photoconversion of Lysotracker Red to a green fluorescent molecule SO CELL RESEARCH LA English DT Letter ID RECEPTOR C1 [Freundt, Eric C.; Lenardo, Michael J.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. [Czapiga, Meggan] NIAID, NIH, Biol Imaging Sect, Res Technol Branch, Bethesda, MD 20892 USA. [Freundt, Eric C.] Univ Oxford, John Radcliffe Hosp, Med Res Council, Human Immunol Unit,Weatherall Inst Mol Med, Oxford OX3 9DS, England. RP Lenardo, MJ (reprint author), NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. EM mlenardo@niaid.nih.gov FU Intramural NIH HHS NR 6 TC 29 Z9 29 U1 2 U2 6 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD NOV PY 2007 VL 17 IS 11 BP 956 EP 958 DI 10.1038/cr.2007.80 PG 3 WC Cell Biology SC Cell Biology GA 245RK UT WOS:000251953300008 PM 17893709 ER PT J AU Erickson, DL Waterfield, NR Vadyvaloo, V Long, D Fischer, ER ffrench-Constant, R Hinnebusch, BJ AF Erickson, David L. Waterfield, Nicholas R. Vadyvaloo, Viveka Long, Daniel Fischer, Elizabeth R. ffrench-Constant, Richard Hinnebusch, B. Joseph TI Acute oral toxicity of Yersinia pseudotuberculosis to fleas: implications for the evolution of vector-borne transmission of plague SO CELLULAR MICROBIOLOGY LA English DT Article ID BACTERIUM PHOTORHABDUS-LUMINESCENS; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; SUICIDE VECTOR; INSECTICIDAL TOXINS; XENOPSYLLA-CHEOPIS; BIOFILM FORMATION; PESTIS; ENTEROCOLITICA; TEMPERATURE AB Yersinia pestis diverged from Yersinia pseudotuberculosis <= 20 000 years ago, during which time it evolved to be transmitted by fleas. In comparing the ability of these closely related species to infect the rat flea Xenopsylla cheopis, we found that Y. pseudotuberculosis, unlike Y. pestis, is orally toxic to fleas. Fleas showed signs of acute toxicity, including diarrhoea, immediately after feeding on blood containing Y. pseudotuberculosis in response to protein toxin(s) produced by the bacteria. Adherence of Y. pseudotuberculosis to the midgut and large intracellular vacuoles in midgut epithelial cells were detected during the first 24 h after infection. The insect pathogen Photorhabdus luminescens and its TcdA1 and TcdB1-TccC1 insecticidal toxin complexes were similarly toxic to fleas, implicating the toxin complex (tc) genes also present in Yersinia species. However, the Y. pestis and Y. pseudotuberculosis TcaAB and TcaC-TccC proteins were non-toxic to fleas, and Y. pseudotuberculosis mutants deleted of tc genes retained acute toxicity. Our results indicate that loss of one or more insect gut toxins was a critical step in the recent evolution of flea-borne transmission in the genus Yersinia. Changes in the tc insecticidal genes do not appear to have been responsible, but may have had other effects on Yersinia-flea interactions. C1 NIAID, Rocky Mt Lab, NIH, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. NIAID, Rocky Mt Lab, NIH, Vet Branch, Hamilton, MT 59840 USA. NIAID, Rocky Mt Lab, NIH, Microscopy Unit, Hamilton, MT 59840 USA. Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. Univ Exeter, Ctr Ecol & Conservat, Exeter EX4 4QJ, Devon, England. RP Hinnebusch, BJ (reprint author), Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA. EM jhinnebusch@niaid.nih.gov OI ffrench-Constant, Richard/0000-0001-5385-9888 FU Intramural NIH HHS NR 41 TC 35 Z9 36 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD NOV PY 2007 VL 9 IS 11 BP 2658 EP 2666 DI 10.1111/j.1462-5822.2007.00986.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 215QO UT WOS:000249824300010 PM 17587333 ER PT J AU Robertson, SL Smedley, JG Singh, U Chakrabarti, G Van Itallie, CM Anderson, JM McClane, BA AF Robertson, Susan L., III Smedley, James G. Singh, Usha Chakrabarti, Ganes Van Itallie, Christina M. Anderson, James M. McClane, Bruce A. TI Compositional and stoichiometric analysis of Clostridium perfringens enterotoxin complexes in Caco-2 cells and claudin 4 fibroblast transfectants SO CELLULAR MICROBIOLOGY LA English DT Article ID TIGHT-JUNCTION STRANDS; STAPHYLOCOCCAL ALPHA-HEMOLYSIN; HEPTAMERIC TRANSMEMBRANE PORE; MAMMALIAN PLASMA-MEMBRANE; PERMEABILITY ALTERATIONS; A ENTEROTOXIN; VERO CELLS; GEL ELECTROPHORESIS; MOLECULAR WEIGHTS; DEATH PATHWAYS AB Clostridium perfringens enterotoxin (CPE) binds to host cell receptors, forming a small complex precursor for two large complexes reportedly having molecular masses of similar to 155 or similar to 200 kDa. Formation of the similar to 155 kDa complex causes a Ca2+ influx that leads to apoptosis or oncosis. CPE complex composition is currently poorly understood, although occludin was identified in the similar to 200 kDa complex. The current study used heteromer gel shift analysis to show both CPE large complexes contain six CPE molecules. Ferguson plots and size exclusion chromatography re-sized the similar to 155 and similar to 200 kDa complexes as similar to 425-500 kDa and similar to 550-660 kDa respectively. Co-immunoprecipitation and electroelution studies demonstrated both CPE-binding and non-CPE-binding claudins are associated with all three CPE complexes in Caco-2 cells and with small complex and similar to 425-500 kDa complex of claudin 4 transfectants. Fibroblast transfectants expressing claudin 4 or C-terminal truncated claudin 4 were CPE-sensitive and formed the similar to 425 kDa complex, indicating claudin-induced cell signalling is not required for CPE action and that expression of a single receptor claudin suffices for similar to 425-500 kDa CPE complex formation. These results identify CPE as a unique toxin that combines with tight junction proteins to form high-molecular-mass hexameric pores and alter membrane permeability. C1 Natl Inst Environm Hlth Sci, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA USA. Roche Pharmaceut, Dept Metab Dis, Nutley, NJ USA. Zydus Res Ctr, Moraiya Ahmedabad, India. Univ N Carolina, Dept Cell & Mol Phys, Chapel Hill, NC USA. RP McClane, BA (reprint author), Natl Inst Environm Hlth Sci, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. EM bamcc@pitt.edu FU NIAID NIH HHS [R37-AI019844-24]; NIDDK NIH HHS [R01 DK 45134] NR 74 TC 31 Z9 31 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD NOV PY 2007 VL 9 IS 11 BP 2734 EP 2755 DI 10.1111/j.1462-5822.2007.00994.x PG 22 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 215QO UT WOS:000249824300016 PM 17587331 ER PT J AU Neckers, L Kern, A Tsutsumi, S AF Neckers, Len Kern, Adam Tsutsumi, Shinji TI Hsp90 inhibitors disrupt mitochondrial homeostasis in cancer cells SO CHEMISTRY & BIOLOGY LA English DT Editorial Material ID SHOCK-PROTEIN 90; PERMEABILITY TRANSITION; TRAP1; CHAPERONES; APOPTOSIS AB Hsp90 is a cytosolic molecular chaperone whose paralog in mitochondria, TRAP1, protects cells from oxidative stress. The recent study in Cell by Kang et al. [1] now identifies the molecular components of the proapoptotic network regulated by TRAP1, that includes Hsp90. Targeting Hsp90/TRAP1 inhibitors to mitochondria induces rapid tumor cell-specific apoptosis. C1 NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, 9000 Rockville Pike,Bldg 10-CRC,Room 1-5940, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 18 TC 28 Z9 30 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 2007 VL 14 IS 11 BP 1204 EP 1206 DI 10.1016/j.chembiol.2007.11.002 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236JK UT WOS:000251299000003 PM 18022558 ER PT J AU Clancy, CM Kiley, JP Weiss, KB AF Clancy, Carolyn M. Kiley, James P. Weiss, Kevin B. TI Eliminating asthma disparities through multistakeholder partnerships SO CHEST LA English DT Editorial Material ID MULTISITE RANDOMIZED-TRIAL; RESEARCH-TEAM-II; ORGANIZATIONAL-CHANGE; PHYSICIAN EDUCATION; CARE; OUTCOMES C1 Agency Healthcare Res & Quality, Rockville, MD USA. NIH, Bethesda, MD USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. RP Weiss, KB (reprint author), Inst Healthcare Stud, Suite 200, 676 N St Claire St, Chicago, IL 60611 USA. EM kevin.weiss@va.gov NR 27 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2007 VL 132 IS 5 BP 1422 EP 1424 DI 10.1378/chest.07-1947 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 231TU UT WOS:000250972700005 PM 17998357 ER PT J AU Taveira-DaSilva, AM Hathaway, OM Sachdev, V Shizukuda, Y Birdsall, CW Moss, J AF Taveira-DaSilva, Angelo M. Hathaway, Olanda M. Sachdev, Vandana Shizukuda, Yukitaka Birdsall, Charles W. Moss, Joel TI Pulmonary artery pressure in lymphangioleiomyomatosis - An echocardiographic study SO CHEST LA English DT Article DE exercise; hypoxemia; pulmonary function tests; pulmonary hypertension ID MILD HYPOXEMIA; DOPPLER-ECHOCARDIOGRAPHY; COPD PATIENTS; HYPERTENSION; EXERCISE; DISEASE; SILDENAFIL; OXYGEN; HEMODYNAMICS; DIAGNOSIS AB Background: Exercise-induced hypoxemia is frequent in patients with lymphangioleiomyomatosis (LAM) and could be associated with pulmonary hypertension. The aims of this study were to determine the prevalence of pulmonary hypertension in patients with LAM, to identify physiologic parameters associated with its occurrence, and to evaluate the effect of oxygen on response to exercise. Methods: Studies were performed in 120 patients. Complete data, including exercise echocardiography, pulmonary function testing, and standard cardiopulmonary exercise testing, were obtained in 95 patients. Results: Resting pulmonary artery pressure (PAP) was 26 +/- 0.7 mm Hg (mean +/- SEM). Eight patients had pulmonary hypertension (43 +/- 3 mm Hg), and two patients had right ventricular dilatation. Ninety-five patients exercised (room air, n = 64; oxygen, n = 31) to a power of 58 +/- 2 W (49% of predicted) and an estimated peak oxygen uptake of 938 +/- 30 mL/min (56% of predicted). Sixty-one patients had a decline in arterial oxygen saturation (SaO(2)) > 3%, and 56 patients had an elevation in PAP > 40 mm Hg. Peak exercise PAP was negatively correlated with exercise SaO(2) (P = 0.0005). Multivariate analysis showed that exercise SaO(2) was the best predictor of exercise PAP (p = 0.012). Conclusions: Although resting pulmonary hypertension is rare in patients with LAM, a rise in PAP at low exercise levels occurs frequently, in part related to exercise-induced hypoxemia. Optimization of oxygen administration during activities of daily living should be undertaken in patients with LAM to prevent hypoxemia and exercise-induced pulmonary hypertension. C1 NHLBI, Pulmonary Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Taveira-DaSilva, AM (reprint author), NHLBI, Pulmonary Crit Care Med Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL002541-12] NR 37 TC 36 Z9 36 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2007 VL 132 IS 5 BP 1573 EP 1578 DI 10.1378/chest.07-1205 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 231TU UT WOS:000250972700026 PM 17890459 ER PT J AU Lamb, ME Orbach, Y Hershkowitz, I Esplin, PW Horowitz, D AF Lamb, Michael E. Orbach, Yael Hershkowitz, Irit Esplin, Phillip W. Horowitz, Dvora TI A structured forensic interview protocol improves the quality and informativeness of investigative interviews with children: A review of research using the NICHD Investigative Interview Protocol SO CHILD ABUSE & NEGLECT LA English DT Review DE forensic interviews; child sexual abuse; interview strategies; questioning styles ID ANATOMICALLY DETAILED DOLLS; SEXUAL-ABUSE; NARRATIVE ELABORATION; EYEWITNESS TESTIMONY; PRESCHOOL-CHILDREN; ALLEGED VICTIMS; UTTERANCE TYPES; AGE-DIFFERENCES; QUESTION TYPE; SUGGESTIBILITY AB Objective: To show how the results of research on children's memory, communicative skills, social knowledge, and social tendencies can be translated into guidelines that improve the quality of forensic interviews of children. Method: We review studies designed to evaluate children's capacities as witnesses, explain the development of the structured NICHD Investigative Interview Protocol, and discuss studies designed to assess whether use of the Protocol enhances the quality of investigative interviews. Results: Controlled studies have repeatedly shown that the quality of interviewing reliably and dramatically improves when interviewers employ the NICHD Protocol. No other technique has been proven to be similarly effective. Conclusions: Use of the structured NICHD Protocol improves the quality of information obtained from alleged victims by investigators, thereby increasing the likelihood that interventions will be appropriate. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Lamb, Michael E.] Univ Cambridge, Fac Social & Polit Sci, Cambridge CB2 3RQ, England. [Orbach, Yael] NICHHD, Bethesda, MD 20892 USA. [Hershkowitz, Irit] Univ Haifa, IL-31999 Haifa, Israel. RP Lamb, ME (reprint author), Univ Cambridge, Fac Social & Polit Sci, Free Sch Lane, Cambridge CB2 3RQ, England. FU Intramural NIH HHS [Z01 HD001115-20]; NIDCR NIH HHS [F35 DE005688-03, F35 DE005688-01, F35 DE005688-02] NR 99 TC 134 Z9 135 U1 10 U2 69 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD NOV-DEC PY 2007 VL 31 IS 11-12 BP 1201 EP 1231 DI 10.1016/j.chiabu.2007.03.021 PG 31 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 242YH UT WOS:000251761600006 PM 18023872 ER PT J AU Hama, Y Urano, Y Koyama, Y Gunn, AJ Choyke, PL Kobayashi, H AF Hama, Yukihiro Urano, Yasuteru Koyama, Yoshinori Gunn, Andrew J. Choyke, Peter L. Kobayashi, Hisataka TI A self-quenched galactosamine-serum albumin - RhodamineX conjugate: A"Smart" fluorescent molecular Imaging probe synthesized with clinically applicable material for detecting peritoneal ovarian cancer Metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR; REPORTER; AVIDIN; CELLS AB Purpose: Fluorophore activation after cellular internalization of a targeted fluorescently labeled conjugate is an effective molecular imaging strategy to increase target-to-background ratios. The D-galactose receptor on ovarian cancer cells has been used to target self-quenched avidinrhodamineX conjugates in which the avidin component binds to D-galactose receptor and the rhodamines are optically activated by dequenching only after cellular internalization. As a non-immunogenic alternative of avidin, galactosamine-conjugated serum albumin (GmSA) targets the D-galactose receptor with higher binding affinity and has more conjugation sites available for rhodamineX than avidin. Experimental Design: GmSA was conjugated with 20 rhodamineX molecules (GmSA-20ROX) to create a self-quenching complex, which was compared with a conjugate consisting of GmSA and a single rhodamineX (GmSA-1ROX) in ex vivo chemical activation characteristics, intracellular activation, and in vivo molecular imaging for detecting peritoneal micrometastases of SHIN3 ovarian cancer. Results: GmSA-20ROX was five times brighter than GmSA-1ROX when incubated with SHIN3 ovarian cancer cells for 3 h. Submillimeter SHIM ovarian cancer implants in the peritoneal cavity were clearly visualized in vivo with spectral fluorescence imaging due to the high tumor-to-background ratio. The sensitivity and specificity of GmSA-20ROX for implant detection were determined by colocalization of the rhodamineX emission with red fluorescent protein expressed constitutively in the SHIN3 tumor implants. Among 336 lesions, sensitivity and specificity were 99%/99%, respectively, for GmSA-20ROX, whereas the results for GmSA-1ROX were only 24%/100% (n = 388), respectively, for lesions similar to 0.8 mm or greater in diameter. Conclusion: Self-quenched GmSA-20ROX is more efficient than previous D-galactose-targeted fluorescent conjugates. C1 NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC 1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 17 TC 35 Z9 35 U1 0 U2 8 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 NOV 1 PY 2007 VL 13 IS 21 BP 6335 EP 6343 DI 10.1158/1078-0432.CCR-07-1004 PG 9 WC Oncology SC Oncology GA 229BZ UT WOS:000250777600012 PM 17975145 ER PT J AU Seam, N Gonzales, DA Kern, SJ Hortin, GL Hoehn, GT Suffredini, AF AF Seam, Nitin Gonzales, Denise A. Kern, Steven J. Hortin, Glen L. Hoehn, Gerard T. Suffredini, Anthony F. TI Quality control of serum albumin, depletion for proteomic analysis SO CLINICAL CHEMISTRY LA English DT Article ID ENHANCED LASER DESORPTION/IONIZATION; FLIGHT MASS-SPECTROMETRY; PLASMA-PROTEINS; DESORPTION IONIZATION; CANCER; FRACTIONATION; PEPTIDES; SAMPLES; MS; IMMUNOGLOBULINS AB Background: Prefractionation techniques such as serum albumin depletion are useful precursors to proteomic analysis, but they may introduce preanalytical bias if the depletion is not reproducible. We examined the reproducibility of albumin immunodepletion and describe a method of QC for this process.' Methods: Depletion of albumin from pooled serum, performed using IgY immunoaffinity spin columns, was assessed for 21 runs on each of 4 columns. We measured albumin concentrations, after albumin depletion, by use of an immunoturbidimetric assay on the Beckman LX 20 analyzer and assessed mass spectra of albumin-depleted samples by use of SELDI-TOF mass spectrometry. Results: There was substantial run-to-run variation in efficiency of albumin depletion, with systematic decline in efficiency after multiple uses of the columns. Mean depletion efficiency was >95% for 15 of the 1st 17 runs and <90% for runs 18 to 21. We evaluated the 10 highest-intensity peaks present in all spectra from runs 1, 8, 17, and 21 and assessed the effect of albumin depletion on SELDI-TOF mass spectrometry reproducibility. Comparing the %CV of relative intensities for low and high m/z measurements revealed a significant difference of run 21 compared with runs 1, 8, and 17 (P <0.0001). Six-fold more peaks were found in albumin-depleted than unfractionated serum at both high and low m/z. Conclusions: Sporadic and systematic variation in efficiency of albumin depletion by spin columns may contribute significant preanalytical bias to proteomic approaches of biomarker discovery. This variation requires ongoing QC of the albumin depletion process by quantification of albumin concentration to assess depletion efficiency. (C) 2007 American Association for Clinical Chemistry. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Seam, N (reprint author), NIH, Dept Crit Care Med, Bldg 10,Rm 2C145,10 Ctr Dr, Bethesda, MD 20892 USA. EM nseam@cc.nih.gov FU Intramural NIH HHS NR 33 TC 33 Z9 37 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2007 VL 53 IS 11 BP 1915 EP 1920 DI 10.1373/clinchem.2007.091736 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 225TT UT WOS:000250541300007 PM 17890439 ER PT J AU Parekh, RS Kao, WHL Meoni, LA Ipp, E Kimmel, PL La Page, J Fondran, C Knowler, WC Klag, MJ AF Parekh, Rulan S. Kao, W. H. Linda Meoni, Lucy A. Ipp, Eli Kimmel, Paul L. La Page, Janine Fondran, Carol Knowler, William C. Klag, Michael J. CA Family Invest Nephropathy Diabet Res Grp TI Reliability of urinary albumin, total protein, and creatinine assays after prolonged storage: The family investigation of nephropathy and diabetes SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FROZEN STORAGE; MICROALBUMINURIA; STABILITY; RADIOIMMUNOASSAY; TEMPERATURE; EXCRETION; MELLITUS; DISEASE; SAMPLES; TIME AB Background and objectives: This study investigated the effect of long-term storage at -70 degrees C on urinary albumin, protein, and creatinine measurements in the Family Investigation of Nephropathy and Diabetes, a multicenter study designed to identify genes for diabetic nephropathy. Design, setting, participants, & measurements: Spot urine samples were collected at eight centers and shipped overnight on ice packs to a central laboratory. Samples were aliquotted and frozen at -70 degrees C for a median of 8 d before initial assay. As part of quality control procedures to determine interassay variability, 351 replicate samples were retrieved from storage at -70 degrees C after a median storage time between original and quality control analyses of 126 d (range 28 to 869 d). Freezer time was characterized as the difference in days between the initial assay and quality control assay. Percentage difference [(quality control - original/original) X 100%] between samples was regressed on storage time and adjusted for original value, age, race, gender, hypertension, and diabetes. Results: After adjustment, freezer time per 30 d was associated with small decreases in percentage difference of urinary albumin (0.25%, P = 0.02), total protein (0.23%. P = 0.02). and albumin-to-creatinine ratio (0.34%, P = 0.001). Urinary creatinine levels were not affected by freezer time (P = 0.25). Conclusions: Measurements of urinary albumin, total protein, and albumin-to-creatinine ratio are minimally affected by storage at -70 degrees C for approximately 2.5 yr. Prolonged storage results in small decreases of urinary albumin and protein that do not substantially affect phenotype classification of overt renal disease. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA. NIDDK, NIH, Bethesda, MD USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA. RP Parekh, RS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Welch Ctr Prevent Epidemiol & Clin Res, 2024 Monument St,Suite 2-511, Baltimore, MD 21205 USA. EM rsparekh@jhmi.edu RI Nelson, Robert/B-1470-2012; Briggs, Josephine/B-9394-2009; OI Briggs, Josephine/0000-0003-0798-1190; Jun, Gyungah/0000-0002-3230-8697; Rasooly, Rebekah/0000-0002-6357-5528 FU Intramural NIH HHS; NCRR NIH HHS [M01RR00425]; NIDDK NIH HHS [1U01-DK-57304-01, 5 K24 DK02856, DK027872, DK02856] NR 21 TC 11 Z9 12 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1156 EP 1162 DI 10.2215/CJN.01030207 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400013 PM 17928473 ER PT J AU Chandrakantan, A McDermott, DH Tran, HTB Jurewicz, M Gallon, L Gaston, R Milford, E Abdi, R AF Chandrakantan, Arun McDermott, David H. Tran, Huong Thi Bich Jurewicz, Mollie Gallon, Lorenzo Gaston, Robert Milford, Edgar Abdi, Reza TI Role of beta 3 integrin in acute renal allograft rejection in humans SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VITRONECTIN RECEPTOR ALPHA-V-BETA-3; GLYCOPROTEIN IIIA; PL(A2) POLYMORPHISM; BETA(3) INTEGRIN; TISSUE FACTOR; RISK-FACTOR; MONOCYTES AB Background and objectives: 133 Integrin may play a role in the process of acute rejection by increasing leukocyte adhesion to the endothelium, cytotoxic T lymphocyte activation, and platelet aggregation. Design, setting, participants, & measurements: For investigation of the role of 133 integrin in the pathogenesis of acute rejection, this study examined the surface expression of 133 integrin on leukocyte subsets and analyzed a common single-nucleotide polymorphism in exon 2 of the gene encoding the beta 3 subunit that generates two beta 3 integrin isoforms, termed Pl(A1) and pl(A2). p1(A) genotype was determined in blood samples from 445 renal allograft recipients at two centers. Patients were then grouped by PIA genotype, and clinical outcomes as recorded in a preexisting database were analyzed. Results: Although almost all monocytes express 133 integrin, its expression was also found on all leukocyte subsets, including T, B, and NK cells. The percentage of patients who experienced acute rejection was noted to be significantly higher in those with pl(A1)/Pl(A1) (TT) genotype versus patients with the pl(A1)/pl(A2) or pl(A2)/pl(A2) (CT or CC) genotypes (33% for TT versus 20% for CT or CC). In a multivariate analysis, the pl(A1)/pl(A1) (TT) genotype remained significantly associated with acute rejection. Patients with pl(A1)/pl(A1) (TT) genotype also exhibited a higher number of acute rejection episodes per patient. Conclusions: The pl(A1)/pl(A1) (TT) genotype is associated with an increased incidence of acute renal allograft rejection in humans, supporting a role for beta 3 integrin in the pathophysiology of acute rejection. C1 Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. Univ Alabama, Div Nephrol, Birmingham, AL USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Div Nephrol & Transplantat, Chicago, IL 60611 USA. RP Abdi, R (reprint author), Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu OI McDermott, David/0000-0001-6978-0867 FU Intramural NIH HHS NR 19 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1268 EP 1273 DI 10.2215/CJN.01380307 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400030 PM 17928472 ER PT J AU Narva, A AF Narva, Andrew TI Screening is part of kidney disease education SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Narva, A (reprint author), 6707 Democracy Blvd,MSC 5458, Bethesda, MD 20892 USA. EM narvaa@niddk.nih.gov NR 6 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1352 EP 1354 DI 10.2215/CJN.02620707 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400038 PM 17928467 ER PT J AU Klingenberg, C Ronnestad, A Anderson, AS Abrahamsen, TG Zorman, J Villaruz, A Flaegstad, T Otto, M Sollid, JE AF Klingenberg, C. Ronnestad, A. Anderson, A. S. Abrahamsen, T. G. Zorman, J. Villaruz, A. Flaegstad, T. Otto, M. Sollid, J. Ericson TI Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article; Proceedings Paper CT Annual Meeting of the European-Society-of-Paediatric-Infectious-Disease CY MAY, 2006 CL Basel, SWITZERLAND SP European Soc Paediat Infect Dis DE coagulase-negative staphylococci; endemic clones; invasive capacity; neonates; typing; virulence factors ID FIELD GEL-ELECTROPHORESIS; EPIDERMIDIS BIOFILM FORMATION; PHENOL-SOLUBLE MODULINS; QUORUM-SENSING CONTROL; BIRTH-WEIGHT INFANTS; METHICILLIN-RESISTANT; MOLECULAR EPIDEMIOLOGY; BINDING-PROTEIN; MEDICAL DEVICES; ICA OPERON AB Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial bacteraemia in neonates. The aim of this study was to investigate whether persistent strains of CoNS possess specific bacterial characteristics as compared with sporadic non-cluster isolates. In total, 180 blood culture isolates (95 contaminants and 85 invasive isolates) obtained from a single neonatal unit over a 12-year period were studied. Pulsed-field gel electrophoresis (PFGE) identified 87 persistent CoNS strains (endemic clones). The two largest PFGE clusters belonged to a single clonal complex according to multilocus sequence typing. Patients colonised or infected with endemic clones were of lower gestational age than those infected with non-cluster strains. One Staphylococcus haemolyticus cluster appeared to selectively colonise and infect the most extreme pre-term infants. Endemic clones were characterised by high levels of antibiotic resistance and biofilm formation. All 51 isolates belonging to the two largest PFGE clusters were ica operon-positive. Genes encoding Staphylococcus epidermidis surface protein B and the production of phenol-soluble modulins (PSMs) were also more prevalent among endemic clones than among non-cluster strains. However, endemic clones were not more prevalent among invasive isolates than among contaminants. These findings indicate that multiple selective factors, including antibiotic resistance, biofilm formation, surface proteins with adhesive properties, and PSMs regulated by agr, increase the ability of CoNS to persist in a hospital environment. It may be more prudent, when searching for new therapeutic targets, to focus on ubiquitous components of CoNS instead of putative virulence factors that do not clearly contribute to increased invasive capacity. C1 Univ Hosp N Norway, Dept Paediat, N-9038 Tromso, Norway. Univ Tromso, Inst Clin Med, Dept Paediat, Tromso, Norway. Radiumhosp Med Ctr, Rikshosp, Dept Paediat, Oslo, Norway. Univ Oslo, Oslo, Norway. Merck & Co Inc, Vaccine & Biol Res, West Point, PA USA. NIAID, Natl Inst Hlth, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. Univ Tromso, Inst Med Biol, Dept Microbiol & Virol, Tromso, Norway. RP Klingenberg, C (reprint author), Univ Hosp N Norway, Dept Paediat, N-9038 Tromso, Norway. EM claus.klingenberg@unn.no RI Rohlf, F/A-8710-2008; OI Otto, Michael/0000-0002-2222-4115 NR 59 TC 55 Z9 59 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD NOV PY 2007 VL 13 IS 11 BP 1100 EP 1111 DI 10.1111/j.1469-0691.2007.01818.x PG 12 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 217NE UT WOS:000249953800011 PM 17850346 ER PT J AU Cantilena, LR Cherstniakova, SA Saviolakis, G Kahn, R Elkashef, A Rose, L Vocci, F AF Cantilena, Louis R. Cherstniakova, Svetlana A. Saviolakis, George Kahn, Roberta Elkashef, Ahmed Rose, Lauren Vocci, Frank TI Prevalence of abnormal liver-associated enzymes in cocaine experienced adults versus healthy volunteers during Phase 1 clinical trials SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE liver-associated enzymes; cocaine; Phase 1; inpatient trials ID NUTRITIONAL-STATUS; DRUG; TRANSAMINASE; METABOLISM; ELEVATION; TOXICITY; PLACEBO; TESTS; DIET AB The frequency and nature of elevation of liver-associated enzymes (LAE) are important safety endpoints in Phase 1 clinical trials of new anti-cocaine agents, yet very little information is available on the prevalence of abnormal LAE in cocaine experienced adults. The aim of this retrospective study was to investigate the alterations of liver-associated enzymes (LAE) aspartate- (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin in healthy "normal" (HN) and cocaine experienced (actively using cocaine preadmission (CE)) adults participating in long term inpatient clinical trials. We examined LAE values collected from 3 inpatient Phase I trials of anti-cocaine agents. Analysis of variance (ANOVA) was applied to determine the significance of various factors on LAE alterations. Gender, baseline BMI, treatment did not demonstrate significant group differences in LAE levels. CE study volunteers were found to have significantly higher AST and ALT values than HN volunteers (P < 0.05) during their respective inpatient stays. 94.1% of the 17 subjects with abnormal LAE were CE, and 37.5% of these CE received placebo. In conclusion, despite normal baseline values, most subjects demonstrated an increase in the ALT level even on placebo. For CE subjects, differences (Delta ALT and Delta AST) between baseline and the maximum observed values were significantly higher than that observed for HN subjects. The potential to obscure important signals for hepatotoxicity during Phase I research may be higher in the CE study population. (c) 2007 Published by Elsevier Inc. C1 Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Toxicol, Bethesda, MD 20814 USA. Natl Inst Drug Abuse, Bethesda, MD USA. RP Cantilena, LR (reprint author), Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol & Toxicol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM lcantilena@usuhs.mil NR 17 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2007 VL 28 IS 6 BP 695 EP 704 DI 10.1016/j.cct.2007.03.005 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 227OE UT WOS:000250666000003 PM 17544338 ER PT J AU Della Sala, S Grafman, J AF Della Sala, Sergio Grafman, Jordan TI Cortex impact factor 2006 SO CORTEX LA English DT Editorial Material C1 Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Della Sala, S (reprint author), Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland. NR 3 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD NOV PY 2007 VL 43 IS 8 BP 1031 EP 1031 PG 1 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 228MG UT WOS:000250733400001 ER PT J AU Huey, ED Zahn, R Grafman, J AF Huey, Edward D. Zahn, Roland Grafman, Jordan TI "[H]e is no more a person now but a whole climate of opinion" (Auden, 1940) SO CORTEX LA English DT Editorial Material C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zahn, Roland/C-4665-2008; OI Zahn, Roland/0000-0002-8447-1453; Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS [Z01 NS002792-19] NR 6 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD NOV PY 2007 VL 43 IS 8 BP 1097 EP 1098 DI 10.1016/S0010-9452(08)70710-X PG 2 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 228MG UT WOS:000250733400012 PM 18044672 ER PT J AU Noguchi, CT Asavaritikrai, P Teng, R Jia, Y AF Noguchi, Constance Tom Asavaritikrai, Pundit Teng, Ruifeng Jia, Yi TI Role of erythropoietin in the brain SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Article DE erythropoietin; receptor; neuroprotection; blood-brain barrier; ischemic preconditioning; brain ischemia; Neurogenesis; endothelium ID NITRIC-OXIDE SYNTHASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; MICE OVEREXPRESSING ERYTHROPOIETIN; ENDOTHELIAL PROGENITOR CELLS; PERMANENT CEREBRAL-ISCHEMIA; NEONATAL HYPOXIA-ISCHEMIA; RECEPTOR MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; IN-VIVO AB Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPOR exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. Intrinsic EPO production in brain and EPO stimulation of endothelial cells contribute to neuroprotection and these are of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NIDDK, NIH, Mol Med Branch, Mol Cell Biol Sect,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIDDK, NIH, Mol Med Branch, Mol Cell Biol Sect,Dept Hlth & Human Serv, Bldg 10,Room 9N307,10 Ctr Dr MSC 1822, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov FU Intramural NIH HHS [Z01 DK025061-32, Z99 DK999999] NR 119 TC 105 Z9 120 U1 0 U2 5 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 NOV PY 2007 VL 64 IS 2 BP 159 EP 171 DI 10.1016/j.critrevonc.2007.03.001 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 226ST UT WOS:000250609500007 PM 17482474 ER PT J AU Montalvo, V Chan, CC Gery, I Campos, MM Wawrousek, EF Bush, RA Lambris, JD AF Montalvo, Vanessa Chan, Chi-Chao Gery, Igal Campos, Maria M. Wawrousek, Eric F. Bush, Ronald A. Lambris, John D. TI Complement deposits on ocular tissues adjacent to sites of inflammation SO CURRENT EYE RESEARCH LA English DT Article DE complement; cornea; experimental autoimmune uveitis; inflammation; lens capsule; light damage; transgenic mice ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; RETINAL DEGENERATION; UVEITIS; GENES AB Purpose: The complement system plays important roles in a variety of chronic ocular diseases such as age-related macular degeneration. Here we examined the deposition of complement components in mouse eyes damaged by various mechanisms. Methods: Mouse eyes were damaged by light or by three models of inflammation, i.e., local transgenic expression of cytokines, interleukin-1 or -7, or by induction of experimental autoimmune uveitis. Eye tissues obtained from each model were immunostained with antibodies against complement components C1q, C3, and C4. Results: No complement deposition was seen in light damaged eyes, while in inflamed eyes we found complement deposition at sites of tissue damage and cellular infiltration. In addition to affected tissues, intense immunoreactivity against complement was unexpectedly observed in corneal tissues and lens capsule, despite lack of inflammation in these tissues. Conclusion: Our observations suggest that ocular tissues adjacent to inflammatory sites undergo changes that facilitate complement deposition. C1 NIH, NEI, Immunol Lab, Bethesda, MD 20892 USA. NIH, NEI, Biol Imaging Core, Bethesda, MD 20892 USA. NIH, NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NIH, Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retina & Macular Degenerat, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Gery, I (reprint author), NIH, NEI, Immunol Lab, Bldg 10,Room 10N208,Ctr Dr, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov RI Wawrousek, Eric/A-4547-2008; OI Lambris, John/0000-0002-9370-5776 FU Intramural NIH HHS NR 19 TC 8 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD NOV PY 2007 VL 32 IS 11 BP 917 EP 922 DI 10.1080/02713680701656343 PG 6 WC Ophthalmology SC Ophthalmology GA 239GJ UT WOS:000251506500001 PM 18027167 ER PT J AU Boirivant, M Strober, W AF Boirivant, Monica Strober, Warren TI The mechanism of action of probiotics SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE anti-inflammatory cytokines; epithelial barrier function; infection of the gastrointestinal tract; inflammatory bowel disease; probiotics; regulatory T cells ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; CHRONIC PSYCHOLOGICAL STRESS; GENE-DEFICIENT MICE; TOLL-LIKE RECEPTORS; COLI NISSLE 1917; CD4(+) T-CELLS; NF-KAPPA-B; CROHNS-DISEASE; LACTOBACILLUS-CASEI AB Purpose of review Probiotics are a heterogeneous group of nonpathologic bacteria that are functionally defined by their ability to allay inflammation when introduced into the inflamed intestine. The purpose of this review is to discuss recent data bearing on the possible mechanisms of action of these bacteria, with a particular focus on the relation of these mechanisms to the pathogenesis of inflammatory bowel disease, their main arena of use. Recent findings Studies of probiotic activity in recent years provide evidence that probiotics counter experimental and human gastrointestinal inflammation (human inflammatory bowel disease) by their effects on epithelial cell function, including epithelial cell barrier function, epithelial cytokine secretion, and their antibacterial effects relating to colonization of the epithelial layer. In addition, there is emerging evidence that probiotics induce regulatory T cells that act as a break on the effector T cells that would otherwise cause inflammation. Summary This review of probiotics and inflammatory bowel disease marshals support for the concept that administration of probiotics ameliorates inflammation by exerting positive effects on the epithelial cell dysfunction and mucosal immune system dysfunction that forms the basis of the inflammation. C1 NIH, NIAID, Bethesda, MD 20892 USA. Italian Natl Inst Hlth, Dept Infect Parasit & Immune Mediated Dis, Rome, Italy. RP Strober, W (reprint author), NIH, NIAID, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov RI BOIRIVANT, MONICA/B-9977-2016 NR 90 TC 146 Z9 158 U1 1 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2007 VL 23 IS 6 BP 679 EP 692 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223IR UT WOS:000250364000015 PM 17906447 ER PT J AU Stroncek, DF AF Stroncek, David F. TI Neutrophil-specific antigen HNA-2a, NB1 glycoprotein, and CD177 SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE CD177; HNA-2a; NB1; neutrophil antigens; PRV-1 ID CHRONIC MYELOPROLIFERATIVE DISORDERS; MESSENGER-RNA EXPRESSION; ACUTE LUNG INJURY; POLYCYTHEMIA RUBRA VERA; TYROSINE KINASE JAK2; ESSENTIAL THROMBOCYTHEMIA; PRV-1 EXPRESSION; PROTEIN EXPRESSION; MOLECULAR-BASIS; V617F MUTATION AB Purpose of review Several advances have been made in characterization of the molecule that carries human neutrophil antigen (HNA)-2a NB1 glycoprotein, the gene that encodes NB1 glycoprotein, CD 177, and the role of antibodies to HNA-2a in transfusion reactions. Recent findings NB1 glycoprotein binds to the endothelial cell adhesion molecule, platelet endothelial cell adhesion molecule-1 (PECAM-1), and participates in neutrophil transmigration. The overexpression of neutrophil CD177 mRNA has become a useful, but nonspecific biomarker of myeloproliferative diseases, especially polycythemia vera. CD177 mRNA overexpression is also a biomarker of a subset of patients with essential thrombocythemia who are at increased risk of thromboembolic complications. In patients with myeloproliferative disorders CD177 mRNA overexpression is secondary to a gain-of-function mutation in JAK2, JAK2 V617F. NB1 glycoprotein is co-localized on neutrophil plasma membranes with proteinase 3 and a complex of NB1 glycoprotein and proteinase 3 may initiate the activation of neutrophils by antineutrophil cytoplasmic antibodies in patients with Wegener's granulomatosis. The inadvertent transfusion of antibodies to HNA-2a with blood components frequently causes pulmonary transfusion reactions. Summary The expression of CD177 is an important biomarker of myeloproliferative diseases, NB1 glycoprotein is a ligand for PECAM-1 and it may have a role in Wegener's granulomatosis, and antibodies to HNA-2a frequently cause pulmonary transfusion reactions. C1 Natl Inst Hlth, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), Natl Inst Hlth, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr MSC 1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 48 TC 27 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2007 VL 14 IS 6 BP 688 EP 693 DI 10.1097/MOH.0b013e3282efed9e PG 6 WC Hematology SC Hematology GA 220OC UT WOS:000250165000014 PM 17898576 ER PT J AU Mielke, S AF Mielke, Stephan TI Individualized phamacotherapy with paclitaxel SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE CYP450; organic anion transporting polypeptide; P-glycoprotein; paclitaxel; pharmacogenetic; pharmacokinetic ID BODY-SURFACE AREA; PERIPHERAL NEUROPATHY; PHASE-I; NONLINEAR PHARMACOKINETICS; ADVANCED CANCER; OVARIAN-CANCER; CREMOPHOR-FREE; SOLID TUMORS; ASSOCIATION; METABOLISM AB Purpose of review More than two decades of clinical experience with paclitaxel as an anticancer drug have contributed significantly to the optimization of today's application schemes and patients' safety. Recent knowledge about interindividual pharmacokinetic variability and population modeling provides a novel scientific basis for an improved and individualized therapeutic approach. Recent findings Age, gender and bilirubin levels were shown to be associated with an altered pharmacokinetic profile. Prolonged exposure to paclitaxel concentrations exceeding the thresholds of 0.05 or 0.1 mu mol/l were predictive for neutropenia, peripheral neuropathy and survival. Due to substantial interindividual diversity observed in paclitaxel pharmacokinetics actual research focuses on common single nucleotide polymorphisms in genes encoding metabolizing enzymes and drug transporters such as CYP450, P-glycoprotein and the organic anion transporting polypeptide OATP1 B3. Polymorphisms of ABCB1 encoding P-glycoprotein were found to be associated with neutropenia and neurotoxicity. A haplotype of CYP3A4 was associated with paclitaxel pharmacokinetics. Summary Several demographic, pharmacokinetic and genetic covariables that have been identified to influence toxicity and tumor responses following chemotherapy with paclitaxel are discussed with regard to their transferability into a bedside approach. C1 Univ Med Ctr, Dept Hematol & Oncol, Freiburg, Germany. RP Mielke, S (reprint author), NHLBI, NIH, DIR, Stem Cell Allogene Transplant Sect,Hematol Branch, Bldg 10,CRC Room 3-5288,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhibi.nih.gov NR 31 TC 17 Z9 21 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2007 VL 19 IS 6 BP 586 EP 589 PG 4 WC Oncology SC Oncology GA 223IJ UT WOS:000250363200007 PM 17906456 ER PT J AU Khawaja, Z Abbasi, F Raveche, E Arthur, D Marti, G AF Khawaja, Zoya Abbasi, Fatima Raveche, Elizabeth Arthur, Diane Marti, Gerald TI The identification of three clonal B-cell populations in a single CLL patient SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Clinical-Cytometry-Society CY OCT 07-09, 2007 CL Washington, DC SP Clin Cytometry Soc C1 US FDA, Ctr Biol Res & Evaluat, Bethesda, MD 20014 USA. NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 BP 486 EP 487 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000021 ER PT J AU Louzao, R Wong, J Denny, T AF Louzao, Raul Wong, John Denny, Thomas TI Evaluation to extended stability (age of blood, age of stain) of the BD-tritest CD3/CD4/CD45 reagents SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Clinical-Cytometry-Society CY OCT 07-09, 2007 CL Washington, DC SP Clin Cytometry Soc C1 Duke Univ, NIAID DAIDS Immunol Qual Assessment Program, Durham, NC 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 BP 487 EP 487 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000024 ER PT J AU Rizzo, K Yuan, C Stetler-Stevenson, M AF Rizzo, Kathryn Yuan, Constance Stetler-Stevenson, Maryalice TI A flow cytometry case of a peripheral T-CELL lymphoma expressing CD19 SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Clinical-Cytometry-Society CY OCT 07-09, 2007 CL Washington, DC SP Clin Cytometry Soc C1 Natl Canc Inst, NIH, Pathol Lab, 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 MA 22 BP 490 EP 490 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000030 ER PT J AU Yagi, R Kohn, MJ Karavanova, I Kaneko, KJ Vullhorst, D DePamphilis, ML Buonanno, A AF Yagi, Rieko Kohn, Matthew J. Karavanova, Irina Kaneko, Kotaro J. Vullhorst, Detlef DePamphilis, Melvin L. Buonanno, Andres TI Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development SO DEVELOPMENT LA English DT Article DE Cdx2; Oct4; Eomes; embryonic stem cell; trophoblast stem cell; morula; blastocyst ID ENHANCER FACTOR-I; STEM-CELL DIFFERENTIATION; GENE-EXPRESSION; PREIMPLANTATION DEVELOPMENT; MOUSE EMBRYOS; E-CADHERIN; FAMILY; DOMAIN; CDX2; SPECIFICATION AB Specification of cell lineages in mammals begins shortly after fertilization with formation of a blastocyst consisting of trophectoderm, which contributes exclusively to the placenta, and inner cell mass ( ICM), from which the embryo develops. Here we report that ablation of the mouse Tead4 gene results in a preimplantation lethal phenotype, and TEAD4 is one of two highly homologous TEAD transcription factors that are expressed during zygotic gene activation in mouse 2- cell embryos. Tead4 (-/-) embryos do not express trophectoderm- specific genes, such as Cdx2, but do express ICM- specific genes, such as Oct4 ( also known as Pou5f1). Consequently, Tead4(-/-) morulae do not produce trophoblast stem cells, trophectoderm or blastocoel cavities, and therefore do not implant into the uterine endometrium. However, Tead4(-/-) embryos can produce embryonic stem cells, a derivative of ICM, and if the Tead4 allele is not disrupted until after implantation, then Tead4(-/-) embryos complete development. Thus, Tead4 is the earliest gene shown to be uniquely required for specification of the trophectoderm lineage. C1 NIH, NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NIH, NICHHD, Mol Neurobiol Sect, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NIH, NICHHD, Lab Mol Growth Regulat, 6 Ctr Dr, Bethesda, MD 20892 USA. EM buonanno@mail.nih.gov FU Intramural NIH HHS NR 40 TC 216 Z9 220 U1 3 U2 19 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 1 PY 2007 VL 134 IS 21 BP 3827 EP 3836 DI 10.1242/dev.010223 PG 10 WC Developmental Biology SC Developmental Biology GA 219PU UT WOS:000250097900007 PM 17913785 ER PT J AU Bembenek, JN Richie, CT Squirrell, JM Campbell, JM Eliceiri, KW Poteryaev, D Spang, A Golden, A White, JG AF Bembenek, Joshua N. Richie, Christopher T. Squirrell, Jayne M. Campbell, Jay M. Eliceiri, Kevin W. Poteryaev, Dmitry Spang, Anne Golden, Andy White, John G. TI Cortical granule exocytosis in C-elegans is regulated by cell cycle components including separase SO DEVELOPMENT LA English DT Article DE anaphase promoting complex; cortical granule exocytosis; egg activation; separase; spindle assembly checkpoint; C. elegans; meiosis ID CAENORHABDITIS-ELEGANS; CHROMOSOME SEGREGATION; MEMBRANE-FUSION; MEIOSIS-I; ANAPHASE; EMBRYO; OOCYTE; MATURATION; SPINDLE; CYTOKINESIS AB In many organisms, cortical granules undergo exocytosis following fertilization, releasing cargo proteins that modify the extracellular covering of the zygote. We identified cortical granules in Caenorhabditis elegans and have found that degranulation occurs in a wave that initiates in the vicinity of the meiotic spindle during anaphase I. Previous studies identified genes that confer an embryonic osmotic sensitivity phenotype, thought to result from abnormal eggshell formation. Many of these genes are components of the cell cycle machinery. When we suppressed expression of several of these genes by RNAi, we observed that cortical granule trafficking was disrupted and the eggshell did not form properly. We conclude that osmotic sensitivity phenotypes occur because of defects in trafficking of cortical granules and the subsequent formation of an impermeable eggshell. We identified separase as a key cell cycle component that is required for degranulation. Separase localized to cortically located filamentous structures in prometaphase I upon oocyte maturation. After fertilization, separase disappeared from these structures and appeared on cortical granules by anaphase I. RNAi of sep- 1 inhibited degranulation in addition to causing extensive chromosomal segregation failures. Although the temperature- sensitive sep- 1( e2406) allele exhibited similar inhibition of degranulation, it had minimal effects on chromosome segregation. These observations lead us to speculate that SEP- 1 has two separable yet coordinated functions: to regulate cortical granule exocytosis and to mediate chromosome separation. C1 Univ Wisconsin, Mol Biol Lab, Madison, WI 53706 USA. NIH, NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. Univ Basel, Biozent, CH-4056 Basel, Switzerland. RP Bembenek, JN (reprint author), Univ Wisconsin, Mol Biol Lab, 1525 Linden Dr, Madison, WI 53706 USA. EM jbembenek@wisc.edu RI Spang, Anne/A-7029-2008; OI Spang, Anne/0000-0002-2387-6203; Eliceiri, Kevin/0000-0001-8678-670X; Bembenek, Joshua/0000-0002-0966-2268 FU Intramural NIH HHS; NIGMS NIH HHS [5F32 GM076867-02, F32 GM076867, R01 GM7583]; NIMH NIH HHS [5R44MH065724, R43 MH065724] NR 60 TC 56 Z9 73 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 1 PY 2007 VL 134 IS 21 BP 3837 EP 3848 DI 10.1242/dev.011361 PG 12 WC Developmental Biology SC Developmental Biology GA 219PU UT WOS:000250097900008 PM 17913784 ER PT J AU Bok, J Brunet, LJ Howard, O Burton, Q Wu, DK AF Bok, Jinwoong Brunet, Lisa J. Howard, Omar Burton, Quianna Wu, Doris K. TI Role of hindbrain in inner ear morphogenesis: Analysis of Noggin knockout mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE noggin; BMP; inner ear; rhombomere; hindbrain; chondrogenesis ID GENE-ENCODING NOGGIN; PROXIMAL SYMPHALANGISM; SPEMANN ORGANIZER; STAPES ANKYLOSIS; XENOPUS EMBRYOS; MUTATIONS; CHICKEN; EXPRESSION; INDUCTION; SOMITE AB Signaling from rhombomeres 5 and 6 of the hindbrain is thought to be important for inner ear patterning. In Noggin -/- embryos, the gross anatomy of the inner ear is distorted and malformed, with cochlear duct outgrowth and coiling most affected. We attributed these defects to a caudal shift of the rhombomeres caused by the shortened body axis and the kink in the neural tube. To test the hypothesis that a caudal shift of the rhombomeres affects inner ear development, we surgically generated chicken embryos in which rhombomeres 5 and 6 were similarly shifted relative to the position of the inner ears, as in Noggin mutants. All chicken embryos with shifted rhombomeres showed defects in cochlear duct formation indicating that signaling from rhombomeres 5 and 6 is important for cochlear duct patterning in both chicken and mice. In addition, the size of the otic capsule is increased in Noggin -/- mutants, which most likely is due to unopposed BMP signaling for chondrogenesis in the peri-otic mesenchyme. Published by Elsevier Inc. C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Ct,Rm 2B34, Rockville, MD 20850 USA. EM wud@nided.nih.gov RI Bok, Jinwoong/B-8982-2016 OI Bok, Jinwoong/0000-0003-1958-1872 FU Intramural NIH HHS [Z01 DC000021-14]; NIGMS NIH HHS [GM 49346, R01 GM049346] NR 31 TC 13 Z9 13 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 2007 VL 311 IS 1 BP 69 EP 78 DI 10.1016/j.ydbio.2007.08.013 PG 10 WC Developmental Biology SC Developmental Biology GA 228CC UT WOS:000250703700006 PM 17900554 ER PT J AU Jia, QS McDill, BW Li, SZ Deng, CX Chang, CP Chen, F AF Jia, Qunshan McDill, Bradley W. Li, Song-Zhe Deng, Chuxia Chang, Ching-Pin Chen, Feng TI Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Smad; neural crest; outflow tract; secondary heart field; congenital heart diseases ID BONE MORPHOGENETIC PROTEIN; EPITHELIAL-MESENCHYMAL TRANSITION; SECONDARY HEART FIELD; ARTERIAL POLE; KNOCKOUT MICE; SMOOTH-MUSCLE; MOUSE HEART; MYOCARDIUM; BETA; DIFFERENTIATION AB Neural crest cells (NCCs) are indispensable for the development of the cardiac outflow tract (OFT). Here, we show that mice lacking Smad4 in NCCs have persistent truncus arteriosus (PTA), severe OFT cushion hypoplasia, defective OFT elongation, and mispositioning of the OFT. Cardiac NCCs lacking Smad4 have increased apoptosis, apparently due to decreased Msx1/2 expression. This contributes to the reduction of NCCs in the OFT. Unexpectedly, mutants have MF20-expressing cardiomyocytes in the splanchnic mesoderm within the second heart field (SHE). This may result from abnormal differentiation or defective recruitment of differentiating SHE cells into OFT. Alterations in Bmp4, Sema3C, and PlexinA2 signals in the mutant OFT, SHE, and NCCs, disrupt the communications among different cell populations. Such disruptions can further affect the recruitment of NCCs into the OFT mesenchyme, causing severe OFT cushion hypoplasia and OFT septation failure. Furthermore, these NCCs have drastically reduced levels of Ids and MT1-MMP, affecting the positioning and remodeling of the OFT. Thus, Smad-signaling in cardiac NCCs has cell autonomous effects on their survival and non-cell autonomous effects on coordinating the movement of multiple cell lineages in the positioning and the remodeling of the OFT. (C) 2007 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, Dept Internal Med,Renal Div, St Louis, MO 63110 USA. NIDDK, NIH, Mammalian Genet Sect, Bethesda, MD USA. Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Chen, F (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, Dept Internal Med,Renal Div, Campus Box 8126, St Louis, MO 63110 USA. EM fchen@im.wustl.edu RI deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [R01 HL085345]; NIDDK NIH HHS [R01 DK067386, R01 DK067386-03, R01DK067386] NR 58 TC 43 Z9 44 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 2007 VL 311 IS 1 BP 172 EP 184 DI 10.1016/j.ydbio.2007.08.044 PG 13 WC Developmental Biology SC Developmental Biology GA 228CC UT WOS:000250703700014 PM 17916348 ER PT J AU Tiong, J Locastro, T Wray, S AF Tiong, Jean Locastro, Thomas Wray, Susan TI Gonadotropin-releasing hormone-1 (GnRH-1) is involved in tooth maturation and biomineralization SO DEVELOPMENTAL DYNAMICS LA English DT Article DE GnRH-1; GnRH-1 receptor; tooth development and biomineralization; GnRH-1-deficient mice ID CENTRAL PRECOCIOUS PUBERTY; INCISOR ENAMEL ORGAN; BONE-MINERAL DENSITY; NEURON-SPECIFIC ENHANCER; RAT INCISOR; PAPILLARY LAYER; FINAL HEIGHT; EXPRESSION; MOUSE; CELLS AB Gonadotropin releasing-hormone-1 (GnRH-1) is expressed in mouse incisors during development. In this report, we identify (1) cell type(s) that express GnRH-1 throughout tooth development, (2) the GnRH-1 receptor, and (3) the role of GnRH-1/GnRH-1 receptor signaling in tooth maturation. Results show that GnRH-1-positive cells in dental epithelium differentiate and populate multiple tooth structures including ameloblast and papillary layers that are involved in enamel formation and mineralization. The GnRH-1 receptor was present, and in vitro a GnRH-1 antagonist attenuated incisor GnRH-1 cell expression. In vivo, in mice lacking GnRH-1 (-/-), the incisors were discolored, longer, and more curved compared to wildtype. Elemental analysis of calcium, phosphorus, and iron revealed changes in -/- incisors consistent with GnRH-1 affecting movement of minerals into the dental matrix. In sum, in tooth development a signal transduction pathway exists for GnRH-1 via the GnRH-1 receptor and disruption of such signaling affects incisor growth and biomineralization. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 35,Room 3A-1012,MSC 3703, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS NR 46 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2007 VL 236 IS 11 BP 2980 EP 2992 DI 10.1002/dvdy.21332 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 233XK UT WOS:000251123400002 PM 17948256 ER PT J AU Biris, KK Dunty, WC Yamaguchi, TP AF Biris, Kristin K. Dunty, William C., Jr. Yamaguchi, Terry P. TI Mouse Ripply2 is downstream of Wnt3a and is dynamically expressed during somitogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE segmentation; Ripply2; mouse; mesoderm; Wnt3a ID LOOP-HELIX PROTEIN; PRESOMITIC MESODERM; SOMITE SEGMENTATION; LUNATIC-FRINGE; GENE; MESP2; NOTCH; HES7; TRANSCRIPTION; PARAXIS AB Somites are blocks of mesoderm that form when segment boundaries are periodically generated in the anterior presomitic mesoderm (PSM). Periodicity is thought to be driven by an oscillating Notch-centered segmentation clock, whereas boundaries are spatially positioned by the secreted signaling molecules Wnt3a and Fgf8. We identified the putative transcriptional corepressor Ripply2 as a differentially expressed gene in wild-type and Wnt3a(-/-) embryos. Here, we show that Ripply2 is expressed in the anterior PSM and that it indeed lies downstream of Wnt3a. Dynamic Ripply2 expression in prospective somites S0 and S-I overlaps with the rostral expression of cycling genes in the Notch pathway, suggesting that Ripply2 may be controlled by the segmentation clock. Continued expression of Ripply2 in embryos lacking Hes7, a molecular oscillator in the Notch clock, indicates that Hes7 is not a major regulator of Ripply2. Our data are consistent with Ripply2 functioning as a segment boundary determination gene during mammalian embryogenesis. C1 NCI, Canc & Dev Biol Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. EM tyamaguchi@ncifcrf.gov FU Intramural NIH HHS NR 30 TC 20 Z9 21 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2007 VL 236 IS 11 BP 3167 EP 3172 DI 10.1002/dvdy.21342 PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 233XK UT WOS:000251123400018 PM 17937396 ER PT J AU Lau, JYF Rijsdijknal, F Gregory, AM McGuffin, P Eley, TC AF Lau, Jennifer Y. F. Rijsdijknal, Fruehling Gregory, Alice M. McGuffin, Peter Eley, Thalia C. TI Pathways to childhood depressive symptoms: The role of social, cognitive, and genetic risk factors SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE depressive symptoms; attributional style; genetic risk; social risk; multifactorial model ID COMPREHENSIVE DEVELOPMENTAL MODEL; MAJOR DEPRESSION; ADOLESCENT DEPRESSION; ANTISOCIAL-BEHAVIOR; MATERNAL DEPRESSION; HOPELESSNESS THEORY; FAMILY ENVIRONMENT; GENDER-DIFFERENCES; DIATHESIS-STRESS; MENTAL-HEALTH AB Childhood depressive conditions have been explored from multiple theoretical approaches but with few empirical attempts to address the interrelationships among these different domains and their combined effects. In the present study, the authors examined different pathways through which social, cognitive, and genetic risk factors may be expressed to influence depressive symptoms in 300 pairs of child twins from a longitudinal study. Path analysis supported several indirect routes. First, risks associated with living in a step- or single-parent family and punitive parenting did not directly influence depressive outcome but were instead mediated through maternal depressive symptoms and child negative attributional style. Second, the effects of negative attributional style on depressive outcome were greatly exacerbated in the presence of precipitating negative life events. Third, independent of these social and cognitive risk mechanisms, modest genetic effects were also implicated in symptoms, with some indication that these risks are expressed through exposure to negative stressors. Together, these routes accounted for approximately 13% of total phenotypic variance in depressive symptoms. Theoretical and analytical implications of these results are discussed in the context of several design-related caveats. C1 NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. Univ London, Univ London Goldsmiths Coll, Dept Psychol, London, England. RP Lau, JYF (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM lauj@mail.nih.gov RI Eley, Thalia/D-4811-2011; McGuffin, Peter/A-1565-2012 OI McGuffin, Peter/0000-0002-9888-2907 FU Medical Research Council [G0500079, G120/635] NR 53 TC 17 Z9 19 U1 2 U2 10 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 2007 VL 43 IS 6 BP 1402 EP 1414 DI 10.1037/0012-1649.43.6.1402 PG 13 WC Psychology, Developmental SC Psychology GA 230GF UT WOS:000250863500010 PM 18020820 ER PT J AU Bertoni, AG Wong, ND Shea, S Ma, S Liu, K Preethi, S Jacobs, DR Wu, C Saad, MF Szklo, M AF Bertoni, Alain G. Wong, Nathan D. Shea, Steven Ma, Shuangge Liu, Kiang Preethi, Srikanthan Jacobs, David R. Wu, Colin Saad, Mohammed F. Szklo, Moyses TI Insulin resistance, metabolic syndrome, and subclinical atherosclerosis: the multi-ethnic study of atherosclerosis (MESA) SO DIABETES CARE LA English DT Article ID EARLY CAROTID ATHEROSCLEROSIS; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; ASSOCIATION; ARTERIES; ADULTS; RISK; MEN; SENSITIVITY; PREVALENCE AB OBJECTIVE - To investigate the association of insulin resistance and clinically defined metabolic syndrome (MetS) with subclinical atherosclerosis and examine whether these relationships vary by race/ethnicity or sex. RESEARCH DESIGN AND METHODS - Subclinical atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-medial thickness (IMT) in 5,810 participants without diabetes in the Multi-Ethnic Study of Atherosclerosis, a cohort of adults aged 45-84 years without prior cardiovascular disease (CVD). Fasting insulin and glucose were utilized to estimate insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR) index, and the revised National Cholesterol Education Program definition of MetS was utilized. Multivariable linear or relative risk regression was used to analyze the association between HOMA-IR and subclinical atherosclerosis and assess its independence from MetS components. RESULTS- HOMA-IR was associated with increased IMT after adjustment for demographics (age, site, and education), smoking, education, and LDL cholesterol in each ethnic group, except Hispanic subjects, and in both men and women. After further adjusting for nonglucose MetS components, HOMA-IR was not associated with increased IMT. Subjects in the highest quintile of HOMA-IR had an elevated prevalence of CAC in each ethnic group and both sexes, after adjustment for demographics, smoking, and LDL but not after further adjustment for nonglucose MetS components. Among those with detectable CAC, there was no significant relationship between HOMA-IR and the amount of CAC. CONCLUSIONS - Although HOMA-IR was associated with increased subclinical atherosclerosis, the association was not independent of the risk factors that comprise MetS. Determi- C1 Wake Forest Univ, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. Univ Calif Irvine, Div Cardiol, Irvine, CA USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. Northwestern Univ, Dept Prevent Med, Evanston, IL USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Epidemiol & Preventat Med, Los Angeles, CA USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. SUNY Stony Brook, Grad Program Publ Hlth, Stony Brook, NY USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Bertoni, AG (reprint author), Med Ctr Blvd, Winston Salem, NC 27157 USA. EM abertoni@wfubmc.edu FU NHLBI NIH HHS [N01-HC-95163, N01-HC-95161, N01-HC-95165, N01-HC-95169, N01-HC-95160, N01-HC-95159, N01-HC-95162, N01-HC-95164] NR 26 TC 59 Z9 61 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2007 VL 30 IS 11 BP 2951 EP 2956 DI 10.2337/dc07-1042 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228CI UT WOS:000250704300037 PM 17704348 ER PT J AU Gautam, D Han, SJ Duttaroy, A Mears, D Hamdan, FF Li, JH Cui, Y Jeon, J Wess, J AF Gautam, D. Han, S.-J. Duttaroy, A. Mears, D. Hamdan, F. F. Li, J. H. Cui, Y. Jeon, J. Wess, J. TI Role of the M-3 muscarinic acetylcholine receptor in beta-cell function and glucose homeostasis SO DIABETES OBESITY & METABOLISM LA English DT Article; Proceedings Paper CT 8th Servier-IGIS Symposium on Animal Models of Islet Dysfunction CY MAR 08-11, 2007 CL St Jean Cap Ferrat, FRANCE DE beta-cell function; acetylcholine; conditional knockout mice; Cre/lox technology; glucose homeostasis; glucose tolerance; insulin release; islets; muscarinic acetylcholine receptors; transgenic mice; type 2 diabetes ID INSULIN-INDUCED HYPOGLYCEMIA; KNOCKOUT MICE; PANCREATIC-ISLETS; CONSCIOUS RATS; PROTEIN; LOCALIZATION; MECHANISMS; SECRETION; SUBTYPES; RELEASE AB The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose-stimulated insulin secretion from pancreatic beta-cells. Studies with isolated islets prepared from whole body M-3 muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M-3 muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M-3 receptors only in pancreatic beta-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M-3 receptors in pancreatic beta-cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet-induced glucose intolerance and hyperglycaemia. These findings indicate that beta-cell M-3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through beta-cell M-3 muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes. C1 NIDDKD, Mol Signalling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD USA. RP Wess, J (reprint author), NIDDKD, Mol Signalling Sect, Bioorgan Chem Lab, Bldg 8A,Room B1A-05,8 Ctr Dr MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Li, Jianhua/B-7671-2011; Han, Sung-Jun/B-9547-2012 OI Li, Jianhua/0000-0002-5744-3182; FU Intramural NIH HHS NR 43 TC 40 Z9 40 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2007 VL 9 SU 2 BP 158 EP 169 DI 10.1111/j.1463-1326.2007.00781.x PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218IZ UT WOS:000250010500019 PM 17919190 ER PT J AU Hollingshead, HE Morimura, K Adachi, M Kennett, MJ Billin, AN Willson, TM Gonzalez, FJ Peters, JM AF Hollingshead, Holly E. Morimura, Keiichirou Adachi, Masahiro Kennett, Mary J. Billin, Andrew N. Willson, Timothy M. Gonzalez, Frank J. Peters, Jeffrey M. TI PPAR beta/delta protects against experimental colitis through a ligand-independent mechanism SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE peroxisome proliferator-activated receptor (PPAR)beta/delta; colitis; inflammatory bowel disease ID ACTIVATED-RECEPTOR-GAMMA; INFLAMMATORY-BOWEL-DISEASE; TRANSCRIPTIONAL REPRESSION; ISCHEMIA-REPERFUSION; PEROXISOME; ALPHA; DELTA; EXPRESSION; INHIBIT; CELLS AB Peroxisome proliferator-activated receptors (PPARs) beta/delta and gamma have overlapping roles in the negative regulation of inflammatory response genes. Ligand activation of PPAR gamma protects against experimental colitis in mice. PPAR beta/delta can negatively regulate inflammation and is highly expressed in the epithelial cells of the colon, therefore PPAR beta/delta may also have a role in experimental colitis. In these studies, colitis was induced by dextran sodium sulfate (DSS) treatment in wild-type and PPAR beta/delta-null mice, with and without the PPAR beta/delta specific ligand GW0742. PPAR beta/delta-null mice exhibited increased sensitivity to DSS-induced colitis, as shown by marked differences in body weight loss, colon length, colonic morphology, myeloperoxidase activity and increased expression of mRNAs encoding the inflammatory markers interferon gamma, tumor necrosis factor-alpha, and interleukin-6 compared to similarly treated wild-type mice. Interestingly, these differences were not affected by ligand activation of PPAR beta/delta in either genotype. These studies demonstrate that PPAR beta/delta expression in the colonic epithelium inhibits inflammation and protects against DSS-induced colitis through a ligand-independent mechanism. C1 Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA89607, CA97999] NR 46 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2007 VL 52 IS 11 BP 2912 EP 2919 DI 10.1007/s10620-006-9644-9 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216ZJ UT WOS:000249917400003 PM 17404849 ER PT J AU Mourra, N Zeitoun, G Buecher, B Finetti, P Lagarde, A Adelaide, J Birnbaum, D Thomas, G Olschwang, S AF Mourra, Najat Zeitoun, Guy Buecher, Bruno Finetti, Pascal Lagarde, Arnaud Adelaide, Jose Birnbaum, Daniel Thomas, Gilles Olschwang, Sylviane TI High frequency of chromosome 14 deletion in early-onset colon cancer SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/108th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2007 CL Washington, DC SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract DE colon cancer; allelic loss; cancer predisposition; chromosome 14; early onset ID NONPOLYPOSIS COLORECTAL-CANCER; CARCINOMA; HETEROZYGOSITY; FEATURES; POPULATION; ALLELOTYPE; FAMILIES; 14Q; AGE AB Purpose: Several genes have been recognized, when mutated in the germline, to highly predispose to colorectal cancer, impairing the DNA mismatch repair system in hereditary nonpolyposis colon cancer syndrome, or APC/MYH in adenomatous polyposis. However, 10 percent of microsatellite stable colorectal cancer is reported to develop in an unexplained context of genetic predisposition. This study was designed to depict the genetic mechanisms underlying early-onset microsatellite stable colon cancers. Methods: Patients younger than aged 50 years undergoing primary surgical resection for colon carcinoma were collected prospectively between 1993 and 2003. A first series of 8 samples has been allelotyped using 361 poly-CA polymorphisms distributed on the 39 autosomal arms within a larger set of 166 sporadic tumors. Genotyping of 24 poly-CA polymorphisms distributed on the 8 chromosomes exhibiting allelic losses in more than 30 percent of the previous cases was then applied to an independent series of 40 tumors. A third series of 70 tumors has been genotyped on chromosome 14 only. Results: Comparison of genomic profile from patients younger and older than aged 50 years at the 8 most frequently lost chromosomes allowed, identify chromosome 14 as showing a significant difference between the two groups. Dense chromosome 14 genotyping detected two partial deletions in a general background of 57 percent allelic loss, pointing at a region located between D14S63 and D14S292. Conclusions: These observations suggest that a tumor-suppressor gene located on chromosome 14 might have an important role in microsatellite stable colon carcinogenesis. Because it seems to be more frequently involved in early-onset cases, it could be a good candidate in inherited conditions. C1 Inst J Paoli I Calmettes, INSERM, UMR599, F-13009 Marseille, France. Hop St Antoine, Dept Pathol, F-75571 Paris, France. Gen Hosp, Dept Surg, Mantes La Jolie, France. Hop Hotel Dieu, Dept Gastroenterol, Nantes, France. NCI, NIH, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. RP Olschwang, S (reprint author), Inst J Paoli I Calmettes, INSERM, UMR599, 232 Blvd Sainte Marguerite, F-13009 Marseille, France. EM olschwangs@marseille.fnclcc.fr RI Olschwang, Sylviane/G-2716-2013; lagarde, arnaud/M-3364-2016 OI lagarde, arnaud/0000-0003-1619-3452 NR 21 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD NOV PY 2007 VL 50 IS 11 BP 1881 EP 1886 DI 10.1007/s10350-007-9040-3 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 229EJ UT WOS:000250785500018 PM 17726634 ER PT J AU Gorodetsky, E Calkins, S Ahn, J Brooks, PJ AF Gorodetsky, Elena Calkins, Sarah Ahn, Julia Brooks, P. J. TI ATM, the Mre11/Rad50/Nbs1 complex, and topoisomerase I are concentrated in the nucleus of Purkinje neurons in the juvenile human brain SO DNA REPAIR LA English DT Article DE double-strand breaks; ataxia telangiectasia; cerebellum; TDP1; Bergmann glia; golgi neuron ID DOUBLE-STRAND BREAKS; MEDIATED DNA-DAMAGE; ATAXIA-TELANGIECTASIA GENE; NERVOUS-SYSTEM; CEREBELLAR NEURONS; CELLS; ACTIVATION; INTERNEURONS; EXPRESSION; INHIBITORS AB The genetic disease ataxia telangiectasia (AT) results from mutations in the ataxia telangiectasia mutated (ATM) gene. AT patients develop a progressive degeneration of cerebellar Purkinje neurons. Surprisingly, while ATM plays a criticial role in the cellular reponse to DNA damage, previous studies have localized ATM to the cytoplasm of rodent and human Purkinje neurons. Here we show that ATM is primarily localized to the nucleus in cerebellar Purkinje neurons in postmortem human brain tissue samples, although some light cytoplasmic ATM staining was also observed. No ATM staining was observed in brain tissue samples from AT patients, verifying the specificity of the antibody We also found that antibodies against components of the Mre11/Rad50/Nbs1 (MRN) complex showed strong staining in Purkinje cell nuclei. However, while ATM is present in both the nucleoplasm and nucleolus, MRN proteins are excluded from the nucleolus. We also observed very high levels of topoisomerase 1 (TOP1) in the nucleus, and specifically the nucleolus, of human Purkinje neurons. Our results have direct implications for understanding the mechanisms of neurodegeneration in AT and AT-like disorder. Published by Elsevier B.V. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Bethesda, MD 20952 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Lane,Room 3S-32,MSC 9412, Bethesda, MD 20952 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-14]; NICHD NIH HHS [N01-HD-4-3383, N01-HD-4-3368] NR 39 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 1 PY 2007 VL 6 IS 11 BP 1698 EP 1707 DI 10.1016/j.dnarep.2007.06.011 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 236EH UT WOS:000251285300014 PM 17706468 ER PT J AU Wang, MZ Wu, JQ Bridges, AS Zeldin, DC Kornbluth, S Tidwell, RR Hall, JE Paine, MF AF Wang, Michael Zhuo Wu, Judy Qiju Bridges, Arlene S. Zeldin, Darryl C. Kornbluth, Sally Tidwell, Richard R. Hall, James Edwin Paine, Mary F. TI Human enteric microsomal CYP4F enzymes o-demethylate the antiparasitic prodrug pafuramidine SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ARACHIDONIC-ACID; HUMAN LIVER; IN-VITRO; INHIBITION; METABOLISM; RAT; CYP2J2; 2,5-BIS(4-AMIDINOPHENYL)FURAN-BIS-O-METHYLAMIDOXIME; INVOLVEMENT; ACTIVATION AB CYP4F enzymes, including CYP4F2 and CYP4F3B, were recently shown to be the major enzymes catalyzing the initial oxidative O-demethylation of the antiparasitic prodrug pafuramidine (DB289) by human liver microsomes. As suggested by a low oral bioavailability, DB289 could undergo first-pass biotransformation in the intestine, as well as in the liver. Using human intestinal microsomes (HIM), we characterized the enteric enzymes that catalyze the initial O-demethylation of DB289 to the intermediate metabolite, M1. M1 formation in HIM was catalyzed by cytochrome P450 (P450) enzymes, as evidenced by potent inhibition by 1-aminobenzotriazole and the requirement for NADPH. Apparent K-m and V-max values ranged from 0.6 to 2.4 mu M and from 0.02 to 0.89 nmol/ min/mg protein, respectively (n = 9). Of the P450 chemical inhibitors evaluated, ketoconazole was the most potent, inhibiting M1 formation by 66%. Two inhibitors of P450-mediated arachidonic acid metabolism, HET0016 (N-hydroxy-N-'-(4-n-butyl-2-methylphenyl) formamidine) and 17-octadecynoic acid, inhibited M1 formation in a concentration-dependent manner (up to 95%). Immunoinhibition with an antibody raised against CYP4F2 showed concentration-dependent inhibition of M1 formation (up to 92%), whereas antibodies against CYP3A4/5 and CYP2J2 had negligible to modest effects. M1 formation rates correlated strongly with arachidonic acid omega-hydroxylation rates (r(2) = 0.94, P < 0.0001, n = 12) in a panel of HIM that lacked detectable CYP4A11 protein expression. Quantitative Western blot analysis revealed appreciable CYP4F expression in these HIM, with a mean (range) of 7 (3-18) pmol/mg protein. We conclude that enteric CYP4F enzymes could play a role in the first-pass biotransformation of DB289 and other xenobiotics. C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. Natl Inst Environm Hlth Sci, Lab Resp Biol, Div Intramural Res, NIH, Res Triangle Pk, NC USA. RP Paine, MF (reprint author), Univ N Carolina, Sch Pharm, 311 Pharm Lane,CB 7360, Chapel Hill, NC 27599 USA. EM mpaine@med.unc.edu RI BRIDGES, ARLENE/N-4534-2013 FU Intramural NIH HHS [Z01 ES025034-13] NR 31 TC 32 Z9 34 U1 1 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2007 VL 35 IS 11 BP 2067 EP 2075 DI 10.1124/dmd.107.016428 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222FV UT WOS:000250282400013 PM 17709372 ER PT J AU Compton, C AF Compton, C. TI Cancer biobanking: The American perspective SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Compton, C.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 5 EP 6 DI 10.1016/S1359-6349(08)70008-9 PG 2 WC Oncology SC Oncology GA 242DX UT WOS:000251705800004 ER PT J AU Khleif, S AF Khleif, S. TI Tumor biomarkers, the need for a new way to conduct business. Perspective from the USFDA SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Khleif, S.] US FDA, Natl Canc Inst, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 11 EP 11 DI 10.1016/S1359-6349(08)70021-1 PG 1 WC Oncology SC Oncology GA 242DX UT WOS:000251705800017 ER PT J AU Khan, J AF Khan, J. TI Diagnostic classification of pediatric cancers using microRNA profiles SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Khan, J.] NIH, Natl Canc Inst, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 12 EP 13 DI 10.1016/S1359-6349(08)70024-7 PG 2 WC Oncology SC Oncology GA 242DX UT WOS:000251705800020 ER PT J AU Jessup, J Jacobson, J Lively, T Lubensky, I Segal, D Taube, S AF Jessup, J. Jacobson, J. Lively, T. Lubensky, I. Segal, D. Taube, S. TI Molecular diagnostics evaluation laboratories (MoDEL), a program to optimize assays for clinically useful cancer biomarkers SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Jessup, J.; Jacobson, J.; Lively, T.; Lubensky, I.; Segal, D.; Taube, S.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 26 EP 26 DI 10.1016/S1359-6349(08)70063-6 PG 1 WC Oncology SC Oncology GA 242DX UT WOS:000251705800059 ER PT J AU Roberts, M Coward, L Noker, P Jia, L AF Roberts, M. Coward, L. Noker, P. Jia, L. TI In vitro bioavailability testing of GGTI-2418 using the Caco-2 model SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Roberts, M.; Coward, L.; Noker, P.] So Res Inst, Birmingham, AL 35205 USA. [Jia, L.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 32 EP 32 DI 10.1016/S1359-6349(08)70085-5 PG 1 WC Oncology SC Oncology GA 242DX UT WOS:000251705800081 ER PT J AU Martinez, ED Botos, J Dohoney, KM Geiman, TM Kolla, SS Olivera, A Qiu, Y Rayasam, GV Stavreva, DA Cohen-Fix, O AF Martinez, Elisabeth D. Botos, Jeannine Dohoney, Kathleen M. Geiman, Theresa M. Kolla, Sarah S. Olivera, Ana Qiu, Yi Rayasam, Geetha Vani Stavreva, Diana A. Cohen-Fix, Orna TI Falling off the academic bandwagon - Women are more likely to quit at the postdoc to principal investigator transition SO EMBO REPORTS LA English DT Editorial Material ID FAMILY C1 NIH, Bethesda, MD 20892 USA. RP Martinez, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM elisabeth.martinez@utsouthwestern.edu; ornacf@helix.nih.gov NR 20 TC 46 Z9 46 U1 6 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2007 VL 8 IS 11 BP 977 EP 981 DI 10.1038/sj.embor.7401110 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WL UT WOS:000250619100004 PM 17972894 ER PT J AU Yoon, HK Cho, HY Kleeberger, SR AF Yoon, Hyoung-Kyu Cho, Hye-Youn Kleeberger, Steven R. TI Protective role of matrix metalloproteinase-9 in ozone-induced airway inflammation SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chemokine; knockout mice; lung; MMP-9; O-3; oxidant ID OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; GELATINASE-B MMP-9; ACUTE LUNG INJURY; MATRIX METALLOPROTEINASES; ALVEOLAR MACROPHAGES; TISSUE INHIBITORS; NEUTROPHIL RECRUITMENT; CELL EGRESSION; MICE AB BACKGROUND: Exposure to ozone causes airway inflammation, hyperreactivity, lung hyperpermeability, and epithelial cell injury. An early inflammatory response induced by inhaled O-3 is characterized primarily by release of inflammatory mediators such as cytokines, chemokines, and airway neutrophil accumulation. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of oxidative lung disorders including acute lung injury, asthma, and chronic obstructive pulmonary disease. OBJECTIVE: We hypothesized that MMPs have an important role in the pathogenesis Of O-3-induced airway inflammation. METHODS: We compared the lung injury responses in either Mmp7- (Mmp7(-/-)) or Mmp9-deficient (Mmp9(-/-)) mice and their wild-type controls (Mmp7(+/+), Mmp9(+/+)) after exposure to 0.3 ppm O-3 or filtered air. RESULTS: Relative to air-exposed controls, MMP-9 activity in bronchoalveolar lavage fluid (BALF) was significantly increased by O-3 exposure in Mmp9(+/+) mice. O-3-induced increases in the concentration of total protein (a marker of lung permeability) and the numbers of neutrophils and epithelial cells in BALF were significantly greater in Mmp9(-/-) mice compared with Mmp9(+/+) mice. Keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 levels in BALF were also significantly higher in Mmp9(-/-) mice than in Mmp9(+/+) mice after O-3 exposure, although no differences in mRNA expression for these chemokines were found between genotypes. Mean BALF protein concentration and numbers of inflammatory cells were not significantly different between Mmp7(+/+) and Mmp7(-/-) mice after O-3 exposure. CONCLUSIONS: Results demonstrated a protective role of MMP-9 but not of MMP-7, in O-3-induced lung neutrophilic inflammation and hyperpermeability. The mechanism through which Mmp9 limits O-3-induced airway injury is not known but may be via posttranscriptional effects on proinflammatory CXC chemokines including KC and MIP-2. C1 NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Catholic Univ Korea, Coll Med, Dept Internal Med, Div Pulm & Crit Care, Seoul, South Korea. RP Kleeberger, SR (reprint author), NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov FU Intramural NIH HHS NR 57 TC 29 Z9 33 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2007 VL 115 IS 11 BP 1557 EP 1563 DI 10.1289/ehp.10289 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 228YY UT WOS:000250769700019 PM 18007984 ER PT J AU Michaud, DS Kogevinas, M Cantor, KP Villanueva, CM Garcia-Closas, M Rothman, N Malats, N Real, FX Serra, C Garcia-Closas, R Tardon, A Carrato, A Dosemeci, M Silverman, DT AF Michaud, Dominique S. Kogevinas, Manolis Cantor, Kenneth P. Villanueva, Cristina M. Garcia-Closas, Monteserrat Rothman, Nathaniel Malats, Nuria Real, Francisco X. Serra, Consol Garcia-Closas, Reina Tardon, Adonina Carrato, Alfredo Dosemeci, Mustafa Silverman, Debra T. TI Total fluid and water consumption and the joint effect of exposure to disinfection by-products on risk of bladder cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bladder cancer; case-control study; chlorination by-products; fluid intake; water intake ID DRINKING-WATER; POPULATION; SMOKING; MEN AB BACKGROUND: Findings on,water and total fluid intake and bladder cancer are inconsistent; this may, in part, be due to different levels of carcinogens in drinking water. High levels of arsenic and chlorinated by-products in drinking water have been associated with elevated bladder cancer risk in most studies. A pooled analysis based on six case-control studies observed a positive association between tap water and bladder cancer but none for nontap, fluid intake, suggesting that contaminants in tap water may be responsible for the excess risk. OBJECTIVES: We examined the association between total fluid and water consumption and bladder cancer risk, as well as the interaction between water intake and trihalomethane (THM) exposure, in a large case-control study in Spain. METHODS: A total of 397 bladder cancer cases and 664 matched controls were available for this analysis. Odds ratios (OR) were estimated using unconditional logistic regression, controlling for potential confounders. RESULTS: Total fluid intake was associated with a decrease in bladder cancer risk [OR = 0,62; 95% confidence interval (CI), 0.40-0.95 for highest vs. lowest quintile comparison]. A significant inverse association was observed for water intake (for > 1,399 vs. < 400 mL/day, OR = 0.47; 95% CI, 0.33-0.66; p for trend < 0.0001), but not for other individual beverages. The inverse association between water intake and bladder cancer persisted within each level of THM exposure; we found no statistical interaction (p for interaction = 0.13). CONCLUSION: Findings from this study suggest that water intake is inversely associated with bladder cancer risk, regardless of THM exposure level. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Municipal Inst Med Res, Ctr Res Environm Epidemiol, Barcelona, Spain. Univ Crete, Sch Med, Iraklion, Greece. Univ Pompeu Fabra, Barcelona, Spain. Consorci Hosp Parc Tauli, Sabadell, Spain. Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain. Univ Oviedo, Oviedo, Spain. Hosp Gen Univ Elche, Elche, Spain. RP Michaud, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Kresge 920,677 Huntington Ave, Boston, MA 02115 USA. EM dmichaud@hsph.harvard.edu RI Serra, C/E-6879-2014; Michaud, Dominique/I-5231-2014; Garcia-Closas, Montserrat /F-3871-2015; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015; OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; Villanueva, Cristina/0000-0002-0783-1259; Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784 NR 19 TC 32 Z9 32 U1 0 U2 12 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2007 VL 115 IS 11 BP 1569 EP 1572 DI 10.1289/ehp.10281 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 228YY UT WOS:000250769700021 PM 18007986 ER PT J AU Korach, KS AF Korach, Kenneth S. TI New deputy editors and medical editor SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, EHP, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, EHP, NIH, Mail Drop EC-15,POB 12233, Res Triangle Pk, NC 27709 USA. EM EHPeditor@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2007 VL 115 IS 11 BP A530 EP A530 DI 10.1289/ehp.10984 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 228YY UT WOS:000250769700002 ER PT J AU Curwin, BD Hein, MJ Sanderson, WT Striley, C Heederik, D Kronihout, H Reynolds, SJ Alavanja, MC AF Curwin, Brian D. Hein, Misty J. Sanderson, Wayne T. Striley, Cynthia Heederik, Dick Kronihout, Hans Reynolds, Stephen J. Alavanja, Michael C. TI Pesticide dose estimates for children of Iowa farmers and non-farmers SO ENVIRONMENTAL RESEARCH LA English DT Article DE pesticides; exposure; children; dose; biological monitoring; urine; herbicides; insecticides ID CENTRAL WASHINGTON-STATE; AGRICULTURAL COMMUNITY; CREATININE CLEARANCE; EXPOSURE; URINARY; CHLORPYRIFOS; PHARMACOKINETICS; WORKERS; HEALTH; CANCER AB Farm children have the potential to be exposed to pesticides. Biological monitoring is often employed to assess this exposure; however, the significance of the exposure is uncertain unless doses are estimated. In the spring and summer of 2001, 118 children (66 farm, 52 nonfarm) of Iowa farm and non-farm households were recruited to participate in a study investigating potential take-home pesticide exposure. Each child provided an evening and morning urine sample at two visits spaced approximately I month apart, with the first sample collection taken within a few days after pesticide application. Estimated doses were calculated for atrazine, metolachlor, chlorpyrifos, and glyphosate from urinary metabolite concentrations derived from the spot urine samples and compared to EPA reference doses. For all pesticides except glyphosate, the doses from farm children were higher than doses from the non-farm children. The difference was statistically significant for atrazine (p<0.0001) but only marginally significant for chlorpyrifos and metolachlor (p = 0.07 and 0.1, respectively). Among farm children, geometric mean doses were higher for children on farms where a particular pesticide was applied compared to farms where that pesticide was not applied for all pesticides except glyphosate; results were significant for atrazine (p = 0.030) and metolachlor (p = 0.042), and marginally significant for chlorpyrifos (p = 0.057). The highest estimated doses for atrazine, chlorpyrifos, metolachlor, and glyphosate were 0.085, 1.96, 3.16, and 0.34 mu g/kg/day, respectively. None of the doses exceeded any of the EPA reference values for atrazine, metolachlor, and glyphosate; however, all of the doses for chlorpyrifos exceeded the EPA chronic population adjusted reference value. Doses were similar for male and female children. A trend of decreasing dose with increasing age was observed for chlorpyrifos. (C) 2007 Elsevier Inc. All rights reserved. C1 NIOSH, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. Univ Iowa, Dept Environm & Occupat Hlth, Iowa City, IA USA. Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO USA. Natl Canc Inst, Div Ctr Epidemiol & Genet, Rockville, MD USA. RP Curwin, BD (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studi, 44676 Columbia Pkwy,MS R-14, Cincinnati, OH 45226 USA. EM bcurwin@cdc.gov NR 37 TC 37 Z9 38 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2007 VL 105 IS 3 BP 307 EP 315 DI 10.1016/j.envres.2007.06.001 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 230FD UT WOS:000250860700003 PM 17659274 ER PT J AU Pierik, FH Klebanoff, MA Brock, JW Longnecker, MP AF Pierik, Frank H. Klebanoff, Mark A. Brock, John W. Longnecker, Matthew P. TI Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta-hexachlorocyclohexane and risk of cryptorchidism in offspring SO ENVIRONMENTAL RESEARCH LA English DT Article DE cryptorchidism; organochlorine pesticides; environment; children; endocrine disruptors ID TESTICULAR DYSGENESIS SYNDROME; IN-UTERO EXPOSURE; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; CONGENITAL CRYPTORCHIDISM; BREAST-MILK; HYPOSPADIAS; TESTIS; PREVALENCE; TRENDS AB Prenatal exposure to environmental endocrine disrupters has been postulated to cause adverse effects on male reproductive health. Exposure to organochlorine pesticides with anti-androgenic and estrogenic potency has been shown to interfere with the sex-hormone-dependent process of testicular descent in animal models. We examined the relation between serum levels of the pesticides heptachlor epoxide (HCE), hexachlorobenzene (HCB), and beta-hexachlorocyclohexane (beta-HCCH) in pregnant women, and the occurrence of cryptorchidism in their sons. These three pesticides were previously suggested as risk factors for cryptorchidism. In a nested case-control design, we compared serum levels between mothers of cases (n = 219) and controls (n =: 564), selected from the Collaborative Perinatal Project, a US birth cohort study of pregnancies in 1959-1966. The offspring of mothers with HCE levels above the 90th percentile compared to those below the 10th percentile had an adjusted odds ratio of cryptorchidisin of 1.2 (95% confidence interval 0.6-2.6); for beta-HCCH the odds ratio was 1.6 (0.7-3.6). For HC13 the adjusted odds ratio was near one. These results provide little support for an association of cryptorchidism with exposure to low levels of HCE or HCB. For beta-HCCH the findings were somewhat suggestive of an association but were inconclusive. Published by Elsevier Inc. C1 TNO Qual Life, Dept Reprod & Perinatol, Leiden, Netherlands. Erasmus MC, Univ Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Atlanta, GA USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Pierik, FH (reprint author), TNO Environm & Hlth, Van Mourik Broekmanweg 6,POB 49, NL-2600 AA Delft, Netherlands. EM frank.pierik@tno.nl OI Longnecker, Matthew/0000-0001-6073-5322 FU Intramural NIH HHS [Z01 ES049016-12] NR 45 TC 24 Z9 26 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2007 VL 105 IS 3 BP 364 EP 369 DI 10.1016/j.envres.2007.04.005 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 230FD UT WOS:000250860700009 PM 17532317 ER PT J AU Catov, JM Newman, AB Roberts, JM Kelsey, SF Sutton-Tyrrell, K Harris, TB Colbert, L Rubin, SM Satterfield, S Ness, RB AF Catov, Janet M. Newman, Anne B. Roberts, James M. Kelsey, Sheryl F. Sutton-Tyrrell, Kim Harris, Tamara B. Colbert, Lisa Rubin, Susan M. Satterfield, Suzanne Ness, Roberta B. CA Hlth ABC Study TI Preterm Delivery and Later Maternal Cardiovascular Disease Risk SO EPIDEMIOLOGY LA English DT Article ID INFANT BIRTH-WEIGHT; BODY-MASS INDEX; GESTATIONAL-AGE; OLDER-ADULTS; PREGNANCY COMPLICATIONS; GROWTH-RETARDATION; INSULIN-RESISTANCE; REMOTE PROGNOSIS; BLOOD-PRESSURE; HEALTH AB Background: Women who have delivered a preterm infant are at elevated risk for cardiovascular disease (CVD), but mechanisms for this association are not understood. Methods: In a cross-sectional study we investigated whether older women with a history of preterm birth (<37 weeks) had a higher prevalence of CVD. Participants were 446 women (mean age 80 years; 47% black) enrolled in the Pittsburgh, PA field center of The Health, Aging and Body Composition Study. Women reported preterm status, birth weight, smoking status, and selected complications for each pregnancy. CVD status was determined by self-report and hospital records. Analysis was limited to first births not explicitly complicated by hypertension or preeclampsia. Results: Women who had delivered a preterm infant (on average 57 years in the past) had a higher prevalence of CVD. After adjustment for race, age, blood pressure, pulse wave velocity, interleukin-6, high-density lipoprotein cholesterol, and statin use, the odds ratio for CVD among women who delivered a preterm infant was 2.85 (95% confidence interval = 1.19-6.85) compared with women who had delivered term infants weighing more than 2500 g. This relationship was not altered by lifetime smoking history. There was evidence of negative confounding by statin use and high-density lipoprotein cholesterol. Among women delivering infants who were both preterm and low birth weight (< 2500 g), the odds ratio was 3.31 (1.06-10.37) for CVD compared with women with term, normal weight infants. Conclusions: These results suggest that vascular and metabolic factors account for some but not all of the increased prevalence of CVD among women many years after a preterm birth. C1 [Catov, Janet M.; Newman, Anne B.; Roberts, James M.; Kelsey, Sheryl F.; Sutton-Tyrrell, Kim; Ness, Roberta B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Catov, Janet M.; Roberts, James M.; Ness, Roberta B.] Magee Womens Res Inst, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Colbert, Lisa] Univ Wisconsin, Dept Kinesiol, Madison, WI USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Catov, JM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM jmcst43@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106] FX Supported by grants N01-AG-6-2101, N01-AG-6-2103, and N01-AG-62106. NR 46 TC 39 Z9 41 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2007 VL 18 IS 6 BP 733 EP 739 DI 10.1097/EDE.0b013e3181567f96 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 392EO UT WOS:000262285900014 PM 17917602 ER PT J AU Karagas, MR Nelson, HH Zens, MS Linet, M Stukel, TA Spencer, S Applebaum, KM Mott, L Mabuchi, K AF Karagas, Margaret R. Nelson, Heather H. Zens, Michael S. Linet, Martha Stukel, Therese A. Spencer, Steve Applebaum, Katie M. Mott, Leila Mabuchi, Kiyohiko TI Squamous Cell and Basal Cell Carcinoma of the Skin in Relation to Radiation Therapy and Potential Modification of Risk by Sun Exposure SO EPIDEMIOLOGY LA English DT Article ID IONIZING-RADIATION; RADIOLOGIC TECHNOLOGISTS; CANCER; MORTALITY; SURVIVORS; RINGWORM; SCALP; RATES AB Background: Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. Methods: We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993 1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). Results: We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). Conclusions: Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure. C1 [Karagas, Margaret R.; Zens, Michael S.; Mott, Leila] Dartmouth Med Sch, Epidemiol & Biostat Sect, Dept Community & Family Med, Lebanon, NH 03756 USA. [Karagas, Margaret R.; Zens, Michael S.; Mott, Leila] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Nelson, Heather H.; Applebaum, Katie M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Linet, Martha; Stukel, Therese A.; Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Resources, Rockville, MD USA. [Spencer, Steve] Dartmouth Med Sch, Dept Med, Dermatol Sect, Lebanon, NH 03756 USA. RP Karagas, MR (reprint author), Dartmouth Med Sch, Epidemiol & Biostat Sect, Dept Community & Family Med, 7927 Rubin 462M-3,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM margaret.karagas@dartmouth.edu FU National Cancer Institute [CA58290, CA57494, CA23108] FX Supported in part by the National Cancer Institute Grants CA58290, CA57494, and CA23108. NR 32 TC 25 Z9 27 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2007 VL 18 IS 6 BP 776 EP 784 DI 10.1097/EDE.0b013e3181567ebe PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 392EO UT WOS:000262285900020 PM 17917604 ER PT J AU Schilbach, L Koubeissi, MZ David, N Vogeley, K Ritzl, EK AF Schilbach, Leonhard Koubeissi, Moharnad Z. David, Nicole Vogeley, Kai Ritzl, Eva K. TI Being with virtual others: Studying social cognition in temporal lobe epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE virtual characters; facial expressions; social cognition; temporal lobe epilepsy ID HUMAN NEURAL SYSTEM; DOMAIN-SPECIFICITY; SELF-PERSPECTIVE; FACE PERCEPTION; BRAIN-FUNCTION; DEFAULT MODE; COMPETENCE; CHILDREN; SURGERY; MIND AB Social cognitive neuroscience has highlighted the importance of frontotemporal neurocircuitry for social cognition. Temporal lobe epilepsy (TLE) impacts these brain areas and their functional connections and might therefore specifically affect social perceptual and cognitive skills. In the study described here, an established paradigm was used to evaluate the social cognitive skills of female patients with left TLE. Study participants were shown dynamic animations in which virtual characters either looked at the human observer directly or looked away toward someone else, thus manipulating self-involvement. The virtual characters then exhibited different facial expressions that were either socially relevant or arbitrary. Participants were asked to rate the communicative intentions of the virtual character. Patients' ratings of communicative intent appeared to be linked to their own self-involvement in the interaction, whereas healthy volunteers' ratings of facial expressions were independent of self-involvement. Potential mechanisms for the observed differences are discussed. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Cologne, Dept Psychiat, D-50924 Cologne, Germany. Res Ctr Juelich, Inst Neurosci & Biophys, BICW, Julich, Germany. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Schilbach, L (reprint author), Univ Cologne, Dept Psychiat, Kerpener Str 62, D-50924 Cologne, Germany. EM leonhard.schilbach@gmx.de RI Schilbach, Leonhard/G-5832-2010; David, Nicole/H-1682-2012; Vogeley, K/E-4860-2012 OI Schilbach, Leonhard/0000-0001-5547-8309; Vogeley, K/0000-0002-5891-5831 NR 45 TC 9 Z9 9 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2007 VL 11 IS 3 BP 316 EP 323 DI 10.1016/j.yebeh.2007.06.006 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 233CK UT WOS:000251067800011 PM 17881294 ER PT J AU Moraes, MCS Jesus, TCL Hashimoto, NN Dey, M Schwartz, KJ Alves, VS Avila, CC Bangs, JD Dever, TE Schenkman, S Castilho, BA AF Moraes, Maria Carolina S. Jesus, Teresa C. L. Hashimoto, Nilce N. Dey, Madhusudan Schwartz, Kevin J. Alves, Viviane S. Avila, Carla C. Bangs, James D. Dever, Thomas E. Schenkman, Sergio Castilho, Beatriz A. TI Novel membrane-bound eIF2 alpha kinase in the flagellar pocket of Trypanosoma brucei SO EUKARYOTIC CELL LA English DT Article ID PROTEIN-KINASE PKR; ENDOPLASMIC-RETICULUM STRESS; INITIATION FACTOR-2 KINASE; TRANSFER-RNA-BINDING; TRANSLATIONAL CONTROL; AFRICAN TRYPANOSOMES; FUNCTIONALLY SUBSTITUTE; SUBSTRATE RECOGNITION; SURFACE GLYCOPROTEIN; YEAST GCN4 AB Translational control mediated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2 alpha) is central to stress-induced programs of gene expression. Trypanosomatids, important human pathogens, display differentiation processes elicited by contact with the distinct physiological milieu found in their insect vectors and mammalian hosts, likely representing stress situations. Trypanosoma brucei, the agent of African trypanosomiasis, encodes three potential eIF2 alpha kinases (TbeIF2K1 to -K3). We show here that TbeIF2K2 is a transmembrane glycoprotein expressed both in procyclic and in bloodstream forms. The catalytic domain of TbeIF2K2 phosphorylates yeast and mammalian eIF2 alpha at Ser51. It also phosphorylates the highly unusual form of eIF2 alpha found in trypanosomatids specifically at residue Thr169 that corresponds to Ser51 in other eukaryotes. T. brucei eIF2 alpha, however, is not a substrate for GCN2 or PKR in vitro. The putative regulatory domain of TbeIF2K2 does not share any sequence similarity with known eIF2 alpha kinases. In both procyclic and bloodstream forms TbeIF2K2 is mainly localized in the membrane of the flagellar pocket, an organelle that is the exclusive site of exo- and endocytosis in these parasites. It can also be detected in endocytic compartments but not in lysosomes, suggesting that it is recycled between endosomes and the flagellar pocket. TbeIF2K2 location suggests a relevance in sensing protein or nutrient transport in T. brucei, an organism that relies heavily on posttranscriptional regulatory mechanisms to control gene expression in different environmental conditions. This is the first membrane-associated eIF2 alpha kinase described in unicellular eukaryotes. C1 Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo, Brazil. NICHHD, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Microbiol & Immunol, Madison, WI USA. RP Castilho, BA (reprint author), Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Rua Botucatu 862, BR-04023062 Sao Paulo, Brazil. EM bacastilho@unifesp.br RI Castilho, Beatriz/C-2503-2012; Alves, Viviane/C-2776-2013; Schenkman, Sergio/A-9227-2013; OI Castilho, Beatriz/0000-0003-4509-5237; Schenkman, Sergio/0000-0001-9353-8480; Dever, Thomas/0000-0001-7120-9678 FU NIAID NIH HHS [AI056866, AI35739, R01 AI035739, R01 AI056866, R29 AI035739] NR 53 TC 39 Z9 39 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2007 VL 6 IS 11 BP 1979 EP 1991 DI 10.1128/EC.00249-07 PG 13 WC Microbiology; Mycology SC Microbiology; Mycology GA 237XR UT WOS:000251410200005 PM 17873083 ER PT J AU Parikh, NI Gona, P Larson, MG Wang, TJ Newton-Cheh, C Levy, D Benjamin, EJ Kannel, WB Vasan, RS AF Parikh, Nisha I. Gona, Philimon Larson, Martin G. Wang, Thomas J. Newton-Cheh, Christopher Levy, Daniel Benjamin, Emelia J. Kannel, William B. Vasan, Ramachandran S. TI Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Article DE renin; cardiovascular disease; hypertension; all-cause mortality; epidemiology ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL; TISSUE ANGIOTENSIN; BLOOD-PRESSURE; ALDOSTERONE; HYPERTENSION; PATHOGENESIS; EVENTS; ATTACK AB Aims Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). Methods and results On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariabte-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (Cl) 1.00-1.30, P=0.046; hypertensives, 1.16, 95% Cl 1.00-1.35, P=0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% Cl 1.04-1.45; hypertensives at 2 years, 1.28, 95% Cl 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% Cl 0.80-1.29; hypertensives, 0.98, 95% Cl 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% Cl 0.85-1.14; hypertensives, 0.96, 95% Cl 0.82-1.12). Conclusion Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community. C1 Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL04334, K23HL074077, N01-HC-25195, R01HL67288] NR 39 TC 40 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2007 VL 28 IS 21 BP 2644 EP 2652 DI 10.1093/eurheartj/ehm399 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238ZA UT WOS:000251485900018 PM 17895253 ER PT J AU Fiorina, C Vizzardi, E Lorusso, R Maggio, M De Cicco, G Nodari, S Faggiano, P Cas, LD AF Fiorina, Claudia Vizzardi, Enrico Lorusso, Roberto Maggio, Marcello De Cicco, Giuseppe Nodari, Savina Faggiano, Pornpitio Cas, Livio Dei TI The 6-min walking test early after cardiac surgery. Reference values and the effects of rehabilitation programme SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE 6-min walking test; cardiac rehabilitation; cardiac surgery; functional capacity ID CORONARY-ARTERY DISEASE; CONGESTIVE-HEART-FAILURE; CHRONIC LUNG-DISEASE; LOW-FAT DIET; MYOCARDIAL-INFARCTION; PHYSICAL EXERCISE; FUNCTIONAL STATUS; OXYGEN-UPTAKE; EXPERIENCE; TRIALS AB Background: The 6-min walking test (6MWT) is a simple test, which does not require expensive equipment or advanced training. It has been used in heart failure patients to assess exercise tolerance, the effects of therapy and prognosis. Accordingly, post-surgical cardiac rehabilitation may be a potential field of application of this test. Materials and method: One thousand three hundred seventy patients (70% mates, mean age 64 +/- 10 years), consecutively admitted for intensive cardiac rehabilitation, underwent 6MWT within 15 days after different types of cardiac surgery (67% coronary artery bypass graft (CABG), 25% valve replacement, 4% both, 4% other). The 6MWT was repeated in a subgroup of 348 patients after 15 +/- 3 days of an in-hospital cardiac rehabilitation programme. Results: 6MWT (expressed as absolute value in metres and as a percentage of the predicted value) was well tolerated in all patients. The mean distance walked in 1370 patients was 304 +/- 89 m (corresponding to 58 +/- 15% of the predicted value). Distances walked were significantly shorter in older patients than younger (p < 0.05) and in women compared to men (251 +/- 78 m, 53 +/- 15%, vs 328 +/- 34 m, 60 +/- 14%, p < 0.001). Furthermore, the absolute distance walked in 6 min was significantly shorter in diabetics compared to non-diabetics (283 +/- 85 m vs 302 +/- 87 m, p = 0.001) and in no CABG compared to CABG patients (285 +/- 91 m vs 303 +/- 84 m, p < 0.001); no relation was found between distance walked and left ventricular ejection fraction (p = 0.5). Gender, age, comorbidities and type of surgery were independently associated with 6MWT in the multivariate model. In the subgroup of patients repeating the 6MWT after the rehabilitation programme, the distance walked significantly increased (from 281 +/- 90 m, 51 +/- 76%, to 411 +/- 107 m, 77 +/- 81%, p < 0.001). The extent of improvement observed was similar according to sex, age, presence /absence of diabetes and type of surgery. Conclusions: Our data suggest that 6MWT is feasible and well tolerated in adult and older patients shortly after uncomplicated cardiac surgery and provides reference values for distance walked after cardiac surgery in this population. (C) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. C1 Univ Brescia, Div Cardiol, Brescia, Italy. Spedali Civil Brescia, Heart Surg Unit, I-25125 Brescia, Italy. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Faggiano, P (reprint author), Via Trainini 14, I-25133 Brescia, Italy. EM faggiano@numerica.it NR 26 TC 32 Z9 37 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD NOV PY 2007 VL 32 IS 5 BP 724 EP 729 DI 10.1016/j.ejcts.2007.08.013 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 231JA UT WOS:000250941700007 PM 17881241 ER PT J AU Beveridge, NER Price, DA Casazza, JP Pathan, AA Sander, CR Asher, TE Ambrozak, DR Precopio, ML Scheinberg, P Alder, NC Roederer, M Koup, RA Douek, DC Hill, AVS McShane, H AF Beveridge, Natalie E. R. Price, David A. Casazza, Joseph P. Pathan, Ansar A. Sander, Clare R. Asher, Tedi E. Ambrozak, David R. Precopio, Melissa L. Scheinberg, Phillip Alder, Nicola C. Roederer, Mario Koup, Richard A. Douek, Daniel C. Hill, Adrian V. S. McShane, Helen TI Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4(+) memory T lymphocyte populations SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+) T cells; human; recombinant viral vectors; tuberculosis ID VACCINIA VIRUS ANKARA; POLYCHROMATIC FLOW-CYTOMETRY; CELL RESPONSES; INTERFERON-GAMMA; PROTECTIVE EFFICACY; EFFECTOR FUNCTIONS; ANTIGEN 85A; BOVIS BCG; IFN-GAMMA; INFECTION AB In the search for effective vaccines against intracellular pathogens such as HIV, tuberculosis and malaria, recombinant viral vectors are increasingly being used to boost previously primed T cell responses. Published data have shown prime-boost vaccination with BCG-MVA85A (modified vaccinia virus Ankara expressing antigen 85A) to be highly immunogenic in humans as measured by ex vivo IFN-gamma ELISPOT. Here, we used polychromatic flow cytometry to investigate the phenotypic and functional profile of these vaccine-induced Mycobacterium tuberculosis (M.tb) antigen 85A-specific responses in greater detail. Promisingly, antigen 85A-specific CD4(+) T cells were found to be highly polyfunctional, producing IFN-gamma, TNF-alpha, IL-2 and MIP-1 beta. Surface staining showed the responding CD4(+) T cells to be relatively immature (CD45RO(+) CD27(int)CD57(-)); this observation was supported by the robust proliferative responses observed following antigenic stimulation. Furthermore, these phenotypic and functional properties were independent of clonotypic composition and epitope specificity, which was maintained through the different phases of the vaccine-induced immune response. Overall, these data strongly support the use of MVA85A in humans as a boosting agent to expand polyfunctional M.tb-specific CD4(+) T cells capable of significant secondary responses. C1 Univ Oxford, Nuffield Dept Med, Ctr Clin Vaccinol & Trop Med, Oxford, England. NIAID, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. Inst Hlth, Bethesda, MD USA. Univ Oxford, Weatherall Inst Mol Med, Oxford, England. NIAID, Immunol Lab, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIAID, Immuno Technol Sect, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Ctr Stat Med, Oxford, England. RP Beveridge, NER (reprint author), Churchill Hosp, CCVTM, Old Rd, Oxford OX3 7LJ, England. EM natalie.beveridge@ndm.ox.ac.uk RI HILL, Adrian/C-1306-2008; Roederer, Mario/G-1887-2011; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [G0501963]; Wellcome Trust [, 076943] NR 65 TC 166 Z9 169 U1 2 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 IS 11 BP 3089 EP 3100 DI 10.1002/eji.2007375041 PG 12 WC Immunology SC Immunology GA 232HP UT WOS:000251009700010 PM 17948267 ER PT J AU Vinhas, V Andrade, BB Paes, F Bomura, A Clarencio, J Miranda, JC Bafica, A Barral, A Barral-Netto, M AF Vinhas, Vera Andrade, Bruno B. Paes, Fabio Bomura, Andria Clarencio, Jorge Miranda, Jose C. Bafica, Andre Barral, Aldina Barral-Netto, Manoel TI Human anti-saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokines; human; saliva; sand fly ID SAND FLY SALIVA; REGULATORY T-CELLS; DELAYED-TYPE HYPERSENSITIVITY; CYTOKINE PRODUCTION; MOSQUITO BITES; IMMUNOMODULATORY PROPERTIES; CUTANEOUS LEISHMANIASIS; INFECTIVE STAGE; IGG4 ANTIBODIES; GLAND LYSATE AB Experiments in animals verified that phlebotomine saliva enhances Leishmania infection, and vaccination with saliva prevents disease. We have shown that individuals from an endemic area of visceral leishmaniasis displayed robust antibody responses to saliva from the vector Lutzomyia longipalpis, which correlated with anti-parasite cell-mediated immunity. Here, we explored human anti-saliva responses following exposure to sand flies, using an in vivo bite model in which normal volunteers were exposed four times to 30 laboratory-reared Lu. longipalpis. Following the third exposure, normal volunteers developed diverse dermatological reactions at the site of insect bite. Serum from normal volunteers displayed high levels of anti-salivary gland sonicate IgG1, IgG4 and IgE as well as several salivary gland proteins. Furthermore, following in vitro stimulation with salivary gland sonicate, there was an increased frequency of CD4(+)CD25(+) and CD8(+)CD25(+) T cells as well as IFN-gamma and IL-10 synthesis. Strikingly, I year after the first exposure, PBMC from the volunteers displayed recall IFN-gamma responses that correlated with a significant reduction in infection rates using a macrophage-lymphocyte autologous culture. Together, these data suggest that human immunization against sand fly saliva is feasible and recall responses are obtained even 1 year after exposure, opening perspectives for vaccination in man. C1 Univ Fed Bahia, FIOCRUZ, Ctr Pesquisas Goncalo Moniz, BR-40295001 Salvador, BA, Brazil. Univ Fed Bahia, Fac Med Bahia, Salvador, Brazil. NIAID, Parasit Dis Lab, NIH, Immunobiol Sect, Bethesda, MD 20892 USA. Inst Milenio, Inst Invest Imunol, Salvador, Brazil. RP Barral-Netto, M (reprint author), Univ Fed Bahia, FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil. EM mbarral@cpqgm-fiocruz.br RI Barral Netto, Manoel/B-3904-2009; Barral, Aldina/B-4191-2009; Clarencio, Jorge/H-3940-2012; Andrade, Bruno/J-9111-2012 OI Barral Netto, Manoel/0000-0002-5823-7903; Barral, Aldina/0000-0002-7177-464X; Andrade, Bruno/0000-0001-6833-3811 FU NIAID NIH HHS [AI 30639] NR 42 TC 40 Z9 40 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 IS 11 BP 3111 EP 3121 DI 10.1002/eji.200737431 PG 11 WC Immunology SC Immunology GA 232HP UT WOS:000251009700012 PM 17935072 ER PT J AU Bajenoff, M Germain, RN AF Bajenoff, Marc Germain, Ronald N. TI Seeing is believing: A focus on the contribution of microscopic imaging to immune system function SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Review DE chemokines; imaging; immunofluorescence; lymph nodes ID DENDRITIC CELL-INTERACTIONS; GREEN-FLUORESCENT PROTEIN; HIGH-ENDOTHELIAL VENULES; LYMPH-NODE CORTEX; CD8(+) T-CELLS; IN-VIVO; GERMINAL-CENTERS; ELECTRON MICROSCOPE; TRANSGENIC MICE; BONE MARROW AB Many cells of the immune system do not occupy fixed tissue locations, but circulate in the blood, traffic through the lymph, and migrate within organized lymphoid organs and periphery tissues. Rare antigen-specific lymphocytes must find one another for productive adaptive immune responses and the different phases of cell-mediated and humoral immune response development take place in distinct sites. This historical feature examines how we have reached our current understanding of these aspects of immune system function. It emphasizes the critical role of ever-improving imaging techniques in determining where immune cells reside and interact and stresses the key past contribution of sequential static immunohistochemical analysis using monoclonal reagents. In combination with genetic studies, these imaging experiments resulted in our current paradigm that views activation-dependent changes in chemokine sensitivity as central to effective cell co-operation. We also highlight the very recent application of two-photon imaging to the direct observation of immune cell dynamics in a natural tissue environment, noting how the application of this technology has reinforced some existing ideas and is changing other long-held views. We conclude with some speculations about the opportunities for further advances using ever more powerful imaging methods. C1 Natl Inst Hlth, NIAID, Lymphocyte Biol Sect, Lab Immunol,Program Syst Immunol & Infect Dis Mod, Bethesda, MD 20892 USA. Natl Inst Hlth, NIAID, Lymphocyte Biol Sect, Immunol Lab, Bethesda, MD USA. RP Germain, RN (reprint author), Natl Inst Hlth, NIAID, Lymphocyte Biol Sect, Lab Immunol,Program Syst Immunol & Infect Dis Mod, DHHS Bldg 10 Rm 11N311, 10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 114 TC 31 Z9 32 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 SU 1 BP S18 EP S33 DI 10.1002/eji.2007376631 PG 16 WC Immunology SC Immunology GA 235NB UT WOS:000251239900003 PM 17972341 ER PT J AU Frazer, IH Lowy, DR Schiller, JT AF Frazer, Ian H. Lowy, Doug R. Schiller, John T. TI Prevention of cancer through immunization: Prospects and challenges for the 21(st) century SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cancer; immunotherapy; infection; vaccines ID HELICOBACTER-PYLORI INFECTION; EPSTEIN-BARR-VIRUS; HEPATITIS-B-VIRUS; HUMAN-PAPILLOMAVIRUS; HEPATOCELLULAR-CARCINOMA; EPITHELIAL-CELLS; IMMUNE-RESPONSE; CERVICAL-CANCER; L1 PROTEIN; VACCINATION AB Persistent infection by several microbial agents is responsible for at least 15% of cancer globally, including most cancers of the liver, stomach., and cervix. The recent development of vaccines that can prevent infection and premalignant disease caused by human papillomaviruses (HPV), which cause virtually all cases of cervical cancer as well as some other cancers, has focused renewed attention on infection control as a means of reducing the global cancer burden. For vaccines to prevent cancer-causing infection with hepatitis C virus, Helicobacter pylori, or Epstein Barr virus, new vaccine technologies to induce more effective protective responses are required. For the two available cancer control vaccines, designed to prevent infection with HPV and hepatitis B virus, the major challenge is to promote effective vaccine deployment through education programs and increased affordability/accessibility for underserved populations, particularly in the developing world, where the cancer burden attributable to infection by these two viruses is greatest. C1 Univ Queensland, Diamantina Inst Canc Immunol & Met Med, Princess Alexandra Hosp, Woolloongabba, Qld 4012, Australia. Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD USA. RP Frazer, IH (reprint author), Univ Queensland, Diamantina Inst Canc Immunol & Met Med, Princess Alexandra Hosp, Ipswich Rd, Woolloongabba, Qld 4012, Australia. EM i.frazer@uq.edu.au OI Frazer, Ian/0000-0002-8002-4680 NR 52 TC 24 Z9 26 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 SU 1 BP S148 EP S155 DI 10.1002/eji.2007378201 PG 8 WC Immunology SC Immunology GA 235NB UT WOS:000251239900017 PM 17972339 ER PT J AU Takata, K Hirata-Fukae, C Becker, AG Chishiro, S Gray, AJ Nishitomi, K Franz, AH Sakaguchi, G Kato, A Mattson, MP LaFerla, FM Aisen, PS Kitamura, Y Matsuoka, Y AF Takata, Kazuyuki Hirata-Fukae, Chiho Becker, Amanda G. Chishiro, Saori Gray, Audrey J. Nishitomi, Kouhei Franz, Andreas H. Sakaguchi, Gaku Kato, Akira Mattson, Mark P. LaFerla, Frank M. Aisen, Paul S. Kitamura, Yoshihisa Matsuoka, Yasuji TI Deglycosylated anti-amyloid beta antibodies reduce microglial phagocytosis and cytokine production while retaining the capacity to induce amyloid beta sequestration SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; immunization; immunotherapy; transgenic mice ID BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; MOUSE MODEL; A-BETA; TRANSGENIC MICE; PLAQUE-FORMATION; IMMUNIZATION; CLEARANCE; RECEPTOR; PEPTIDE AB Accumulation of amyloid beta (Abeta) is a pathological hallmark of Alzheimer's disease, and lowering Abeta is a promising therapeutic approach. Intact anti-Abeta antibodies reduce brain Abeta through two pathways: enhanced microglial phagocytosis and Abeta transfer from the brain to the periphery (Abeta sequestration). While activation of microglia, which is essential for microglial phagocytosis, is necessarily accompanied by undesired neuroinflammatory events, the capacity for sequestration does not seem to be linked to such effects. We and other groups have found that simple Abeta binding agents are sufficient to reduce brain Abeta through the sequestration pathway. In this study, we aimed to eliminate potentially deleterious immune activation from antibodies without affecting the ability to induce sequestration. The glycan portion of immunoglobulin is critically involved in interactions with immune effectors including the Fc receptor and complement c1q; deglycosylation eliminates these interactions, while antigen (Abeta)-binding affinity is maintained. In this study, we investigated whether deglycosylated anti-Abeta antibodies reduce microglial phagocytosis and neuroinflammation without altering the capacity to induce Abeta sequestration. Deglycosylated antibodies maintained Abeta binding affinity. Deglycosylated antibodies did not enhance Abeta phagocytosis or cytokine release in primary cultured microglia, whereas intact antibodies did so significantly. Intravenous injection of deglycosylated antibodies elevated plasma Abeta levels and induced Abeta sequestration to a similar or greater degree compared with intact antibodies in an Alzheimer's transgenic mouse model without or with Abeta plaque pathology. We conclude that deglycosylated antibodies effectively induced Abeta sequestration without provoking neuroinflammation; thus, these deglycosylated antibodies may be optimal for sequestration therapy for Alzheimer's disease. C1 Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. Kyoto Pharmaceut Univ, Dept Neurol, Kyoto 6078414, Japan. 21st Century COE Program, Kyoto 6078414, Japan. Shionogi & Co Ltd, Discovery Res Labs, Shiga 5203423, Japan. Univ Pacific, Dept Chem, Stockton, CA USA. Natl Inst Ageing Intramural Res Program, Neurosci Lab, Baltimore, MD USA. Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA. RP Matsuoka, Y (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. EM ym56@georgetown.edu RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS; NIA NIH HHS [AG022455, AG026478] NR 43 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2007 VL 26 IS 9 BP 2458 EP 2468 DI 10.1111/j.1460-9568.2007.05852.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 227GQ UT WOS:000250645600005 PM 17970733 ER PT J AU Antachopoulos, C Walsh, TJ Roilides, E AF Antachopoulos, Charalampos Walsh, Thomas J. Roilides, Emmanuel TI Fungal infections in primary immunodeficiencies SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Review DE primary immunodeficiencies; fungal infections; antifungal agents; Candida; Aspergillus ID CHRONIC GRANULOMATOUS-DISEASE; HYPERIMMUNOGLOBULIN-E SYNDROME; INTERFERON-GAMMA THERAPY; HYPER-IGE SYNDROME; COMMON VARIABLE IMMUNODEFICIENCY; STEM-CELL TRANSPLANTATION; LEUKOCYTE MYELOPEROXIDASE DEFICIENCY; CHRONIC MUCOCUTANEOUS CANDIDIASIS; IN-VITRO ACTIVITIES; INVASIVE ASPERGILLOSIS AB Patients with phagocytic, cellular, combined and other primary immunodeficiencies exhibit immune deficits that confer increased susceptibility to fungal infections. A number of yeasts and moulds, most commonly Candida and Aspergillus but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon, Penicillium and other, rarely isolated, fungal organisms, have been variably implicated in causing disease in patients with chronic granulomatous disease, severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency. Differences in the spectrum of fungal pathogens as well as in the incidence and clinical presentation of the infections may be observed among patients, depending upon different immune disorders. Fungal infections in these individuals may occasionally be the presenting clinical manifestation of a primary immunodeficiency and can cause significant morbidity and potentially fatal outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and establishment of diagnosis should actively be pursued using appropriate imaging, mycological and histological studies. A number of antifungal agents introduced over the last fifteen years, such as the lipid formulations of amphotericin B, the second-generation triazoles, and the echinocandins, increase the options for medical management of these infections. Surgery may also be needed in some cases, while the role of adjunctive immunotherapy has not been systematically evaluated. The low incidence of primary immunodeficiencies in the general population complicates single-center prospective or retrospective clinical studies aiming to address diagnostic or therapeutic issues pertaining to fungal infections in these patients. C1 Aristotle Univ Thessaloniki, Hippokratio Gen Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. Natl Canc Inst, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Hippokratio Gen Hosp, Dept Pediat 3, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr NR 196 TC 88 Z9 90 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD NOV PY 2007 VL 166 IS 11 BP 1099 EP 1117 DI 10.1007/s00431-007-0527-7 PG 19 WC Pediatrics SC Pediatrics GA 213HC UT WOS:000249656500002 PM 17551753 ER PT J AU Nevo, U Hauben, E AF Nevo, Uri Hauben, Ehud TI Ecoimmunity: immune tolerance by symmetric co-evolution SO EVOLUTION & DEVELOPMENT LA English DT Review ID STEM-CELL TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; T-CELLS; BENEFICIAL AUTOIMMUNITY; CLASS-I; ANTIGEN RECOGNITION; TISSUE HOMEOSTASIS; EPITHELIAL-CELLS; SKIN GRAFTS; MOUSE MODEL AB It is widely accepted that immune tolerance toward "self" is established by central and peripheral adaptations of the immune system. Mechanisms that have been demonstrated to play a role in the induction and maintenance of tolerance include thymic deletion of self-reactive T cells, peripheral T cell anergy and apoptosis, as well as thymic and peripheral induction of regulatory T cells. However, a large body of experimental findings cannot be rationalized solely based on adaptations of the immune system to its environment. Here we propose a new model termed Ecoimmunity, where the immune system and the tissue are viewed as two sides of a continuously active and co-evolving predator-prey system. Ecoimmunity views self-tolerance, not as an equilibrium in which autoimmunity is chronically suppressed, but as a symmetrical balanced conflict between the ability of immune cells to destroy tissue cells by numerous mechanisms, and the capacity of adapted tissue cells to avoid predation. This balance evolves during ontogeny, in parallel to immune adaptations, embryonic tissue cells adapt their phenotype to the corresponding immune activity by developing the ability to escape or modulate damaging local immune responses. This phenotypic plasticity of tissue cells is directed by epigenetic selection of gene expression pattern and cellular phenotype amidst an ongoing immune pressure. Thus, whereas some immune cells prey predominantly on pathogens and infected cells, self-reactive cells continuously prey on incompetent tissue cells that fail to express the adapted phenotype and resist predation. This model uses ecological generalization to reconcile current contradictory observations as well as classical enigmas related to both autoimmunity and to tolerance toward foreign tissues. Finally, it provides empirical predictions and alternative strategies toward clinical challenges. C1 Natl Inst Human Hlth & Child Dev, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. San Raffaele Telethon Inst Gene Therapy HSR TIGET, I-20132 Milan, Italy. RP Nevo, U (reprint author), Natl Inst Human Hlth & Child Dev, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, 13 S Dr, Bethesda, MD 20892 USA. EM nevouri@mail.nih.gov FU Intramural NIH HHS NR 109 TC 3 Z9 4 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1520-541X J9 EVOL DEV JI Evol. Dev. PD NOV-DEC PY 2007 VL 9 IS 6 BP 632 EP 642 PG 11 WC Evolutionary Biology; Developmental Biology; Genetics & Heredity SC Evolutionary Biology; Developmental Biology; Genetics & Heredity GA 226JW UT WOS:000250586300012 PM 17976058 ER PT J AU Yuan, BZ Jefferson, AM Millecchia, L Popescu, NC Reynolds, SH AF Yuan, Bao-Zhu Jefferson, Amy M. Millecchia, Lyndell Popescu, Nicholas C. Reynolds, Steven H. TI Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE DLC1; NSCLC; morphology; apoptosis; protein nuclear translocation ID GTPASE-ACTIVATING PROTEIN; HUMAN BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; RHO-GTPASES; PHOSPHOLIPASE-C; GENE; EXPRESSION; TUMORIGENICITY; PROLIFERATION; CYTOSKELETON AB We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer. Published by Elsevier Inc. C1 NIOSH, Lab Mol Genet Toxicol, Morgantown, WV 26505 USA. NCI, NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Yuan, BZ (reprint author), NIOSH, Lab Mol Genet Toxicol, 1095 Willowdale Rd,Mailstop L-3014, Morgantown, WV 26505 USA. EM bby1@cdc.gov NR 37 TC 28 Z9 29 U1 0 U2 4 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 NOV 1 PY 2007 VL 313 IS 18 BP 3868 EP 3880 DI 10.1016/j.yexcr.2007.08.009 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 224VA UT WOS:000250473500007 PM 17888903 ER PT J AU Liu, G Wang, Z Zhang, Y Kang, Z Haviernikova, E Cui, Y Hennighausen, L Moriggl, R Wang, D Tse, W Bunting, KD AF Liu, Geqiang Wang, Zhengqi Zhang, Yi Kang, Zizhen Haviernikova, Elconora Cui, Yongzhi Hennighausen, Lothar Moriggl, Richard Wang, Demin Tse, William Bunting, Kevin D. TI STAT5 requires the N-domain to maintain hernatopoietic stem cell repopulating function and appropriate lymphoid-myeloid lineage output SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MICE LACKING EXPRESSION; PERIPHERAL T-CELLS; BONE-MARROW; BINDING-SITES; DIFFERENTIATION; TRANSCRIPTION; DEFECTS; DIMERS; DEPHOSPHORYLATION; RESPONSIVENESS AB Objective. Signal transducer and activator of transcription 5 (STAT5) is a critical regulator of hematopoietic development and its impaired activation is associated with hematopoietic and immune cell defects. However, much of this information has been learned from knockout mice that still retain the potential for expression of STAT5 proteins that are N-terminally truncated due to alternative internal translation initiation codons. The goal of these studies was to use transplantation-based assays to analyze the degree of STAT5 Delta N activity in hematopoietic stem cells (HSC and throughout lymphomyeloid development. Methods. We have directly compared E14.5 fetal liver cells from mice with potential to express STAT5ab Delta N (STAT5ab(Delta N/Delta N)) with mice completely lacking STAT5a and STAT5b (STAT5ab (null/null)). We have also utilized retroviral complementation of STAT5ab null/null fetal liver HSC to enforce expression of full-length STAT5a or STAT5a lacking the first 136 amino acids (STAT5a Delta N). Results. We report that STAT5 is required for HSC, lymphocyte, and erythrocyte development. We demonstrate that restored expression of STAT5a in STAT5ab null/null HSC provides a strong selective advantage, correcting T- and B-lymphocyte and erythrocyte development. Interestingly, Gr-l(+) blood cells were inversely correlated with B lymphocytes and both were normalized by STAT5a expression. In contrast, transduction of STAT5a Delta N only provided partial B-lymphocyte development. Conclusions. These studies define the role of STAT5 in maintaining normal lymphoid vs myeloid balance during hematopoiesis and highlight a major role for the N-domain in HSC function. The platform of retroviral complementation described here will be particularly useful for future studies to subdefine the N-domain regions that are critical for hematopoiesis. (C) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 Case Western Reserve Univ, Dept Med, Div Hematol Oncol, Sch Med, Cleveland, OH 44106 USA. NIDDK, NIH, Bethesda, MD USA. Ludwig Boltzmann Inst Canc Res, Vienna, Austria. Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53233 USA. Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. Case Comprehens Canc Ctr, Cleveland, OH USA. Ctr Stem Cell & Regenerat Med, Cleveland, OH USA. RP Bunting, KD (reprint author), Case Western Reserve Univ, Dept Med, Div Hematol Oncol, Sch Med, WRB 2-131, Cleveland, OH 44106 USA. EM Kevin.Bunting@case.edu NR 39 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2007 VL 35 IS 11 BP 1684 EP 1694 DI 10.1016/j.exphem.2007.08.026 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 230FF UT WOS:000250860900009 ER PT J AU Weiss, JM Subleski, JJ Wigginton, JM Wiltrout, RH AF Weiss, Jonathan M. Subleski, Jeff J. Wigginton, Jon M. Wiltrout, Robert H. TI Immunotherapy of cancer by IL-12-based cytokine combinations SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cancer; cytokine; IL-12; immunoregulation ID INTERLEUKIN-12 GENE-THERAPY; COLONY-STIMULATING FACTOR; RENAL-CELL CARCINOMA; CD8(+) T-CELLS; PHASE-I TRIAL; RECOMBINANT HUMAN INTERLEUKIN-12; GAMMA-INDUCIBLE PROTEIN-10; MURINE DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS AB Cancer is a multi-faceted disease comprising complex interactions between neoplastic and normal cells. Over the past decade, there has been considerable progress in defining the molecular, cellular and environmental contributions to the pathophysiology of tumor development. Despite these advances, the conventional treatment of patients still generally involves surgery, radiotherapy and/or chemotherapy, and the clinical outcome for many of these efforts remains unsatisfactory. Recent studies have highlighted the feasibility of using immunotherapeutic approaches that seek to enhance host immune responses to developing tumors. These strategies include immunomodulatory cytokines,-with TNF-alpha, type I or type II IFNs, IL-2, IL-12, IL-15 and IL-18 being among the most potent inducers of antitumor activity in a variety of preclinical studies. More recently, some exciting new cytokines have been characterized, such as IL-21, IL-23, IL-27 and their immunomodulatory and antitumor effects in vitro and in vivo suggest that they may have considerable promise for future immunotherapy protocols. The promise of cytokine therapy does indeed derive from the identification of these novel cytokines but even more fundamentally, the field is greatly benefiting from the ever-expanding amount of preclinical data that convincingly demonstrate synergistic and/or novel biologic effects, which may be achieved through the use of several combinations of cytokines with complementary immune-stimulating capabilities. One cytokine in particular, IL-12, holds considerable promise by virtue of the fact that it plays a central role in regulating both innate and adaptive immune responses, can by itself induce potent anticancer effects, and synergizes with several other cytokines for increased immunoregulatory and antitumor activities. This review discusses the antitumor activity of IL-12, with a special emphasis on its ability to synergize with other cytokines for enhancement of immune effector cell populations and regulation of host-tumor cell interactions and the overall tumor microenvironment. C1 Natl Canc Inst, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr, Ft Detrick, MD 21702 USA. Merck Res Labs, N Wales, PA 19454 USA. RP Weiss, JM (reprint author), Natl Canc Inst, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr, Ft Detrick, MD 21702 USA. RI Bell, Tiffany/F-4403-2010 FU Intramural NIH HHS [Z01 BC009262-25, Z99 CA999999] NR 135 TC 101 Z9 111 U1 1 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD NOV PY 2007 VL 7 IS 11 BP 1705 EP 1721 DI 10.1517/14712598.7.11.1705 PG 17 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 228LT UT WOS:000250732100008 PM 17961093 ER PT J AU Luke, BT AF Luke, Brian T. TI Cambridge Healthtech Institute's 2007 Biomarker Discovery Summit SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material C1 NCI, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21702 USA. RP Luke, BT (reprint author), NCI, Adv Biomed Comp Ctr, SAIC, PO Box B, Frederick, MD 21702 USA. EM lukeb@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 7 TC 0 Z9 0 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD NOV PY 2007 VL 7 IS 6 BP 755 EP 757 DI 10.1586/14737159.7.6.755 PG 3 WC Pathology SC Pathology GA 239LW UT WOS:000251520800006 PM 18020904 ER PT J AU Telek, A Biro, T Bodo, E Toth, BI Borbiro, I Kunos, G Paus, R AF Telek, Andrea Biro, Tamas Bodo, Eniko Toth, Balazs I. Borbiro, Istvan Kunos, George Paus, Ralf TI Inhibition of human hair follicle growth by endo- and exocannabinoids SO FASEB JOURNAL LA English DT Article DE cannabinoid receptor; proliferation; apoptosis; hair cycle ID CANNABINOID RECEPTORS; TUMOR-GROWTH; ENDOGENOUS CANNABINOIDS; HEMODYNAMIC PROFILE; KNOCKOUT MICE; HPA AXIS; SKIN; STRESS; ANGIOGENESIS; INVOLVEMENT AB Recent studies strongly suggest that the cannabinoid system is a key player in cell growth control. Since the organ-culture of human hair follicles (HF) offers an excellent, clinically relevant model for complex tissue interaction systems, we have asked whether the cannabinoid system plays a role in hair growth control. Here, we show that human scalp HF, intriguingly, are both targets and sources of endocannabinoids. Namely, the endocannabinoid N-arachidonoylethanolamide ( anandamide, AEA) as well as the exocannabinnoid Delta (9)-tetrahydrocannabinol dose-dependently inhibited hair shaft elongation and the proliferation of hair matrix keratinocytes, and induced intraepithelial apoptosis and premature HF regression (catagen). These effects were inhibited by a selective antagonist of cannabinoid receptor-1 (CB1). In contrast to CB2, CB1 was expressed in a hair cycle-dependent manner in the human HF epithelium. Since we successfully identified the presence of endocannabinoids in human HF, our data strongly suggest that human HF exploit a CB1-mediated endocannabinoid signaling system for negatively regulating their own growth. Clinically, CB1 agonists may therefore help to manage unwanted hair growth, while CB1 antagonists might counteract hair loss. Finally, human HF organ culture offers an instructive, physiologically relevant new research tool for dissecting "nonclassical" effects of endocannabinoids and their receptor-mediated signaling in general. C1 Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, H-4032 Debrecen, Hungary. Univ Debrecen, Cell Physiol Res Grp, Hungarian Acad Sci, Res Ctr Mol Med,Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary. Med Univ Lubeck, Univ Hosp Schleswig Holstein, Dept Dermatol, D-23538 Lubeck, Germany. NIAAA, NIH, Bethesda, MD USA. RP Biro, T (reprint author), Univ Debrecen, Dept Physiol, Med & Hlth Sci Ctr, Res Ctr Mol Med, Nagyerdie Krt 98 POB 22, H-4032 Debrecen, Hungary. EM biro@phys.dote.hu RI Toth, Balazs/K-1214-2013; OI Borbiro, Istvan/0000-0002-8366-6881 NR 53 TC 39 Z9 40 U1 4 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2007 VL 21 IS 13 BP 3534 EP 3541 DI 10.1096/fj.06-7689com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 225KW UT WOS:000250517800016 PM 17567570 ER PT J AU Feinberg, EC Larsen, FW Wah, RM Alvero, RJ Armstrong, AY AF Feinberg, Eve C. Larsen, Frederick W. Wah, Robert M. Alvero, Ruben J. Armstrong, Alicia Y. TI Economics may not explain Hispanic underutilization of assisted reproductive technology services SO FERTILITY AND STERILITY LA English DT Editorial Material ID OUTCOMES; CARE AB In a lower cost, equal-access-to-care setting, Hispanic use of assisted reproductive technology was less than half of what would have been expected based on patient demographics. Despite this use disparity, there were no significant differences between Hispanic and Caucasian women with regard to infertility diagnoses, assisted reproductive technology cycle parameters, clinical pregnancy rates, live birth rates, spontaneous abortion rates, and implantation rates. C1 Uniformed Serv Univ Hlth Sci, Walter Reed Army Med Ctr, Natl Inst Hlth, Combined Fed Fellowship Reprod Endocrinol & I, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, WRAMC Assisted Reprod Technol Program, Washington, DC 20307 USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. RP Armstrong, AY (reprint author), NIH, NICHHD, 10 Ctr Dr,MSC 1109,Bldg 10,CRC,1-3140, Bethesda, MD 20892 USA. EM armstroa@mail.nih.gov NR 5 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2007 VL 88 IS 5 BP 1439 EP 1441 DI 10.1016/j.fertnstert.2007.01.031 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 231XA UT WOS:000250981300027 PM 17561005 ER PT J AU Wittenberger, MD Nelson, LM AF Wittenberger, Michael D. Nelson, Lawrence M. TI Triple repeat diseases and unstable gonadal function - Reply SO FERTILITY AND STERILITY LA English DT Letter ID PREMUTATION C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. RP Wittenberger, MD (reprint author), NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2007 VL 88 IS 5 BP 1477 EP 1477 DI 10.1016/j.fertnstert.2007.07.022 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 231XA UT WOS:000250981300040 ER PT J AU Collins, PL Bukreyev, A AF Collins, Peter L. Bukreyev, Alexander TI Advances in the development of vaccines against Marburg and Ebola viruses SO FUTURE VIROLOGY LA English DT Editorial Material ID VESICULAR STOMATITIS-VIRUS; NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER; GUINEA-PIGS; INFECTION; PARTICLES; PROTECTS; VECTORS; TRANSMISSION; IMMUNIZATION C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr,Room 6505, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov; ab176v@nih.gov NR 29 TC 1 Z9 1 U1 2 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD NOV PY 2007 VL 2 IS 6 BP 537 EP 541 DI 10.2217/17460794.2.6.537 PG 5 WC Virology SC Virology GA 232PY UT WOS:000251032800002 ER PT J AU Flood, A Mai, V Pfeiffer, R Kahle, L Remaley, AT Lanza, E Schatzkin, A AF Flood, Andrew Mai, Volker Pfeiffer, Ruth Kahle, Lisa Remaley, Alan T. Lanza, Elaine Schatzkin, Arthur TI Elevated serum concentrations of insulin and glucose increase risk of recurrent colorectal adenomas SO GASTROENTEROLOGY LA English DT Article ID FACTOR BINDING PROTEIN-1; GROWTH-FACTOR-I; CANCER-RISK; C-PEPTIDE; GLYCOSYLATED HEMOGLOBIN; BLOOD-GLUCOSE; WOMEN; RESISTANCE; ASSOCIATION; MORTALITY AB Background & Aims: Indicators of insulin resistance have been hypothesized to promote colorectal cancer. Methods: We assayed fasting serum from 375 subjects with and 375 subjects without a recurrent adenoma during the course of the Polyp Prevention Trial to determine baseline concentrations of insulin and glucose, as well as changes in these measurements over the course of 4 years of follow-up evaluation. To estimate the relative risk of adenoma recurrence for each of these serum measures, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models adjusting for age, sex, body mass index, intervention group, and an interaction term for sex and intervention group. Results: For both insulin and glucose, we found higher risk for subjects in the high quartile compared with the low quartile (OR, 1.56; 95% CI, 1.00-2.43 for insulin; OR, 1.49; 95% CI, 0.95-2.31 for glucose). The association for glucose was most apparent for advanced adenomas (OR, 2.43; 95% CI, 1.23-4.79) but for insulin, we did not observe this pattern. When we restricted the analysis to those without a family history of colorectal cancer, we observed an even stronger association between increased glucose at study entry and adenoma recurrence (OR, 1.78; 95% CI, 1.06-3.01 for all adenomas; OR, 3.52; 95% CI, 1.47-8.42 for advanced adenoma). Conclusions: Our findings suggest that patients with increased insulin and glucose are at higher risk of adenoma recurrence, and for those with increased glucose, the increase in risk for recurrence of advanced adenomas is even greater. C1 Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55454 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Natl Inst Hlth, Ctr Clin, Dept Lab Med, Bethesda, MD USA. RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM flood009@umn.edu RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS; NCI NIH HHS [K07 CA108910-01A1] NR 25 TC 27 Z9 27 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2007 VL 133 IS 5 BP 1423 EP 1429 DI 10.1053/j.gastro.2007.08.040 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229QV UT WOS:000250820100009 PM 17904132 ER PT J AU Yang, ZQ Fuss, IJ Watanabe, T Asano, N Davey, MP Rosenbaum, JT Strober, W Kitani, A AF Yang, Zhiqiong Fuss, Ivan J. Watanabe, Tomohiro Asano, Naoki Davey, Michael P. Rosenbaum, James T. Strober, Warren Kitani, Atsushi TI NOD2 transgenic mice exhibit enhanced MDP-mediated down-regulation of TLR2 responses and resistance to colitis induction SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; CROHNS-DISEASE; EXPRESSION; CELLS; SUSCEPTIBILITY; DIPEPTIDE; PATHWAYS; INJURY; RATS AB Background & Aims: Mutations in the CARD15 gene encoding NOD2 are susceptibility factors in Crohn's disease. We explored the mechanism of this susceptibility using mice that over express NOD2. Methods: Cellular and molecular responses of mice bearing an NOD2 transgene or administered plasmids that express wild-type and mutated NOD2 constructs were examined Results; In initial studies, we showed that splenocytes from NOD2 transgenic mice as compared with littermate controls exhibit decreased interleukin (IL)-12p70 responses to peptidoglycan (PGN), a TLR2 ligand that contains muramyl dipeptide, but not other TLR ligands; in contrast, IL-12 responses to PAM(3)CSK(4), a TLR2 ligand that does not contain muramyl dipeptide, were normal. Similarly, transgenic mice as compared with controls exhibited greatly decreased IL-12p40 responses to intraperitoneal administration of PGN but not to lipopolysaccharide. In further studies, we showed using electrophoretic mobility shift assay that PGN-stimulated cells from transgenic mice exhibited decreased activation of nuclear factor kappa B. Finally, in a series of studies on the effect of the NOD2 on susceptibility to induced colitis, we found that (1) transgenic mice were highly resistant to induction of PGN colitis and partially resistant to induction of trinitrobenzene sulfonic acid (TNBS) colitis and (2) mice administered a plasmid expressing a wild-type NOD2 gene were completely resistant to TNBS colitis whereas mice administered a plasmid expressing an NOD2 gene with the Crohn's disease frameshift mutation were only slightly resistant to TNBS colitis. Conclusions: These data offer new evidence that NOD2 mutations contribute to inflammatory bowel disease by causing excessive TLR2 cytokine responses. C1 NIAID, Host Def Lab, Mucosal Immun Sect, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Kitani, A (reprint author), NIAID, Host Def Lab, Mucosal Immun Sect, Bldg 10-CRC,5W3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM akitani@niaid.nih.gov OI Asano, Naoki/0000-0003-4452-8459 FU Intramural NIH HHS [Z99 AI999999] NR 25 TC 57 Z9 58 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2007 VL 133 IS 5 BP 1510 EP 1521 DI 10.1053/j.gastro.2007.07.025 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229QV UT WOS:000250820100019 PM 17915219 ER PT J AU Gottwein, JM Scheel, TKH Hoegh, AM Lademann, JB Eugen-Olsen, J Lisby, G Bukh, J AF Gottwein, Judith M. Scheel, Troels K. H. Hoegh, Anne M. Lademann, Jacob B. Eugen-Olsen, Jesper Lisby, Gorm Bukh, Jens TI Robust hepatitis C genotype 3a cell culture releasing adapted intergenotypic 3a/2a (S52/JFH1) viruses SO GASTROENTEROLOGY LA English DT Article ID INFECTION IN-VITRO; MOLECULAR CLONE; REPLICATION; RECOMBINANT; STEATOSIS; CHIMERAS; GENOME; VIVO; P7 AB Background & Aims: Recently, full viral life cycle hepatitis C virus (HCV) cell culture systems were developed for strain JFH1 (genotype 2a) and an intragenotypic 2a/2a genome (J6/JFH). We aimed at exploiting the unique JFH1 replication characteristics to develop culture systems for genotype 3a, which has a high prevalence worldwide. Methods: Huh7.5 cells were transfected with RNA transcripts of an intergenotypic 3a/JFH1 recombinant with core, E1, E2, p7, and NS2 of the 3a reference strain S52, and released viruses were passaged. Cultures were examined for HCV core and/or NS5A expression (immunostaining), HCV RNA titers (real-time PCR), and infectivity titers (50% tissue culture infectious dose). The role of mutations identified by sequencing of recovered S52/ JFH1 viruses was analyzed by reverse genetics studies. Results: S52/JFH1 and J6/JFH viruses passaged in Huh7.5 cells showed comparable growth kinetics and similar peak HCV RNA and infectivity titers. However, analysis of S52/JFH1 viruses identified 9 putative adaptive mutations in core, E2, p7, NS3, and NSSA. All 7 S52/JFH1 recombinants with an amino acid change in p7 combined with a change in NS3 or NS5A, but only 2 of 9 recombinants with individual mutations (in p7 and NS3, respectively) were fully viable without the requirement for additional mutations. The biological relevance of our system was shown by studying dependence of 3a/JFH1 infection on CD81, and its impact on distribution of intracellular lipids. Conclusions: We developed a robust intergenotypic recombinant cell culture system for HCV genotype 3a, providing a valuable tool for studies of 3a core-NS2 and related therapeutics. C1 Copenhagen Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark. Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. Copenhagen Univ Hosp, Dept Clin Microbiol, DK-2650 Hvidovre, Denmark. Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM jbukh@niaid.nih.gov OI Eugen-Olsen, jesper/0000-0002-4630-4275; Scheel, Troels/0000-0003-1545-4067 NR 23 TC 115 Z9 125 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2007 VL 133 IS 5 BP 1614 EP 1626 DI 10.1053/j.gastro.2007.08.005 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229QV UT WOS:000250820100028 PM 17983807 ER PT J AU Naumann, N De Ravin, SS Choi, U Moayeri, M Whiting-Theobald, N Linton, GF Ikeda, Y Malech, HL AF Naumann, N. De Ravin, S. S. Choi, U. Moayeri, M. Whiting-Theobald, N. Linton, G. F. Ikeda, Y. Malech, H. L. TI Simian immunodeficiency virus lentivector corrects human X-linked chronic granulomatous disease in the NOD/SCID mouse xenograft SO GENE THERAPY LA English DT Article DE chronic granulomatous disease; lentiviral vector; simian immunodeficiency virus; Gp91(phox); hematopoietic stem cell; RD114 ID MEDIATED GENE-TRANSFER; HUMAN CD34(+) CELLS; HEMATOPOIETIC STEM-CELLS; RESPIRATORY BURST ACTIVITY; BONE-MARROW-CELLS; LENTIVIRAL VECTORS; STABLE TRANSDUCTION; REPOPULATING CELLS; OXIDASE DEFECT; HOST-DEFENSE AB X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the phagocyte nicotinamide dinucleotide phosphate oxidase catalytic subunit gp91(phox). Gene therapy targeting hematopoietic stem cells (HSCs) can correct CGD, but permanent correction remains a challenge. Lentiviral vectors have become attractive tools for gene transfer, and they may have the potential to transduce very primitive HSCs. We used a self-inactivating RD114/ TR-pseudotyped simian immunodeficiency virus (SIVmac)-based vector encoding human gp91(phox) for ex vivo transduction of peripheral blood-mobilized stem cells (PBSCs) from patients with X-CGD. In PBSCs from two patients, ex vivo transduction efficiencies of 40.5 and 46% were achieved, and correction of oxidase activity was observed in myeloid cells differentiating in culture. When transduced PBSCs from these patients were transplanted into nonobese diabetic/severe combined immunodeficient mice and compared to normal control, 10.5 and 7.3% of the human myeloid cells in bone marrow developing at 6 weeks from the human xenografts expressed the gp91(phox) transgene. Sustained functional correction of oxidase activity was documented in myeloid cells differentiated from engrafted transduced PBSCs. Transgene marking was polyclonal as assessed by vector integration site analysis. These data suggest that RD114/TR SIVmac-based vectors might be suitable for gene therapy of CGD and other hereditary hematologic diseases. C1 NIAID, Host Def Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Program Mol Med, Rochester, MN USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, Natl Inst Hlth, Bldg 10-CRC,Room 5-3750,10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM hmalech@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS [Z01 AI000988-01, Z01 AI000644-16] NR 50 TC 14 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 2007 VL 14 IS 21 BP 1513 EP 1524 DI 10.1038/sj.gt.3303010 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 221KO UT WOS:000250226400002 PM 17728796 ER PT J AU Himelhoch, S Chander, G Fleishman, JA Hellinger, J Gaist, P Gebo, KA AF Himelhoch, Seth Chander, Geetanjali Fleishman, John A. Hellinger, James Gaist, Paul Gebo, Kelly A. CA HIV Res Network TI Access to HAART and utilization of inpatient medical hospital services among HIV-infected patients with co-occurring serious mental illness and injection drug use SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE HAART; inpatient medical hospital services; HIV-infected patients ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; AIDS PATIENTS; PSYCHIATRIC-INPATIENTS; HEPATITIS-B; CARE; SEROPREVALENCE; PREVALENCE; SCHIZOPHRENIA; DISORDERS AB Objective: Among HIV-infected individuals, we examined whether having co-occurring serious mental illness (SMI) and injection drug use (IDU) impacts: (a) receipt of highly active antiretroviral therapy (HAART), and (b) utilization of inpatient HIV services, compared to those who have SMI only, IDU only or neither SMI nor IDU. Method: Demographic, clinical and resource utilization data were collected from medical records of 5119 patients in HIV primary care at four US HIV care sites in different geographic regions with on-site mental health services in 2001. We analyzed receipt of HAART using multivariate logistic regression and the number of medical hospital admissions using multivariate logistic and Poisson regression analyses, which controlled for demographic factors, receipt of HAART, CD4 count and HIV-1 RNA. Results: Those with co-occurring SMI and IDU [adjusted odds ratio (AOR)=0.52; 95% confidence interval (95% CI)=0.41-0.81] and those with IDU alone (AOR=0.64;, 95% CI=0.58-0.85) were significantly less likely to receive HAART than those with neither SMI nor IDU, controlling for demographic and clinical factors. Those with co-occurring SMI and IDU were more likely to use any inpatient medical services (AOR=2.22; 95% CI=1.64-3.01) and were significantly more likely to use them more frequently (incidence rate ratio=1.33; 95% CI=1.13-1.55) than those with neither SMI nor IDU, SMI only or IDU only. Conclusion: HIV-infected individuals with co-occurring SMI and IDU are significantly more likely to utilize HIV-related medical inpatient services than individuals with no comorbidity or with only one comorbidity. Individuals with both SMI and IDU did not differ from those with IDU only in receipt of HAART. Inpatient hospitalizations are expensive, and efforts should be targeted towards these populations to reduce potentially avoidable inpatient care. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Med, Dept Psychiat, Div Res Serv, Baltimore, MD 21212 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Agcy Hlthcare Res & Qual, Rockville, MD USA. Tufts Univ, Boston, MA 02111 USA. NIH, Off AIDS Res, Bethesda, MD 20892 USA. RP Himelhoch, S (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Div Res Serv, Baltimore, MD 21212 USA. EM shimelho@psych.umaryland.edu RI Gebo, Kelly/B-9223-2009 FU NIDA NIH HHS [K23 DA019820, K23 DA019820-02, K23 DA019820-01, K23 DA000523, K23 DA019820-03, K23 DA 00523, K23 DA 019820] NR 47 TC 18 Z9 18 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2007 VL 29 IS 6 BP 518 EP 525 DI 10.1016/j.genhosppsych.2007.03.008 PG 8 WC Psychiatry SC Psychiatry GA 236KU UT WOS:000251302700009 PM 18022045 ER PT J AU Andres, AM Clark, AG Shimmin, L Boerwinkle, E Sing, CF Hixson, JE AF Andres, Aida M. Clark, Andrew G. Shimmin, Lawrence Boerwinkle, Eric Sing, Charles F. Hixson, James E. TI Understanding the accuracy of statistical haplotype inference with sequence data of known phase SO GENETIC EPIDEMIOLOGY LA English DT Article DE kallekrein; KLK; haplotype reconstruction; phase; LD ID POPULATION GENOTYPE DATA; LINKAGE-DISEQUILIBRIUM; HUMAN GENOME; RECONSTRUCTION; INDIVIDUALS; RESOLUTION; SAMPLES; MODEL; IDENTIFICATION; ASSOCIATION AB Statistical methods for haplotype inference from multi-site genotypes of unrelated individuals have important application in association studies and population genetics. Understanding the factors that affect the accuracy of this inference is important, but their assessment has been restricted by the limited availability of biological data with known phase. We created hybrid cell lines monosomic for human chromosome 19 and produced single-chromosome complete sequences of a 48 kb genomic region in 39 individuals of African American (AA) and European American (EA) origin. We employ these phase-known genotypes and coalescent simulations to assess the accuracy of statistical haplotype reconstruction by several algorithms. Accuracy of phase inference was considerably low in our biological data even for regions as short as 25-50 kb, suggesting that caution is needed when analyzing reconstructed haplotypes. Moreover, the reliability of estimated confidence in phase inference is not high enough to allow for a reliable incorporation of site-specific uncertainty information in subsequent analyses. We show that, in samples of certain mixed ancestry (AA and EA populations), the most accurate haplotypes are probably obtained when increasing sample size by considering the largest, pooled sample, despite the hypothetical problems associated with pooling across those heterogeneous samples. Strategies to improve confidence in reconstructed haplotypes, and realistic alternatives to the analysis of inferred haplotypes, are discussed. C1 NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. Univ Texas, Ctr Hlth Sci, Ctr Human Genet, Houston, TX USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Andres, AM (reprint author), NHGRI, Natl Inst Hlth, 50 S Dr,Bldg 50 Rm 5527, Bethesda, MD 20892 USA. EM andresa@mail.nih.gov RI Andres, Aida/B-4088-2014; OI Andres, Aida/0000-0002-8590-9672; Sing, Charles/0000-0001-5872-7956 FU NIGMS NIH HHS [GM65509, P50 GM065509, P50 GM065509-06] NR 45 TC 39 Z9 41 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2007 VL 31 IS 7 BP 659 EP 671 DI 10.1002/gepi.20185 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 230VS UT WOS:000250904800001 PM 17922479 ER PT J AU Wang, P Lyman, RF Shabalina, SA Mackay, TFC Anholt, RRH AF Wang, Ping Lyman, Richard F. Shabalina, Svetlana A. Mackay, Trudy F. C. Anholt, Robert R. H. TI Association of polymorphisms in odorant-binding protein genes with variation in olfactory response to benzaldehyde in Drosophila SO GENETICS LA English DT Article ID RNA SECONDARY STRUCTURE; QUANTITATIVE TRAIT GENE; GUIDED BEHAVIOR; MOLECULAR EVOLUTION; NATURAL-SELECTION; DNA POLYMORPHISM; ANTENNAL LOBE; MELANOGASTER; FAMILY; PHEROMONE AB Adaptive evolution of animals depends on behaviors that are essential for their survival and reproduction. The olfactory system of Drosophila melanogaster has emerged as one of the best characterized olfactory systems, which in addition to a family of odorant receptors, contains an approximately equal number of odorant-binding proteins (OBPs), encoded by a multigene family of 51 genes. Despite their abundant expression, little is known about their role in chemosensation, largely due to the lack of available mutations in these genes. We capitalized on naturally occurring mutations (polymorphisms) to gain insights into their functions. We analyzed the sequences of 13 Obp genes in two chromosomal clusters in a population of wild-derived inbred lines, and asked whether polymorphisms in these genes are associated with variation in olfactory responsiveness. Four polymorphisms in 3 Obp, genes exceeded the statistical permutation threshold for association with responsiveness to benzaldehyde, suggesting redundancy and/or combinatorial recognition by these OBPs of this odorant. Model predictions of alternative pre-mRNA secondary structures associated with polymorphic sites suggest that alterations in Obp mRNA structure could contribute to phenotypic variation in olfactory behavior. C1 N Carolina State Univ, WM Keck Ctr Behav Biol, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Zool, Raleigh, NC 27695 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Anholt, RRH (reprint author), N Carolina State Univ, WM Keck Ctr Behav Biol, Campus Box 7617, Raleigh, NC 27695 USA. EM anholt@ncsu.edn RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 FU Intramural NIH HHS; NIGMS NIH HHS [GM-059469, R01 GM059469] NR 54 TC 34 Z9 44 U1 2 U2 18 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2007 VL 177 IS 3 BP 1655 EP 1665 DI 10.1534/genetics.107.079731 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 237JA UT WOS:000251368800030 PM 17720903 ER PT J AU Persky, S Kaphingst, KA Condit, CM McBride, CM AF Persky, Susan Kaphingst, Kimberly A. Condit, Celeste M. McBride, Colleen M. TI Assessing hypothetical scenario methodology in genetic susceptibility testing analog studies: a quantitative review SO GENETICS IN MEDICINE LA English DT Review DE genetic testing; uptake; hypothetical; methodology ID OVARIAN-CANCER SUSCEPTIBILITY; HEREDITARY PROSTATE-CANCER; BREAST-CANCER; GENERAL-POPULATION; DECISION-MAKING; WOMENS INTEREST; RISK; ATTITUDES; INFORMATION; KNOWLEDGE AB Hypothetical scenario methodology is commonly employed in the study of genetic susceptibility testing uptake estimation. The methodology, however, has not been rigorously assessed and sizeable gaps exist between estimated and actual uptake for tests that have recently become available. This quantitative review explores the effect of several theoretically based factors on genetic test uptake accuracy among a sample of 38 articles. These factors include verbal immediacy and temporal proximity of test scenarios, method of decision assessment, content of testing detail provided, processing demand required, and study features related to administration and sample. A number of assessed factors influenced uptake accuracy. Among these, temporal proximity of the genetic susceptibility test appeared to be the most consistent. There was also some evidence for effects of verbal immediacy and decision-assessment method on interest in testing. We recommend strategies for increasing accuracy using hypothetical scena rio methodology to examine genetic susceptibility test uptake prediction. C1 NHGRI, Bethesda, MD USA. Univ Georgia, Athens, GA 30602 USA. RP Persky, S (reprint author), NHGRI, NIH, 31 Ctr Dr, Room B1B54D, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov FU Intramural NIH HHS NR 56 TC 45 Z9 45 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2007 VL 9 IS 11 BP 727 EP 738 DI 10.1097/GIM.0b013e318159a344 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 235KS UT WOS:000251233500001 PM 18007141 ER PT J AU Walker, AP Tucker, DC Hall, MA Lohman, K Harrison, H Harrison, BW Reiss, J Acton, RT Adams, PC Diaz, S Holup, J Thomson, E Ellis, SD McLaren, CE AF Walker, Ann P. Tucker, Diane C. Hall, Mark A. Lohman, Kurt Harrison, Helen Harrison, Barbara W. Reiss, Jacob Acton, Ronald T. Adams, Paul C. Diaz, Sharmin Holup, Joan Thomson, Elizabeth Ellis, Shellie D. McLaren, Christine E. CA Hemochromatosis Iron Overload Stud TI Results communication and patient education after screening for possible hemochromatosis and iron overload: experience from the HEIRS study of a large ethnically and linguistically diverse group SO GENETICS IN MEDICINE LA English DT Article DE genetic counseling; genetics education; health literacy; hemochromatosis screening; HFE gene ID HEREDITARY HEMOCHROMATOSIS; POPULATION; HEALTH; INFORMATION; ATTITUDES; MUTATION; GENETICS; PROGRAM; DISEASE; IMPACT AB Purpose: We assessed the effectiveness of educational interventions for conveying clinical findings and information about hereditary hemochromatosis (HH) and iron overload (IO) to individuals evaluated clinically after initial screening for HH/IO with serum ferritin (SF) concentration, transferrin saturation (TS), and HFE genotyping. Methods: A questionnaire mailed to 2300 cases and controls 1 month after a letter summarizing clinical findings measured understanding of results and recommendations, knowledge of HH/IO, and satisfaction with information received. Results: Of 1622 (70.5%) participants completing relevant items, 83.6% were satisfied with receiving initial screening results by mail, 93.4% found information clear and easy to understand, 89.2% generally felt they got enough information, but 47.5% still had questions. C282Y/C282Y homozygosity with normal TS/SF predicted the best understanding of genetic results. Many with no mutations thought relatives were at risk. Iron levels created most confusion, and a third incorrectly recalled treatment recommendations. Having any abnormal result, lower education, older age, and being non-white, and/or non-English speaking predicted lower understanding. Conclusions: Combining genotypic and phenotypic screening for HH/IO creates additional difficulties in communicating results-particularly to those with low health literacy. Explaining aberrant iron TS and SF levels and low-risk genotypes, follow-up recommendations, and risk to relatives will need creative, culturally appropriate strategies. C1 Univ Calif Irvine, Med Ctr, Dept Pediat, Div Human Genet, Orange, CA 92868 USA. Univ Calif Irvine, Med Ctr, Genet Counseling Program, Orange, CA USA. Univ Alabama, Dept Psychol, Birmingham, AL USA. Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. Hlth Sci Ctr, Dept Med, London, ON, Canada. Harvard Univ, Dept Psychol, Washington, DC USA. Kaiser Permanente, Dept Genet, Portland, OR USA. Univ Alabama, Dept Microbiol, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL USA. Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHGRI, Bethesda, MD USA. Duke Clin Res Inst, Outcome Res, Durham, NC USA. Univ Calif Irvine, Irvine, CA 92717 USA. RP Walker, AP (reprint author), Univ Calif Irvine, Med Ctr, Dept Pediat, Div Human Genet, 101 The City Dr, Orange, CA 92868 USA. EM awalker@uci.edu RI Ellis, Shellie/I-4811-2015 OI Ellis, Shellie/0000-0002-3599-0804 FU NCRR NIH HHS [M01-RR10284, 5M01RR 00827-29]; NHLBI NIH HHS [N01-HC-05188, N01-HC-05192, N01-HC-05186, N01-HC-05189, N01-HC-05190, N01-HC-05185, N01-HC-05191] NR 27 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV PY 2007 VL 9 IS 11 BP 778 EP 791 DI 10.1097/GIM.0b013e318159a303 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 235KS UT WOS:000251233500007 PM 18007147 ER PT J AU Parker, HG Kukekova, AV Akey, DT Goldstein, O Kirkness, EF Baysac, KC Mosher, DS Aguirre, GD Acland, GM Ostrander, EA AF Parker, Heidi G. Kukekova, Anna V. Akey, Dayna T. Goldstein, Orly Kirkness, Ewen F. Baysac, Kathleen C. Mosher, Dana S. Aguirre, Gustavo D. Acland, Gregory M. Ostrander, Elaine A. TI Breed relationships facilitate fine-mapping studies: A 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds SO GENOME RESEARCH LA English DT Article ID CONGENITAL POSTERIOR ECTASIA; MULTILOCUS GENOTYPE DATA; ROD-CONE DEGENERATION; DOMESTIC DOG; POPULATION-STRUCTURE; LINKAGE DISEQUILIBRIUM; GENETIC-VARIATION; COAT COLOR; GENOME; MICROSATELLITES AB The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJI gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage. C1 NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA. Cornell Univ, Coll Vet Med, Baker Inst Anim Hlth, Ithaca, NY 14853 USA. Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. Inst Genom Res, Rockville, MD 20850 USA. Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov RI Parker, Heidi/C-6954-2008; OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NEI NIH HHS [EY06855, R01 EY006855] NR 43 TC 79 Z9 80 U1 6 U2 37 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2007 VL 17 IS 11 BP 1562 EP 1571 DI 10.1101/gr.6772807 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 227FD UT WOS:000250641700003 PM 17916641 ER PT J AU Paz, N Levanon, EY Amariglio, N Heimberger, AB Ram, Z Constantini, S Barbash, ZS Adamsky, K Safran, M Hirschberg, A Krupsky, M Ben-Dov, I Cazacu, S Mikkelsen, T Brodie, C Eisenberg, E Rechavi, G AF Paz, Nurit Levanon, Erez Y. Amariglio, Ninette Heimberger, Amy B. Ram, Zvi Constantini, Shlomi Barbash, Zohar S. Adamsky, Konstantin Safran, Michal Hirschberg, Avi Krupsky, Meir Ben-Dov, Issachar Cazacu, Simona Mikkelsen, Tom Brodie, Chaya Eisenberg, Eli Rechavi, Gideon TI Altered adenosine-to-inosine RNA, editing in human cancer SO GENOME RESEARCH LA English DT Article ID HUMAN BLADDER-CANCER; PRE-MESSENGER-RNA; HUMAN TRANSCRIPTOME; DNA METHYLATION; GENE-EXPRESSION; BREAST-CANCER; ALU ELEMENTS; C-MYC; DEAMINASE; RECEPTOR AB Adenosine-to-inosine (A-to-I) RNA editing was recently shown to be abundant in the human transcriptome, affecting thousands of genes. Employing a bioinformatic approach, we identified significant global hypoediting of AN repetitive elements in brain, prostate, lung, kidney, and testis tumors. Experimental validation confirmed this finding, showing significantly reduced editing in Alu sequences within MED13 transcripts in brain tissues. Looking at editing of specific recoding and noncoding sites, including in cancer-related genes, a more complex picture emerged, with a gene-specific editing pattern in tumors vs. normal tissues. Additionally, we found reduced RNA levels of all three editing mediating enzymes, ADAP, ADARB1, and ADARB2, in brain tumors. The reduction of ADARB2 correlated with the grade of malignancy of glioblastoma multiforme, the most aggressive of brain tumors, displaying a 99% decrease in ADARB2 RNA levels. Consistently, overexpression of ADAR and ADARB1 in the U87 glioblastoma multiforme cell line resulted in decreased proliferation rate, suggesting that reduced A-to-l editing in brain tumors is involved in the pathogenesis of cancer. Altered epigenetic control was recently shown to play a central role in oncogenesis. We suggest that A-to-l RNA editing may serve as an additional epigenetic mechanism relevant to cancer development and progression. C1 Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Compugen Ltd, IL-69512 Tel Aviv, Israel. Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Brain Tumor Ctr, Houston, TX 77030 USA. Sourasky Med Ctr, Dept Neurosurg, IL-64239 Tel Aviv, Israel. Sourasky Med Ctr, Dept Pediat Neurosurg, Dana Childrens Hosp, IL-64239 Tel Aviv, Israel. Chaim Sheba Med Ctr, Dept Internal Med, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Pulm Inst, IL-52621 Tel Hashomer, Israel. Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sch Phys & Astron, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. RP Rechavi, G (reprint author), Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel. EM gidi.rechavi@sheba.health.gov.il RI Eisenberg, Eli/D-2587-2009; Levanon, Erez/A-8128-2012 OI Eisenberg, Eli/0000-0001-8681-3202; Levanon, Erez/0000-0002-3641-4198 NR 49 TC 160 Z9 170 U1 5 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2007 VL 17 IS 11 BP 1586 EP 1595 DI 10.1101/gr.6493107 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 227FD UT WOS:000250641700005 PM 17908822 ER PT J AU Pontius, JU Mullikin, JC Smith, DR Lindblad-Toh, K Gnerre, S Clamp, M Chang, J Stephens, R Neelam, B Volfovsky, N Schaffer, AA Agarwala, R Narfstrom, K Murphy, WJ Giger, U Roca, AL Antunes, A Menotti-Raymond, M Yuhki, N Pecon-Slattery, J Johnson, WE Bourque, G Tesler, G O'Brien, SJ AF Pontius, Joan U. Mullikin, James C. Smith, Douglas R. Lindblad-Toh, Kerstin Gnerre, Sante Clamp, Michele Chang, Jean Stephens, Robert Neelam, Beena Volfovsky, Natalia Schaeffer, Alejandro A. Agarwala, Richa Narfstroem, Kristina Murphy, William J. Giger, Urs Roca, Alfred L. Antunes, Agostinho Menotti-Raymond, Marilyn Yuhki, Naoya Pecon-Slattery, Jill Johnson, Warren E. Bourque, Guillaume Tesler, Glenn O'Brien, Stephen J. CA Agencourt Sequencing Team NISC Comparat Sequencing Prog TI Initial sequence and comparative analysis of the cat genome SO GENOME RESEARCH LA English DT Review ID FELINE LEUKEMIA VIRUSES; MAJOR HISTOCOMPATIBILITY COMPLEX; MAMMALIAN CHROMOSOME EVOLUTION; DISEASE TYPE-IV; DOMESTIC CAT; NUCLEAR GENOME; GENETIC INDIVIDUALIZATION; G(M2) GANGLIOSIDOSIS; MITOCHONDRIAL GENOME; MOLECULAR-BASIS AB The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing -65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence. C1 SAIC Frederick Inc, Lab Genom Divers, NCI Frederick, Frederick, MD 21702 USA. NHGRI, Comparat Genom Unit, Rockville, MD 20892 USA. Agencourt Biosci Corp, Beverly, MA 01915 USA. Broad Inst Harvard, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. SAIC Frederick Inc, Adv Biomed Comp Ctr, NCI Frederick, Frederick, MD 21702 USA. Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Missouri, Dept Vet Med & Surg, Dept Ophthalmol, Mason Eye Inst, Columbia, MO 65211 USA. Texas A&M Univ, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. Univ Penn, Sch Vet Med, Med Genet Sect, Philadelphia, PA 19104 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Porto, REQUIMTE, Dept Quim, Fac Ciencias, P-4169007 Oporto, Portugal. Univ Porto, CIMAR, Ctr Interdisciplinar Invest Marinha & Ambiental, P-4050123 Oporto, Portugal. Genome Inst Singapore, Singapore 138672, Singapore. Univ Calif San Diego, Dept Math, San Diego, CA 92093 USA. NHGRI, NISC, NIH, Bethesda, MD 20892 USA. RP Pontius, JU (reprint author), SAIC Frederick Inc, Lab Genom Divers, NCI Frederick, Frederick, MD 21702 USA. EM Pontiusj@ncifcrf.gov; Obrien@ncifcrf.gov RI Schaffer, Alejandro/F-2902-2012; REQUIMTE, AL/H-9106-2013; Scientific output, CIIMAR/E-5122-2012; Johnson, Warren/D-4149-2016; OI Scientific output, CIIMAR/0000-0001-6270-2153; Johnson, Warren/0000-0002-5954-186X; Antunes, Agostinho/0000-0002-1328-1732 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]; NCRR NIH HHS [P40 RR002512, RR 02512] NR 102 TC 172 Z9 176 U1 3 U2 44 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2007 VL 17 IS 11 BP 1675 EP 1689 DI 10.1101/gr.6380007 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 227FD UT WOS:000250641700014 PM 17975172 ER PT J AU Landgren, O Pfeiffer, R Kristinsson, SY Caporaso, NE Goldin, LR Bjorkholm, M AF Landgren, O. Pfeiffer, R. Kristinsson, S. Y. Caporaso, N. E. Goldin, L. R. Bjorkholm, M. TI Autoimmunity and Hodgkin lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Landgren, O.; Bjorkholm, M.] NIH, Natl Canc Inst, Bethesda, MD USA. [Landgren, O.; Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Univ Hosp, Div Hematol, Karolinska Inst, Dept Med, Stockholm, Sweden. RI Pfeiffer, Ruth /F-4748-2011; Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 11 EP 11 PG 1 WC Hematology SC Hematology GA 224UA UT WOS:000250470800029 ER PT J AU Mealiffe, ME Goldin, LR McMaster, ML Wiernik, PH Lynch, HT Tucker, MA Horwitz, MS AF Mealiffe, M. E. Goldin, L. R. McMaster, M. L. Wiernik, P. H. Lynch, H. T. Tucker, M. A. Horwitz, M. S. TI KLHDC8B: A candidate Hodgkin's Lymphoma susceptibility gene SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Mealiffe, M. E.; Horwitz, M. S.] Univ Washington, Seattle, WA USA. [Goldin, L. R.; McMaster, M. L.; Tucker, M. A.] DCEG, Natl Canc Inst, Bethesda, MD USA. [Wiernik, P. H.] New York Med Coll, Bronx, NY USA. [Lynch, H. T.] Creighton Univ, Omaha, NE USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 13 EP 13 PG 1 WC Hematology SC Hematology GA 224UA UT WOS:000250470800036 ER PT J AU O'Mahony, D Janik, JE Carrasquillo, JA Brechbiel, M Paik, CH Le, N Whaley, M Jaffe, E Fleischer, TA Lee, C Gao, D Fioravanti, S O'Hagan, D Waldmann, T Morris, JC AF O'Mahony, D. Janik, J. E. Carrasquillo, J. A. Brechbiel, M. Paik, C. H. Le, N. Whaley, M. Jaffe, E. Fleischer, T. A. Lee, C. Gao, D. Fioravanti, S. O'Hagan, D. Waldmann, Ta. Morris, J. C. TI Yttrium-90 radiolabeled humanized anti-CD25 monoclonal antibody, daclizumab, provides effective therapy for refractory and relapsed Hodgkin's lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [O'Mahony, D.; Janik, J. E.; Carrasquillo, J. A.; Brechbiel, M.; Paik, C. H.; Le, N.; Whaley, M.; Jaffe, E.; Fleischer, T. A.; Lee, C.; Gao, D.; Fioravanti, S.; O'Hagan, D.; Waldmann, Ta.; Morris, J. C.] NIH, Nucl Med Radiat Oncol & Dept Clin Pathol, NCI, Pathol Lab,Metab Branch, Bethesda, MD USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 1 Z9 1 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 18 EP 19 PG 2 WC Hematology SC Hematology GA 224UA UT WOS:000250470800050 ER PT J AU Anderson, LA Pfeiffer, RM Rapkin, JS Gridley, G Mellemk-Jaer, L Hemminki, K Bjorkholm, M Goldin, LR Landgren, O AF Anderson, L. A. Pfeiffer, R. M. Rapkin, J. S. Gridley, G. Mellemk-jaer, L. Hemminki, K. Bjorkholm, M. Goldin, L. R. Landgren, O. TI Survival patterns among Hodgkin lymphoma patients with a family history of lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Anderson, L. A.; Pfeiffer, R. M.; Rapkin, J. S.; Gridley, G.; Goldin, L. R.; Landgren, O.] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Anderson, L. A.] NCI, NIH, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Mellemk-jaer, L.] Danish Canc Soc, Copenhagen, Denmark. [Hemminki, K.; Bjorkholm, M.] Karolinska Inst, S-10401 Stockholm, Sweden. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 26 EP 26 PG 1 WC Hematology SC Hematology GA 224UA UT WOS:000250470800068 ER PT J AU Domingo-Domenech, E Benavente, Y Gonzalez-Barca, E Montalban, C Guma, J Bosch, R Wang, SS Lan, Q Whitby, D de Sevilla, AF Rothman, N de Sanjose, S AF Domingo-Domenech, Eva Benavente, Yolanda Gonzalez-Barca, Eva Montalban, Carlos Guma, Josep Bosch, Ramon Wang, Sophia S. Lan, Qing Whitby, Denise de Sevilla, Alberto Fernandez Rothman, Nathaniel de Sanjose, Silvia TI Impact of interleukin-10 polymorphisms (-1082 and -3575) on the survival of patients with lymphoid neoplasms SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE IL-10 polymorphisms; lymphoid neoplasms; survival ID B-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; VERSUS-HOST-DISEASE; GENE PROMOTER; IL-10; RISK; SERUM; CLASSIFICATION; CORRELATE AB Background and Objectives Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms Of IL-10-(1082A>G) and IL-10-(3575T>A) with the overall survival in patients with lymphoid neoplasms. Design and Methods We analyzed two IL-10 SNP (-1082 and -3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis. Results Lymphoma patients with the IL-10-(3575T>A) genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin's lymphoma (NHL) (p=0.05). Patients with the IL10(1082GG) genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10-(3575AA) genotype was the only independent prognostic factor for survival (HR=0.20, 95%Cl 0.05-0.92). Patients with the IL-10-(1082A>G) and -3575 G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%Cl 0.08-0.83). Interpretation and Conclusions The IL-10-(357BA/A) genotype was identified as a marker of favorable survival. Because the IL-10-(1082) and -3575 G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10-(1082GG) genotype. These results need to be replicated in larger series and examined in different NHL subtypes. C1 Hosp Llobregat, Inst Catala Oncol, Dept Hematol, Barcelona 08907, Spain. Hosp Llobregat, Inst Catala Oncol, Dept Epidemiol, Barcelona 08907, Spain. Hosp Ramon & Cajal, Dept Internal Med, E-28034 Madrid, Spain. Hosp Univ San Joan, Dept Oncol, Reus, URV, Spain. Hosp Verge Cinta, Dept Pathol, Tortosa, Spain. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Domingo-Domenech, E (reprint author), Hosp Llobregat, Inst Catala Oncol, Dept Hematol, Avda Gran Via S-N,Km 2-7, Barcelona 08907, Spain. EM edomigo@iconcologia.net RI de Sanjose Llongueras, Silvia/H-6339-2014; Bosch Princep, Ramon/F-4229-2016; Benavente, Yolanda/H-9810-2014 OI Bosch Princep, Ramon/0000-0003-4104-5515; NR 24 TC 17 Z9 18 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 IS 11 BP 1475 EP 1481 DI 10.3324/haematol.11350 PG 7 WC Hematology SC Hematology GA 226AU UT WOS:000250560400006 PM 18024395 ER PT J AU Bouville, A Likhtarev, IA Kovgan, LN Minenko, VF Shinkarev, SM Drozdovitch, VV AF Bouville, Andre Likhtarev, Illya A. Kovgan, Lina N. Minenko, Victor F. Shinkarev, Sergei M. Drozdovitch, Vladimir V. TI Radiation dosimetry for highly contaminated Belarusian, Russian and Ukrainian populations, and. for less contaminated populations in Europe SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY 2006 CL Arlington, VA SP Natl Council Radiat Protect & Measurements DE National Council on Radiation Protection and Measurements; Chernobyl; thyroid; iodine ID THYROID DOSE RECONSTRUCTION; SHORT-LIVED RADIOIODINES; CHERNOBYL ACCIDENT; CANCER; BYELARUS; CHILDREN; I-131; EXPOSURE; MODEL AB The explosions at the Chernobyl Nuclear Power Plant (CNPP) in Ukraine early in the morning of 26 April 1986 led to a considerable release of radioactive materials during 10 d. The cloud from the reactor spread many different radionuclides, particularly those of iodine (I-131) and cesium (Cs-134 and Cs-137), over the majority of European countries, but the greatest contamination occurred over vast areas of Belarus, the Russian Federation and Ukraine. As the major health effect of Chernobyl is an elevated thyroid cancer incidence in children and adolescents, much attention has been paid to the thyroid doses resulting from intakes of 1311, which were delivered within 2 mo following the accident. The thyroid doses received by the inhabitants of the contaminated areas of Belarus, Russia, and Ukraine varied in a wide range, mainly according to age, level of ground contamination, milk consumption rate, and origin of the milk that was consumed. Reported individual thyroid doses varied up to similar to 40,000 mGy, with average doses of a few to 1,000 mGy, depending on the area where people were exposed. In addition, the presence in the environment of long-lived Cs-134 and Cs-137 has led to a relatively homogeneous exposure of all organs and tissues of the body via external and internal irradiation, albeit at low rates. Excluding the thyroid doses, the whole-body (or effective) dose estimates for the general population accumulated during 20 y after the accident (1986-2005) range from a few millisieverts (mSv) to some hundred mSv with an average dose of similar to 10 mSv in the contaminated areas of Belarus, Russia, and Ukraine. In other European countries, both the thyroid and the effective doses are, on average, much smaller. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Ukraine Acad Med Sci, ATS Ukraine & Sci Ctr Radiat Med, Ukrainian Radiat Protect Inst, UA-04050 Kiev, Ukraine. Pract Ctr Radiat Med, Republican Sci, Minsk, Byelarus. State Res Ctr Inst Boiphys, Fed Med Biol Agcy, Moscow 123182, Russia. Int Agcy Res Canc, F-69008 Lyon, France. RP Bouville, A (reprint author), NCI, 6120 Execut Blvd,EPS 7094, Bethesda, MD 20892 USA. EM bouvilla@mail.nih.gov NR 44 TC 13 Z9 15 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2007 VL 93 IS 5 BP 487 EP 501 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 221HG UT WOS:000250217400014 PM 18049225 ER PT J AU Ron, E AF Ron, Elaine TI Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY 2006 CL Arlington, VA SP Natl Council Radiat Protect & Measurements DE National Council on Radiation Protection and Measurements; cancer; thyroid; Chernobyl ID POWER-STATION ACCIDENT; POST-CHERNOBYL; NUCLEAR ACCIDENT; HIGH PREVALENCE; BRAF MUTATIONS; PAPILLARY CARCINOMAS; IODINE DEFICIENCY; BRYANSK REGION; ADULT PATIENTS; LOW-FREQUENCY AB As a result of the Chernobyl nuclear power plant accident, massive amounts of radioactive materials were released into the environment and large numbers of individuals living in Belarus, Russia, and Ukraine were exposed to radioactive iodines, primarily I-131. Iodine-131 concentrated in the thyroid gland of residents of the contaminated areas, with children and adolescents being particularly affected. In the decade after the accident, a substantial increase in thyroid cancer incidence was observed among exposed children in the three affected countries, and compelling evidence of an association between pediatric thyroid cancer incidence and radiation exposure to the thyroid gland accumulated. The data currently available suggest that both the magnitude and patterns of thyroid cancer risk are generally consistent with those reported following external exposure. Based on data from case-control studies, iodine deficiency appeared to enhance the risk of developing thyroid cancer following exposure from Chernobyl. Results from a recent large cohort study, however, did not support these findings. Data on adult exposure are limited and not entirely consistent. Similarly, information on thyroid cancer risks associated with in utero exposure is insufficient to draw conclusions. The lack of information on these two population groups indicates an important gap that needs to be filled. Twenty years after the accident, excess thyroid cancers are still occurring among persons exposed as children or adolescents, and, if external radiation can be used as a guide, we can expect an excess of radiation-associated thyroid cancers for several more decades. Since considerable uncertainties about the long-term health effects from Chernobyl remain, continued follow-up of the exposed populations should provide valuable information. C1 NCI, NIH, DHHS, Div Canc Epidemiol & Genet,Radiat Epidemiol B, Bethesda, MD 20892 USA. RP Ron, E (reprint author), NCI, NIH, DHHS, Div Canc Epidemiol & Genet,Radiat Epidemiol B, Bethesda, MD 20892 USA. EM eron@mail.nih.gov NR 71 TC 48 Z9 52 U1 5 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2007 VL 93 IS 5 BP 502 EP 511 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 221HG UT WOS:000250217400015 PM 18049226 ER PT J AU Colon-Ramos, U Lindsay, AC Monge-Rojas, R Greaney, ML Campos, H Peterson, KE AF Colon-Ramos, Uriyoan Lindsay, Ana C. Monge-Rojas, Rafael Greaney, Mary L. Campos, Hannia Peterson, Karen E. TI Translating research into action: a case study on trans fatty acid research and nutrition policy in Costa Rica SO HEALTH POLICY AND PLANNING LA English DT Article DE health policy; nutrition; Costa Rica; developing countries; trans fatty acids ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; DECISION-MAKERS; HEALTH-POLICY; PUBLIC-HEALTH; DIETARY-FAT; ADIPOSE-TISSUE; INCREASED RISK; FOLLOW-UP; WOMEN AB Mounting epidemiologic evidence worldwide has fostered policy regulation of industrially made trans fatty acids (TFA) in several developed countries. Despite country-specific evidence about the effects of TFA on cardiovascular disease in Costa Rica, policy regulation has yet to occur. This qualitative study uses a conceptual framework to identify factors that may impede or promote the process of translation of scientific evidence about TFA into policy in the specific context of Costa Rica. We used single case-study methodology to integrate two sources of data: review of relevant internal documents and in-depth, semi-structured interviews with 21 respondents purposively sampled from three sectors: the cooking oil and food industries, research and academia, and government entities. Content analysis, guided by a conceptual framework of research utilization, revealed 68 emergent themes divided across four categories of analysis. In brief, study participants perceived the political context suitable for discussing policies related to healthy fats. Nevertheless, TFA regulation was not part of the Costa Rican political agenda. Barriers perceived by respondents that impede knowledge translation included: (1) lack of awareness of in-country scientific studies on health effects of TFA; (2) lack of consensus or information about policy options (nutrition labelling, dietary guidelines, legislative mandates); (3) perceived distrust and disparate attitudes between sectors, believed by study participants to result in (4) limited collaboration across sectors. Commissioned task forces and other mechanisms to foster research engagement and facilitate sustained interaction and systematic collaboration among government, food industry and researcher sectors appear crucial in the consideration and adoption of nutrition policy in Costa Rica and other emerging economies. C1 NCI, Hlth Promot Res Branch, Behav Res Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Program Publ Hlth Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc, Boston, MA 02115 USA. RP Colon-Ramos, U (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, 6130 Execut Blvd MSC 7335, Bethesda, MD 20892 USA. EM colonramosu@mail.nih.gov NR 62 TC 12 Z9 14 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1080 J9 HEALTH POLICY PLANN JI Health Policy Plan. PD NOV PY 2007 VL 22 IS 6 BP 363 EP 374 DI 10.1093/heapol/czm030 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 232RF UT WOS:000251036200002 PM 17951318 ER PT J AU Trotter, JF Wisniewski, KA Terrault, NA Everhart, JE Kinkhabwala, M Weinrieb, RM Fair, JH Fisher, RA Koffron, AJ Saab, S Merion, RM AF Trotter, James F. Wisniewski, Karen A. Terrault, Norah A. Everhart, James E. Kinkhabwala, Milan Weinrieb, Robert M. Fair, Jeffrey H. Fisher, Robert A. Koffron, Alan J. Saab, Sammy Merion, Robert M. CA Grp, AS TI Outcomes of donor evaluation in adult-to-adult living donor liver transplantation SO HEPATOLOGY LA English DT Article; Proceedings Paper CT World Transplant Congress CY JUL 22-27, 2006 CL Boston, MA AB The purpose of donor evaluation for adult-to-adult living donor liver transplantation (LDLT) is to discover medical conditions that could increase the donor postoperative risk of complications and to determine whether the donor can yield a suitable graft for the recipient. We report the outcomes of LDLT donor candidates evaluated in a large multicenter study of LDLT. The records of all donor candidates and their respective recipients between 1998 and 2003 were reviewed as part of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). The outcomes of the evaluation were recorded along with demographic data on the donors and recipients. Of the 10 11 donor candidates evaluated, 405 (40%) were accepted for donation. The donor characteristics associated with acceptance (P < 0.05) were younger age, lower body mass index, and biological or spousal relationship to the recipient. Recipient characteristics associated with donor acceptance were younger age, lower Model for End-stage Liver Disease score, and shorter time from listing to first donor evaluation. Other predictors of donor acceptance included earlier year of evaluation and transplant center. Conclusion: Both donor and recipient features appear to affect acceptance for LDLT. These findings may aid the donor evaluation process and allow an objective assessment of the likelihood of donor candidate acceptance. C1 Univ Colorado, Dept Surg, Denver, CO 80202 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. NIDDK, NIH, Bethesda, MD USA. Columbia Univ, Columbia Presbyterian Med Ctr, Dept Surg, New York, NY 10032 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Surg, Richmond, VA 23298 USA. Northwestern Univ, Sch Med, Dept Surg, Chicago, IL 60611 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Trotter, JF (reprint author), Univ Colarado Hosp, 1635 N Ursula,Campus Box 154, Aurora, CO 80262 USA. EM james.trotter@uchsc.edu FU NIDDK NIH HHS [U01 DK062484, U01 DK062444, U01 DK062467, U01 DK062483, U01 DK062494, U01 DK062496, U01 DK062498, U01 DK062505, U01 DK062531, U01 DK062536, U01 DK062536-01, U01 DK062536-02, U01 DK062536-03, U01 DK062536-04, U01 DK062536-05, U01 DK062536-05S1, U01 DK062536-06, U01 DK062536-06S1, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK62536] NR 14 TC 36 Z9 39 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2007 VL 46 IS 5 BP 1476 EP 1484 DI 10.1002/hep.21845 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228BF UT WOS:000250701200021 PM 17668879 ER PT J AU Feld, JJ Nanda, S Huang, Y Chen, WP Cam, M Pusek, SN Schweigler, LM Theodore, D Zacks, SL Liang, TJ Fried, MW AF Feld, Jordan J. Nanda, Santosh Huang, Ying Chen, Weiping Cam, Maggie Pusek, Susan N. Schweigler, Lisa M. Theodore, Dickens Zacks, Steven L. Liang, T. Jake Fried, Michael W. TI Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response SO HEPATOLOGY LA English DT Article ID C VIRUS-INFECTION; INTERFERON-ALPHA; PLUS RIBAVIRIN; TRANSCRIPTIONAL REGULATION; CASPASE ACTIVATION; ANTIVIRAL THERAPY; NONRESPONDERS; GENOTYPE-1; MECHANISM; CELLS AB The reasons for hepatitis C treatment failure remain unknown but may be related to different host responses to therapy. In this study, we compared hepatic gene expression in patients prior to and during peginterferon and ribavirin therapy. In the on-treatment group, patients received either ribavirin for 72 hours prior to peginterferon alpha-2a injection or peginterferon alpha-2a for 24 hours, prior to biopsy. The patients were grouped into rapid responders (RRs) with a greater than 2-log drop and slow responders (SRs) with a less than 2-log drop in hepatitis C virus RNA by week 4. Pretreatment biopsy specimens were obtained from a matched control group. The pretreatment patients were grouped as RRs or SRs on the basis of the subsequent treatment response. Gene expression profiling was performed with Affymetrix microarray technology Known interferon stimulated genes (ISGs) were induced in treated patients. In the pretreatment group, future SRs had higher pretreatment ISG expression than RRs. On treatment, RRs and SRs had similar absolute ISG expression, but when it was corrected for the baseline expression with the pretreatment group, RRs showed a greater fold change in ISGs, whereas SRs showed a greater change in interferon (IFN)-inhibitory pathways. The patients pretreated with ribavirin had heightened induction of IFN-related genes and down-regulation of genes involved in IFN inhibition and hepatic stellate cell activation. Conclusion: These data suggest that ISG inducibility is important for the treatment response and that ribavirin may improve outcomes by enhancing hepatic gene responses to peginterferon. Collectively, these mechanisms may provide a molecular basis for the improved efficacy of combination therapy. C1 NIDDK, Liver Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NIDDK, Microarray Facil, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, Natl Inst Hlth, Bldg 10,Room 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM jakel@intra.niddk.nih.gov FU Intramural NIH HHS [Z01 DK054505-11, Z01 DK054505-12, Z99 DK999999, ZIA DK054505-13]; NCRR NIH HHS [M01 RR000046, RR 000046]; NIDDK NIH HHS [DK06614] NR 33 TC 195 Z9 198 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2007 VL 46 IS 5 BP 1548 EP 1563 DI 10.1002/hep.21853 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228BF UT WOS:000250701200029 PM 17929300 ER PT J AU DeRusso, PA Ye, W Shepherd, R Haber, BA Shneider, BL Whitington, PF Schwarz, KB Bezerra, JA Rosenthal, P Karpen, S Squires, RH Magee, JC Robuck, PR Sokoll, RJ AF DeRusso, Patricia A. Ye, Wen Shepherd, Ross Haber, Barbara A. Shneider, Benjamin L. Whitington, Peter F. Schwarz, Kathleen B. Bezerra, Jorge A. Rosenthal, Philip Karpen, Saul Squires, Robert H. Magee, John C. Robuck, Patricia R. Sokoll, Ronald J. CA Biliary Atresia Res Consortium TI Growth failure and outcomes in infants with biliary atresia: A report from the biliary atresia research consortium SO HEPATOLOGY LA English DT Article ID STAGE LIVER-DISEASE; LONG-TERM SURVIVAL; NUTRITIONAL SUPPORT; ENERGY-EXPENDITURE; BODY-COMPOSITION; KASAI OPERATION; CHILDREN; TRANSPLANTATION; MALNUTRITION AB Malnutrition is a significant clinical problem in infants with biliary atresia. The natural history of poor growth and its potential association with early transplantation or death in children with biliary atresia was determined. Serial weight- and length-for-age z-scores were computed as part of a retrospective study of 100 infants who underwent hepatoportoenterostomy (HPE) for biliary atresia at 9 U.S. pediatric centers between 1997 and 2000. Poor outcome was defined as transplantation or death by 24 months of age (n = 46) and good outcome was defined as survival with native liver at 24 months ofage with total serum bilirubin less dun 6 mg/dL (n = 54). Growth velocity was significantly slower in the poor outcome group compared to the good outcome group (P < 0.001 for both weight and length). Mean weight z-scores were significantly lower by 6 months after HPE in the poor outcome group (-2.1 +/- 1.4) compared to the good outcome group (- 1.2 +/- 1.4) (P < 0.001). In a subgroup with total bilirubin between 2 and 6 mg/dL at 3 months after HPE (n = 28), the weight z-scores at 3 months after HPE were significantly lower in the poor outcome group (-2.0 +/- 1.2) compared to the good outcome group (- 1.0 +/- 1.2) (P = 0.04) despite similar bilirubin concentrations. Conclusiom Growth failure after HPE was associated with transplantation or death by 24 months of age. The combination of intermediate bilirubin concentrations and poor mean weight z-scores 3 months after HPE was also associated with poor clinical outcome. C1 Johns Hopkins Sch Med, Baltimore, MD USA. Johns Hopkins Childrens Ctr, Baltimore, MD USA. Univ Michigan Hlth Syst, Taubman Ctr 2926, Ann Arbor, MI 48109 USA. Washington Univ, Sch Med, St Louis, MO USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp, Pittsburgh, PA 15213 USA. NIDDK, NIH, Bethesda, MD USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Childrens Hosp, Denver, CO 80218 USA. RP Magee, JC (reprint author), Univ Michigan Hlth Syst, Taubman Ctr 2926, Box 0331,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM mageej@umich.edu FU NIDDK NIH HHS [U01 DK062500, U01 DK062436, U01 DK062445, U01 DK062452, U01 DK062453, U01 DK062456, U01 DK062470, U01 DK062470-02, U01 DK062481, U01 DK062497, U01 DK062503, U01DK062436, U01DK062445, U01DK062452, U01DK062453, U01DK062456, U01DK062481, U01DK062497, U01DK062500, U01DK062503, UO1DK062470] NR 20 TC 35 Z9 38 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2007 VL 46 IS 5 BP 1632 EP 1638 DI 10.1002/hep.21923 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228BF UT WOS:000250701200036 PM 17929308 ER PT J AU Handelsman, E Cheng, I Thompson, B Hershow, R Mofenson, LM Hollinger, FB Chen, KT Burchett, SK Klinzman, D Stapleton, JT AF Handelsman, E. Cheng, I. Thompson, B. Hershow, R. Mofenson, L. M. Hollinger, F. B. Chen, K. T. Burchett, S. K. Klinzman, D. Stapleton, Jack T. CA Women Infants Transmiss Study Grp TI Impact of GB virus type c infection on mother-to-child HIV transmission in the women and infants transmission study cohort SO HIV MEDICINE LA English DT Article DE GB virus type C; hepatitis G; HIV; vertical transmission ID HEPATITIS-G VIRUS; C/HEPATITIS-G VIRUS; ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION; COINFECTION; RNA; INDIVIDUALS; SURVIVAL; VIREMIA; INHIBITION AB Background GB virus type C (GBV-C) viraemia is associated with a beneficial outcome in HIV-infected individuals in several though not all studies. GBV-C viraemia was examined in a matched case-control study of 133 HIV-infected pregnant women who transmitted HIV to their infants ('cases') and 266 non-transmitting controls. Methods HIV-infected children and controls were pair-matched for high-risk delivery, race and year of delivery. GBV-C status was determined in maternal plasma samples obtained at or within 3 months of delivery. Results Pregnant women with GBV-C viraemia (11% of those studied) had lower HIV RNA levels (P=0.01) and higher CD4 percentages (P=0.006) than women without GBV-C. A trend towards decreased mother-to-child transmission in the multivariate analysis was observed among GBV-C viraemic women delivering after highly active antiretroviral therapy (HAART) became available [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.08-1.05; P=0.06], but not in women delivering prior to the widespread use of HAART. Conclusions GBV-C viraemia was associated with a beneficial effect on CD4 percentage and HIV RNA level in these pregnant women, and was also associated with a trend towards reduced risk of mother-to-child HIV transmission among women after HAART became available. Further studies with larger or multiple cohorts are necessary to assess possible benefits in this population. C1 SUNY Downstate, Brooklyn, NY USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Illinois, Coll Med, Chicago, IL USA. NICHD, PAMA, NIH, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Iowa, Dept Internal Med, GH, Iowa City, IA 52242 USA. RP Stapleton, JT (reprint author), Univ Iowa, Dept Internal Med, GH, SW34-P, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR000188, RR000645]; NIAID NIH HHS [1 U01 AI 050274-01, AI58740, N01 AI 085339, U01 AI 034841, U01 AI 034858]; NICHD NIH HHS [U01 HD 036117, U01 HD 041983]; NIDA NIH HHS [U01 DA 015053, 9U01 DA 015054] NR 46 TC 7 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD NOV PY 2007 VL 8 IS 8 BP 561 EP 567 DI 10.1111/j.1468-1293.2007.00510.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 221YK UT WOS:000250263100012 PM 17944690 ER PT J AU Stam, CJ Nolte, G Daffertshofer, A AF Stam, Cornelis J. Nolte, Guido Daffertshofer, Andreas TI Phase lag index: Assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources SO HUMAN BRAIN MAPPING LA English DT Article DE phase lag index; phase synchronization; coherence; volume conduction; EEG; MEG; functional connectivity; absence seizure; Alzheimer's disease ID LARGE-SCALE; HUMAN BRAIN; SYNCHRONIZATION; COHERENCE; OSCILLATORS; INTEGRATION; SIGNALS; AREAS; MAGNETOENCEPHALOGRAPHY; ELECTRODE AB Objective: To address the problem of volume conduction and active reference electrodes in the assessment of functional connectivity, we propose a novel measure to quantify phase synchronization, the phase lag index (PLI), and compare its performance to the well-known phase coherence (PC), and to the imaginary component of coherency (IC). Methods: The PLI is a measure of the asymmetry of the distribution of phase differences between two signals. The performance of PLI, PC, and IC was examined in (i) a model of 64 globally coupled oscillators, (ii) an EEG with an absence seizure, (iii) an EEG data set of 15 Alzheimer patients and 13 control subjects, and (iv) two MEG data sets. Results: PLI and PC were more sensitive than IC to increasing levels of true synchronization in the model. PC and IC were influenced stronger than PLI by spurious correlations because of common sources. All measures detected changes in synchronization during the absence seizure. In contrast to PC, PLI and IC were barely changed by the choice of different montages. PLI and IC were superior to PC in detecting changes in beta band connectivity in AD patients. Finally, PLI and IC revealed a different spatial pattern of functional connectivity in MEG data than PC. Conclusion: The PLI performed at least as well as the PC in detecting true changes in synchronization in model and real data but, at the same token and like-wise the IC, it was much less affected by the influence of common sources and active reference electrodes. C1 Vrije Univ Amsterdam Med Ctr, Dept Clin Neurophysiol, NL-1007 MB Amsterdam, Netherlands. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Fraunhofer Inst, Berlin, Germany. VU, Inst Fundamental & Clin Movement Sci, Amsterdam, Netherlands. RP Stam, CJ (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Clin Neurophysiol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM CJ.Stam@vumc.nl NR 43 TC 370 Z9 371 U1 9 U2 46 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2007 VL 28 IS 11 BP 1178 EP 1193 DI 10.1002/hbm.20346 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 229QT UT WOS:000250819900008 PM 17266107 ER PT J AU Voutetakis, A Zheng, C Wang, J Goldsmith, CM Afione, S Chiorini, JA Wenk, ML Vallant, M Irwin, RD Baum, BJ AF Voutetakis, A. Zheng, C. Wang, J. Goldsmith, C. M. Afione, S. Chiorini, J. A. Wenk, M. L. Vallant, M. Irwin, R. D. Baum, B. J. TI Gender differences in serotype 2 adeno-associated virus biodistribution after administration to rodent salivary glands SO HUMAN GENE THERAPY LA English DT Article ID MOUSE SUBMANDIBULAR-GLAND; SEXUAL-DIMORPHISM; GENE-EXPRESSION; VIRAL VECTORS; SJOGRENS-SYNDROME; MICE; THERAPEUTICS; TRANSDUCTION; TESTOSTERONE; DISEASE AB Salivary glands (SGs) have proven useful targets for clinical applications of gene therapeutics. In this toxicology and biodistribution study, which conforms to U. S. Food and Drug Administration Good Laboratory Practice regulations, four doses (10(7)-10(10) particles) of a serotype 2 adeno-associated viral (AAV2) vector encoding human erythropoietin were directly administered to the right submandibular gland of male and female BALB/c mice ( n = 21 per gender dose group). Control-treated (saline administered; n = 66) and vectortreated ( n = 168) animals did not differ in clinical appearance, morbidity and mortality rates, food and water consumption, weight gain ratios, and final weight. Clinical hematology values also were unaffected by AAV2 administration except for parameters influenced by the expression of the recombinant protein (e. g., hematocrit). Mice were killed on days 3, 30, 55, and 92. No major vector-related toxicity was uncovered after complete pathology and histopathology review. However, a significant gender-related difference in vector biodistribution was revealed by quantitative polymerase chain reaction. In male mice vector (group receiving 1010 particles/animal) effectively transduced, and was primarily confined within, the SGs (i.e., similar to 800 times more copies in SGs than in liver; day 3) and long lived. In contrast, in female mice, SG transduction was less efficient (260-fold less than in males; day 3) and short lived, and vector was disseminated widely via both the bloodstream (SG: liver copy ratio, similar to 1) and saliva (30-fold greater than in males). The observed vector biodistribution is likely due to differences in AAV2 receptor targets and structural differences affecting SG integrity. Sexual dimorphism is a factor of major significance that could potentially affect gene therapy clinical applications in SGs. C1 NIH, NIDCR, GTTB, Bethesda, MD 20892 USA. BioReliance Invitrogen Bioserv, Div Toxicol, Rockville, MD 20850 USA. NIH, Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Baum, BJ (reprint author), NIH, NIDCR, GTTB, Bldg 10,Rm 1N113, Bethesda, MD 20892 USA. EM bbaum@mail.nih.gov FU Intramural NIH HHS NR 39 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2007 VL 18 IS 11 BP 1109 EP 1118 DI 10.1089/hum.2007.072 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 232WP UT WOS:000251051700001 PM 17939749 ER PT J AU Zhang, QJ Zulfiqar, F Xiao, X Riazuddin, SA Ahmad, Z Caruso, R MacDonald, I Sieving, P Riazuddin, S Hejtmancik, JF AF Zhang, Qingjiong Zulfiqar, Fareeha Xiao, Xueshan Riazuddin, S. Amer Ahmad, Zahoor Caruso, Raphael MacDonald, Ian Sieving, Paul Riazuddin, Sheikh Hejtmancik, J. Fielding TI Severe retinitis pigmentosa mapped to 4p15 and associated with a novel mutation in the PROM1 gene SO HUMAN GENETICS LA English DT Article ID ROD RETINAL DYSTROPHY; HEMATOPOIETIC STEM; OCULAR PHENOTYPE; DEGENERATION; MAPS; ABCR; CHROMOSOME-4; PROMININ; PROTEIN; UPDATE AB Mutation in the PROM1 gene previously has been identified in one family with retinal degeneration for which neither ERG recordings nor detailed information about visual impairment is available. A large family with multiple individuals affected by retinal degeneration was ascertained in the Punjab province of Pakistan. The visual acuity of all affected patients in the family was severely compromised beginning in early childhood. The retinal disease in this family is a severe form of retinitis pigmentosa (RP) accompanied by macular degeneration. Fundus changes advanced with age. Choriocapillaris atrophy and posterior RPE atrophy were obvious allowing visualization of the large choroidal vessels in patients over 40 years of age. Rod and cone responses on ERG recordings were extinguished in patient's teens. A genome-wide scan mapped the disease to a 34.7 cM region of chromosome 4p14-p16 between D4S1599 and D4S405. A maximum lod score of 3.96 with D4S403 and D4S391 is seen at theta= 0. Sequence analysis of PROM1 located in the linkage interval identified a c.1726C > T homozygous transition in exon 15: resulting in p.Gln576X in the translated protein. This mutation is found in a homozygous state in all six affected individuals and was heterozygous in five of the six unaffected family members examined. The mutation was not detected in 192 chromosomes of unrelated control individuals of the same ethnicity and from the same region. This delineates the phenotypic characteristics of retinopathy caused by mutations in PROM1. C1 NCI, NEI, OGCSB, Bethesda, MD 20892 USA. NIH, NEI, Ophthalmic Genet & Visual Funct Branch, Bethesda, MD 20982 USA. Sun Yat Sen Univ, Zhongsan Ophthalmic Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Peoples R China. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. RP Zhang, QJ (reprint author), NCI, NEI, OGCSB, Bldg 10,Rm 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM qingjiongzhang@yahoo.com; riaz@lhr.comsats.net.pk; f3h@helix.nih.gov RI SHEIKH, RIAZUDDIN/L-2406-2015; OI MacDonald, Ian/0000-0001-7472-8385 NR 28 TC 49 Z9 50 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2007 VL 122 IS 3-4 BP 293 EP 299 DI 10.1007/s00439-007-0395-2 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 221OI UT WOS:000250236800007 PM 17605048 ER PT J AU Rebibo-Sabbah, A Nudelman, I Ahmed, ZM Baasov, T Ben-Yosef, T AF Rebibo-Sabbah, Annie Nudelman, Igor Ahmed, Zubair M. Baasov, Timor Ben-Yosef, Tamar TI In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome SO HUMAN GENETICS LA English DT Article ID PREMATURE STOP MUTATIONS; MAMMALIAN TRANSLATION SYSTEM; SYNDROME TYPE 1F; RECESSIVE DEAFNESS; ALLELIC MUTATIONS; CYSTIC-FIBROSIS; GENE-MUTATIONS; MYOSIN VIIA; ANTIBIOTICS; PROTOCADHERIN-15 AB Type 1 Usher syndrome (USH1) is a recessively inherited condition, characterized by profound prelingual deafness, vestibular areflexia, and prepubertal onset of retinitis pigmentosa (RP). While the auditory component of USH1 can be treated by cochlear implants, to date there is no effective treatment for RP. USH1 can be caused by mutations in each of at least six genes. While truncating mutations of these genes cause USH1, some missense mutations of the same genes cause nonsyndromic deafness. These observations suggest that partial or low level activity of the encoded proteins may be sufficient for normal retinal function, although not for normal hearing. In individuals with USH1 due to nonsense mutations, interventions enabling partial translation of a full-length functional protein may delay the onset and/or progression of RP. One such possible therapeutic approach is suppression of nonsense mutations by small molecules such as aminoglycosides. We decided to test this approach as a potential therapy for RP in USH1 patients due to nonsense mutations. We initially focused on nonsense mutations of the PCDH15 gene, underlying USH1F. Here, we show suppression of several PCDH15 nonsense mutations, both in vitro and ex vivo. Suppression was achieved both by commercial aminoglycosides and by NB30, a new aminoglycoside-derivative developed by us. NB30 has reduced cytotoxicity in comparison to commercial aminoglycosides, and thus may be more efficiently used for therapeutic purposes. The research described here has important implications for the development of targeted interventions that are effective for patients with USH1 caused by various nonsense mutations. C1 Technion Israel Inst Technol, Rappaport Family Inst Res Med Sci, Rappaport Fac Med, Dept Genet, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Inst Catalysis Sci & Technol, Dept Chem, IL-32000 Haifa, Israel. Natl Inst Hlth, Natl Inst Deafness & Other Communicat Disorders, Mol Genet Lab, Rockville, MD 20850 USA. RP Ben-Yosef, T (reprint author), Technion Israel Inst Technol, Rappaport Family Inst Res Med Sci, Rappaport Fac Med, Dept Genet, PO Box 9649,Bat Galim, IL-31096 Haifa, Israel. EM benyosef@tx.technion.ac.il FU NIDCD NIH HHS [1 Z01 DC000039-09, 1 Z01 DC000035-09] NR 35 TC 42 Z9 42 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2007 VL 122 IS 3-4 BP 373 EP 381 DI 10.1007/s00439-007-0410-7 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 221OI UT WOS:000250236800015 PM 17653769 ER PT J AU Cui, CY Kunisada, M Esibizione, D Grivennikov, SI Piao, Y Nedospasov, SA Schlessinger, D AF Cui, Chang-Yi Kunisada, Makoto Esibizione, Diana Grivennikov, Sergei I. Piao, Yulan Nedospasov, Sergei A. Schlessinger, David TI Lymphotoxin-beta regulates periderm differentiation during embryonic skin development SO HUMAN MOLECULAR GENETICS LA English DT Article ID CORNIFIED CELL ENVELOPES; ECTODERMAL DYSPLASIA; HAIR FOLLICLE; MOUSE MODEL; PROTEIN; GENE; MICE; INDUCTION; SURFACE; DEATH AB Lymphotoxin-beta (LT beta) is a key regulator of immune system development, but also affects late stages in hair development. In addition, high expression of LTb at an early stage in epidermis hinted at a further function in hair follicle induction or epithelial development. We report that hair follicles were normally induced in LTb-/- skin, but the periderm detached from the epidermis earlier, accompanied by premature appearance of keratohyalin granules. Expression profiling revealed dramatic down-regulation of a gene cluster encoding periderm-specific keratin-associated protein 13 and four novel paralogs in LTb-/- skin prior to periderm detachment. Epidermal differentiation markers, including small proline-rich proteins, filaggrins and several keratins, were also affected, but transiently in LTb-/- skin at the time of abnormal periderm detachment. As expected, Tabby mice, which lack the EDA gene, the putative upstream regulator of LTb in skin, showed similar though milder periderm histopathology and alterations in gene expression. Overall, LTb shows a primary early function in periderm differentiation, with later transient effects on epidermal and hair follicle differentiation. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Bologna, Dept Histol Embryol & Appl Biol, I-40126 Bologna, Italy. NCI, Basic Res Lab, Frederick, MD 21702 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia. RP Schlessinger, D (reprint author), NIA, Genet Lab, NIH, 333 Cassel Dr,Suite 3000, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU Intramural NIH HHS NR 31 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 2007 VL 16 IS 21 BP 2583 EP 2590 DI 10.1093/hmg/ddm210 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SV UT WOS:000250679000006 PM 17673451 ER PT J AU Dobrowolski, SF Ellingson, CE Caldovic, L Tuchman, M AF Dobrowolski, Steven F. Ellingson, Clinton E. Caldovic, Ljubica Tuchman, Mendel TI Streamlined assessment of gene variants by high resolution melt profiling utilizing the ornithine Transcarbamylase gene as a model system SO HUMAN MUTATION LA English DT Article DE mutation analysis; genotyping; high resolution melting; molecular screening; urea cycle; OTC; DNA analysis ID MUTATIONS; POLYMORPHISM AB Ornithine transcarbamylase (OTC) deficiency is an X,linked, semidominant genetic disorder and the most prevalent inherited defect of the urea cycle. Molecular genetic testing of the OTC gene is critically important for clinical diagnosis, carrier testing, and prenatal diagnosis. Private mutations are observed throughout the OTC gene with more than 340 reported disease-causing mutations. High resolution melt profiling was adapted to perform homogeneous analysis of the 10 coding regions and their intronic flanks in a 96-well plate format. The 10 DNA fragments ranging from 146 bp to 266 bp are amplified in a PCR run. A common analysis condition simultaneously generates melting profiles from all 10 fragments. To streamline analysis, deviant profiles resulting from common polymorphic variants are triaged using redundant assessment with melt profile controls in selected whole-exon assays and a separate multiplex genotyping assay. The test is further streamlined by recovering dye-stained amplification product from the melt profiling plate to serve as DNA sequencing template. Described herein is the comprehensive analysis of the OTC gene in 23 OTC-deficient patients. This system provides a rapid means to localize sequence variants, markedly reducing the need for DNA sequencing, and is applicable to other genes and disorders. C1 Idaho Technol, Salt Lake City, UT USA. George Washington Univ, Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC USA. RP Dobrowolski, SF (reprint author), NIDDK, Natl Inst Hlth, Salt Lake City, UT 84108 USA. EM steven_dobrowolski@idahotech.com OI Caldovic, Ljubica/0000-0002-9140-5585 FU NIDDK NIH HHS [R01DK47870, R44DK069106] NR 14 TC 24 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2007 VL 28 IS 11 BP 1133 EP 1140 DI 10.1002/humu.20558 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 226TA UT WOS:000250610200011 PM 17565723 ER PT J AU Agarwal, B Ahmed, A Rushing, EJ Bloom, M Kadom, N Vezina, G Krasnewich, D Santi, M AF Agarwal, Beamon Ahmed, Atif Rushing, Elisabeth J. Bloom, Miriam Kadom, Nadja Vezina, Gilbert Krasnewich, Donna Santi, Mariarita TI Congenital disorder of glycosylation-X: clinicopathologic study of an autopsy case with distinct neuropathologic features SO HUMAN PATHOLOGY LA English DT Article DE autopsy; brain; cirrhosis; glycosylation; transferrin ID CHILDREN; INFANTS; IA AB Congenital disorders of glycosylation are a recently recognized group of inherited, multisystem disorders caused by aberrant biosynthesis of glycoproteins. We report the clinical and postmortem findings in a 3-year-old boy with a history of multiple medical issues including developmental delay, epilepsy, chronic protein-losing enteropathy, respiratory failure, nephropathy, coagulopathy, and cardiomyopathy. As part of the workup, isoelectric focusing for congenital disorders of glycosylation showed carbohydrate-deficient transferrin with the mono-oligo/dioligo ratio of 0.700 (normal, 0.075-0.109), indicating an increased level of abnormally glycosylated transferrin. After supportive care, he died secondary to multisystem complications of his disease. General autopsy findings were notable for micronodular liver cirrhosis with iron overload, myocardial ischemia and calcification, and hypertrophied glomeruli. Examination of the brain revealed cerebral and cerebellar atrophy, diffuse astrogliosis, and meningeal fibrosis. This article reveals complete autopsy findings of untyped congenital disorders of glycosylation, congenital disorders of glycosylation-x, with an undefined metabolic basis. Published by Elsevier Inc. C1 Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. Howard Univ, Sch Med, Dept Pathol, Washington, DC 20059 USA. Childrens Natl Med Ctr, Div Pathol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Complex Referral & Radiol, Div Radiol, Washington, DC 20010 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Rushing, EJ (reprint author), Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. EM elisabeth.rushing@gmail.com OI Ahmed, Atif/0000-0002-8791-5785; Kadom, Nadja/0000-0002-7073-956X NR 17 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2007 VL 38 IS 11 BP 1714 EP 1719 DI 10.1016/j.humpath.2007.05.028 PG 6 WC Pathology SC Pathology GA 228PZ UT WOS:000250743300016 PM 17954208 ER PT J AU Horne, FM Blithe, DL AF Horne, Frances McFarland Blithe, Diana L. TI Progesterone receptor modulators and the endometrium: changes and consequences SO HUMAN REPRODUCTION UPDATE LA English DT Article; Proceedings Paper CT Meeting on Progesterone Receptor Modulators CY APR 07-08, 2006 CL Bethesda, MD ID LOW-DOSE MIFEPRISTONE; ENDOTHELIAL GROWTH-FACTOR; CONTROLLED OVARIAN HYPERSTIMULATION; HORMONE REPLACEMENT THERAPY; LONG-TERM TREATMENT; EARLY LUTEAL-PHASE; CANCER-CELL-LINES; OPEN-LABEL TRIAL; WOMEN 40 YEARS; ANDROGEN RECEPTOR AB Progesterone receptor modulators (PRMs) have been used for contraceptive research, as well as for treatment of fibroids, endometriosis and heavy or irregular menstrual bleeding. Long-term treatment with these compounds results in changes to the endometrium resulting in potential confusion in trying to characterize endometrial biopsies. A meeting was held to discuss the properties of PRMs, the effects of perturbed hormonal control of the endometrium and the need for further understanding of the biology of progesterone receptor action to facilitate the development of new PRMs. A panel of pathologists was convened to evaluate endometrial changes associated with a minimum of three months of chronic treatment with PRMs. Four different agents were used in the treatment regimens but the pathologists were blinded to treatment regimen or agent. The panel agreed that the endometrial biopsies did not fit into a classification of either proliferative or secretory endometrium but exhibited an unusual architecture that could be characterized as glandular dilatation. There was little evidence of mitosis, consistent with a proposed anti-proliferative effect of PRMs. The panel concluded that the biopsies did not reveal evidence of safety concern and that pathologists and investigators familiar with endometrial effects of chronic PRM exposure should consider working with pharmaceutical companies and regulatory agencies to develop standard descriptions of PRM-associated endometrial changes as well as the types of histologic changes that would signal a need for intervention. C1 NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. Rose Li & Associates Inc, Bethesda, MD 20817 USA. RP Blithe, DL (reprint author), NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, 6100 Execut Blvd,Room 8B13, Bethesda, MD 20892 USA. EM blithed@mail.nih.gov NR 173 TC 34 Z9 36 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD NOV-DEC PY 2007 VL 13 IS 6 BP 567 EP 580 DI 10.1093/humupd/dmm023 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 227TE UT WOS:000250679900006 PM 17630398 ER PT J AU Margolis, KL Piller, LB Ford, CE Henriquez, MA Cushman, WC Einhorn, PT Colon, PJ Vidt, DG Christian, R Wong, ND Wright, JT Goff, DC AF Margolis, Karen L. Piller, Linda B. Ford, Charles E. Henriquez, Mario A. Cushman, William C. Einhorn, Paula T. Colon, Pedro J., Sr. Vidt, Donald G. Christian, Rudell Wong, Nathan D. Wright, Jackson T., Jr. Goff, David C., Jr. CA Antihypertensive Lipid-Lowering Tr TI Blood pressure control in Hispanics in the antihypertensive and lipid-lowering treatment to prevent heart attack trial SO HYPERTENSION LA English DT Article DE hypertension; Hispanic; ethnicity; race; clinical trials; blood pressure control ID TERMINAL DIGIT PREFERENCE; MEXICAN-AMERICANS; HYPERTENSION TREATMENT; ETHNIC-DIFFERENCES; QUALITY-CONTROL; MEDICATION USE; UNITED-STATES; PRIMARY-CARE; RISK-FACTORS; HEALTH AB Historically, blood pressure control in Hispanics has been considerably less than that of non-Hispanic whites and blacks. We compared determinants of blood pressure control among Hispanic white, Hispanic black, non-Hispanic white, and non-Hispanic black participants (N = 32 642) during follow-up in a randomized, practice-based, active-controlled trial. Hispanic blacks and whites represented 3% and 16% of the cohort, respectively; 33% were non-Hispanic black and 48% were non-Hispanic white. Hispanics were less likely to be controlled (< 140/90 mm Hg) at enrollment, but within 6 to 12 months of follow-up, Hispanics had a greater proportion < 140/90 mm Hg compared with non-Hispanics. At 4 years of follow-up, blood pressure was controlled in 72% of Hispanic whites, 69% of Hispanic blacks, 67% of non-Hispanic whites, and 59% of non-Hispanic blacks. Compared with non-Hispanic whites, Hispanic whites had a 20% greater odds of achieving BP control by 2 years of follow-up (odds ratio: 1.20; 95% CI: 1.10 to 1.31) after controlling for demographic variables and comorbidities, Hispanic blacks had a similar odds of achieving BP control (odds ratio: 1.04; 95% CI: 0.86 to 1.25), and non-Hispanic blacks had a 27% lower odds (odds ratio: 0.73; 95% CI: 0.69 to 0.78). We conclude that in all patients high levels of blood pressure control can be achieved with commonly available medications and that Hispanic ethnicity is not associated with inferior control in the setting of a clinical trial in which hypertensive patients had equal access to medical care, and medication was provided at no cost. C1 HealthPartners Res Fdn, Minneapolis, MN 55440 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Bronx Nephrol Hypertens, Bronx, NY USA. Memphis Vet Affairs Med Ctr, Res & Dev Serv, Memphis, TN USA. NHLBI, Bethesda, MD 20892 USA. Ctr Cardiovasc Caguas, Caguas, PR USA. Cleveland Clin, Cleveland, OH 44106 USA. NitroMed, Lexington, MA USA. Univ Calif Irvine, Heart Dis Program, Irvine, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. RP Margolis, KL (reprint author), HealthPartners Res Fdn, POB 1524,Mailstop 21111R, Minneapolis, MN 55440 USA. EM Karen.L.Margolis@HealthPartners.com FU NHLBI NIH HHS [N01-HC-35130]; NIMHD NIH HHS [P60 MD002265] NR 39 TC 26 Z9 28 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2007 VL 50 IS 5 BP 854 EP 861 DI 10.1161/HYPERTENSIONAHA.107.092650 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225LA UT WOS:000250518200010 PM 17846352 ER PT J AU Lee, DS Massaro, JM Wang, TJ Kannel, WB Benjamin, EJ Kenchaiah, S Levy, D D'Agostino, RB Vasan, RS AF Lee, Douglas S. Massaro, Joseph M. Wang, Thomas J. Kannel, William B. Benjamin, Emelia J. Kenchaiah, Satish Levy, Daniel D'Agostino, Ralph B., Sr. Vasan, Ramachandran S. TI Antecedent blood pressure, body mass index, and the risk of incident heart failure in later life SO HYPERTENSION LA English DT Article DE hypertension; blood pressure; obesity; body mass index; congestive heart failure; cohort studies ID LEFT-VENTRICULAR MASS; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; PRIMARY-CARE; FRAMINGHAM; HYPERTENSION; PREDICTORS; GUIDELINES; OBESITY; STROKE AB Higher blood pressure and body mass index (BMI) are risk factors for heart failure. It is unknown whether the presence of these risk factors in midadulthood affect the future development of heart failure. In the community-based Framingham Heart Study, we examined the associations of antecedent blood pressure and BMI with heart failure incidence in later life. We studied 3362 participants (57% women; mean age: 62 years) who attended routine examinations between 1969 and 1994 and examined their systolic and diastolic blood pressure, pulse pressure, and BMI at current (baseline), recent (average of readings obtained 1 to 10 years before baseline), and remote (average of readings obtained 11 to 20 years before baseline) time periods. During 67 240 person-years of follow-up, 518 participants (280 women) developed heart failure. Current, recent, and remote systolic pressure; pulse pressure; and BMI were individually associated with incident heart failure (all P < 0.001). Recent systolic pressure (hazards ratio [HR] per 1-SD increment: 1.31; 95% CI: 1.11 to 1.55), pulse pressure (HR per 1-SD increment: 1.33; 95% CI: 1.14 to 1.54), and BMI (HR per unit increase: 1.15; 95% CI: 1.08 to 1.23) were associated with heart failure risk even after adjusting for current measures. Similarly, remote systolic pressure (HR per 1 SD: 1.17; 95% CI: 1.04 to 1.31), pulse pressure (HR per 1 SD: 1.17; 95% CI: 1.06 to 1.31), and BMI (HR per unit: 1.09; 95% CI: 1.05 to 1.14) remained associated with incident heart failure after adjusting for current measurements. Higher blood pressure and BMI in midlife are harbingers of increased risk of heart failure in later life. Early risk factor modification may decrease heart failure burden. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Univ Toronto, Clin Evaluat Sci & Univ Hlth Network, Toronto, ON, Canada. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Univ Calif Irvine, Med Ctr, Div Cardiol, Orange, CA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; Kenchaiah, Satish/A-1519-2016; OI Benjamin, Emelia/0000-0003-4076-2336; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K23HL074077, 2K24HL04334]; NIA NIH HHS [AG028321]; PHS HHS [N01-25195] NR 29 TC 44 Z9 48 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2007 VL 50 IS 5 BP 869 EP 876 DI 10.1161/HYPERTENSIONAHA.107.095380 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225LA UT WOS:000250518200012 PM 17893376 ER PT J AU Stein, PK Lundequam, EJ Oliveira, LPJ Claw, DJ Freedland, KE Carney, RM Domitrovich, PP AF Stein, Phyllis K. Lundequam, Eric J. Oliveira, Leonardo P. J. Claw, Daniel J. Freedland, Kenneth E. Carney, Robert M. Domitrovich, Peter P. TI Cardiac autonomic modulation - Analyzing circadian and ultradian rhythms SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID HEART-RATE-VARIABILITY C1 Washington Univ, Sch Med, St Louis, MO 63108 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Fed Fluminense, Lab Exercise Sci, BR-24220000 Niteroi, RJ, Brazil. Washington Univ, Heart Variabil Lab, St Louis, MO USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Georgia, Athens, GA 30602 USA. Univ Michigan, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Adv Clin Res, Ann Arbor, MI 48109 USA. NIH, US Dept Def, Bethesda, MD 20892 USA. Amer Coll Rheumatol, Washington, DC USA. Washington Univ, Sch Med, Behav Med Ctr, St Louis, MO 63130 USA. Univ Missouri, Columbia, MO 65211 USA. Washington Univ, Sch Med, Heart Rate Variabil Lab, St Louis, MO USA. Univ Tubingen, D-72074 Tubingen, Germany. RP Stein, PK (reprint author), Washington Univ, Sch Med, St Louis, MO 63108 USA. FU NHLBI NIH HHS [R01HL65356] NR 5 TC 5 Z9 7 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD NOV-DEC PY 2007 VL 26 IS 6 BP 14 EP 18 DI 10.1109/MEMB.2007.907092 PG 5 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 236YR UT WOS:000251340000004 PM 18189081 ER PT J AU Longmire, MR Gunn, AJ Morgan, NY Smith, PD Pohida, TJ Koyama, Y Kobayashi, H Choyke, PL AF Longmire, Michelle R. Gunn, Andrew J. Morgan, Nicole Y. Smith, Paul D. Pohida, Thomas J. Koyama, Yoshinori Kobayashi, Hisataka Choyke, Peter L. TI Real-time fluorescence-enhanced imaging as an aid to surgery in ovarian cancer SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE cancer; fluorescence imaging; image-guided surgery; imaging; metastasis detection; molecular imaging; ovarian cancer; radiology; real-time imaging; targeted therapeutics ID AVIDIN AB Epithelial ovarian cancer has the highest mortality among all gynecologic cancers. Due to the nonspecific nature of its symptoms, most women with ovarian cancer present with advanced stage disease, resulting in a poor overall prognosis. Surgical tumor debulking is one of the most effective interventions to improve the outcome for these patients. However, reducing the amount of residual tumor to microscopic levels is often complicated by the small size of the implants and poor visual contrast between small tumor implants and normal tissue under white light conditions found in most operating rooms. Therefore, one proposed method to improve the resection of metastatic ovarian cancer is to apply tumor-targeted optical fluoropbores that could identify sites of metastasis with high sensitivity and specificity, providing the surgeon with an intraoperative guide to tumor location. Herein, we describe a novel method of identifying ovarian cancer metastases using fluorescent tagging and a real-time fluorescence camera that allows the resection of metastatic disease that would otherwise not be visible to the surgeon. C1 [Longmire, Michelle R.; Gunn, Andrew J.; Koyama, Yoshinori; Kobayashi, Hisataka] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Longmire, Michelle R.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Gunn, Andrew J.] Univ S Dakota, Sanford Sch Med, Sioux Falls, SD 57105 USA. [Koyama, Yoshinori] Gunma Univ, NIH, Gunma 3718510, Japan. [Koyama, Yoshinori] Gunma Univ, Grad Sch Med, Gunma 3718510, Japan. [Morgan, Nicole Y.; Smith, Paul D.; Pohida, Thomas J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Longmire, MR (reprint author), NCI, Mol Imaging Program, Bethesda, MD 20892 USA. EM longmiremr@od.nih.gov; andrew.gunn@usd.edu; morgann@mail.nih.gov; pdsmith@helix.nih.gov; pohidat@exchange.nih.gov; onoff@showa.gunma-u.ac.jp; kobayashi@mail.nih.gov; pchoyke@mail.nih.gov NR 11 TC 3 Z9 3 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2007 VL 13 IS 6 BP 1602 EP 1609 DI 10.1109/JSTQE.2007.910998 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 249UP UT WOS:000252255800003 ER PT J AU Peyrat, JM Sermesant, M Pennec, X Delingette, H Xu, CY McVeigh, ER Ayache, N AF Peyrat, Jean-Marc Sermesant, Maxime Pennec, Xavier Delingette, Herve Xu, Chenyang McVeigh, Elliot R. Ayache, Nicholas TI A computational framework for the statistical analysis of cardiac diffusion tensors: Application to a small database of canine hearts SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE atlas; cardiac; diffusion tensor imaging (DTI); diffusion tensor magnetic resonance imaging (DT-MRI); fiber architecture; heart; laminar sheets; statistics ID FIBER-ORIENTATION; LAMINAR ARCHITECTURE; MRI; REGISTRATION; STRAIN; MODEL; TRANSFORMATIONS; DEFORMATIONS; GEOMETRY; CALCULUS AB We propose a unified computational framework to build a statistical atlas of the cardiac fiber architecture front diffusion tensor magnetic resonance images (DT-MRIs). We apply this framework to a small database of nine ex vivo canine hearts. An average cardiac fiber architecture and a measure of its variability are computed using most recent advances in diffusion tensor statistics. This statistical analysis confirms the already established good stability of the fiber orientations and a higher variability of the laminar sheet orientations within a given species. The statistical comparison between the canine atlas and a standard human cardiac DT-MRI shows a better stability of the fiber orientations than their laminar sheet orientations between the two species. The proposed computational framework can be applied to larger databases of cardiac DT-MRIs from various species to better establish intraspecies and interspecies statistics on the anatomical structure of cardiac fibers. This information will be useful to guide the adjustment of average fiber models onto specific patients from in vivo anatomical imaging modalities. C1 INRIA, Asclepios Res Project, F-06902 Sophia Antipolis, France. Kings Coll London, Rayne Inst, IMIG, Div Imaging Sci,St Thomas Hosp, London SE1 7EH, England. Siemens Corp Res, Dept Imaging & Visualizat, Princeton, NJ 08540 USA. NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. RP Peyrat, JM (reprint author), INRIA, Asclepios Res Project, F-06902 Sophia Antipolis, France. EM jean-marc.peyrat@inria.fr RI Pennec, Xavier/L-2537-2013; OI Pennec, Xavier/0000-0002-6617-7664; Sermesant, Maxime/0000-0002-6256-8350 FU Intramural NIH HHS; NHLBI NIH HHS [Z01-HL4004609] NR 57 TC 70 Z9 71 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2007 VL 26 IS 11 BP 1500 EP 1514 DI 10.1109/TMI.2007.907286 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 230TB UT WOS:000250897700009 PM 18041265 ER PT J AU Freidlin, RZ Ozarslan, E Komlosh, ME Chang, LC Koay, CG Jones, DK Basser, PJ AF Freidlin, Raisa Z. Oezarslan, Evren Komlosh, Michal E. Chang, Lin-Ching Koay, Cheng Guan Jones, Derek K. Basser, Peter J. TI Parsimonious model selection for tissue segmentation and classification applications: A study using simulated and experimental DTI data SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE diffusion tensor; diffusion tensor imaging (DTI); diffusion tensor magnetic resonance imaging (DT-MRI); hierarchical; magnetic resonance imaging (MRI); model selection; parsimonious; segmentation; tissue classification ID DIFFUSION TENSOR; FIBER ORIENTATION; HUMAN BRAIN; SPINAL-CORD; MR-IMAGES; IN-VIVO; ANISOTROPY; MICROSCOPY AB One aim of this work is to investigate the feasibility of using a hierarchy of models to describe diffusion tensor magnetic resonance (MR) data in fixed tissue. Parsimonious model selection criteria are used to choose among different models of diffusion within tissue. Using this information, we assess whether we can perform simultaneous tissue segmentation and classification. Both numerical phantoms and diffusion weighted imaging (DWI) data obtained from excised pig spinal cord are used to test and validate this model selection framework. Three hierarchical approaches are used for parsimonious model selection: the Schwarz criterion (SC), the F-test t-test (F-t), proposed by Hext, and the F-test F-test (F-F), adapted from Snedecor. The F - t approach is more robust than the others for selecting between isotropic and general anisotropic (full tensor) models. However, due to its high sensitivity to the variance estimate and bias in sorting eigenvalues, the F - F and SC are preferred for segmenting models with transverse isotropy (cylindrical symmetry). Additionally, the SC method is easier to implement than the F - t and F - F methods and has better performance. As such, this approach can be efficiently used for evaluating large MRI data sets. In addition, the proposed voxel-by-voxel segmentation framework is not susceptible to artifacts caused by the inhomogeneity of the variance in neighboring voxels with different degrees of anisotropy, which might contaminate segmentation results obtained with the techniques based on voxel averaging. C1 NIH, Telemed & Appl Imaging Sect, Computat Biosci & Engn Lab, Div Computat Biosci,Ctr Informat Technol, Bethesda, MD 20892 USA. George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. NICHHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. Cardiff Univ, Sch Psychol, Brain & Repair Imaging Ctr, Cardiff CF10 3XQ, Wales. RP Freidlin, RZ (reprint author), NIH, Telemed & Appl Imaging Sect, Computat Biosci & Engn Lab, Div Computat Biosci,Ctr Informat Technol, Bethesda, MD 20892 USA. RI Jones, Derek/D-1460-2009; Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011; OI Ozarslan, Evren/0000-0003-0859-1311; Jones, Derek/0000-0003-4409-8049 FU Intramural NIH HHS NR 37 TC 13 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2007 VL 26 IS 11 BP 1576 EP 1584 DI 10.1109/TMI.2007.907294 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 230TB UT WOS:000250897700016 PM 18041272 ER PT J AU Van Laethem, F Sarafova, SD Park, JH Tai, X Pobezinsky, L Guinter, TI Adoro, S Adams, A Sharrow, SO Feigenbaum, L Singer, A AF Van Laethem, Frangois Sarafova, Sophia D. Park, Jung-Hyun Tai, Xuguang Pobezinsky, Leonid Guinter, Terry I. Adoro, Stanley Adams, Anthony Sharrow, Susan O. Feigenbaum, Lionel Singer, Alfred TI Deletion of CD4 and CD8 coreceptors permits generation of alpha beta T cells that recognize antigens independently of the MHC SO IMMUNITY LA English DT Article ID PROTEIN-KINASE P56LCK; IMMUNOLOGICAL SYNAPSE; NEGATIVE SELECTION; LINEAGE COMMITMENT; POSITIVE SELECTION; CYCLE PROGRESSION; RECEPTOR COMPLEX; REGULATES CD4; ACTIVATION; EXPRESSION AB The thymus generates major histocompatibility complex (MHC)-restricted alpha beta T cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that MHC specificity might be imposed on a broader alpha beta TCR repertoire during thymic selection by CD4 and CD8 coreceptors; that bind and effectively sequester the tyrosine kinase Lck, thereby preventing T cell receptor (TCR) signaling by non-MHC ligands that do not engage either coreceptor. This hypothesis predicts that, in coreceptor-deficient mice, alpha beta thymocytes would be signaled by non-MHC ligands to differentiate into alpha beta T cells lacking MHC specificity. We now report that MHC-independent alpha beta T cells were indeed generated in mice deficient in both coreceptors as well as MHC ("quad-deficient" mice) and that such mice contained a diverse alpha beta T cell repertoire whose MHC independence was confirmed at the clonal level. We conclude that CD4 and CD8 coreceptors impose MHC specificity on a broader alpha beta TCR repertoire during thymic selection by preventing thymocytes from being signaled by non-MHC ligands. C1 NCI, Natl Inst Hlth, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. RP Singer, A (reprint author), Davidson Coll, Dept Biol, Davidson, NC 28035 USA. EM singera@nih.gov FU Intramural NIH HHS NR 40 TC 93 Z9 94 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 735 EP 750 DI 10.1016/j.immuni.2007.10.007 PG 16 WC Immunology SC Immunology GA 235YA UT WOS:000251269000008 PM 18023370 ER PT J AU Horai, R Mueller, KL Handon, RA Cannons, JL Anderson, SM Kirby, MR Schwartzberg, PL AF Horai, Reiko Mueller, Kristen L. Handon, Robin A. Cannons, Jennifer L. Anderson, Stacie M. Kirby, Martha R. Schwartzberg, Pamela L. TI Requirements for selection of conventional and innate T lymphocyte lineages SO IMMUNITY LA English DT Article ID NKT-CELL-DEVELOPMENT; TEC FAMILY KINASES; NF-KAPPA-B; POSITIVE SELECTION; NEGATIVE SELECTION; CUTTING EDGE; CD4(+)CD8(+) THYMOCYTES; PERIPHERAL HOMEOSTASIS; HEMATOPOIETIC-CELLS; THYMIC SELECTION AB Mice deficient in the Tec kinase Itk develop a large population of CD8(+) T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8(+) T cells can be selected on hematopoietic cells' We demonstrate that these CD8(+) T cell phenotypes resulted from selection on hematopoietic cells-forcing selection on the thymic stroma reduced the number and innate phenotypes of mature ltk-deficient CD8(+) T cells. We further show that, similar to NKT cells, selection of innate-type CD8(+) T cells in Itk(-/-) mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8(+) T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells. C1 NIH, NHGRI, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NIH, NHGRI, Bethesda, MD 20892 USA. EM pams@mail.nih.gov FU Intramural NIH HHS [Z01 HG000123-10] NR 56 TC 72 Z9 73 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 775 EP 785 DI 10.1016/j.immuni.2007.09.012 PG 11 WC Immunology SC Immunology GA 235YA UT WOS:000251269000011 PM 18031697 ER PT J AU Deane, JA Pisitkun, P Barrett, RS Feigenbaum, L Town, T Ward, JM Flavell, RA Bolland, S AF Deane, Jonathan A. Pisitkun, Prapaporn Barrett, Rebecca S. Feigenbaum, Lionel Town, Terrence Ward, Jerrold M. Flavell, Richard A. Bolland, Silvia TI Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation SO IMMUNITY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ACTIVATE B-CELLS; MURINE LUPUS; AUTOANTIBODY PRODUCTION; DEFICIENT MICE; I INTERFERON; TLR7; RNA; INDUCTION; RESPONSES AB Nucleic acid-binding innate immune receptors such as Toll-like receptor 7 (TLR7) and TLR9 have been implicated in the development of some autoimmune pathologies. The Y chromosome-linked genomic modifier Yaa, which correlates with a duplication of Tlr7 and 16 other genes, exacerbates lupus-like syndromes in several mouse strains. Here we demonstrated that duplication of the Tlr7 gene was the sole requirement for this accelerated autoimmunity, because reduction of Tlr7 gene dosage abolished the Yaa phenotype. Further, we described new transgenic lines that overexpressed TLR7 alone and found that spontaneous autoimmunity developed beyond a 2-fold increase in TLR7 expression. Whereas a modest increase in Tlr7 gene dosage promoted autoreactive lymphocytes with RNA specificities and myeloid cell proliferation, a substantial increase in TLR7 expression caused fatal acute inflammatory pathology and profound dendritic cell dysregulation. These results underscore the importance of tightly regulating expression of TLR7 to prevent spontaneous triggering of harmful autoreactive and inflammatory responses. C1 Immunogenet Lab, Rockville, MD 20852 USA. NIAID, NIH, Infect Dis Pathogenesis Sect, Comparat Med Branch, Rockville, MD 20852 USA. NCI, NIH, Sci Applicat Int Corp, Lab Anim Sci Program, Ft Detrick, MD 21702 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. RP Bolland, S (reprint author), Immunogenet Lab, Rockville, MD 20852 USA. EM sbolland@nih.gov FU Intramural NIH HHS [Z01 AI000912-06] NR 41 TC 232 Z9 239 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 801 EP 810 DI 10.1016/j.immuni.2007.09.009 PG 10 WC Immunology SC Immunology GA 235YA UT WOS:000251269000013 PM 17997333 ER PT J AU Le, Y Zhu, BM Harley, B Park, SY Kobayashi, T Manis, JP Luo, HR Yoshimura, A Hennighausen, L Silberstein, LE AF Le, Yi Zhu, Bing-Mei Harley, Brendan Park, Shin-Young Kobayashi, Takashi Manis, John P. Luo, Hongbo R. Yoshimura, Akihiko Hennighausen, Lothar Silberstein, Leslie E. TI SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis SO IMMUNITY LA English DT Article ID FOCAL ADHESION KINASE; HUMAN BONE-MARROW; PRECURSOR CELLS; NEGATIVE REGULATION; MUTATIONAL ANALYSES; MEMBRANE DOMAINS; CYTOKINE; MICE; RESPONSES; ACTIVATION AB The chemokine CXCL12 induces prolonged focal adhesion kinase (FAK) phosphorylation and sustained proadhesive responses in progenitor bone-marrow (BM) B cells, but not in mature peripheral B cells. Here we demonstrate that suppressor of cytokine signaling 3 (SOCS3) regulated CXCL12-induced FAK phosphorylation through the ubiquitin-proteasome pathway. CXCL12 triggered increased FAK ubiquitination in mature B cells, but not in progenitor B cells. Accordingly, SOCS3 expression was low in progenitor B cells, increased in immature B cells, and highest in mature B cells. SOCS3 overexpression in pro-B cells impaired CXCL12-induced FAK phosphorylation and proadhesive responses. Conversely, SOCS3-deficient mature B cells from Cre(MMTV)Socs3(fl/fl) mice exhibited prolonged FAK phosphorylation and adhesion to VCAM-1. In contrast to wild-type mice, Cre(MMTV)Socs3(fl/fl) mice had a 2-fold increase in immature B cells, which were evenly distributed in endosteal and perisinusoidal BM compartments. We propose that the developmental regulation of CXCR4-FAK signaling by SOCS3 is an important mechanism to control the lodgement of B cell precursors in the BM microenvironment. C1 Childrens Hosp, Harvard Med Sch, Joint Program Transfusion Med, Boston, MA 02115 USA. NIH, NIDDK, Lab Genet & Physiol, Bethesda, MD 20892 USA. Kyushu Univ, Div Mol & Cellular Immunol, Fukuoka, Japan. RP Silberstein, LE (reprint author), Childrens Hosp, Harvard Med Sch, Joint Program Transfusion Med, Boston, MA 02115 USA. EM leslie.silberstein@childrens.harvard.edu RI Yoshimura, Akihiko/K-5515-2013; OI Harley, Brendan/0000-0001-5458-154X FU NHLBI NIH HHS [HL074355, HL56949] NR 56 TC 34 Z9 34 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 811 EP 823 DI 10.1016/j.immuni.2007.09.011 PG 13 WC Immunology SC Immunology GA 235YA UT WOS:000251269000014 PM 18031698 ER PT J AU Lan, Q Shen, M Garcia-Rossi, D Chanock, S Zheng, TZ Berndt, SI Puri, V Li, GL He, XZ Welch, R Zahm, SH Zhang, LP Zhang, YW Smith, M Wang, SS Chiu, BCH Linet, M Hayes, R Rothman, N Yeager, M AF Lan, Qing Shen, Min Garcia-Rossi, Dino Chanock, Stephen Zheng, Tongzhang Berndt, Sonja I. Puri, Vinita Li, Guilan He, Xingzhou Welch, Robert Zahm, Shelia H. Zhang, Luoping Zhang, Yawei Smith, Martyn Wang, Sophia S. Chiu, Brian C. -H. Linet, Martha Hayes, Richard Rothman, Nathaniel Yeager, Meredith TI Genotype frequency and F-ST analysis of polymorphisms in immunoregulatory genes in Chinese and Caucasian populations SO IMMUNOGENETICS LA English DT Article DE genotype frequency; F-ST; genetic diversity; cytokine genes; Chinese; caucasians ID NON-HODGKIN-LYMPHOMA; COAL COMBUSTION EMISSIONS; INTERLEUKIN-4 GENE; PROMOTER POLYMORPHISM; ETHNIC-GROUPS; LUNG-CANCER; IL-4 GENE; RISK; IL4; ASSOCIATION AB Selection and genetic drift can create genetic differences between populations. Cytokines and chemokines play an important role in both hematopoietic development and the inflammatory response. We compared the genotype frequencies of 45 SNPs in 30 cytokine and chemokine genes in two healthy Chinese populations and one Caucasian population. Several SNPs in IL4 had substantial genetic differentiation between the Chinese and Caucasian populations (F-ST similar to 0.40), and displayed a strikingly different haplotype distribution. To further characterize common genetic variation in worldwide populations at the IL4 locus, we genotyped 9 SNPs at the IL4 gene in the Human Diversity Panel's (N=1056) individuals from 52 world geographic regions. We observed low haplotype diversity, yet strikingly different haplotype frequencies between non-African populations, which may indicate different selective pressures on the IL4 gene in different parts of the world. SNPs in CSF2, IL6, IL10, CTLA4, and CX3CR1 showed moderate genetic differentiation between the Chinese and Caucasian populations (0.15 < F-ST < 0.25). These results suggest that there is substantial genetic diversity in immune genes and exploration of SNP associations with immune-related diseases that vary in incidence across these two populations may be warranted. C1 Natl Canc Inst, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD USA. Yale Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. China Ctr Dis Control & Prevent, Inst Occupant Hlth & Poison Control, Beijing, Peoples R China. China Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing, Peoples R China. NW Univ Med Sch, Dept Prevent Med, Chicago, IL USA. RP Yeager, M (reprint author), Natl Canc Inst, Core Genotyping Facil, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Gaithersburg, MD USA. EM yeagerm@mail.nih.gov RI Zahm, Shelia/B-5025-2015; OI Hayes, Richard/0000-0002-0918-661X NR 58 TC 18 Z9 18 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD NOV PY 2007 VL 59 IS 11 BP 839 EP 852 DI 10.1007/s00251-007-0253-3 PG 14 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 231VW UT WOS:000250978300002 PM 17938902 ER PT J AU Moayeri, M Wiggins, JF Leppla, SH AF Moayeri, Mahtab Wiggins, Jason F. Leppla, Stephen H. TI Anthrax protective antigen cleavage and clearance from the blood of mice and rats SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; LETHAL FACTOR; MONOCLONAL-ANTIBODIES; BIOLOGICAL-ACTIVITY; CELLULAR RECEPTOR; N-TERMINUS; TOXIN; FURIN; MACROPHAGES; PROTEASE AB Bacillus anthracis protective antigen (PA) is an 83-kDa (PA83) protein that is cleaved to the 63-kDa protein (PA63) as an essential step in binding and internalizing lethal factor (LF). To assess in vivo receptor saturating PA concentrations, we injected mice with PA variants and measured the PA remaining in the blood at various times using PA83- and PA63-specific enzyme-linked immunosorbent assays. We found that both wild-type PA (WT-PA) and a receptor-binding-defective mutant (Ub-PA) were cleaved to PA63 independent of their ability to bind cells. This suggested a PA-acting protease activity in the blood. The protease cleaved PA at the furin cleavage sequence because furin site-modified PA mutants were not cleaved. Cleavage measured in vitro was leupeptin sensitive and dependent on calcium. Cell surface cleavage was important for toxin clearance, however, as Ub-PA and uncleavable PA mutants were cleared at slower rates than WT-PA. The cell binding-independent cleavage of PA was also verified by using Ub-PA (which is still cleaved) to rescue mice from toxin challenge by competitively binding circulating LF. This mutant was able to rescue mice even when given 12 h before toxin challenge. Its therapeutic ability was comparable to that of dominant-negative PA, which binds cells but does not allow LF translocation, and to the protection afforded through receptor clearance by WT-PA and uncleavable receptor binding-competent mutants. The PA cleavage and clearance observed in mice did not appear to have a role in the differential mouse susceptibility as it occurred similarly in lethal toxin (LT)resistant DBA/2J and LT-sensitive BALB/cJ mice. Interestingly, PA63 was not found in LT-resistant or -sensitive rats and PA83 clearance was slower in rats than in mice. Finally, to determine the minimum amount of PA required in circulation for LT toxicity in mice, we administered time-separated injections of PA and LF and showed that lethality of LF for mice after PA was no longer measurable in circulation, suggesting active PA sequestration at tissue surfaces. C1 NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, NIH, Bldg 33,Room 1w20, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural NIH HHS NR 27 TC 41 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2007 VL 75 IS 11 BP 5175 EP 5184 DI 10.1128/IAI.00719-07 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 224MU UT WOS:000250451900012 PM 17724066 ER PT J AU Cui, XZ Besch, V Khaibullina, A Hergen, A Quezado, M Eichacker, P Quezado, ZMN AF Cui, Xizhong Besch, Virginia Khaibullina, Alfia Hergen, Adrienne Quezado, Martha Eichacker, Peter Quezado, Zenaide M. N. TI Neuronal nitric oxide synthase deficiency decreases survival in bacterial peritonitis and sepsis SO INTENSIVE CARE MEDICINE LA English DT Article DE sepsis; peritonitis; NOS1; nNOS; NO; Rodents ID FACTOR-KAPPA-B; MYOCARDIAL DYSFUNCTION; RAT NEUTROPHILS; MESSENGER-RNA; INDUCIBLE NOS; MICE; 7-NITROINDAZOLE; MORTALITY; ENDOTOXIN; SHOCK AB Objective: To investigate the role of neuronal nitric oxide synthase (NOS1) in murine polymicrobial peritonitis and sepsis. Design: Randomized experimental trial. Setting: Animal research facility. Subjects: B6129S NOS1(+/+) and B6; 129S4 NOS-/- mice. Interventions: NOS1(+/+) and NOS1(-/-) animals underwent cecal ligation and puncture (CLP) or sham surgery and received the NOS1 inhibitor 7-nitroindazole (7-NI) or vehicle. Measurements and main results: After CLP, genetic deficiency and pharmacologic inhibition of NOS1 significantly increased risk of mortality [8.69 (3.27, 23.1), p < 0.0001 and 1.71 (1.00, 2.92) p = 0.05, hazard ratio of death (95% confidence interval) for NOS1(-/-) and 7-NI-treated NOS1(+/+) respectively] compared with NOS1(+/+) animals. In 7-NI-treated NOS1(+/+) animals, there were increases (6 h) and then decreases (24 h), whereas in NOS-/- animals persistent increases in blood bacteria counts (p = 0.04 for differing effects of 7-NI and NOS1(-/-)) were seen compared with NOS1+/+ animals. After CLP, NOS1(-/-) had upregulation of inducible NOS and proinflammatory cytokines and greater increases in serum tumor necrosis factor-alpha and interleukin-6 levels compared with NOS1+/+ mice (all p < 0.05). Following CLP, there were similar significant decreases in circulating leukocytes and lung lavage cells (p = 0.0008) and significant increases in peritoneal lavage cells (p = 0.0045) in all groups. Over 6 h and 24 h following CLP, compared with NOS1(+/+), NOS-/- mice had significantly higher peritoneal cell concentrations {respectively 0.40 +/- 0.09 vs 0.79 +/- 0.15 [ log(x 10(4)cells/ml)] averaged over both times p = 0.038}. Conclusions: Deficiency and inhibition of NOS1 increases mortality, possibly by increasing proinflammatory cytokine response and impairing bacterial clearance after CLP. These data suggest that NOS1 is important for survival, bacterial clearance, and regulation of cytokine response during infection and sepsis. C1 Natl Inst Hlth Clin Ctr, NIH, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA. Natl Inst Hlth Clin Ctr, NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Quezado, M (reprint author), Natl Inst Hlth Clin Ctr, NIH, Dept Anesthesia & Surg Serv, 10 Ctr Dr,Bldg 10,Room 2C624,MSC-1512, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [Z01 CL008047-06, Z01 CL009009-01] NR 33 TC 15 Z9 16 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2007 VL 33 IS 11 BP 1993 EP 2003 DI 10.1007/s00134-007-0814-9 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 223WZ UT WOS:000250407600020 PM 17684724 ER PT J AU Suppes, T Kelly, DI Keck, PE McElroy, SL Altshuler, LL Mintz, J Frye, MA Nolen, WA Luckenbaugh, DA Post, RM Leverich, GS Kupka, RW Grunze, H AF Suppes, Trisha Kelly, Dorothy I. Keck, Paul E., Jr. McElroy, Susan L. Altshuler, Lori L. Mintz, Jim Frye, Mark A. Nolen, Willem A. Luckenbaugh, David A. Post, Robert M. Leverich, Gabriele S. Kupka, Ralph W. Grunze, Heinz TI Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; bipolar depression; cycling; quetiapine ID TREATMENTS CANMAT GUIDELINES; PLACEBO-CONTROLLED TRIAL; I-DISORDER; DOUBLE-BLIND; ADJUNCTIVE QUETIAPINE; CANADIAN NETWORK; MOOD STABILIZER; FOLLOW-UP; OLANZAPINE; MAINTENANCE AB Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder. Prospectively collected life chart data from 63 outpatients with bipolar disorders, most recent episodes depressed, manic, or cycling, who received adjunctive quetiapine therapy as part of standard acute treatment were analyzed. Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes. Patients were grouped by baseline symptoms; depression only, mania only, or both mania and depression (cycling group). Owing to small mania and well groups (n=4), differences between depression and cycling groups were examined and mania and well groups excluded. Fifty-five patients were included in the analyses. The primary outcome measure was change in mood severity from baseline to change in treatment regimen, as measured by the NIMH Life Charting Method. Patients received adjunctive quetiapine for a mean of 122 (SD=149) days. Both groups showed significant improvement in depression ratings and time spent depressed by week 10. Both groups showed significant improvement in overall mood. No between-group differences in improvement were found. Adjunctive quetiapine may be useful as continuation treatment in bipolar populations with both pure depressive and cycling symptoms. Further controlled studies are warranted. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mayo Coll Med, Rochester, MI USA. Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. Penn State Coll Med, Hershey, PA USA. NIMH, NIH, New York, NY USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Ludwig Maximilians Univ Munchen, Munich, Germany. RP Suppes, T (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Trisha.Suppes@UTSouthwestern.edu RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [R01 MH079261] NR 32 TC 10 Z9 10 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD NOV PY 2007 VL 22 IS 6 BP 376 EP 381 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 222RP UT WOS:000250315000009 PM 17917557 ER PT J AU Zhang, FF Hon, LF Terry, MB Lissowska, J Morabia, A Chen, JB Yeager, M Zatonski, W Chanock, S Chow, WH AF Zhang, Fang Fang Hon, Lifang Terry, Mary Beth Lissowska, Jolanta Morabia, Alfredo Chen, Jinbo Yeager, Meredith Zatonski, Witold Chanock, Stephen Chow, Wong-Ho TI Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE stomach cancer; alcohol metabolism; genetic polymorphism ID ALDEHYDE DEHYDROGENASE; GASTRIC-CANCER; EPIDEMIOLOGY; CONSUMPTION; ESOPHAGEAL; SEQUENCE; HEAD AB Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes. including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (EX8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A >G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p = 0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR = 2.63, 95% CI = 1.00-6.88) and 3-fold risk (OR = 3.66, 95% CI = 1.19-11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer. (c) 2007 Wiley-Liss, Inc. C1 Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol, Ft Worth, TX 76107 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. Marie Curie Inst Oncol, Warsaw, Poland. CUNY Queens Coll, Ctr Viol Nat Syst, Flushing, NY 11367 USA. Univ Penn, Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Natl Canc Inst, Ctr Adv Technol, Core Genotyping Facil, Gaithersburg, MD USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Zhang, FF (reprint author), Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM fazhang@hsc.unt.edu OI Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 23 TC 24 Z9 25 U1 1 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 NOV 1 PY 2007 VL 121 IS 9 BP 2060 EP 2064 DI 10.1002/ijc.22973 PG 5 WC Oncology SC Oncology GA 214EF UT WOS:000249718100023 PM 17631643 ER PT J AU Chavez, M Insel, TR AF Chavez, Mark Insel, Thomas R. TI Special issue on diagnosis and classification SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Editorial Material C1 NIMH, Div Adult Translat Res & Treatment Dev, Rockville, MD 20852 USA. RP Chavez, M (reprint author), NIMH, Div Adult Translat Res & Treatment Dev, 6001 Execut Rd,Rm 7101, Rockville, MD 20852 USA. EM mchavez1@mail.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2007 VL 40 SU S BP S2 EP S2 DI 10.1002/eat.20452 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 221LS UT WOS:000250229900002 ER PT J AU Houston, DK Ding, J Nicklas, BJ Harris, TB Lee, JS Nevitt, MC Rubin, SM Tylavsky, FA Kritchevsky, SB AF Houston, D. K. Ding, J. Nicklas, B. J. Harris, T. B. Lee, J. S. Nevitt, M. C. Rubin, S. M. Tylavsky, F. A. Kritchevsky, S. B. TI The association between weight history and physical performance in the Health, Aging and Body Composition study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BMI; aging; physical performance; physical function ID LOWER-EXTREMITY FUNCTION; QUALITY-OF-LIFE; MASS INDEX; SUBSEQUENT DISABILITY; OLDER PERSONS; RISK-FACTORS; MIDDLE-AGE; NHANES-I; OBESITY; WOMEN AB Objective: Although the association between current obesity and physical disability is well known, the cumulative effect of obesity is unknown. Using data from the Health, Aging and Body Composition study, we examined the association between weight history in young and middle adulthood and weight status in late adulthood with physical performance in late adulthood. Design: Longitudinal cohort study. Subjects: White and black men and women aged 70-79 years at study baseline (n = 2803). Measures: Body mass index (BMI; kg/m(2)) was calculated using recalled height at age 25 and weight at age 25 and 50 and measured height and weight at ages 70-79. Physical performance at ages 70-79 was assessed using a short physical performance battery (SPPB) and a 400- m walk test. Results: In this well- functioning cohort, approximately 24% of men and 8% of women reported being overweight or obese (BMI >= 25 kg/m(2)) at age 25, 51% of men and 37% of women reported being overweight or obese at age 50, and 69% of men and 66% of women were overweight or obese at ages 70-79. Men and women who were obese (BMI >= 30 kg/m(2)) at ages 25, 50 and 70-79 had significantly worse SPPB scores and 400- m walk times than those who were normal weight. Women who were overweight (BMI 25-29.9 kg/m(2)) at ages 25, 50 and 70-79 also had significantly worse physical performance. Furthermore, men and women who had a history of being overweight or obese at ages 25 or 50 had worse physical performance compared to those who were normal weight throughout or who were overweight or obese at ages 70-79 but not in midlife or earlier. Conclusions: Maintaining a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of physical disability. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Genet Med, Winston Salem, NC 27157 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RP Houston, DK (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Genet Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dhouston@wfubmc.edu FU Intramural NIH HHS; NIA NIH HHS [P30-AG21332] NR 40 TC 25 Z9 26 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 2007 VL 31 IS 11 BP 1680 EP 1687 DI 10.1038/sj.ijo.0803652 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 224SL UT WOS:000250466600006 PM 17515911 ER PT J AU Kim, MK Kim, YJ Cho, DH Yi, TH Soung, NK Yang, DC AF Kim, Myung Kyum Kim, Yu-Jin Cho, Dong-Ha Yi, Tae-Hoo Soung, Nak-Kyun Yang, Deok-Chun TI Solimonas soli gen. nov., sp nov., isolated from soil of a ginseng field SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PROTEOBACTERIA; BACTERIA AB A micro-organism, DCY12(T), comprising Gram-negative, non-motile, pale-yellow rods was isolated from soil from a ginseng field in South Korea and was investigated to determine its taxonomic status. It grew optimally at 30 degrees C and at pH 7.0, the G + C content of its DNA was 40.5 mol%, the major components of the fatty acid profile were C16:0 and C18:1 and the major ubiquinone was Q-8. A phylogenetic analysis based on the 16S rRNA gene sequence revealed that the novel isolate was most closely related to Hydrocarboniphaga effusa AP103(T) (89.2 %), Nevskia ramosa Soel (88.8%) and Pseudomonas aeruginosa ATCC 10145(T) (83.2 %). The phenotypic, physiological, metabolic and phylogenetic properties of DCY12(T) suggest that it represents a novel genus (class Gammaproteobacteria) and species, for which the name Solimonas soli gen. nov., sp. nov. is proposed. The type strain of Solimonas soli is DCY12(T) (=KCTC 12834(T) =LMG 24014(T)). C1 Kyung Hee Univ, Coll Life Sci, Dept Oriental Med Mat & Proc, Yongin 449701, Kyunggi Do, South Korea. Kangwon Natl Univ, Sch Biosci & Biotech, Chunchon 200701, South Korea. NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Coll Life Sci, Dept Oriental Med Mat & Proc, 1 Seocheon Dong, Yongin 449701, Kyunggi Do, South Korea. EM deokchunyang@yahoo.co.kr NR 16 TC 9 Z9 9 U1 1 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD NOV PY 2007 VL 57 BP 2591 EP 2594 DI 10.1099/ijs.0.64938-0 PN 11 PG 4 WC Microbiology SC Microbiology GA 238FO UT WOS:000251432900026 PM 17978223 ER PT J AU Weiss, JS Kruth, HS Kuivaniemi, H Tromp, G White, PS Winters, RS Lisch, W Henn, W Denninger, E Krause, M Wasson, P Ebenezer, N Mahurkar, S Nickerson, ML AF Weiss, Jayne S. Kruth, Howard S. Kuivaniemi, Helena Tromp, Gerard White, Peter S. Winters, R. Scott Lisch, Walter Henn, Wolfram Denninger, Elke Krause, Matthias Wasson, Paul Ebenezer, Neil Mahurkar, Sunil Nickerson, Michael L. TI Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause schnyder crystalline corneal dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; CHOLESTEROL EFFLUX; APOLIPOPROTEIN-E; TERE1; HYPERLIPOPROTEINEMIA; ASSOCIATION; METABOLISM; 1P34.1-P36; CARCINOMA; BLADDER AB PURPOSE. Schnyder crystalline corneal dystrophy ( SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid deposition in the cornea, leading to progressive corneal opacification. Although SCCD has been mapped to a genetic interval between markers D1S1160 and D1S1635, reclassification of a previously unaffected individual expanded the interval to D1S2667 and included nine additional genes. Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed. METHODS. DNA samples were obtained from six families with clinically confirmed SCCD. Analysis of FRAP1, ANGPTL7, and UBIAD1 was performed by PCR-based DNA sequencing, to examine protein-coding regions, RNA splice junctions, and 5 ' untranslated region ( UTR) exons. RESULTS. No disease-causing mutations were found in the FRAP1 or ANGPTL7 gene. A mutation in UBIAD1 was identified in all six families: Five families had the same N102S mutation, and one family had a G177R mutation. Predictions of the protein structure indicated that a prenyl-transferase domain and several transmembrane helices are affected by these mutations. Each mutation cosegregated with the disease in four families with DNA samples from both affected and unaffected individuals. Mutations were not observed in 100 control DNA samples ( 200 chromosomes). CONCLUSIONS. Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD families, and a potential mutation hot spot was observed at amino acid N102. The mutations are expected to interfere with the function of the UBIAD1 protein, since they are located in highly conserved and structurally important domains. C1 Wayne State Univ, Sch Med, Kresge Eye Inst, Dept Ophthalmol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. NIH, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Klinikum Hanau, Dept Ophthalmol, Hanau, Germany. Univ Saarland, Dept Human Genet, D-6650 Homburg, Germany. Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. UCL, Inst Ophthalmol, Dept Mol Genet, London, England. Transgenom, Gaithersburg, MD USA. RP Weiss, JS (reprint author), Wayne State Univ, Sch Med, Kresge Eye Inst, Dept Ophthalmol, 4717 St Antoine, Detroit, MI 48201 USA. EM jweiss@med.wayne.edu RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NEI NIH HHS [EY12972] NR 39 TC 54 Z9 59 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2007 VL 48 IS 11 BP 5007 EP 5012 DI 10.1167/iovs.07-0845 PG 6 WC Ophthalmology SC Ophthalmology GA 228MU UT WOS:000250734800022 PM 17962451 ER PT J AU Chucair, AJ Rotstein, NP SanGiovanni, JP During, A Chew, EY Politi, LE AF Chucair, Ana J. Rotstein, Nora P. SanGiovanni, John Paul During, Alexandrine Chew, Emily Y. Politi, Luis E. TI Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: Relation with docosahexaenoic acid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; RETINA PHOTORECEPTORS; RAT RETINA; IN-VITRO; MONOCLONAL-ANTIBODIES; NEURITE GROWTH; UNITED-STATES; DIETARY-FAT; CELL-DEATH AB PURPOSE. Oxidative stress has been proposed as a major pathogenic factor in age- related macular degeneration ( AMD), the leading cause of vision loss among elderly people of western European ancestry. Lutein ( LUT) and zeaxanthin ( ZEA), major components in macular pigment, are among the retinal antioxidants. Though xanthophyll intake may reduce the likelihood of having advanced AMD, direct evidence of neuroprotection is lacking. Prior work has shown that docosahexaenoic acid ( DHA), the major polyunsaturated fatty acid in the retina, delays apoptosis and promotes differentiation of photoreceptors. This study was conducted to investigate whether LUT, ZEA, and beta- carotene ( BC), major dietary carotenoids protect photoreceptors from oxidative stress and whether this protection is synergistic with that of DHA. METHODS. Pure rat retinal neurons in culture, supplemented with LUT, ZEA, or BC, with or without DHA, were subjected to oxidative stress induced with paraquat and hydrogen peroxide. Apoptosis, preservation of mitochondrial membrane potential, cytochrome c translocation, and opsin expression were evaluated. RESULTS. Pretreatment with DHA, LUT, ZEA, and BC reduced oxidative stress- induced apoptosis in photoreceptors, preserved mitochondrial potential, and prevented cytochrome c release from mitochondria. ZEA and LUT also enhanced photoreceptor differentiation. In control cultures, photoreceptors failed to grow their characteristic outer segments; addition of DHA, ZEA, or LUT increased opsin expression and promoted the development of outer- segment - like processes. CONCLUSIONS. These results show for the first time the direct neuroprotection of photoreceptors by xanthophylls and suggest that ZEA and LUT, along with DHA, are important environmental influences that together promote photoreceptor survival and differentiation. C1 Univ Nacl Sur, Buenos Aires, DF, Argentina. NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA. Univ Catholique Louvain, Biochim Cellulaire Lab, B-1348 Louvain La Neuve, Belgium. RP Politi, LE (reprint author), CC 857,B8000FWB Bahia Blanca, Buenos Aires, DF, Argentina. EM inpoliti@criba.edu.ar RI SanGiovanni, John Paul/A-7605-2008; During, Alexandrine/I-5405-2015; OI During, Alexandrine/0000-0002-6878-0870 FU Intramural NIH HHS [Z99 EY999999, ZIA EY000485-01] NR 51 TC 90 Z9 100 U1 0 U2 16 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2007 VL 48 IS 11 BP 5168 EP 5177 DI 10.1167/iovs.07-0037 PG 10 WC Ophthalmology SC Ophthalmology GA 228MU UT WOS:000250734800041 PM 17962470 ER PT J AU Fu, YL Ponce, ML Thill, M Yuan, P Wang, NS Csaky, KG AF Fu, Yingli Ponce, M. Lourdes Thill, Michelle Yuan, Peng Wang, Nam Sun Csaky, Karl G. TI Angiogenesis inhibition and choroidal neovascularization suppression by sustained delivery of an integrin antagonist, EMD478761 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; TREATED RAT MODEL; MACULAR DEGENERATION; TUMOR-GROWTH; ALPHA(V)BETA(3); ALPHA-V-BETA-3; REGRESSION; EFFICACY; THERAPY; RABBIT AB PURPOSE. To evaluate the angiogenic inhibitory effects of an alpha(v)beta(3)/alpha(v)beta(5) integrin antagonist, EMD478761, released from a polymeric implant in a chick chorioallantoic membrane ( CAM) assay and laser- induced experimental choroidal neovascularization ( CNV) in rats. METHODS. Polyvinyl alcohol- based reservoir implants releasing EMD478761 were designed for placement onto a CAM or intravitreally in rats. In vitro release rates of the implants were measured using HPLC. Angiogenesis was induced on 10- day-old chick embryos by basic fibroblast growth factor ( bFGF), and areas of neovascularization were measured. Experimental CNV was induced in the Brown- Norway rat with a diode laser. EMD478761 or sham microimplants were placed within the vitreous chamber of Brown- Norway rats. Two weeks later, areas of CNV were determined by FITC- dextran staining of choroidal flatmounts. RESULTS. Sustained delivery of EMD478761 significantly inhibited bFGF- induced angiogenesis in CAM, as determined by a reduction in angiogenesis areas, without drug toxicity to the normal CAM vasculature. In an experimental rat model, intravitreal EMD478761 implants significantly suppressed laser- induced CNV compared with intravitreal sham implants, with the mean area reduced by 63% ( P < 0.05). CONCLUSIONS. Sustained delivery of EMD478761demonstrates potent antiangiogenic properties in vivo. These results suggest that an EMD478761 implant may be beneficial in the treatment of neovascular ocular diseases. C1 NEI, Ctr Clin, Natl Inst Hlth, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. RP Csaky, KG (reprint author), Duke Univ, Ctr Eye, Wadsworth 153,2530 Erwin Rd, Durham, NC 27705 USA. EM karl.csaky@duke.edu RI Fu, Yingli/B-8057-2012; Wang, Nam Sun/E-4253-2016 NR 41 TC 22 Z9 27 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2007 VL 48 IS 11 BP 5184 EP 5190 DI 10.1167/iovs.07-0469 PG 7 WC Ophthalmology SC Ophthalmology GA 228MU UT WOS:000250734800043 PM 17962472 ER PT J AU Hadigan, C Liebau, J Andersen, R Holalkere, NS Sahani, DV AF Hadigan, Colleen Liebau, James Andersen, Rebecca Holalkere, Nagaraj-Setry Sahani, Dushyant V. TI Magnetic resonance Spectroscopy of hepatic lipid content and associated risk factors in HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; steatosis; insulin resistance; visceral adiposity; metabolic syndrome ID HUMAN-IMMUNODEFICIENCY-VIRUS; NONALCOHOLIC FATTY LIVER; MULTICENTER AIDS COHORT; TRIGLYCERIDE CONTENT; INSULIN-RESISTANCE; ANTIRETROVIRAL THERAPY; METABOLIC SYNDROME; C VIRUS; ACCUMULATION; LIPODYSTROPHY AB Background: Liver-related illness is increasingly recognized as a source of morbidity in HIV-infiected patients. Fatty infiltration of the liver is potentially an important consequence of HIV and treatment with antiretroviral (ARV) therapy. Objective: The aim of the present study was to evaluate HIV-infected men and women for hepatic steatosis using noninvasive magnetic resonance spectroscopy (MRS) and to assess the relationship between liver fat content, insulin resistance, and other associated risk factors. Methods: We examined 33 consecutively recruited HIV-infected adults without specific referral for liver disease. Subjects with alcohol abuse within 3 years or end-stage liver disease were excluded. The primary clinical measures were hepatic fat content measured by MRS, homeostasis model for assessment of insulin resistance (HOMA-IR), and body fat distribution assessed by cross-sectional computed tomography. Results: We identified hepatic steatosis (liver fat content >= 5%) in 42% of subjects. Hepatic fat content was significantly correlated with HOMA-IR (r = 0.68, P < 0.0001) and increased visceral adiposity (r = 0.60, P < 0.001). Subjects with steatosis had significantly increased body mass index and alanine aminotransferase and triglyceride levels, with lower muscle attenuation (ie, increased intramuscular fat) compared to subjects without steatosis. However, steatosis was not related to duration of HIV, ARV exposure, or HCV coinfection. Conclusions: These data suggest that hepatic steatosis may be very common in HIV, not limited to those with HCV coinfection, and may play an important role in the metabolic profile among HIV-infected men and women. C1 NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Nutr Metab, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hadigan, C (reprint author), NIAID, NIH, Immunoregulat Lab, 10 Ctr Dr,Bldg 10,Rm 11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [P30 DK040561, K23 DK02844, P30 DK040561-11, P30-DK040561] NR 37 TC 32 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2007 VL 46 IS 3 BP 312 EP 317 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 226RZ UT WOS:000250607500009 PM 17721396 ER PT J AU Rasamimari, A Dancy, B Talashek, M Park, CG AF Rasamimari, Amnuayporn Dancy, Barbara Talashek, Marie Park, Chang Gi TI Predictors of sexual behaviors among Thai young adults SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE LA English DT Article DE HIV knowledge; negotiation for safer sex; sexual behaviors; Thai young adults ID IMMUNODEFICIENCY-VIRUS-INFECTION; CONDOM USE; TRANSMITTED DISEASES; VOCATIONAL STUDENTS; NORTHERN THAILAND; SCHOOL-STUDENTS; AIDS KNOWLEDGE; HIV-INFECTION; RISK BEHAVIOR; MEN AB To identify correlates of sexual behaviors among Thai young adults between 18 and 24 years, the authors used a cross-sectional survey of 405 young adults from eight randomly selected Thai urban and rural vocational schools. The young adults completed self-report questionnaires. Logistic regressions were used to determine the correlates between a Thai young adult's ever having had sexual intercourse and the correlates of the number of sexual partners and consistent condom use among those who-Were sexually active. The independent variables were age, gender, socioeconomic status, geographic residence, parental residence, parental-young adult communication, HIV knowledge, and negotiation for safer sex. The results showed that geographic residence and negotiation for safer sex were related to a young adult's ever having had sexual intercourse; gender, HIV knowledge, and negotiation for safer sex were related to the number of sexual partners; and geographic residence was related to condom use. HIV prevention programs should incorporate HIV knowledge and negotiation skills for both genders and for all geographical areas. C1 NINR, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Illinois, Coll Nursing, Chicago, IL USA. RP Rasamimari, A (reprint author), NINR, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 35 TC 9 Z9 9 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1055-3290 J9 J ASSOC NURSE AIDS C JI J. Assoc. Nurses Aids Care PD NOV-DEC PY 2007 VL 18 IS 6 BP 13 EP 21 DI 10.1016/j.jana.2007.08.001 PG 9 WC Nursing SC Nursing GA 233WK UT WOS:000251120800003 PM 17991595 ER PT J AU Gregory, AM Rijsdijk, FV Lau, JYF Napolitano, M McGuffin, P Eley, TC AF Gregory, Alice M. Rijsdijk, Fruehling V. Lau, Jennifer Y. F. Napolitano, Maria McGuffin, Peter Eley, Thalia C. TI Genetic and environmental influences on interpersonal cognitions and associations with depressive symptoms in 8-year-old twins SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE depression; interpersonal; cognitions; twins; children ID SELF-PERCEIVED COMPETENCE; CHILDRENS DEPRESSION; DEVELOPMENTAL ORIGINS; CHILDHOOD DEPRESSION; ANTISOCIAL-BEHAVIOR; YOUNG ADOLESCENTS; REPORTED ANXIETY; TRIPARTITE MODEL; DIMENSIONS; DISORDERS AB Less is known about depression in children than in adults. This study integrates fields by combining cognitive and interpersonal research investigating childhood depression symptoms through the use of a genetic framework. Three research questions are addressed. First, what are the associations among interpersonal cognitions, anxiety, and depression? Second, what are the relative magnitudes of genetic and environmental influences on interpersonal cognitions? Third, to what extent do genetic and environmental influences explain associations between interpersonal cognitions and depression? Three hundred pairs of 8-year-old twins reported on symptoms of depression and anxiety by completing the Children's Depression Inventory and the Screen for Childhood Anxiety-Related Emotional Disorders. The authors examined interpersonal cognitions with the Children's Expectation of Social Behaviors and the Perceptions of Peers and Self Questionnaires. Interpersonal cognitions were more strongly correlated with depression (mean r =.35) than with anxiety (mean r =.13). Genetic influence on interpersonal cognitions was small (M = 3%), and associations between interpersonal cognitions and depression were mainly explained by environmental influences. These latter findings may result from interpersonal cognitions in young children, reflecting life experiences as opposed to trait-like cognitive biases. C1 Kings Coll London, Social Genet & Dev Psychiat Ctr, MRC, Inst Psychiat, London SE5 8AF, England. Univ London, Dept Psychol, Univ London Goldsmiths Coll, London WC1E 7HU, England. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Gregory, AM (reprint author), Kings Coll London, Social Genet & Dev Psychiat Ctr, MRC, Inst Psychiat, Box P080,De Crespigny Pk, London SE5 8AF, England. EM a.gregory@iop.kcl.ac.uk RI Eley, Thalia/D-4811-2011; Rijsdijk, Fruhling/B-4191-2011; McGuffin, Peter/A-1565-2012 OI McGuffin, Peter/0000-0002-9888-2907 FU Medical Research Council [G0500079, G120/635] NR 63 TC 6 Z9 6 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2007 VL 116 IS 4 BP 762 EP 775 DI 10.1037/0021-843X.116.4.762 PG 14 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 231HO UT WOS:000250937700009 PM 18020722 ER PT J AU Platts-Mills, TAE Satinover, SM Naccara, L Litonjua, AA Phipatanakul, W Carter, MC Heymann, PW Woodfolk, JA Peters, EJ Gold, DR AF Platts-Mills, Thomas A. E. Satinover, Shama M. Naccara, Lisa Litonjua, Augusto A. Phipatanakul, Wanda Carter, Melody C. Heymann, Peter W. Woodfolk, Judith A. Peters, Edward J. Gold, Diane R. TI Prevalence and titer of IgE antibodies to mouse allergens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergy; mouse allergen; Mus m 1; asthma; inner-city; sensitization ID INNER-CITY CHILDREN; LABORATORY-ANIMAL WORKERS; RAT URINARY ALLERGENS; MODIFIED TH2 RESPONSE; RISK-FACTORS; CAT ALLERGEN; DUST-MITE; ASTHMA; EXPOSURE; SENSITIZATION AB Background: Positive skin tests to allergens derived from mouse urine have been reported among patients with asthma. Very few data are available detailing the titer of IgE Ab to mouse allergen and how it varies by location and population. Objective: To evaluate further the prevalence and titer of IgE Ab to mouse-derived allergens and their relevance to total IgE and asthma. Methods: IgE Ab to mouse allergens was measured in 1165 sera from diverse populations including children and adults. The results were compared with IgE Ab to other allergens and total serum IgE. Results: Positive results were found in 79 sera, but only 15 had an IgE Ab titer >= 10 IU/mL. Results for IgE Ab to Mus m I showed a close quantitative correlation with IgE Ab to mouse allergen (r = 0.93; P <.001). Cohorts in neither Atlanta nor Virginia contained sera in which IgE Ab to mouse was dominant over other allergens or contributed significantly to total IgE. By contrast, among 319 mothers from minority groups in Boston, 11 sera had >= 10 IU/mL. In these sera, specific IgE Ab to mouse made a significant contribution to the total. Conclusion: Mouse allergen sensitization may contribute significantly to total IgE and allergy in African American and Hispanic populations from some northern cities. Analysis of the significance of an IgE Ab response should include quantitative comparison with other responses and total IgE. Clinical implications: Significance of rodent infestation and IgE Ab varies dramatically in different populations and areas of the United States. C1 Univ Virginia, Asthma & Allerg Dis Ctr, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Platts-Mills, TAE (reprint author), Univ Virginia, Asthma & Allerg Dis Ctr, POB 801355, Charlottesville, VA 22908 USA. EM tap2z@Virginia.edu OI Litonjua, Augusto/0000-0003-0422-5875 FU NIAID NIH HHS [AI050989, AI20565] NR 37 TC 14 Z9 14 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2007 VL 120 IS 5 BP 1058 EP 1064 DI 10.1016/j.jaci.2007.06.032 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 231TZ UT WOS:000250973400012 PM 17767949 ER PT J AU Arbes, SJ Gergen, PJ Vaughn, B Zeldin, DC AF Arbes, Samuel J., Jr. Gergen, Peter J. Vaughn, Ben Zeldin, Darryl C. TI Asthma cases attributable to atopy: Results from the third national health and nutrition examination survey SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergens; allergic sensitization; allergy skin test; asthma; atopy; epidemiology; NHANES III; skin prick test; survey ID HOUSE-DUST MITE; COMMON ALLERGENS; CAT ALLERGEN; ASSOCIATION; SENSITIZATION; POPULATION; EXPOSURE; ADOLESCENTS; REACTIVITY; CHILDHOOD AB Background: The percentage of asthma cases attributable to atopy is the subject of debate. Objectives: The objectives were to estimate the percentage of asthma cases in the US population attributable to atopy and to examine associations between allergen-specific skin tests and asthma. Methods: Data were obtained from the Third National Health and Nutrition Examination Survey, in which subjects age 6 to 59 years were skin tested with 10 allergens. Atopy was defined as at least 1 positive allergen-specific test. Doctor-diagnosed current asthma was assessed by questionnaire. Results: In the United States, 56.3% of the asthma cases were attributable to atopy, and that percentage was greater among males than females, among persons in the highest education category than in lower education categories, and among persons living in highly populated metropolitan areas than in all other areas. Each allergen-specific test was strongly associated with asthma before adjustment (odds ratios varied from 2.1 to 4.5); however, after adjustment by all the allergens, only tests to cat, Alternaria, white oak, and perennial rye were independently associated with asthma. Perennial rye was inversely associated with asthma. Of the 10 allergens, a positive response to cat accounted for the highest percentage of asthma cases (29.3%). Conclusion: About half of the current asthma cases in the US population represented by the Third National Health and Nutrition Examination Survey were attributable to atopy. Some allergen-specific skin tests were not independently associated with asthma. Clinical implications: If atopy could be prevented or reversed, or its effect on asthma blocked, then a large percentage of asthma cases in the US population could be prevented. C1 NIEHS, Lab Resp Biol, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. Rho Inc, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), NIEHS, Lab Resp Biol, Div Intramural Res, NIH, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025041-10] NR 22 TC 114 Z9 115 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2007 VL 120 IS 5 BP 1139 EP 1145 DI 10.1016/j.jaci.2007.07.056 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 231TZ UT WOS:000250973400024 PM 17889931 ER PT J AU Morosco, G Kiley, J AF Morosco, Gregory Kiley, James TI National asthma education and prevention program - Expert panel report 3: Guidelines for the diagnosis and management of asthma summary report 2007 - Preface SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material C1 NHLBI, Div Applicat Res Dicoveries, Bethesda, MD 20892 USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. RP Morosco, G (reprint author), NHLBI, Div Applicat Res Dicoveries, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 3 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2007 VL 120 IS 5 SU S BP S93 EP S93 DI 10.1016/j.jaci.2007.09.043 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 235PU UT WOS:000251247600001 ER PT J AU Zeldin, DC Card, JW Carey, MA Voltz, JW AF Zeldin, Darryl C. Card, Jeffrey W. Carey, Michelle A. Voltz, James W. TI Rebuttal from Dr. Mitzner SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Letter ID AIRWAY RESPONSIVENESS; INFLAMMATION; MICE C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2007 VL 103 IS 5 BP 1906 EP 1906 PG 1 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 224WZ UT WOS:000250480400061 PM 18098389 ER PT J AU Palmer, RJ Stoodley, P AF Palmer, Robert J., Jr. Stoodley, Paul TI Biofilms 2007: Broadened horizons and new emphases SO JOURNAL OF BACTERIOLOGY LA English DT Review ID PSEUDOMONAS-AERUGINOSA BIOFILMS; STAPHYLOCOCCUS-AUREUS BIOFILM; ENTERICA SEROVAR TYPHIMURIUM; QUORUM-SENSING INHIBITORS; BACTERIAL BIOFILMS; ESCHERICHIA-COLI; POLYMORPHONUCLEAR LEUKOCYTES; PLANKTONIC CELLS; GENE-EXPRESSION; CYSTIC-FIBROSIS C1 NIH, Natl Inst Fent & Craniofacial Res, Oral Infect & Immunity Branch, Oral Biofilm Communicat Unit, Bethesda, MD 20892 USA. Ctr Genomic Sci, Allegheny Singer Res Inst, Pittsburgh, PA 15090 USA. RP Palmer, RJ (reprint author), NIH, Natl Inst Fent & Craniofacial Res, Oral Infect & Immunity Branch, Oral Biofilm Communicat Unit, Bldg 30,Rm 310,30 Convent Dr, Bethesda, MD 20892 USA. EM rjpalmer@mail.nih.gov RI Stoodley, Paul/E-5079-2013 OI Stoodley, Paul/0000-0001-6069-273X FU Intramural NIH HHS NR 77 TC 32 Z9 33 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2007 VL 189 IS 22 BP 7948 EP 7960 DI 10.1128/JB.00787-07 PG 13 WC Microbiology SC Microbiology GA 232AU UT WOS:000250991300002 PM 17766421 ER PT J AU Hiller, NL Janto, B Hogg, JS Boissy, R Yu, SS Powell, E Keefe, R Ehrlich, NE Shen, K Hayes, J Barbadora, K Klimke, W Dernovoy, D Tatusova, T Parkhill, J Bentley, SD Post, JC Ehrlich, GD Hu, FZ AF Hiller, N. Luisa Janto, Benjamin Hogg, Justin S. Boissy, Robert Yu, Susan Powell, Evan Keefe, Randy Ehrlich, Nathan E. Shen, Kai Hayes, Jay Barbadora, Karen Klimke, William Dernovoy, Dmitry Tatusova, Tatiana Parkhill, Julian Bentley, Stephen D. Post, J. Christopher Ehrlich, Garth D. Hu, Fen Z. TI Comparative genomic analyses of seventeen Streptococcus pneumoniae strains: Insights into the pneumococcal supragenome SO JOURNAL OF BACTERIOLOGY LA English DT Article ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; ACUTE OTITIS-MEDIA; OBSTRUCTIVE PULMONARY-DISEASE; MIDDLE-EAR MUCOSA; ABORIGINAL INFANTS; INVASIVE-DISEASE; YOUNG-CHILDREN; GENE-TRANSFER; SEQUENCE; CARRIAGE AB The distributed-genome hypothesis (DGH) states that pathogenic bacteria possess a supragenome that is much larger than the genome of any single bacterium and that these pathogens utilize genetic recombination and a large, noncore set of genes as a means of diversity generation. We sequenced the genomes of eight nasopharyngeal strains of Streptococcus pneumoniae isolated from pediatric patients with upper respiratory symptoms and performed quantitative genomic analyses among these and nine publicly available pneumococcal strains. Coding sequences from all strains were grouped into 3,170 orthologous gene clusters, of which 1,454 (46%) were conserved among all 17 strains. The majority of the gene clusters, 1,716 (54%), were not found in all strains. Genic differences per strain pair ranged from 35 to 629 orthologous clusters, with each strain's genome containing between 21 and 32% noncore genes. The distribution of the orthologous clusters per genome for the 17 strains was entered into the finite-supragenome model, which predicted that (i) the S. pneumoniae supragenome contains more than 5,000 orthologous clusters and (ii) 99% of the orthologous clusters (similar to 3,000) that are represented in the S. pneumoniae population at frequencies of >= 0.1 can be identified if 33 representative genomes are sequenced. These extensive genic diversity data support the DGH and provide a basis for understanding the great differences in clinical phenotype associated with various pneumococcal strains. When these findings are taken together with previous studies that demonstrated the presence of a supragenome for Streptococcus agalactiae and Haemophilus influenzae, it appears that the possession of a distributed genome is a common host interaction strategy. C1 Allegheny Gen Hosp, Allegheny Singer Res Inst, Ctr Genom Sci, Pittsburgh, PA 15212 USA. Drexel Univ, Coll Med, Dept Microbiol & Immunol, Pittsburgh, PA 15212 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Sanger Inst, Cambridge CB10 1SA, England. RP Hu, FZ (reprint author), Allegheny Gen Hosp, Ctr Genom Sci, 320 E N Ave, Pittsburgh, PA 15212 USA. EM fhu@wpahs.org RI Parkhill, Julian/G-4703-2011; Janto, Benjamin/E-7459-2010; Hiller, N. Luisa/A-3739-2016 OI Parkhill, Julian/0000-0002-7069-5958; Janto, Benjamin/0000-0002-3841-4917; Hiller, N. Luisa/0000-0001-6572-1368 FU NIDCD NIH HHS [DC04173, DC02148, DC05659, R01 DC002148, R01 DC004173, R01 DC005659]; Wellcome Trust NR 44 TC 169 Z9 172 U1 1 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2007 VL 189 IS 22 BP 8186 EP 8195 DI 10.1128/JB.00690-07 PG 10 WC Microbiology SC Microbiology GA 232AU UT WOS:000250991300028 PM 17675389 ER PT J AU Jenkins, LS Powell, JL Schron, EB McBurnie, MA Bosworth-Farrell, S Moore, R Exner, DV AF Jenkins, Louise S. Powell, Judy L. Schron, Eleanor B. McBurnie, Mary Ann Bosworth-Farrell, Susan Moore, Richard Exner, Derek V. CA AVID Investigators TI Partner quality of life in the antiarrhythmics versus implantable defibrillators trial SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE implantable cardioverter defibrillators; Medical Outcomes Short Form-36; partners; quality of life; Quality of Life Index; spouse; ventricular dysrhythmias ID INTERNAL CARDIOVERTER-DEFIBRILLATOR; MEDICAL OUTCOMES; ACCEPTANCE; THERAPY; DEATH AB Background and Objective: The quality of life (QOL) of patients with ventricular dysrhythmias is well studied, but less is known about the QOL of their partners. This study describes the QOL of partners of patients with serious ventricular dysrhythmias enrolled in the Antiarrhythmics Versus Implantable Defibrillators trial. Subjects and Methods: A convenience sample of 124 partners of patients randomized to antiarrhythmic drugs (n = 59) or an implantable cardioverter defibrillator (n = 65) in the Antiarrhythmics versus Implantable Defibrillators trial was obtained. The Short Form-36 and Quality of Life Index were assessed at baseline (postrandomization) and at 3-, 6-, and 12-month follow-up. Results and Conclusions: The mean age of the partners was 62 years. Most were white and female. Their mean Short Form-36 scores were comparable to a normative age group. Partner and participant mean Short Form-36 and Quality of Life Index scores correlated modestly (range 0.25-0.36). The physical summary scores of partners using the Short Form-36 declined over time, whereas their mental summary scores remained stable. Partner concerns related to death, dysrhythmia recurrence, and the impact of dysrhythmias on enjoyment of life lessened from baseline to 12 months. Concern about implantable cardioverter defibrillator function remained stable over time. Although the sample size of this study was relatively small and limited by missing data for some assessments, it is the largest prospective study of QOL in partners of patients with serious dysrhythmias. The results offer a foundation for future research of the partners of patients with serious dysrhythmias in terms of identifying their needs, offering support, and maximizing QOL. C1 Univ Washington, Dept Biostat, Seattle, WA 98105 USA. Univ Maryland, Sch Nursing, Inst Educators Nursing & Hlth Profess, Baltimore, MD 21201 USA. NHLBI, Atherotherombosis & Coronary Artery Dis Branch, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Maine Med Ctr, Div Cardiol, Portland, ME 04102 USA. Univ Calgary, Alberta Heritage Fdn Med Res, Canadian Inst Hlth Res, Calgary, AB, Canada. RP Powell, JL (reprint author), Univ Washington, Dept Biostat, 1107 NE 45th St,Suite 505, Seattle, WA 98105 USA. EM jlpowell@u.washington.edu FU NHLBI NIH HHS [N01 HC-25117] NR 29 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD NOV-DEC PY 2007 VL 22 IS 6 BP 472 EP 479 PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 230BK UT WOS:000250850100015 PM 18090188 ER PT J AU Smyth, JT DeHaven, WI Bird, GS Putney, JW AF Smyth, Jeremy T. DeHaven, Wayne I. Bird, Gary S. Putney, James W., Jr. TI Role of the microtubule cytoskeleton in the function of the store-operated Ca2+ channel activator STIM1 SO JOURNAL OF CELL SCIENCE LA English DT Article DE calcium channels; calcium signaling; ion channels; microtubules; store-operated channels ID CAPACITATIVE CALCIUM-ENTRY; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; COUPLING MODEL; CRAC CHANNELS; CELLS; INFLUX; ORAI1; INHIBITION; PROTEINS AB We examined the role of the microtubule cytoskeleton in the localization and store-operated Ca2+ entry (SOCE) function of the endoplasmic reticulum (ER) Ca2+ sensor stromal interaction molecule 1 (STIM1) in HEK 293 cells. STIM1 tagged with an enhanced yellow fluorescent protein (EYFP-STIM1) exhibited a fibrillar localization that colocalized with endogenous alpha-tubulin. Depolymerization of microtubules with nocodazole caused a change from a fibrillar EYFP-STIM1 localization to one that was similar to that of the ER. Treatment of HEK 293 cells with nocodazole had a detrimental impact on SOCE and the associated Ca2+ release-activated Ca2+ current (I-CRAC). This inhibition was significantly reversed in cells overexpressing EYFP-STIM1, implying that the primary inhibitory effect of nocodazole is related to STIM1 function. Surprisingly, nocodazole treatment alone induced significant SOCE and I-CRAC in cells expressing EYFP-STIM1, and this was accompanied by an increase in EYFP-STIM1 fluorescence near the plasma membrane. We conclude that microtubules play a facilitative role in the SOCE signaling pathway by optimizing the localization of STIM1. C1 NIEHS, NIH, Dept Hlth & Human Serv, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090087-11, Z99 ES999999] NR 25 TC 75 Z9 75 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2007 VL 120 IS 21 BP 3762 EP 3771 DI 10.1242/jcs.015735 PG 10 WC Cell Biology SC Cell Biology GA 234EX UT WOS:000251144600006 PM 17925382 ER PT J AU Woodard, GE Rosado, JA AF Woodard, Geoffrey E. Rosado, Juan A. TI Recent advances in natriuretic peptide research SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE natriuretic peptides; heart failure; renoprotective effect; nesiritide; biomarkers ID DECOMPENSATED HEART-FAILURE; WORSENING RENAL-FUNCTION; EMERGENCY-DEPARTMENT PRIDE; INTRAVENOUS NESIRITIDE; FACTOR RECEPTORS; CONTROLLED-TRIAL; PORCINE BRAIN; PRIMARY-CARE; INFUSION; RAT AB The natriuretic peptides are a family of related hormones that play a crucial role in cardiovascular and renal homeostasis. They have recently emerged as potentially important clinical biomarkers in heart failure. Natriuretic peptides, particularly brain natriuretic peptide (BNP) and the inactive N-terminal fragment of BNP, NT-proBNP, that has an even greater half-life than BNP, are elevated in heart failure and therefore considered to be excellent predictors of disease outcome. Nesiritide, a recombinant human BNP, has been shown to provide symptomatic and haemodynamic improvement in acute decompensated heart failure, although recent reports have suggested an increased short-term risk of death with nesiritide use. This review article describes: the current use of BNP and its inactive precursor NT-proBNP in diagnosis, screening, prognosis and monitoring of therapy for congestive heart failure, the renoprotective actions of natriuretic peptides after renal failure and the controversy around the therapeutic use of the recombinant human BNP nesiritide. C1 [Woodard, Geoffrey E.] NIAID, NIH, Bethesda, MD 20892 USA. [Rosado, Juan A.] Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIAID, NIH, 10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM GeoffreyW@niaid.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 76 TC 25 Z9 31 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD NOV-DEC PY 2007 VL 11 IS 6 BP 1263 EP 1271 DI 10.1111/j.1582-4934.2007.00125.x PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 251TC UT WOS:000252396800008 PM 18205700 ER PT J AU O'Neil, JN Mouton, PR Tizabi, Y Ottinger, MA Lei, DL Ingram, DK Manaye, KF AF O'Neil, Jahn N. Mouton, Peter R. Tizabi, Yousef Ottinger, Mary Ann Lei, De-Liang Ingram, Donald K. Manaye, Kebreten F. TI Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP/PS1 mice SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE substantia nigra; ventral tegmental area; unbiased stereology; APP/PS1 mice; tyrosine hydroxylase ID AMYLOID-PRECURSOR-PROTEIN; TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; CELL LOSS; STEREOLOGICAL ESTIMATION; PRESENILIN-1 TRANSGENES; MUTANT PRESENILIN-1; NUCLEUS COERULEUS; BETA-PEPTIDE; PLAQUE LOAD AB Alzheimer's disease (AD) is the most common type of dementia afflicting the elderly. In addition to the presence of cortical senile plaques and neurofibrillary tangles, AD is characterized at autopsy by extensive degeneration of brainstem locus coeruleus (LC) neurons that provide noradrenergic innervation to cortical neuropil, together with relative stability of dopaminergic neuron number in substantia nigra (SN) and ventral tegmental area (VTA). The present study used design-based stereological methods to assess catecholaminergic neuronal loss in brains of double transgenic female mice that co-express two human mutations associated with familial AD, amyloid precursor protein (APP(swe)) and presenilin-1 (PSI Delta E9). Mice were analyzed at two age groups, 3-6 months and 16-23 months, when deposition of Delta D-type beta-amyloid (A beta) plaques occurs in cortical brain regions. Blocks of brain tissue containing the noradrenergic LC nucleus and two nuclei of dopaminergic neurons, the SN and VTA, were sectioned and sampled in a systematic-random manner and immunostained for tyrosine hydroxylase (TH), a specific marker for catecholaminergic neurons. Using the optical fractionator method we found a 24% reduction in the total number of TH-positive neurons in LC with no changes in SN-VTA of aged dtg APP/PS1 mice compared with non-transgenic controls. No significant differences were observed in numbers of TH-positive neurons in LC or SN-VTA in brains of young female dtg APP/PS I mice compared to their age-matched controls. The findings of selective neurodegeneration of LC neurons in the brains of aged female dtg APP/PS1 mice mimic the neuropathology in the brains of AD patients at autopsy. These findings support the use of murine models of A beta deposition to develop novel strategies for the therapeutic management of patients afflicted with AD. (C) 2007 Elsevier B.V. All rights reserved. C1 Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. NIA, NIH, Lab Expt Gerontol, Baltimore, MD 21224 USA. Stereol Resource Ctr, Baltimore, MD USA. Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha, Peoples R China. RP Manaye, KF (reprint author), Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. EM kmanaye@howard.edu FU Intramural NIH HHS; NIMH NIH HHS [R24 MH067627, MH076541-02A1]; NINDS NIH HHS [SNR2PU54NS039407-07] NR 58 TC 45 Z9 45 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD NOV PY 2007 VL 34 IS 3-4 BP 102 EP 107 DI 10.1016/j.jchemneu.2007.05.008 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 219XA UT WOS:000250120300004 PM 17658239 ER PT J AU Gresh, N Cisneros, GA Darden, TA Piquemal, JP AF Gresh, Nohad Cisneros, G. Andres Darden, Thomas A. Piquemal, Jean-Philip TI Anisotropic, polarizable molecular mechanics studies of inter- and intramoecular interactions and ligand-macromolecule complexes. A bottom-up strategy SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Review ID PARALLEL AB-INITIO; METALLO-BETA-LACTAMASE; INTRAMOLECULAR INTERACTION ENERGIES; INTERMOLECULAR INTERACTION ENERGIES; BIOLOGICALLY RELEVANT LIGANDS; CHARGE-TRANSFER CONTRIBUTION; HIV-1 NUCLEOCAPSID PROTEIN; DENSITY-FUNCTIONAL THEORY; FRAGMENT POTENTIAL METHOD; ATOMIC MULTIPOLE MOMENTS AB We present an overview of the SIBFA polarizable molecular mechanics procedure, which is formulated and calibrated on the basis of quantum chemistry (QC). It embodies nonclassical effects such as electrostatic penetration, exchange-polarization, and charge transfer. We address the issues of anisotropy, nonadditivity, and transferability by performing parallel QC computations on multimolecular complexes. These encompass multiply H-bonded complexes and polycoordinated complexes of divalent cations. Recent applications to the docking of inhibitors to Zn-metalloproteins are presented next, namely metallo-beta-lactamase, phosphomannoisomerase, and the nucleocapsid of the HIV-1 retrovirus. Finally, toward third-generation intermolecular potentials based on density fitting, we present the development of a novel methodology, the Gaussian electrostatic model (GEM), which relies on ab initio-derived fragment electron densities to compute the components of the total interaction energy. As GEM offers the possibility of a continuous electrostatic model going from distributed multipoles to densities, it allows an inclusion of short-range quantum effects in the molecular mechanics energies. The perspectives of an integrated SIBFA/GEM/QM procedure are discussed. C1 Univ Paris 06, INSERM, UFR Biomed, Lab Pharmacochim Mol & Cellulaire, F-75006 Paris, France. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Paris 06, CNRS, UMR 7616, Chim Theor Lab, F-75252 Paris, France. RP Gresh, N (reprint author), Univ Paris 06, INSERM, UFR Biomed, Lab Pharmacochim Mol & Cellulaire, 45 Rue St Peres, F-75006 Paris, France. EM nohad.gresh@univ-paris5.fr; jpp@lct.jussieu.fr RI Cisneros, Gerardo/B-3128-2010; Piquemal, Jean-Philip/B-9901-2009 OI Piquemal, Jean-Philip/0000-0001-6615-9426 FU Intramural NIH HHS [NIH0011757912, Z01 ES090601-11] NR 184 TC 204 Z9 204 U1 1 U2 58 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD NOV-DEC PY 2007 VL 3 IS 6 BP 1960 EP 1986 DI 10.1021/ct700134r PG 27 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 232MQ UT WOS:000251024200008 PM 18978934 ER PT J AU Posner, K Melvin, GA Murray, DW Gugga, SS Fisher, P Skrobala, A Cunningham, C Vitiello, B Abikoff, HB Ghuman, JK Kollins, S Wigal, SB Wigal, T McCracken, JT McGough, JJ Kastelic, E Boorady, R Davies, M Chuang, SZ Swanson, JM Riddle, MA Greenhill, LL AF Posner, Kelly Melvin, Glenn A. Murray, Desiree W. Gugga, S. Sonia Fisher, Prudence Skrobala, Anne Cunningham, Charles Vitiello, Benedetto Abikoff, Howard B. Ghuman, Jaswinder K. Kollins, Scott Wigal, Sharon B. Wigal, Tim McCracken, James T. McGough, James J. Kastelic, Elizabeth Boorady, Roy Davies, Mark Chuang, Shirley Z. Swanson, James M. Riddle, Mark A. Greenhill, Laurence L. TI Clinical presentation of attention-deficit/hyperactivity disorder in preschool children: The preschoolers with attention-deficit/hyperactivity treatment study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DIAGNOSTIC INTERVIEW SCHEDULE; DISRUPTIVE BEHAVIOR; OPPOSITIONAL DEFIANT; CRITERION VALIDITY; CONDUCT DISORDER; PREVALENCE RATES; FOLLOW-UP; IV; ADHD AB Objective: The aim of this study was to describe the clinical presentation of preschoolers diagnosed with moderate to severe attention-deficit/hyperactivity disorder (ADHD) recruited for the multisite Preschool ADHD Treatment Study (PATS). The diagnosis and evaluation process will also be described. Method: A comprehensive multidimensional, multi-informant assessment protocol was implemented including the semistructured PATS Diagnostic Interview. Parent- and teacher-report measures were used to supplement information from interviews. Consensus agreement by a cross-site panel on each participant's diagnoses was required. Analyses were conducted to describe the sample and to test associations between ADHD severity and demographic and clinical variables. Results: The assessment protocol identified 303 preschoolers (3-5.5 years) with moderate to severe ADHD Hyperactive/Impulsive or Combined type. The majority of participants (n = 211, 69.6%) experienced co-morbid disorders, with oppositional defiant disorder, communication disorders, and anxiety disorders being the most common. Participants with co-morbid communication disorders were found to be more anxious and depressed. ADHD severity was found to correlate with more internalizing difficulties and lower functioning. Although boys and girls had similar symptom presentations, younger children had significantly higher ADHD severity. Conclusions: Preschoolers with moderate to severe ADHD experience high co-morbidity and impairment, which have implications for both assessment and treatment. C1 [Posner, Kelly; Melvin, Glenn A.; Gugga, S. Sonia; Fisher, Prudence; Skrobala, Anne; Davies, Mark; Greenhill, Laurence L.] Columbia Univ, New York State Psychiat Inst, Div Child & Adolescent Psychiat, U74, New York, NY 10032 USA. [Murray, Desiree W.; Kollins, Scott] Duke Univ, Med Ctr, Durham, NC USA. [Cunningham, Charles] McMaster Univ, Hamilton, ON, Canada. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Abikoff, Howard B.; Boorady, Roy] NYU, Ctr Child Study, New York, NY 10021 USA. [Wigal, Sharon B.; Wigal, Tim; Swanson, James M.] Univ Calif Irvine, Irvine, CA USA. [Kollins, Scott; McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ USA. [Kastelic, Elizabeth; Riddle, Mark A.] Johns Hopkins Univ, Baltimore, MD USA. [Chuang, Shirley Z.] Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. RP Posner, K (reprint author), Columbia Univ, New York State Psychiat Inst, Div Child & Adolescent Psychiat, U74, 1051 Riverside Dr, New York, NY 10032 USA. EM posnerk@childpsych.columbia.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [K23 MH001883-06] NR 51 TC 58 Z9 59 U1 4 U2 12 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 547 EP 562 DI 10.1089/cap.2007.0075 PG 16 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400002 PM 17979577 ER PT J AU Ghuman, JK Riddle, MA Vitiello, B Greenhill, LL Chuang, SZ Wigal, SB Kollins, SH Abikoff, HB McCracken, JT Kastelic, E Scharko, AM McGough, JJ Murray, DW Evans, L Swanson, JM Wigal, T Posner, K Cunningham, C Davies, M Skrobala, AM AF Ghuman, Jaswinder K. Riddle, Mark A. Vitiello, Benedetto Greenhill, Laurence L. Chuang, Shirley Z. Wigal, Sharon B. Kollins, Scott H. Abikoff, Howard B. McCracken, James T. Kastelic, Elizabeth Scharko, Alexander M. McGough, James J. Murray, Desiree W. Evans, Lori Swanson, James M. Wigal, Tim Posner, Kelly Cunningham, Charles Davies, Mark Skrobala, Anne M. TI Comorbidity moderates response to methylphenidate in the Preschoolers with attention-deficit/hyperactivity disorder Treatment Study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MULTIMETHOD CLINICAL PROTOCOL; MOTHER CHILD INTERACTIONS; DEVELOPMENTAL-CHANGES; STIMULANT RESPONSE; PREVALENCE RATES; ADHD; AGE; VALIDITY; SYMPTOMS AB Objective: The aim of this study was to examine whether demographic or pretreatment clinical and social characteristics influenced the response to methylphenidate (MPH) in the Preschoolers with ADHD Treatment Study (PATS). Methods: Exploratory moderator analyses were conducted on the efficacy data from the PATS 5-week, double-blind, placebo-controlled six-site titration trial. Children (N = 165, age 3-5.5 years) were randomized to 1 week each of four MPH doses (1.25, 2.5, 5, and 7.5 mg) and placebo administered three times per day (t.i.d.). We assessed the fixed effects on the average slope in the regression outcome on moderators, weight-adjusted dose, and the moderator-by- dose interaction using SAS PROC GENMOD. Results: A significant interaction effect was found for a number of co-morbid disorders diagnosed in the preschoolers at baseline (p = 0.005). Preschoolers with three or more co-morbid disorders did not respond to MPH (Cohen's d at 7.5 mg dose relative to placebo = -0.37) compared to a significant response in the preschoolers with 0, 1, or 2 co-morbid disorders (Cohen's d = 0.89, 1.00, and 0.56, respectively). Preschoolers with more co-morbidity were found to have more family adversity. No significant interaction effect was found with the other variables. Conclusions: In preschoolers with ADHD, the presence of no or one co-morbid disorder (primarily oppositional defiant disorder) predicted a large treatment response at the same level as has been found in school-aged children, and two co-morbid disorders predicted moderate treatment response; whereas the presence of three or more co-morbid disorders predicted no treatment response to MPH. C1 [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ 85724 USA. [Riddle, Mark A.; Kastelic, Elizabeth] Johns Hopkins Univ, Baltimore, MD USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Greenhill, Laurence L.; Chuang, Shirley Z.; Posner, Kelly; Davies, Mark; Skrobala, Anne M.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Wigal, Sharon B.; Swanson, James M.; Wigal, Tim] Univ Calif Irvine, Irvine, CA USA. [Kollins, Scott H.; Murray, Desiree W.] Duke Univ, Med Ctr, Durham, NC USA. [Abikoff, Howard B.; Evans, Lori] NYU, Ctr Child Study, New York, NY USA. [McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Scharko, Alexander M.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Cunningham, Charles] McMaster Univ, Hamilton, ON, Canada. RP Ghuman, JK (reprint author), Univ Arizona, Room AHSC 7304,1501 N Campbell Ave, Tucson, AZ 85724 USA. EM jkghuman@email.arizona.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [K23 MH 01883-01A1, K23 MH001883-03, U01 MH 60642, U01 MH 60833, U01 MH 60848, U01 MH 60900, U01 MH 60903, U01 MH 60943] NR 54 TC 33 Z9 34 U1 3 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 563 EP 579 DI 10.1089/cap.2007.0071 PG 17 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400003 PM 17979578 ER PT J AU Abikoff, HB Vitiello, B Riddle, MA Cunningham, C Greenhill, LL Swanson, JM Chuang, SZ Davies, M Kastelic, E Wigal, SB Evans, L Ghuman, JK Kollins, SH McCracken, JT McGough, JJ Murray, DW Posner, K Skrobala, AM Wigal, T AF Abikoff, Howard B. Vitiello, Benedetto Riddle, Mark A. Cunningham, Charles Greenhill, Laurence L. Swanson, James M. Chuang, Shirley Z. Davies, Mark Kastelic, Elizabeth Wigal, Sharon B. Evans, Lori Ghuman, Jaswinder K. Kollins, Scott H. McCracken, James T. McGough, James J. Murray, Desiree W. Posner, Kelly Skrobala, Anne M. Wigal, Tim TI Methylphenidate effects on functional outcomes in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID HYPERACTIVE-CHILDREN; CRITERION VALIDITY; CONTROLLED TRIAL; ADHD; PARENT; BEHAVIOR; SAMPLE; RELIABILITY; POPULATION; MOTHERS AB Objective: The purpose of this study was to examine the effects of methylphenidate (MPH) on functional outcomes, including children's social skills, classroom behavior, emotional status, and parenting stress, during the 4-week, double-blind placebo controlled phase of the Preschoolers with Attention Deficit/ Hyperactivity Disorder (ADHD) Treatment Study (PATS). Methods: A total of 114 preschoolers who had improved with acute MPH treatment, were randomized to their best MPH dose (M = 14.22 mg/day; n = 63) or placebo (PL; n = 51). As-sessments included the Clinical Global Impression-Severity (CGI-S), parent and teacher versions of the Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale (SCS), Social Skills Rating System (SSRS), and Early Childhood Inventory (ECI), and Parenting Stress Index (PSI). Results: Medication effects varied by informant and outcome measure. Parent measures and teacher SWAN scores did not differentially improve with MPH. Parent-rated depression (p = 0.02) and dysthymia (p = 0.001) on the ECI worsened with MPH, but scores were not in the clinical range. Significant medication effects were found on clinician CGI-S (p = 0.0001) and teacher social competence ratings (SCS, p = 0.03). Conclusions: Preschoolers with ADHD treated with MPH for 4 weeks improve in some aspects of functioning. Additional improvements might require longer treatment, higher doses, and/or intensive behavioral treatment in combination with medication. C1 [Abikoff, Howard B.; Evans, Lori] NYU, Ctr Child Study, New York, NY 10016 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD USA. [Riddle, Mark A.; Kastelic, Elizabeth] Johns Hopkins Univ, Baltimore, MD USA. [Greenhill, Laurence L.; Chuang, Shirley Z.; Davies, Mark; Posner, Kelly; Skrobala, Anne M.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Cunningham, Charles] McMaster Univ, Hamilton, ON, Canada. [Swanson, James M.; Wigal, Sharon B.; Wigal, Tim] Univ Calif Irvine, Irvine, CA USA. [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ USA. [Kollins, Scott H.; Murray, Desiree W.] Duke Univ, Med Ctr, Durham, NC USA. [McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Abikoff, HB (reprint author), NYU, Ctr Child Study, 215 Lexington Ave,14th Floor, New York, NY 10016 USA. EM howard.abikoff@med.nyu.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [U01 MH 60833, K23 MH 01883-01A1, K23 MH001883-06, U01 MH 60642, U01 MH 60848, U01 MH 60900, U01 MH 60903, U01 MH 60943] NR 47 TC 29 Z9 31 U1 3 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 581 EP 592 DI 10.1089/cap.2007.0068 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400004 PM 17979579 ER PT J AU Vitiello, B Abikoff, HB Chuang, SZ Kollins, SH McCracken, JT Riddle, MA Swanson, JM Wigal, T McGough, JJ Ghuman, JK Wigal, SB Skrobala, AM Davies, M Posner, K Cunningham, C Greenhill, LL AF Vitiello, Benedetto Abikoff, Howard B. Chuang, Shirley Z. Kollins, Scott H. McCracken, James T. Riddle, Mark A. Swanson, James M. Wigal, Tim McGough, James J. Ghuman, Jaswinder K. Wigal, Sharon B. Skrobala, Anne M. Davies, Mark Posner, Kelly Cunningham, Charles Greenhill, Laurence L. TI Effectiveness of methylphenidate in the 10-month continuation phase of the Preschoolers with ADHD Treatment Study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; STIMULANT MEDICATION; CRITERION VALIDITY; CONDUCT DISORDER; CHILDREN; POPULATION; SYMPTOMS; TOLERABILITY; RELIABILITY; TRENDS AB Objective: The aim of this study was to examine immediate-release methylphenidate effectiveness during the 10-month open-label continuation phase of the Preschoolers with attention-deficit/hyperactivity disorder (ADHD) Treatment Study (PATS). Methods: One hundred and forty preschoolers with ADHD, who had improved with acute immediate-release methylphenidate (IR-MPH) treatment, entered a 10-month, open-label medication maintenance at six sites. Assessments included the Clinical Global Impression-Severity (CGI-S), CGI-Improvement (CGI-I), Children's Global Assessment Scale (C-GAS), Swanson, Nolan, and Pelham Questionnaire (SNAP), Scale Strengths and Weaknesses of ADHD-Symptoms and Normal Behaviors (SWAN), Social Competence Scale, Social Skills Rating System (SSRS), and Parenting Stress Index-Short Form (PSI-SF). Results: For the 95 children who completed the 10-month treatment, improvement occurred on the CGI-S (p = 0.02), CGI-I (p < 0.01), C-GAS (p = 0.001), and SSRS (p = 0.01). SNAP and SWAN scores remained stable. Forty five children discontinued: 7 for adverse effects, 7 for behavior worsening, 7 for switching to long-acting stimulants, 3 for inadequate benefit, and 21 for other reasons. The mean MPH dose increased from 14.04 mg/day +/- SD 7.57 (0.71 +/- 0.38 mg/kg per day) at month 1 to 19.98 mg/day +/- 9.56 (0.92 +/- 0.40 mg/kg per day) at month 10. Conclusions: With careful monitoring and gradual medication dose increase, most preschoolers with ADHD maintained improvement during long-term IR-MPH treatment. There was substantial variability in effective and tolerated dosing. C1 [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. [Abikoff, Howard B.] NYU, Sch Med, Ctr Child Study, New York, NY USA. [Chuang, Shirley Z.; Skrobala, Anne M.; Davies, Mark; Posner, Kelly; Greenhill, Laurence L.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Kollins, Scott H.] Duke Univ, Med Ctr, Durham, NC USA. [McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Riddle, Mark A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Swanson, James M.; Wigal, Tim; Wigal, Sharon B.] Univ Calif Irvine, Irvine, CA USA. [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ USA. [Cunningham, Charles] McMaster Univ, Hamilton, ON, Canada. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [K23 MH001883-06, U01 MH 60642, U01 MH 60833, U01 MH 60848, U01 MH 60900, U01 MH 60903, U01 MH 60943] NR 29 TC 33 Z9 33 U1 2 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 593 EP 603 DI 10.1089/cap.2007.0058 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400005 PM 17979580 ER PT J AU Murray, DW Kollins, SH Hardy, KK Abikoff, HB Swanson, JM Cunningham, C Vitiello, B Riddle, MA Davies, M Greenhill, LL McCracken, JT McGough, JJ Posner, K Skrobala, AM Wigal, T Wigal, SB Ghuman, JK Chuang, SZ AF Murray, Desiree W. Kollins, Scott H. Hardy, Kristina K. Abikoff, Howard B. Swanson, James M. Cunningham, Charles Vitiello, Benedetto Riddle, Mark A. Davies, Mark Greenhill, Laurence L. McCracken, James T. McGough, James J. Posner, Kelly Skrobala, Anne M. Wigal, Tim Wigal, Sharon B. Ghuman, Jaswinder K. Chuang, Shirley Z. TI Parent versus teacher ratings of attention-deficit/hyperactivity disorder symptoms in the preschoolers with attention-deficit/hyperactivity disorder treatment study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; EMOTIONAL-PROBLEMS; SITUATIONAL SPECIFICITY; CRITERION VALIDITY; ELEMENTARY-SCHOOL; CHILD-BEHAVIOR; HIGH AGREEMENT; LOW KAPPA; ADHD AB Objective. To assess parent-teacher concordance on ratings of DSM-IV symptoms of attention-deficit/ hyperactivity disorder (ADHD) in a sample of preschool children referred for an ADHD treatment study. Methods. Parent and teacher symptom ratings were compared for 452 children aged 3-5 years. Agreement was calculated using Pearson correlations, Cohen's kappa, and conditional probabilities. Results. The correlations between parent and teacher ratings were low for both Inattentive (r = .24) and Hyperactive-Impulsive (r = .26) symptom domains, with individual symptoms ranging from .01-.28. Kappa values for specific symptoms were even lower. Conditional probabilities suggest that teachers are only moderately likely to agree with parents on the presence or abscence of symptoms. Parents were quite likely to agree with teachers' endorsement of symptoms, but much less likely to agree when teachers indicated that a symptom was not present. Conclusions. Results provide important data regarding base rates and concordance rates in this age group and support the hypothesis that preschool-aged children at risk for ADHD exhibit significant differences in behavior patterns across settings. Obtaining ratings from multiple informants is therefore considered critical for obtaining a full picture of young children's functioning. C1 [Murray, Desiree W.; Kollins, Scott H.; Hardy, Kristina K.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Kollins, Scott H.; McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Abikoff, Howard B.] NYU, Ctr Child Study, New York, NY USA. [Swanson, James M.] Univ Calif Irvine, Irvine, CA USA. [Cunningham, Charles] McMaster Univ, Hamilton, ON, Canada. [Vitiello, Benedetto; Wigal, Tim; Wigal, Sharon B.] NIMH, Bethesda, MD 20892 USA. [Riddle, Mark A.] Johns Hopkins Univ, Baltimore, MD USA. [Davies, Mark; Greenhill, Laurence L.; Posner, Kelly; Skrobala, Anne M.; Chuang, Shirley Z.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ USA. RP Murray, DW (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3431, Durham, NC 27710 USA. EM dwmurray@duke.edu RI Kollins, Scott/G-2965-2012; OI Hardy, Kristina/0000-0002-5479-5043 FU NIMH NIH HHS [K23 MH001883-06] NR 35 TC 36 Z9 38 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 605 EP 619 DI 10.1089/cap.2007.0060 PG 15 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400006 PM 17979581 ER PT J AU Hardy, KK Kollins, SH Murray, DW Riddle, MA Greenhill, L Cunningham, C Abikoff, HB McCracken, JT Vitiello, B Davies, M McGough, JJ Posner, K Skrobala, AM Swanson, JM Wigal, T Wigal, SB Ghuman, JK Chuang, SZ AF Hardy, Kristina K. Kollins, Scott H. Murray, Desiree W. Riddle, Mark A. Greenhill, Laurence Cunningham, Charles Abikoff, Howard B. McCracken, James T. Vitiello, Benedetto Davies, Mark McGough, James J. Posner, Kelly Skrobala, Anne M. Swanson, James M. Wigal, Tim Wigal, Sharon B. Ghuman, Jaswinder K. Chuang, Shirley Z. TI Factor structure of parent- and teacher-rated attention-deficit/hyperactivity disorder symptoms in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CONFIRMATORY FACTOR-ANALYSIS; EXPLORATORY FACTOR-ANALYSIS; CRITERION VALIDITY; PARALLEL ANALYSIS; RATING-SCALE; SCHOOL-CHILDREN; SAMPLE-SIZE; ADHD; NUMBER AB Objective: This study examines one-, two-, and three-factor models of attention-deficit/hyperactivity disorder (ADHD) using the existing 18 Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV) symptoms in a sample of symptomatic preschoolers. Methods: Parent and/or teacher ratings of DSM-IV symptoms were obtained for 532 children (aged 3-5.5) who were screened for the Preschool ADHD Treatment Study (PATS). Confirmatory factor analysis (CFA) using symptoms identified on the Conners' Parent and Teacher Rating Scales was conducted to assess a two-factor model representing the DSM-IV dimensions of inattention (IN) and hyperactivity/impulsivity (H/I), a three-factor model reflecting inattention, hyperactivity, and impulsivity, and a single-factor model of all ADHD symptoms. Exploratory factor analysis (EFA) was subsequently used to examine the latent structure of the data. Results: For parent ratings, the two-factor and three-factor models were marginally acceptable according to several widely used fit indices, whereas the one-factor model failed to meet minimum thresholds for goodness-of-fit. For teachers, none of the models was a solid fit for the data. Maximum likelihood EFAs resulted in satisfactory two-and three-factor models forboth parents and teachers, although all models contained several moderate cross loadings. Factor loadings were generally concordant with those published for older children and community-based samples. Conclusion: ADHD subtypes according to current DSM-IV specifications may not be the best descriptors of the disorder in the preschool age group. C1 [Hardy, Kristina K.; Kollins, Scott H.; Murray, Desiree W.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Abikoff, Howard B.] NYU, Ctr Child Study, New York, NY USA. [Swanson, James M.; Wigal, Tim; Wigal, Sharon B.] Univ Calif Irvine, Irvine, CA USA. [Cunningham, Charles] McMaster Univ, Toronto, ON, Canada. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Riddle, Mark A.] Johns Hopkins Univ, Baltimore, MD USA. [Greenhill, Laurence; Davies, Mark; Posner, Kelly; Skrobala, Anne M.; Chuang, Shirley Z.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [McCracken, James T.; McGough, James J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ghuman, Jaswinder K.] Univ Arizona, Tucson, AZ USA. RP Hardy, KK (reprint author), Duke Univ, Med Ctr, Box 3431, Durham, NC 27710 USA. EM hardy017@mc.duke.edu RI Kollins, Scott/G-2965-2012; OI Hardy, Kristina/0000-0002-5479-5043 FU NIMH NIH HHS [K23 MH001883-06, U01 MH 60848] NR 52 TC 25 Z9 25 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 621 EP 633 DI 10.1089/cap.2007.0073 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400007 PM 17979582 ER PT J AU Swanson, JM Moyzis, RK McGough, JJ McCracken, JT Riddle, MA Kollins, SH Greenhill, LL Abikoff, HB Wigal, T Wigal, SB Posner, K Skrobala, AM Davies, M Ghuman, JK Cunningham, C Vitiello, B Stehli, A Smalley, SL Grady, D AF Swanson, James M. Moyzis, Robert K. McGough, James J. McCracken, James T. Riddle, Mark A. Kollins, Scott H. Greenhill, Laurence L. Abikoff, Howard B. Wigal, Tim Wigal, Sharon B. Posner, Kelly Skrobala, Anne M. Davies, Mark Ghuman, Jaswinder K. Cunningham, Charles Vitiello, Benedetto Stehli, Annamarie Smalley, Susan L. Grady, Deborah TI Effects of source of DNA on genotyping success rates and allele percentages in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; METHYLPHENIDATE RESPONSE; DOPAMINE SYSTEM; GENE LOCUS; ADHD; CHILDREN; ASSOCIATION; DRD4; POLYMORPHISMS; POPULATION AB Objective: In children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and their parents, who were participants of the Preschool ADHD Treatment Study (PATS), we assessed the effect of source of DNA (from buccal or blood cells) on the genotyping success rate and allele percentages for the five polymorphisms in three candidate genes (DAT1, DRD4, and SNAP 25) investigated in the PATS pharmacogenetic study of response to stimulant medication. Method: At baseline assessment, 241 individuals (113 probands and 128 parents) consented to participate; 144 individuals (52 probands and 92 parents) provided blood samples from venipuncture, and 97 individuals (61 probands and 36 parents) provided buccal samples from cheek swab as specimens for isolation of DNA. Three types of polymorphisms-variable number of tandem repeat (VNTR) polymorphism, tandem duplication polymorphism (TDP), and single nucleotide polymorphism (SNP)-were evaluated, including the DRD4 gene 48-bp VNTR in exon III, the DAT1 gene 40-bp VNTR in 3'-untranslated region, the DRD4 gene TDP 120-bp duplication in the promoter region, the SNAP-25 gene TC-1069 SNP, and the SNAP-25 gene TG-1065 SNP. Standard procedures were used to genotype individuals for each of these five polymorphisms. Results: Using the methods available in 2004, the genotyping success rate was on the average much greater for DNA from blood cells than buccal cells (e. g., 91% vs. 54% in probands). For some polymorphisms (DRD4-VNTR, DRD4-TDP, and SNAP25-TC SNP), allele proportion also varied by blood versus buccal source of DNA (e.g., 26.5% vs. 18.6% for the 7-repeat allele of the DRD4 gene). Conclusions: The much lower success rate for genotyping based on DNA from buccal than blood cells is likely due to the quality of DNA derived from these two sources. The observed source differences in allele proportion may be due to self-selection related to choice of how specimens were collected (from cheek swab or venipuncture), or to a selective detection of some alleles based on differences in DNA quality. C1 [Swanson, James M.; Wigal, Tim; Wigal, Sharon B.; Stehli, Annamarie] Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. [Moyzis, Robert K.; Grady, Deborah] Univ Calif Irvine, Dept Biol Chem, Irvine, CA USA. [McGough, James J.; McCracken, James T.; Smalley, Susan L.] Univ Calif Los Angeles, Semel Inst Neurosci & Huma Behav, Los Angeles, CA USA. [Greenhill, Laurence L.; Posner, Kelly; Skrobala, Anne M.; Davies, Mark] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. [Riddle, Mark A.] Johns Hopkins Univ, Div Child Psychiat, Baltimore, MD USA. [Kollins, Scott H.] Duke Univ, Div Child Psychiat, Durham, NC USA. [Abikoff, Howard B.] NYU, Ctr Child Study, New York, NY USA. [Ghuman, Jaswinder K.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Cunningham, Charles] McMaster Univ, Dept Psychol, Hamilton, ON, Canada. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Swanson, JM (reprint author), Univ Calif Irvine, Child Dev Ctr, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM jmswanso@uci.edu RI Kollins, Scott/G-2965-2012 FU NIMH NIH HHS [K23 MH001883-06, U01 MH 60642, U01 MH 60833, U01 MH 60848, U01 MH 60900, U01 MH 60903, U01 MH 60943] NR 33 TC 4 Z9 4 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 635 EP 645 DI 10.1089/cap.2007.0076 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400008 PM 17979583 ER PT J AU Donfrancesco, R Calderoni, D Vitiello, B AF Donfrancesco, Renato Calderoni, Dario Vitiello, Benedetto TI Open-label amantadine in children with attention-deficit/hyperactivity disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; NORMATIVE DATA; PLACEBO; SYMPTOMS; ADHD; METHYLPHENIDATE; DOPAMINE; HYDROCHLORIDE AB Objectives: The purpose of this study was to explore the possible efficacy and tolerability of amantadine in the treatment of attention-deficit/hyperactivity disorder (ADHD) in stimulant-naive children. Methods: Twenty four children (5-13 years old) with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD (4 inattentive, 2 hyperactive, and 18 combined type) entered a 6-week open-label treatment with amantadine (50-150 mg) given as a single morning dose. Parent and teacher ADHD rating scales and the parent Child Behavior Checklist (CBCL) were administered at baseline and at week 6. Results: Twenty three subjects completed the 6-week treatment. One child dropped out at week 2 because of persistent headache, and another 12 children reported adverse effects, most commonly transient appetite decrease. The parent ADHD score decreased from mean 41.04 +/- D 6.9 at baseline to 28.9 +/- 8.7 at week 6 (p < 0.001, effect size d = 1.5), and the teacher ADHD score from 35.8 +/- 9.6 to 26.2 +/- 9.5 (p < 0.001, effect size d = 1.0). Response rate (a 25% or greater decline in ADHD score) was 58% based on parents and 46% based on teachers. Conclusions: These data suggest that amantadine has acceptable acute tolerability at single doses up to 150 mg/day and is possibly efficacious in decreasing ADHD symptoms, although its activity appears to be more modest than that of stimulant medications. C1 [Calderoni, Dario] Natl Hlth Syst, Dept Child Neuropsychiat, I-00133 Rome, Italy. [Donfrancesco, Renato] La Scarpetta Hosp, Dept Child Neuropsychiat, Rome, Italy. [Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Calderoni, D (reprint author), Natl Hlth Syst, Dept Child Neuropsychiat, Via di Tarrenova 20, I-00133 Rome, Italy. EM dario.calderoni@fastwebnet.it NR 38 TC 6 Z9 6 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 657 EP 663 DI 10.1089/cap.2006.0128 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400010 PM 17979585 ER PT J AU Pacak, K AF Pacak, Karel TI Approach to the patient - Preoperative management of the pheochromocytoma patient SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2; HIPPEL-LINDAU-SYNDROME; ALPHA-METHYL-TYROSINE; PERIOPERATIVE MANAGEMENT; BLOOD-PRESSURE; CATECHOLAMINE METABOLISM; CLINICAL-EXPERIENCE; DIAGNOSIS; SURGERY; BLOCKADE AB Pheochromocytomas are rare neuroendocrine tumors with a highly variable clinical presentation, but they most commonly present as spells of headaches, sweating, palpitations, and hypertension. Patients with pheochromocytoma may develop complicated and potentially lethal cardiovascular and other complications, especially in the setting of diagnostic or interventional procedures ( e. g. upon induction of anesthesia or during surgery). The serious and potentially lethal nature of such complications is due to the potent effect of paroxysmal release of catecholamines. Because this warrants prompt diagnosis and treatment, the physician should be aware of the clinical manifestations and complications of catecholamine excess and be able to provide proper preoperative management to minimize catecholamine-related pre-, intra-, and postoperative adverse events. The following clinical scenario and discussion aim to enhance the knowledge of the physician regarding the behavior of pheochromocytoma and to outline current approaches to comprehensive preoperative management of patients suffering from this tumor. C1 NICHHD, Sect Med Neuroendocrinol, NIH, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, NIH, Reprod & Adult Endocrinol Program, Bldg 10,CRC,Room 1E-3140,10 ctr Dr MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural NIH HHS NR 86 TC 160 Z9 176 U1 3 U2 17 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2007 VL 92 IS 11 BP 4069 EP 4079 DI 10.1210/jc.2007-1720 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228WR UT WOS:000250763800001 PM 17989126 ER PT J AU Olney, RC Prickett, TCR Yandle, TG Espiner, EA Han, JC Mauras, N AF Olney, Robert C. Prickett, Timothy C. R. Yandle, Timothy G. Espiner, Eric A. Han, Joan C. Mauras, Nelly TI Amino-terminal propeptide of C-type natriuretic peptide and linear growth in children: Effects of puberty, testosterone, and growth hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ATDC5 CELLS; RECEPTOR; SYSTEM; BOYS; MICE AB Context: C-type natriuretic peptide ( CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP ( NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. Objective: We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. Design: This was a retrospective analysis of samples obtained during previous studies. Setting: The study was conducted at a pediatric clinical research center. Subjects: Children with short stature due to GH deficiency, idiopathic short stature ( ISS), or constitutional delay of growth and maturation ( CDGM) were studied ( n = 37). A cohort of normal-statured adolescent boys was also studied ( n = 23). Interventions: Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. Main Outcome Measures: The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Results: Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. Conclusions: NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy. C1 Nemours Childrens Clin Jacksonville, Div Pediat Endocrinol, Jacksonville, FL 32207 USA. Christchurch Sch Med & Hlth Sci, Dept Med, Christchurch 8140, New Zealand. NICHHD, Unit Growth & Obes, Bethesda, MD 20892 USA. RP Olney, RC (reprint author), Nemours Childrens Clin Jacksonville, Div Pediat Endocrinol, Jacksonville, FL 32207 USA. EM rolney@nemours.org FU NIDDK NIH HHS [R01DK43802] NR 18 TC 23 Z9 26 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2007 VL 92 IS 11 BP 4294 EP 4298 DI 10.1210/jc.2007-0567 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228WR UT WOS:000250763800036 PM 17684048 ER PT J AU Long, SH Berna, MJ Thill, M Pace, A Pradhan, TK Hoffmann, KM Serrano, J Jensen, RT AF Long, Scott H. Berna, Marc J. Thill, Michelle Pace, Andrea Pradhan, Tapas K. Hoffmann, K. Martin Serrano, Jose Jensen, Robert T. TI Secretin-receptor and secretin-receptor-variant expression in gastrinomas: Correlation with clinical and tumoral features and secretin and calcium provocative test results SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; DOMINANT-NEGATIVE ACTIVITY; SERUM GASTRIN; PANCREATIC ADENOCARCINOMA; DUODENAL GASTRINOMAS; SURFACE EXPRESSION; HORMONE RECEPTOR; CELL-LINE; DIAGNOSIS; NEOPLASIA AB Context/Objectives: The diagnosis of Zollinger-Ellison syndrome requires secretin testing in 60% of patients. Even with secretin, the diagnosis may be difficult because variable responses occur, and 6-30% have negative testing. The basis for variability or negative responses is unclear. It is unknown whether the tumor density of secretin receptors or the presence of a secretin-receptor-variant, which can act as a dominant negative, is important. The aim of this study was to investigate these possibilities. Patients/Methods: Secretin-receptor and variant mRNA expression was determined in gastrinomas using real-time PCR from 54 Zollinger-Ellison syndrome patients. Results were correlated with Western blotting, secretin-receptor immunohistochemistry, with gastrin-provocative test results and tumoral/clinical/laboratory features. Results: Secretin-receptor mRNA was detectible in all gastrinomas but varied 132-fold with a mean of 0.89 +/- 0.12 molecules per beta-actin. Secretin-receptor PCR results correlated closely with Western blotting ( r = 0.95; P < 0.0001) and receptor immunohistochemistry ( P = 0.0015; r = 0.71). The variant was detected in all gastrinomas, but levels varied 102-fold and were 72-fold lower than the total. Secretin-receptor levels correlated with variant levels, Delta secretin, but not Delta calcium and with tumor location, but not growth, extent, or clinical responses. Variant levels did not correlate with the Delta secretin. Detailed analysis provides no evidence that variant expression modified the secretin-receptor response or accounted for negative tests. Conclusions: Secretin-receptor and secretin-receptor-variant expressions occur in all gastrinomas. Because the expression of the total, but not variant, correlated with the secretin results and no evidence for dominant negative activity of the variant was found, our results suggest that the total secretin-receptor density is an important determinant of the secretin test response. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Klinikum Hamburg Eppendorf, Med Klin 1, D-20256 Hamburg, Germany. Med Univ Graz, Dept Pediat & Adolescent Med, A-8036 Graz, Austria. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov FU Intramural NIH HHS [Z01 DK053200-16] NR 47 TC 14 Z9 14 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2007 VL 92 IS 11 BP 4394 EP 4402 DI 10.1210/jc.2007-0986 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228WR UT WOS:000250763800053 PM 17711922 ER PT J AU Shaib, YH Davila, JA Henderson, L McGlynn, KA El-Serag, HB AF Shaib, Yasser H. Davila, Jessica A. Henderson, Louise McGlynn, Katherine A. El-Serag, Hashem B. TI Endoscopic and surgical therapy for intrahepatic Cholangiocarcinoma in the united states - A population-based study SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE intrahepatic cholangiocarcinoma; outcomes AB Background: Intrahepatic cholangiocarcinoma (W-C) is a highly fatal disease with limited therapeutic options. The determinants, trends, and outcomes of different therapies for ICC are largely unknown in the United States. Methods: Using data from the Surveillance, Epidemiology, and End-Results-(SEER) Medicare database, we compared ICC patients receiving different therapies between 1992 and 1999. Univariate and multivariate analyses were performed and adjusted odds ratios (AORs) were calculated. Hazard ratios were calculated for the survival analysis. Results: Eight hundred sixty-two cases were included. The mean age at diagnosis was 77.9 years (SD = 7. 1). Only 6.3 % received surgical resection, 65.5% received palliative interventions (16.1 % surgical, 44.0% endoscopic), 24.4% received only chemo or radiation therapy whereas 3.8% did not receive any treatment. The median survival was 708 days [95% confidence interval (CI): 458-945] for surgical resection, 227 days (95% CI: 182-294) for surgical palliation, and 123 days (95% CI: 108-148) for endoscopic palliation. Patients receiving surgical resection were younger (AOR = 5.6, 95% CI: 2.9-11. 1), more likely to be diagnosed later in the study period (AOR 2.2, 95% CI: 1.1-4.2), and had better mortality (hazard ratio 0.3, 95% CI: 0.2-0.4). Patients receiving surgical palliation were younger (AOR = 1.6, 95% CI: 1.1-2.3), more likely to be diagnosed in the early time period (AOR = 1.5, 95% CI: 1.1-2.2), and had similar mortality to those receiving endoscopic palliation. Conclusions: Only a minority of patients with ICC receives potentially curative therapy. Young age is the strongest predictor of receiving potentially curative treatment. Older patients and those diagnosed in recent time periods are more likely to receive endoscopic palliation. Surgical resection was associated with improved survival. There was no difference in survival between surgical and endoscopic palliation. C1 Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, NIH,DHHS, Bethesda, MD USA. Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Bethesda, MD USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. RP Shaib, YH (reprint author), Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, NIH,DHHS, Bethesda, MD USA. EM yshaib@bcm.tmc.edu NR 17 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2007 VL 41 IS 10 BP 911 EP 917 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228XF UT WOS:000250765200008 PM 18090160 ER PT J AU Stewart, DM Candotti, F Nelson, DL AF Stewart, Donn M. Candotti, Fabio Nelson, David L. TI The phenomenon of spontaneous genetic reversions in the Wiskott-Aldrich syndrome: A report of the workshop of the ESID Genetics Working Party at the XIIth Meeting of the European Society for Immunodeficiencies (ESID). Budapest, Hungary - October 4-7, 2006 SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Editorial Material DE Wiskott-Aldrich syndrome; mutation; reversion; flow cytometry ID IN-VIVO REVERSION; SELF-INDUCED CORRECTION; TYROSINEMIA TYPE-I; REVERTANT MOSAICISM; ECTODERMAL DYSPLASIA; INHERITED MUTATION; 2ND-SITE MUTATION; SOMATIC MOSAICISM; PATIENT; PROTEIN AB The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disease caused by mutations in the Wiskott-Aldrich Protein (WASP) gene, which typically leads to absent WASP protein expression in WAS leukocytes. However, some patients have been found with small populations of WASP-expressing cells caused by reverse or second-site mutations that allow protein expression. An international consortium was established to further investigate these phenomena. This paper summarizes data collected by this consortium that was presented at a workshop held during the XIIth Meeting of the European Society for Immunodeficiencies (ESID), October, 2006. WASP reversions were noted in approximately 11% of 272 patients tested. Many different cell lineages showed reversions. These data form the foundation for further investigation into this phenomenon, which has implications for therapy of this disease. C1 NCI, NIH, Metab Branch, Immunophysiol Sect, Bethesda, MD 20892 USA. NIH, NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Stewart, DM (reprint author), NCI, NIH, Metab Branch, Immunophysiol Sect, Room 4N-115,10 Ctr Dr, Bethesda, MD 20892 USA. EM dstew@helix.nih.gov NR 23 TC 22 Z9 24 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2007 VL 27 IS 6 BP 634 EP 639 DI 10.1007/s10875-007-9121-z PG 6 WC Immunology SC Immunology GA 230NU UT WOS:000250884000012 PM 17690954 ER PT J AU Luo, J Ho, PP Buckwalter, MS Hsu, T Lee, LWY Zhang, H Kim, DK Kim, SJ Gambhir, SS Steinman, L Wyss-Coray, T AF Luo, Jian Ho, Peggy P. Buckwalter, Marion S. Hsu, Tiffany Lee, Lowen Y. Zhang, Hui Kim, Dae-Kee Kim, Seong-Jin Gambhir, Sanjiv S. Steinman, Lawrence Wyss-Coray, Tony TI Glia-dependent TGF-beta signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NF-KAPPA-B; FIBRILLARY ACIDIC PROTEIN; REGULATORY T-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSES; MESSENGER-RNA AB Autoimmune encephalomyelitis, a mouse model for multiple sclerosis, is characterized by the activation of immune cells, demyelination of axons in the CNS, and paralysis. We found that TGF-beta 1 synthesis in glial cells and TGF-beta-induced signaling in the CNS were activated several days before the onset of paralysis in mice with autoimmune encephalomyelitis. While early production of TGF-beta 1 was observed in glial cells TGF-beta signaling was activated in neurons and later in infiltrating T cells in inflammatory lesions. Systemic treatment with a pharmacological inhibitor of TGF-beta signaling ameliorated the paralytic disease and reduced the accumulation of pathogenic T cells and expression of IL-6 in the CNS. Priming of peripheral T cells was not altered, nor was the generation of TH17 cells, indicating that this effect was directed within the brain, yet affected the immune system. These results suggest that early production of TGF-beta 1 in the CNS creates a permissive and dangerous environment for the initiation of autoimmune inflammation, providing a rare example of the brain modulating the immune system. Importantly, inhibition of TGF-beta signaling may have benefits in the treatment of the acute phase of autoimmune CNS inflammation. C1 Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA. Ewha Womans Univ, Coll Pharm, Seoul, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Radiol, Sch Med, Bio X Program, Stanford, CA 94305 USA. Stanford Univ, Sch Med, MIPS, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Palo Alto, CA USA. RP Wyss-Coray, T (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, SUMC Room A343, Stanford, CA 94305 USA. EM twc@stanford.edu RI Luo, Jian/B-8449-2014 OI Luo, Jian/0000-0002-2064-8467 FU NCI NIH HHS [CA114747 ICMIC P5, P50 CA114747]; NIA NIH HHS [R01 AG020603, AG20603, AG23708, R21 AG023708] NR 58 TC 71 Z9 71 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3306 EP 3315 DI 10.1172/JCI31763 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000023 PM 17965773 ER PT J AU Thorne, SH Hwang, THH O'Gorman, WE Bartlett, DL Sei, S Kanji, F Brown, C Werier, J Cho, JH Lee, DE Wang, Y Bell, J Kirn, DH AF Thorne, Steve H. Hwang, Tae-Ho H. O'Gorman, William E. Bartlett, David L. Sei, Shizuko Kanji, Femina Brown, Christopher Werier, Joel Cho, Jin-Han Lee, Dong-Ewon Wang, Yaohe Bell, John Kirn, David H. TI Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VACCINIA VIRUS; THYMIDINE KINASE; REPLICATION; ADENOVIRUS; THERAPY; CANCER; EXPRESSION; VIRULENCE; EFFICACY; CELLS AB Replication-selective oncolytic viruses (virotherapeutics) are being developed as novel cancer therapies with unique mechanisms of action, but limitations in i.v. delivery to tumors and systemic efficacy have highlighted the need for improved agents for this therapeutic class to realize its potential. Here we describe the rational, stepwise design and evaluation of a systemically effective virotherapeutic (JX-963). We first identified a highly potent poxvirus strain that also trafficked efficiently to human tumors after i.v. administration. This strain was then engineered to target cancer cells with activation of the transcription factor 13217 and the EGFR pathway by deletion of the thymidine kinase and vaccinia growth factor genes. For induction of tumor-specific cytotoxic T lymphocytes, we further engineered the virus to express human GM-CSF. JX-963 was more potent than the previously used virotherapeutic Onyx-015 adenovirus and as potent as wild-type vaccinia in all cancer cell lines tested. Significant cancer selectivity of JX-963 was demonstrated in vitro in human tumor cell lines, in vivo in tumor-bearing rabbits, and in primary human surgical samples ex vivo. Intravenous administration led to systemic efficacy against both primary carcinomas and widespread organ-based metastases in immunocompetent mice and rabbits. JX-963 therefore holds promise as a rationally designed, targeted virotherapeutic for the systemic treatment of cancer in humans and warrants clinical testing. C1 Jennerex Biotherapeut, San Francisco, CA 94105 USA. Stanford Univ, Sch Med, James H Clark Ctr, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, James H Clark Ctr, Bio X Program, Stanford, CA 94305 USA. Dong A Univ, Coll Med, Dept Pharmacol, Pusan, South Korea. Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Univ Pittsburgh, Dept Surg, Div Surg Oncol, Pittsburgh, PA USA. NCI, Viral Vector Toxicol Sect, LHTP, SAIC Frederick Inc, Frederick, MD 21701 USA. Ottawa Hlth Res Inst, Ottawa, ON, Canada. Univ Ottawa, Biochem Microbiol & Immunol Dept, Ottawa, ON, Canada. Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. Dong A Univ, Coll Med, Dept Pharmacol, Pusan, South Korea. Dong A Univ, Coll Med, Dept Radiol, Pusan, South Korea. Queen Marys Univ London, Barts & London Sch Med & Dent, London, England. RP Thorne, SH (reprint author), Jennerex Biotherapeut, 1 Market St, San Francisco, CA 94105 USA. FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 23 TC 116 Z9 121 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3350 EP 3358 DI 10.1172/JC132727 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000027 PM 17965776 ER PT J AU Ray, P Sharma, S Agarwal, RK Longmei, K Gentsch, JR Paul, VK Glass, RI Bhan, AK AF Ray, Pratima Sharma, S. Agarwal, R. K. Longmei, K. Gentsch, J. R. Paul, V. K. Glass, R. I. Bhan, A. K. TI First detection of G12 rotaviruses in newborns with neonatal rotavirus infection at all India institute of medical sciences, New Delhi, India SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-A ROTAVIRUSES; STRAINS; CHILDREN; DIARRHEA; GENE; SPECIFICITY; ANTIBODIES; EMERGENCE; SEROTYPES; GENOTYPE AB Rotavirus genotype G12 strains were detected for the first time among newborns with asymptomatic rotavirus infection (74% of 39 rotavirus strains isolated from the infected infants were genotype G12) in the nursery of the All India Institute of Medical Sciences during a period from 2005 to 2006. Sequence analysis of the VP7 genes from these neonatal strains indicated a high level of homology to other G12 strains reported worldwide, suggesting the recent emergence of these strains in humans. Such nosocomial infections of newborns represent a potential source of introduction of novel rotavirus serotypes into the community. C1 All India Inst Med Sci, Ctr Diarrheal Dis Res, Dept Pediat, Neonatol Unit, New Delhi 110029, India. Ctr Dis Control & Prevent, Gastroenteritis & Respiratory Viruses Lab Branch, Atlanta, GA USA. NIH, Fogarty Int Ctr, Bethesda, MD USA. RP Ray, P (reprint author), All India Inst Med Sci, Ctr Diarrheal Dis Res, Dept Pediat, New Delhi 110029, India. EM pratimaray@gmail.com OI Ray, Pratima/0000-0002-2182-2279 NR 21 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2007 VL 45 IS 11 BP 3824 EP 3827 DI 10.1128/JCM.01288-07 PG 4 WC Microbiology SC Microbiology GA 231FU UT WOS:000250932700060 PM 17728476 ER PT J AU Chen, C Kane, M Song, J Campana, J Raben, A Hu, K Harrison, L Quon, H Dancey, J Baron, A Said, S Eckhardt, SG Raben, D AF Chen, Changhu Kane, Madeleine Song, John Campana, John Raben, Adam Hu, Kenneth Harrison, Louis Quon, Harry Dancey, Janet Baron, Anna Said, Sherif Eckhardt, S. Gail Raben, David TI Phase I trial of gefitinib in combination with radiation or chemoradiation for patients with locally advanced squamous cell head and neck cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol ID TYROSINE KINASE INHIBITOR; SOLID TUMORS; ZD1839 IRESSA; LUNG-CANCER; GROWTH; THERAPY; CARCINOMA; RADIOTHERAPY; RECURRENT; ENHANCEMENT AB Purpose To establish the safety and toxicity profile of daily gefitinib with radiation alone or with concurrent chemoradiotherapy in previously untreated patients with locally advanced squamous cell head and neck cancer (LAHNC). Patients and Methods Patients with intermediate-stage LAHNC were treated with concomitant boost radiation (RT) alone with escalating doses of daily gefitinib (250 or 500 mg; cohort I). Once a safety profile was determined with RT alone, patients with high-risk disease were then treated with daily gefitinib (250 or 500 mg), weekly cisplatin (CDDP; 30 mg/m(2)), and once-daily RT (cohort II). Patients also received post-RT gefitinib at 250 mg daily for a period of up to 2 years. Results Twenty-three patients were enrolled and assessable for toxicity. No dose-limiting toxicities (DLTs) were observed in patients treated in cohort 1 at either 250 or 500 mg of gefitinib daily with concomitant boost RT to 72 Gy. In patients receiving chemoradiotherapy and gefitinib (cohort II), DLTs included one grade 4 diarrhea and one grade 4 neutropenic fever. Fifteen patients started maintenance gefitinib, and eight (53%) experienced grade 1 to 2 acne-like skin rash and diarrhea, but no grade 3 or 4 toxicity occurred. Conclusion Gefitinib (250 or 500 mg daily) was well tolerated with concomitant boost RT or concurrent chemoradiotherapy with weekly CDDP. Protracted administration of gefitinib for up to 2 years at 250 mg daily was also tolerated well. C1 Univ Colorado, Ctr Hlth Sci, Dept Radiat Oncol, Aurora, CO 80045 USA. Univ Colorado, Ctr Hlth Sci, Dept Med Oncol, Aurora, CO 80045 USA. Univ Colorado, Ctr Hlth Sci, Dept Otolaryngol, Aurora, CO 80045 USA. Univ Colorado, Ctr Hlth Sci, Dept Prevent Med, Aurora, CO 80045 USA. Univ Colorado, Ctr Hlth Sci, Dept Biometr, Aurora, CO 80045 USA. Univ Colorado, Ctr Hlth Sci, Dept Pathol, Aurora, CO 80045 USA. Christiana Hosp Med Ctr, Dept Radiat Oncol, Wilmington, DE USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, New York, NY 10003 USA. Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. RP Raben, D (reprint author), Univ Colorado, Ctr Hlth Sci, Dept Radiat Oncol, 1665 N Ursula St,Mail Stop F706, Aurora, CO 80045 USA. EM David.Raben@uchsc.edu NR 25 TC 47 Z9 48 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2007 VL 25 IS 31 BP 4880 EP 4886 DI 10.1200/JCO.2007.12.9650 PG 7 WC Oncology SC Oncology GA 233EV UT WOS:000251074100005 PM 17971583 ER PT J AU Freidlin, B Korn, EL George, SL Gray, R AF Freidlin, Boris Korn, Edward L. George, Stephen L. Gray, Robert TI Randomized clinical trial design for assessing noninferiority when superiority is expected SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; PHASE-III TRIAL; BREAST-CANCER; POSTMENOPAUSAL WOMEN; OPEN-LABEL; EQUIVALENCE; THERAPY; CHEMOTHERAPY; ANASTROZOLE; FULVESTRANT AB The randomized clinical trial (RCT) is the gold standard for definitive evaluation of new therapies. RCTs designed to show that the therapeutic efficacy of a new therapy is not unacceptably inferior to that of standard therapy are called noninferiority trials. Traditionally, noninferiority trials have required very large sample sizes. Sometimes, a new treatment regimen with a favorable toxicity and/or tolerability profile is also expected to have some modest improvement in efficacy. In such specialized settings we describe a hybrid trial-design approach that requires a dramatically smaller sample size than that of a standard noninferiority design. This hybrid design can naturally incorporate a formal test of superiority as well as noninferiority. C1 NCI, Div Canc Treatment & Diagnosis, Biomet Res Branch, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. Duke Univ, Sch Med, Canc Leukemia Grp B Stat Ctr, Durham, NC USA. Harvard Univ, Sch Publ Hlth, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. RP Freidlin, B (reprint author), NCI, Div Canc Treatment & Diagnosis, Biomet Res Branch, 6130 Execut Blvd,EPN-8122,MSC 7434, Bethesda, MD 20892 USA. EM freidlinb@ctep.nci.nih.gov FU NCI NIH HHS [U10CA033601] NR 24 TC 26 Z9 26 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2007 VL 25 IS 31 BP 5019 EP 5023 DI 10.1200/JCO.2007.11.8711 PG 5 WC Oncology SC Oncology GA 233EV UT WOS:000251074100025 PM 17971602 ER PT J AU Rodriguez, ED Bluebond-Langner, R Brazio, P Collins, M AF Rodriguez, Eduardo D. Bluebond-Langner, Rachel Brazio, Philip Collins, Michael TI Near-total mandible reconstruction with a single fibula flap containing fibrous dysplasia in McCune Albright syndrome SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE McCune Albright Syndrome; free fibula flap; fibrous dysplasia ID OROMANDIBULAR RECONSTRUCTION; PRECOCIOUS PUBERTY; RADIAL FOREARM; BONE-GRAFTS; CONTINUITY; PLATES; PIGMENTATION; DEFECTS; PATIENT AB We present the case of an 18-year-old girl with McCune Albright Syndrome (MAS) and a near total mandibular defect reconstructed with a free fibula flap. There are three reports of mandibular reconstruction in a patient with MAS using the free fibula flap; however this case is unique for two reasons. One, the continuity defect in our patient was much larger than previously reported, representing nearly the entire length of the mandible (21 cm) and required the entire harvestable length of the fibula. Two, the progression of the patient's disease limited options for reconstruction and dictated the use of a fibula with small dysplastic changes. C1 Univ Maryland, Sect Chief Plast & Reconstruct Surg, R Adams Cowley Shock Trauma Ctr, Med Ctr, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Rodriguez, ED (reprint author), Univ Maryland, Sect Chief Plast & Reconstruct Surg, R Adams Cowley Shock Trauma Ctr, Med Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM erodriguez@umm.edu NR 29 TC 2 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD NOV PY 2007 VL 18 IS 6 BP 1479 EP 1482 PG 4 WC Surgery SC Surgery GA 239KP UT WOS:000251517500045 PM 17993908 ER PT J AU Terracciano, A McCrae, RR AF Terracciano, Antonio McCrae, Robert R. TI Perceptions of Americans and the Iraq Invasion: Implications for Understanding National Character Stereotypes SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 113th Annual Convention of the American-Psychological-Association CY AUG 18-21, 2005 CL Washington, DC SP Amer Psychol Assoc DE national character stereotypes; personality traits; cross-cultural; stereotype change; auto and hetero-stereotype agreement ID PERSONALITY-TRAITS; INTERGROUP CONTACT; RACIAL STEREOTYPES; COLLEGE-STUDENTS; IN-GROUP; CULTURES; FAVOURITISM; PERCEPTION; PROFILES; THREAT AB This study examines perceptions of the "typical American" from 49 cultures around the world. Contrary to the ethnocentric bias hypothesis, a strong agreement was found between in-group and out-group ratings on the American profile (assertive, open-minded, but antagonistic). In fact, Americans had a somewhat less desirable view of Americans than did others. Within cultures, in-group ratings were not systematically more favorable than out-group ratings. The Iraq invasion had a slight negative effect on perceptions of the typical American, but people around the world seem to draw a clear distinction between U.S. foreign policy and the character of the American people. National character stereotypes appear to have a variety of sources and to be perpetuated by both cognitive mechanisms and sociocultural forces. C1 NIA, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Personal & Cognit, Bethesda, MD 20892 USA. RP Terracciano, A (reprint author), NIA, Natl Inst Hlth, Dept Hlth & Human Serv, Lab Personal & Cognit, Bethesda, MD 20892 USA. EM terraccianoa@grc.nia.nih.gov; mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008 FU Intramural NIH HHS [ZIA AG000180-26, Z99 AG999999, ZIA AG000180-25] NR 70 TC 24 Z9 24 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD NOV PY 2007 VL 38 IS 6 BP 695 EP 710 DI 10.1177/0022022107308586 PG 16 WC Psychology, Social SC Psychology GA 224HP UT WOS:000250438400003 PM 18618011 ER PT J AU Slade, GD Diatchenko, L Bhalang, K Sigurdsson, A Fillingim, RB Belfer, I Max, MB Goldman, D Maixner, W AF Slade, G. D. Diatchenko, L. Bhalang, K. Sigurdsson, A. Fillingim, R. B. Belfer, I. Max, M. B. Goldman, D. Maixner, W. TI Influence of psychological factors on risk of temporomandibular disorders SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE temporomandibular joint disorders; cohort studies; psychology; catechol O-methyltransferase; genetics ID PAIN; SCHIZOPHRENIA; POLYMORPHISM; SENSITIVITY; ASSOCIATION; HAPLOTYPE; RESPONSES; SUMMATION; GENOTYPE AB Psychological characteristics potentially may be a cause or consequence of temporomandibular disorder (TMD). We hypothesized that psychological characteristics associated with pain sensitivity would influence risk of first-onset TMD, but the effect could be attributed to variation in the gene encoding catechol-O-methyltransferase (COMT). We undertook a prospective cohort study of healthy female volunteers aged 1834 yrs. At baseline, participants were genotyped, they completed psychological questionnaires, and underwent quantitative sensory testing to determine pain sensitivity. We followed 171 participants for up to three years, and 8.8% of them were diagnosed with first-onset TMD. Depression, perceived stress, and mood were associated with pain sensitivity and were predictive of 2- to 3-fold increases in risk of TMD (P < 0.05). However, the magnitude of increased TMD risk due to psychological factors remained unchanged after adjustment for the COMT haplotype. Psychological factors linked to pain sensitivity influenced TMD risk independently of the effects of the COMT haplotype on TMD risk. C1 Univ Adelaide, Sch Dent, Australian Res Ctr Populat Oral Hlth, Adelaide, SA 5005, Australia. Univ N Carolina, Chapel Hill, NC USA. Chulalongkorn Univ, Bangkok, Thailand. Univ Florida, Coll Dent, Gainesville, FL USA. NIDCR, NIH, DHHS, Bethesda, MD USA. NIAAA, NIH, DHHS, Rockville, MD 20852 USA. RP Slade, GD (reprint author), Univ Adelaide, Sch Dent, Australian Res Ctr Populat Oral Hlth, Adelaide, SA 5005, Australia. EM gary.slade@adelaide.edu.au RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS; NIAID NIH HHS [AR/AI-44564]; NIDCR NIH HHS [DE007333, DE07509]; NINDS NIH HHS [NS045685] NR 25 TC 95 Z9 103 U1 1 U2 6 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2007 VL 86 IS 11 BP 1120 EP 1125 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 223YX UT WOS:000250413200019 PM 17959908 ER PT J AU Zhang, G Hirai, H Cai, T Miura, J Yu, P Huang, H Schiller, MR Swaim, WD Leapman, RD Notkins, AL AF Zhang, Guofeng Hirai, Hiroki Cai, Tao Miura, Junnosuke Yu, Ping Huang, Hanxia Schiller, Martin R. Swaim, William D. Leapman, Richard D. Notkins, Abner L. TI RESP18, a homolog of the luminal domain IA-2. is found in dense core vesicles in pancreatic islet cells and is induced by high glucose SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; ENDOCRINE-SPECIFIC PROTEIN-18; DEPENDENT DIABETES-MELLITUS; TRANSMEMBRANE PROTEIN; CAENORHABDITIS-ELEGANS; INSULIN-SECRETION; MOLECULAR-CLONING; EXPRESSION; AUTOANTIGEN; BETA AB The regulated endocrine-specific protein, RESP18, first found in the rat pituitary, was thought to be regulated by dopaminergic drugs. Bioinformatics studies showed that RESP18 shares sequence homology with the luminal region of IA-2, a dense core vesicle (DCV) transmembrane protein involved in insulin secretion. The present study was initiated to examine the genomic structure and subcellular localization of RESP18 and the effect of glucose on its expression. Human RESP18 was isolated from a pancreas cDNA library and its subcellular localization was determined by immunoelectron microscopy. MIN6 cells and mouse islets were used to study the effect of glucose on RESP18 expression. Bioinformatics analysis revealed that RESP18 and IA-2 are tandemly arranged within a 45 kb region on human chromosome 2 and shire corm-non intron-exon boundaries. By confocal microscopy, RESP18 was found in alpha, beta and delta cells in the pancreatic islets. Electron microscopy revealed that RESP18 is present in the lumen of DCVs. The expression of RESP18 in beta cells is markedly increased following exposure to high glucose and also elevated in the islets of diabetic, but not non-diabetic, NOD mice. We conclude that RESP18 is a luminal protein of DCVs and its expression is regulated by exposure to glucose. C1 NIDCR, Expt Med Sect, OIIB, NIH, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Mol Microbiol & Struct Biol, Farmington, CT 06030 USA. NIDCR, Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Cai, T (reprint author), NIDCR, Expt Med Sect, OIIB, NIH, Bethesda, MD 20892 USA. EM tcai@mail.nih.gov FU Intramural NIH HHS NR 26 TC 14 Z9 17 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2007 VL 195 IS 2 BP 313 EP 321 DI 10.1677/JOE-07-0252 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 234KQ UT WOS:000251160700012 PM 17951542 ER PT J AU Ge, B Jiang, P Han, F Saleh, NK Dhiman, N Fedorko, DP Nelson, NA Meng, JH AF Ge, Beilei Jiang, Ping Han, Feifei Saleh, Nasreen K. Dhiman, Nivedita Fedorko, Daniel P. Nelson, Nancy A. Meng, Jianghong TI Identification and antimicrobial susceptibility of lactic acid bacteria from retail fermented foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; TETRACYCLINE RESISTANCE DETERMINANTS; 16S-23S RIBOSOMAL-RNA; ANTIBIOTIC-RESISTANCE; MOLECULAR CHARACTERIZATION; PROBIOTIC PRODUCTS; MULTIPLEX PCR; SPACER REGION; GENES; LACTOBACILLI AB One important safety criterion of using lactic acid bacteria (LAB) in food applications is to ensure that they do not carry transferable antimicrobial resistance (AR) determinants. In this study, 63 LAB belonging to six genera, Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Leuconostoc, and Pediococcus, were recovered from 28 retail fermented food products in Maryland, identified to species with 16S-23S rRNA spacer PCRs, and characterized for antimicrobial susceptibility against eight antimicrobials. Besides intrinsic resistance to ciprofloxacin or vancomycin in some lactobacilli, tetracycline resistance was observed in two Streptococcus thermophilus isolates from one cheese and one sour cream sample and was associated with the presence of a nonconjugative tet(S) gene. The results indicated a low level of AR among naturally occurring and starter LAB cultures in fermented dairy and meat products in the United States; therefore, the probability for foodborne LAB to serve as reservoirs of AR is low. Further studies involving a larger sample size are needed to assess the potential risk of AR gene transfer from LAB in fermented food products. C1 Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. Guizhou Univ, Dept Food Sci & Technol, Guiyang 550025, Peoples R China. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Ge, B (reprint author), Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. EM bge@lsu.edu NR 40 TC 10 Z9 13 U1 3 U2 8 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2007 VL 70 IS 11 BP 2606 EP 2612 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 228QH UT WOS:000250744100022 PM 18044442 ER PT J AU Negrete, A Yang, LC Mendez, AF Levy, JR Kotin, RM AF Negrete, Alejandro Yang, Linda C. Mendez, Andres F. Levy, Justin R. Kotin, Robert M. TI Economized large-scale production of high yield of rAAV for gene therapy applications exploiting baculovirus expression system SO JOURNAL OF GENE MEDICINE LA English DT Article DE rAAV; baculovirus; large-scale; MOT; TOT; gene therapy; adeno-associated vectors ID ADENOASSOCIATED VIRUS VECTORS; CALIFORNICA NUCLEOPOLYHEDROVIRUS INFECTION; PROTEIN-MEDIATED INHIBITION; INSECT-CELL CULTURES; RECOMBINANT-BACULOVIRUS; VIRAL VECTORS; CYCLE ARREST; STABILITY; BIOREACTOR; ADENOVIRUS AB Background The versatility of recombinant adeno-associated vector (rAAV) as a gene delivery system is due to the vector's ability to transduce different cell types as well as dividing and non-dividing cells. Large-scale production of rAAV remains one of the major challenges for continued development of pre-clinical and clinical studies, and for its potential commercialization. The baculovirus expression vectors (BEVS) and insect cells represent a potential method to produce rAAV economically at large scale. This technology uses three different BEVS (Bac-Rep, Bac-GFP, and Bac-VP) each at a multiplicity of infection (MOI) of 3. We reported previously the production of rAAV at 40 L scale using a stirred-tank bioreactor (STB). However, production in larger volumes is limited by the stability of the BEVs and amount of BEVs needed to achieve the target MOI of 3 per BEV. Here, the production parameters were optimized and the baculovirus stability was determined. Methods The stability of the three types of baculovirus used to produce rAAV was determined for six expansion passages by protein expression analysis. To economize baculovirus, MOI and cell density at time of infection (TOI) were evaluated initially at small scale and then applied to the 10 L scale. Results An MOI = 0.03 and TOI cell density of 1 X 10(6) cells/mL produced high titer rAAV without comprising yield. To confirm the scalability of the process, rAAV was produced in a 10 L STB using the optimized parameters obtaining a 10x increase in yield (similar to 1 x 10(14) rAAV DNAse-resistant particles per liter). Conclusion These findings contribute to the process development for large-scale production of rAAV for gene therapy applications and its commercialization. Published in 2007 by John Wiley & Sons, Ltd. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, NIH, 10 Ctr Dr,Bldg 10,Room 7D05, Bethesda, MD 20892 USA. EM kotinr@mail.nih.gov RI kotin, robert/B-8954-2008 FU Intramural NIH HHS NR 34 TC 27 Z9 30 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD NOV PY 2007 VL 9 IS 11 BP 938 EP 948 DI 10.1002/jgm.1092 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 238SO UT WOS:000251468100002 PM 17764098 ER PT J AU Dohan, D Levintova, M AF Dohan, Daniel Levintova, Marya TI Barriers beyond words: Cancer, culture, and translation in a community of Russian speakers SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE immigrant health; communication; cancer; qualitative research; vulnerable populations ID LIMITED ENGLISH PROFICIENCY; SPANISH-SPEAKING PATIENTS; HEALTH-CARE-SYSTEMS; QUALITY-OF-LIFE; BREAST-CANCER; INTERPRETER SERVICES; MEDICAL-CARE; PAP-SMEARS; LANGUAGE; IMPACT AB Background: Language and culture relate in complex ways. Addressing this complexity in the context of language translation is a challenge when caring for patients with limited English proficiency (LEP). Objective: To examine processes of care related to language, culture and translation in an LEP population is the objective of this study. Design: We used community based participatory research to examine the experiences of Russian-speaking cancer patients in San Francisco, California. A Russian Cancer Information Taskforce (RCIT), including community-based organizations, local government, and clinics, participated in all phases of the study. Participants: A purposeful sample of 74 individuals were the participants of the study. Approach: The RCIT shaped research themes and facilitated access to participants. Methods were focus groups, individual interviews, and participant observation. RCIT reviewed data and provided guidance in interpreting results. Results: Four themes emerged. (1) Local Russian-language resources were seen as inadequate and relatively unavailable compared to other non-English languages; (2) a taboo about the word "cancer" led to language "games" surrounding disclosure; (3) this taboo, and other dynamics of care, reflected expectations that Russian speakers derived from experiences in their countries of origin; (4) using interpreters as cultural brokers or establishing support groups for Russian speakers could help address barriers. Conclusions: The language barriers experienced by this LEP population reflect cultural and linguistic issues. Providers should consider partnering with trained interpreters to address the intertwining of language and culture. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Dohan, D (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, 333 Calif St Suite 265,UCSF 0936, San Francisco, CA 94143 USA. EM Daniel.Dohan@ucsf.edu FU PHS HHS [HHSA 290200600023I] NR 47 TC 16 Z9 16 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 SU 2 BP 300 EP 305 DI 10.1007/s11606-007-0325-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 230HI UT WOS:000250866700007 PM 17957415 ER PT J AU Kotwani, N Danis, M AF Kotwani, Namrata Danis, Marion TI Tackling the health-poverty nexus: Primary care medicine and intersectoral health action SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. RP Danis, M (reprint author), Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA. EM mdanis@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1632 EP 1633 DI 10.1007/s11606-007-0378-y PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200026 PM 17896162 ER PT J AU Milescu, M Vobecky, J Roh, SH Kim, SH Jung, HJ Il Kim, J Swartz, KJ AF Milescu, Mirela Vobecky, Jan Roh, Soung H. Kim, Sung H. Jung, Hoi J. Il Kim, Jae Swartz, Kenton J. TI Tarantula toxins interact with voltage sensors within lipid membranes SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID DEPENDENT K+ CHANNEL; GATING MODIFIER TOXINS; TRYPTOPHAN FLUORESCENCE-SPECTRA; LOG-NORMAL COMPONENTS; BETA-SCORPION TOXIN; POTASSIUM CHANNEL; MOLECULAR DETERMINANTS; INTERFACIAL REGION; SODIUM-CHANNELS; ION CHANNELS AB Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (K-v) channels that has been proposed to move at the protein-lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit K-v channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin-membrane interaction is not sufficient to inhibit K-v channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin-channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid-channel interactions. C1 Natl Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. RP Milescu, M (reprint author), Natl Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr, Mol Physiol & Biophys Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. EM milescum@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002945-13] NR 55 TC 76 Z9 77 U1 1 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 2007 VL 130 IS 5 BP 497 EP 511 DI 10.1085/jgp.200709869 PG 15 WC Physiology SC Physiology GA 228ZW UT WOS:000250772100006 PM 17938232 ER PT J AU Chen, Z Schiffman, M Herrero, R Burk, RD AF Chen, Zigui Schiffman, Mark Herrero, Rolando Burk, Robert D. TI Identification and characterization of two novel human papillomavi ruses (HPVs) by overlapping PICR: HPV102 and HPV106 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PCR METHOD; TRANSCRIPTION; SEQUENCE; CARCINOGENICITY; SITES; CELLS; DNA; E6 AB Complete genomes of HPV102 (8078 bp) and HPV106 (8035 bp) were PCR amplified and cloned from cervicovaginal cells of a 49-year-old Hispanic female with reactive changes on her Pap test and a 42-year-old Hispanic female with a Pap test diagnosis of atypical squamous cells of unknown significance (ASCUS), respectively. The nucleotide sequence similarity of the complete L1 open reading frame (ORF) determined that HPV102 and HPV1 06 are most closely related to HPV83 (84.1 % identity) and HPV90 (83.5 % identity), respectively, placing them in the genital HPV groups, papillomaviruses species alpha 3 and alpha 15. HPV1 02 and HPV1 06 contain five early genes (E6, E7, E1, E2, and E4) and two late genes (L2 and L1), and both lack an E5 ORF. On the basis of phylogenetic analyses and available clinical information, these two novel HPV types expand the heterogeneity of HPVs detected in the lower genital tract. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. US Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NCI, NIH, Bethesda, MD USA. Costa Rican Fdn Hlth Sci, San Jose, Costa Rica. Albert Einstein Coll Med, Dept Pediat, Dept Epidemiol & Populat Hlth, Dept Obstet Gynecol & Womans Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. RP Burk, RD (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM burk@aecom.yu.edu RI Chen, Zigui/E-8490-2017 FU NCI NIH HHS [R01 CA078527, U01 CA078527, CA78527] NR 20 TC 13 Z9 13 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2007 VL 88 BP 2952 EP 2955 DI 10.1099/vir.0.83178-0 PN 11 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 229HX UT WOS:000250795000005 PM 17947516 ER PT J AU Shavers, VL Fagan, P McDonald, P AF Shavers, Vickie L. Fagan, Pebbles McDonald, Paige TI Health disparities across the cancer continuum SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM shaversv@mail.nih.gov NR 5 TC 10 Z9 11 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2007 VL 18 IS 4 SU S BP 1 EP 5 DI 10.1353/hpu.2007.0122 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 239EQ UT WOS:000251502000001 PM 18065848 ER PT J AU Shavers, VL AF Shavers, Vickie L. TI Unsung heroes: Mr. Frank Jackson and Dr. Richard Bragg SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Biographical-Item C1 NCI, Bethesda, MD 20892 USA. RP Shavers, VL (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2007 VL 18 IS 4 SU S BP 6 EP 9 DI 10.1353/hpu.2007.0111 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 239EQ UT WOS:000251502000002 PM 18065849 ER PT J AU Fagan, P Shavers, VL Lawrence, D Gibson, JT O'Connell, ME AF Fagan, Pebbles Shavers, Vickie L. Lawrence, Deirdre Gibson, James Todd O'Connell, Mary E. TI Employment characteristics and socioeconomic factors associated with disparities in smoking abstinence and former smoking among US workers SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE socioeconomic; self-employment; part-time work; multiple job holders; smoking; quitting ID PART-TIME WORK; UNITED-STATES; JOB STRESS; HEART-DISEASE; HEALTH; ADOLESCENTS; RISK; CONSEQUENCES; POPULATION; INTENSITY AB This study examines the associations among employment and socioeconomic factors and the outcomes, current smoking, cigarette abstinence and former smoking among adult U.S. workers ages 18-64 (n=288,813). Methods. Multivariate logistic regression was used to examine the associations among the variables using cross-sectional data from the 1998-1999 and 2001-2002 Tobacco Use Supplements to the Current Population Survey. Results. Lower odds of current smoking was observed among part-time workers compared to those working variable hours and multiple job holders compared to persons holding one job. The self-employed, part-time workers and multiple job holders had higher odds of former smoking than comparison groups. Employment factors were not associated with short-term abstinence or 12-month abstinence from smoking, but income, education, marital status, and duration of smoking were associated with 12-month abstinence. Conclusions. These data suggest that while employment factors are associated with current and former smoking, socioeconomic factors are associated with long-term quitting. C1 NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, EPN 4042,6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. EM faganp@mail.nih.gov NR 62 TC 18 Z9 18 U1 2 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2007 VL 18 IS 4 SU S BP 52 EP 72 DI 10.1353/hpu.2007.0119 PG 21 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 239EQ UT WOS:000251502000005 PM 18065852 ER PT J AU Willis, G Zahnd, E AF Willis, Gordon Zahnd, Elaine TI Questionnaire design from a cross-cultural perspective: An empirical investigation of Koreans and non-Koreans SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE race/ethnicity; Korean; cross-cultural comparability; cognitive interviews; language; linguistic barriers; cultural adaptation ID HEALTH-CARE; ACCULTURATION; QUALITY; ACCESS; LIFE AB A persistent challenge to self-report data across racial, ethnic, or cultural groups is the inherent difficulty of attaining cross-cultural comparability of key measures. The current research study investigated the cross-cultural functioning of health-survey questions presented to four groups: (1) Koreans who were monolingual in Korean; (2) non-Korean native speakers of English; (3) bilingual Koreans interviewed in English, and (4) bilingual Koreans interviewed in Korean. This design allowed us to include those likely to be medically underserved, and to assess both linguistic and cultural barriers to collecting health survey data. A total of 36 cognitive interviews were conducted to identify (a) translation problems; (b) problems of cultural adaptation that impede cross-cultural comparability; and (c) generic problems of questionnaire design that affect all groups. An important category of problems was identified that appeared to result from the interaction of respondent and question characteristics. Such problems can best be assessed through explicit consideration of the socio-cultural backgrounds of survey respondents, as opposed to the more usual focus on details of item translation and wording. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Inst Publ Hlth, Oakland, CA USA. RP Willis, G (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM willisg@mail.nih.gov NR 31 TC 13 Z9 13 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2007 VL 18 IS 4 SU S BP 197 EP 217 DI 10.1353/hpu.2007.0118 PG 21 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 239EQ UT WOS:000251502000013 PM 18065860 ER PT J AU Sharabi, Y Goldstein, DS Bentho, O Saleem, A Pechnik, S Geraci, MF Holmes, C Pacak, K Eisenhofer, G AF Sharabi, Yehonatan Goldstein, David S. Bentho, Oladi Saleem, Ahmed Pechnik, Sandra Geraci, Marilla F. Holmes, Courtney Pacak, Karel Eisenhofer, Graeme TI Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma SO JOURNAL OF HYPERTENSION LA English DT Article DE adrenal medulla; catecholamines; hypertension; metanephrines; pheochromocytoma; pseudopheochromocytoma; sympathetic nervous system ID ADRENAL-MEDULLARY HYPERPLASIA; PANIC DISORDER; NORADRENERGIC FUNCTION; BIOCHEMICAL-DIAGNOSIS; HEALTHY-SUBJECTS; BLOOD-PRESSURE; PHEOCHROMOCYTOMA; PLASMA; CLONIDINE; ANXIETY AB Objectives The causes of paroxysmal hypertension in patients in whom pheochromocytoma has been excluded ('pseudopheochromocytoma') usually remain unclear. Blood pressure disturbances and symptoms of catecholamine excess in these patients may reflect activation of the sympathetic nervous and adrenal medullary systems. We therefore examined sympathoadrenal function in patients with pseudopheochromocytoma compared with age-matched control subjects in whom there was no suspicion of pheochromocytoma. Methods Plasma catecholamines and hemodynamics were examined in response to intravenous glucagon, yohimbine, and trimethaphan in 11 patients with pseudopheochromocytoma and a comparison group of nine normotensive and five hypertensive volunteers. Adrenomedullary function was also assessed by abdominal F-18-fluorodopamine positron emission tomography and measurements of plasma metanephrine, the O-methylated metabolite of epinephrine. Results Compared with controls, patients with pseudopheochromocytoma had normal plasma concentrations of norepinephrine, but 120% higher (P<0.05) baseline plasma concentrations of epinephrine, 80% higher (P<0.01) baseline plasma concentrations of metanephrine, and sixfold larger (P<0.05) increases in plasma epinephrine after glucagon. Adrenal F-18-fluorodopamine-derived radioactivity did not differ between groups. Compared with changes in plasma norepinephrine, falls in blood pressure after trimethaphan were 13-fold larger (P<0.005) and increases in blood pressure after yohimbine were threefold larger (P<0.01) in pseudopheochromocytoma patients than in controls. Conclusion Patients with pseudopheochromocytoma exhibit a pattern of normal sympathetic noradrenergic outflow, adrenomedullary activation, and augmented blood pressure responses to changes in the sympathoneural release of norepinephrine. C1 Univ Dresden, Dept Med & Clin Chem, D-01307 Dresden, Germany. NICHHD, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), Univ Dresden, Dept Med & Clin Chem, Fetscherstr 74, D-01307 Dresden, Germany. EM graeme.eisenhofer@uniklinikum-dresden.de FU Intramural NIH HHS NR 47 TC 17 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2007 VL 25 IS 11 BP 2286 EP 2295 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 224XV UT WOS:000250482600017 PM 17921824 ER PT J AU Zhao, Y Bennett, AD Zheng, Z Wang, QJ Robbins, PF Yu, LYL Li, Y Molloy, PE Dunn, SM Jakobsen, BK Rosenberg, SA Morgan, RA AF Zhao, Yangbing Bennett, Alan D. Zheng, Zhili Wang, Qiong J. Robbins, Paul F. Yu, Lawrence Y. L. Li, Yi Molloy, Peter E. Dunn, Steven M. Jakobsen, Bent K. Rosenberg, Steven A. Morgan, Richard A. TI High-affinity TCRs generated by phage display provide CD4(+) T cells with the ability to recognize and kill tumor cell lines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DENDRITIC CELLS; NEGATIVE SELECTION; POSITIVE SELECTION; CD8 CORECEPTOR; IN-VITRO; RECEPTOR; LYMPHOCYTES; COMPLEX; MHC; PEPTIDE AB We examined the activity of human T cells engineered to express variants of a single TCR (1G4) specific for the cancer/testis Ag NY-ESO-1, generated by bacteriophage display with a wide range of affinities (from 4 mu M to 26 pM). CD8(+) T cells expressing intermediate- and high-affinity 1G4 TCR variants bound NY-ESO-1/HLA-A2 tetramers with high avidity and Ag specificity, but increased affinity was associated with a loss of target cell specificity of the TCR gene-modified cells. T cells expressing the highest affinity TCR (K. value of 26 pM) completely lost Ag specificity. The TCRs with affinities in the midrange, K-D 5 and 85 nM, showed specificity only when CD8 was absent or blocked, while the variant TCRs with affinities in the intermediate range-with K. values of 450 nM and 4 mu M - demonstrated Ag-specific recognition. Although the biological activity of these two relatively low-affinity TCRs was comparable to wild-type reactivity in CD8(+) T cells, introduction of these TCR dramatically increased the reactivity of CD4(+) T cells to tumor cell lines. C1 NCI, Natl Inst Hlth, Canc Res Ctr, Surg Branch, Bethesda, MD 20892 USA. Avidex Ltd, Abingdon, Oxon, England. RP Morgan, RA (reprint author), NCI, Natl Inst Hlth, Canc Res Ctr, Surg Branch, 10 Ctr Dr,MSC 1201,Bldg 10,Rm 3W5940, Bethesda, MD 20892 USA. EM rmorgan@inail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 40 TC 98 Z9 101 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2007 VL 179 IS 9 BP 5845 EP 5854 PG 10 WC Immunology SC Immunology GA 223QS UT WOS:000250388000029 PM 17947658 ER PT J AU Kuchen, S Robbins, R Sims, GP Sheng, C Phillips, TM Lipsky, PE Ettinger, R AF Kuchen, Stefan Robbins, Rachel Sims, Gary P. Sheng, Chen Phillips, Terence M. Lipsky, Peter E. Ettinger, Rachel TI Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4(+) T cell-B cell collaboration SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; LYMPHOCYTES-T; CD40 LIGAND; DIFFERENTIATION; EXPRESSION; IMMUNOGLOBULIN; RESPONSES; RECEPTOR; ANTIBODY; MEMORY AB During T cell-B cell collaboration, plasma cell (PC) differentiation and Ig production are known to require T cell-derived soluble factors. However, the exact nature of the cytokines produced by activated T cells that costimulate PC differentiation is not clear. Previously, we reported that costimulation of purified human B cells with IL-21 and anti-CD40 resulted in efficient PC differentiation. In this study, we addressed whether de novo production of IL-21 was involved in direct T cell-induced B cell activation, proliferation, and PC differentiation. We found that activated human peripheral blood CD4(+) T cells expressed mRNA for a number of cytokines, including iL-21, which was confirmed at the protein level. Using a panel of reagents that specifically neutralize cytokine activity, we addressed which cytokines are essential for B cell activation and PC differentiation induced by anti-CD3-activated T cells. Strikingly, neutralization of IL-21 with an IL-21R fusion protein (IL-21R-Fc) significantly inhibited T cell-induced B cell activation, proliferation, PC differentiation, and Ig production. Inhibition of PC differentiation was observed even when the addition of IL-21R-Fc was delayed until after initial B cell activation and expansion had occurred. Importantly, IL-21 was found to be involved in PC differentiation from both naive and memory B cells. Finally, IL-21R-Fc did not inhibit anti-CD3-induced CD4(+) T cell activation, but rather directly blocked T cell-induced B cell activation and PC differentiation. These data are the first to document that B cell activation, expansion, and PC differentiation induced by direct interaction of B cells with activated T cells requires IL-21. C1 NIH, NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. NIH, Off Res Serv, Ultramicro Analyt Immunochem Res Div Bioengn Phys, Bethesda, MD 20892 USA. Inflammat & Aotuimmun MedImmune, Gaithersburg, MD 20878 USA. RP Ettinger, R (reprint author), NIH, NIAMSD, Bldg 10,Rm 6D-47B, Bethesda, MD 20892 USA. EM ettingerr@mail.nih.gov FU Intramural NIH HHS NR 55 TC 146 Z9 151 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2007 VL 179 IS 9 BP 5886 EP 5896 PG 11 WC Immunology SC Immunology GA 223QS UT WOS:000250388000033 PM 17947662 ER PT J AU Rinderknecht, CH Belmares, MP Catanzarite, TLW Bankovich, AJ Holmes, TH Garcia, KC Nanda, NK Busch, R Kovats, S Mellins, ED AF Rinderknecht, Cornelia H. Belmares, Michael P. Catanzarite, Tatiana L. W. Bankovich, Alexander J. Holmes, Tyson H. Garcia, K. Christopher Nanda, Navreet K. Busch, Robert Kovats, Susan Mellins, Elizabeth D. TI Posttranslational regulation of I-E-d by affinity for CLIP SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; INVARIANT CHAIN PEPTIDE; ANTIGEN-PRESENTING CELL; DENDRITIC CELLS; SURFACE EXPRESSION; POINT MUTATIONS; UP-REGULATION; B-CELLS; MOLECULES; BINDING AB Several MHC class II alleles linked with autoimmune diseases form unusually low stability complexes with CLIP, leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. To investigate cellular consequences of altering class II/CLIP affinity, we evaluated invariant chain (Ii) mutants with varying CLIP affinity for a mouse class II allele, I-E-d, which has low affinity for wild-type CLIP and is associated with a mouse model of spontaneous, autoimmune joint inflammation. Increasing CLIP affinity for I-Ed resulted in increased cell surface and total cellular abundance and half-life of I-Ed. This reveals a post-endoplasmic reticulum chaperoning capacity of Ii via its CLIP peptides. Quantitative effects on I-E-d were less pronounced in DM-expressing cells, suggesting complementary chaperoning effects mediated by Ii and DM, and implying that the impact of allelic variation in CLIP affinity on immune responses will be highest in cells with limited DM activity. Differences in the ability of cell lines expressing wild-type or high-CLIP-affinity mutant Ii to present Ag to T cells suggest a model in which increased CLIP affinity for class II serves to restrict peptide loading to DM-containing compartments, ensuring proper editing of antigenic peptides. C1 Stanford Univ, Dept Pediat, Program Immunol, Stanford, CA 94305 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Dept Mol & Cell Physiol Struct Biol, Stanford, CA 94305 USA. Stanford Univ, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. Natl Inst Hlth, NIAID, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Arthritis & Immunol Res Program, Oklahoma City, OK 73104 USA. Arbor Vita Corp, Sunnyvale, CA 94085 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Cambridge Sidney Sussex Coll, Dept Med, Cambridge, England. RP Mellins, ED (reprint author), Stanford Univ, Sch Med, Dept Pediat, 269 Campus Dr,CCSR 2115c, Stanford, CA 94305 USA. EM mellins@stanford.edu OI Bankovich, Alexander/0000-0003-2368-4479; Kovats, Susan/0000-0001-5479-9952 FU NIAID NIH HHS [T32 AI007290] NR 68 TC 6 Z9 6 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 NOV 1 PY 2007 VL 179 IS 9 BP 5907 EP 5915 PG 9 WC Immunology SC Immunology GA 223QS UT WOS:000250388000035 PM 17947664 ER PT J AU Yang, JC Hughes, H Kammula, U Royal, R Sherry, RM Topalian, SL Suri, KB Levy, C Allen, T Mavroukakis, S Lowy, I White, DE Rosenberg, SA AF Yang, James C. Hughes, Harybeth Kammula, Udai Royal, Riehard Sherry, Riehard M. Topalian, Suzanne L. Suri, Kimberly B. Levy, Catherine Allen, Tamika Mavroukakis, Sharon Lowy, Israel White, Donald E. Rosenberg, Steven A. TI Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE renal cancer; immunotherapy; CTLA-4; ipilimumab; costimulation ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; CTLA-4 BLOCKADE; MELANOMA; IMMUNOTHERAPY; AUTOIMMUNITY; CARCINOMA; RESPONSES; TRANSPLANTATION; INTERLEUKIN-2; RECEPTORS AB The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells for both normal and tumor-associated antigens. Murine experiments suggested that blockade of CTLA4 might have antitumor activity and a clinical experience with the blocking antibody ipilimumab in patients with metastatic melanoma did show durable tumor regressions in some patients. Therefore, a phase II study of ipilimumab was conducted in patients with metastatic renal cell cancer with a primary end point of response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two sequential cohorts received either 3 mg/kg followed by 1 mg/kg or all doses at 3 mg/kg every 3 weeks (with no intention of comparing cohort response rates). Major toxicities were enteritis and endocrine deficiencies of presumed autoimmune origin. One of 21 patients receiving the lower dose had a partial response. Five of 40 patients at the higher dose had partial responses (95% confidence interval for cohort response rate 4% to 27%) and responses were seen in patients who had previously not responded to IL-2. Thirty-three percent of patients experienced a grade III or IV immune-mediated toxicity. There was a highly significant association between autoimmune events (AEs) and tumor regression (response rate = 30% with AE, 0% without AE). CTLA4 blockade with ipilimumab induces cancer regression in some patients with metastatic clear cell renal cancer, even if they have not responded to other immunotherapies. These regressions are highly associated with other immune-mediated events of presumed autoimmune origin by mechanisms as yet undefined. C1 [Yang, James C.; Hughes, Harybeth; Kammula, Udai; Royal, Riehard; Sherry, Riehard M.; Topalian, Suzanne L.; Suri, Kimberly B.; Levy, Catherine; Allen, Tamika; Mavroukakis, Sharon; White, Donald E.; Rosenberg, Steven A.] NCI, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. [Lowy, Israel] Medarex Corp, Princeton, NJ USA. RP Yang, JC (reprint author), Rm 10-3-5952,9000 Rockville Pike, Bethesda, MD 20892 USA. EM JamesYang@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 24 TC 288 Z9 296 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 825 EP 830 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700005 PM 18049334 ER PT J AU Szmania, S Gnjatic, S Tricot, G Stone, K Zhan, F Moreno, A Thuro, B Melenhorst, J Barrett, J Shaughnessy, J Old, LJ Barlogie, B Brichard, VG Van Rhee, F AF Szmania, Susann Gnjatic, Sacha Tricot, Guido Stone, Katie Zhan, Fenghuang Moreno, Amberly Thuro, Brad Melenhorst, Jos Barrett, John Shaughnessy, John Old, Lloyd J. Barlogie, Bart Brichard, Vincent G. Van Rhee, Frits TI Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE MAGE-A3; immunization; transplantation; myeloma ID STEM-CELL TRANSPLANTATION; PLASMODIUM-FALCIPARUM MALARIA; DONOR LYMPHOCYTE INFUSION; CYTOTOXIC T-LYMPHOCYTES; CANCER-TESTIS ANTIGENS; RISK MULTIPLE-MYELOMA; IMMUNE-RESPONSES; ALLOGENEIC TRANSPLANTATION; TUMOR-ANTIGENS; GERM-LINE AB MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200 mg/m(2) syngeneic peripheral blood stem cell transplant, primed donor cells collected after immunizations were transferred and followed by repeated patient immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific antibody, cytotoxic T=lymphocyte (CTL), and T-helper responses were induced in both twins. A humoral response was transferred to the patient with the donor peripheral blood stem cells and increased by booster immunization. The CTL response targeted a previously undescribed HLA-A*6801 binding MAGE-A3(115-123) peptide. MACE-A3(115-123) CTLs were detected in the patient more than 1 year after the last immunization. Multiple T-helper cellular responses were detected with the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient remains in remission 2.5 years after the second transplant. This report shows for the first time that immunization of a healthy donor with a defined cancer-testis protein induces immune responses that can be transferred and expanded posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM. C1 [Szmania, Susann; Tricot, Guido; Stone, Katie; Zhan, Fenghuang; Moreno, Amberly; Thuro, Brad; Shaughnessy, John; Barlogie, Bart; Van Rhee, Frits] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Gnjatic, Sacha; Old, Lloyd J.] Ludwig Inst Canc Res, New York, NY USA. [Melenhorst, Jos; Barrett, John] NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, Bethesda, MD 20892 USA. [Brichard, Vincent G.] GlaxoSmithKline Biol, Rixensart, Belgium. RP Van Rhee, F (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham, Little Rock, AR 72205 USA. EM vanrheefrits@uams.edu OI Thuro, Bradley/0000-0003-1465-5297 FU NCI NIH HHS [P01 CA558919-10] NR 53 TC 21 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 847 EP 854 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700008 PM 18049337 ER PT J AU Yang, JC Dudley, ME Restifo, NP Rosenberg, SA AF Yang, James C. Dudley, Mark E. Restifo, Nicholas P. Rosenberg, Steven A. TI Adoptive cellular therapy: Sustained regression of large tumor burdens with in vitro expanded T-cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Yang, James C.; Dudley, Mark E.; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD USA. RI Restifo, Nicholas/A-5713-2008 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 862 EP 862 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700033 ER PT J AU Malyguine, AM Shafer-Weaver, KA Zaritskaya, L Strobl, SL Gregory, MK Baseler, M AF Malyguine, Anatob M. Shafer-Weaver, Kimberly A. Zaritskaya, Liubov Strobl, Susan L. Gregory, Melissa K. Baseler, Michael TI Monitoring T-cell responses in cancer vaccine clinical trials SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Malyguine, Anatob M.; Shafer-Weaver, Kimberly A.; Zaritskaya, Liubov; Strobl, Susan L.; Gregory, Melissa K.; Baseler, Michael] NCI, SAIC Frederick Inc, Lab Cell Mediat Immun, Frederick, MD 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 863 EP 864 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700037 ER PT J AU Rossi, GR Morris, JC Malyguine, AM Strobl, SL Zaritskaya, L Gregory, MK Shafer-Weaver, KA Vahanian, N Link, CJ AF Rossi, Gnbriela R. Morris, John C. Malyguine, Anatoli M. Strobl, Susan L. Zaritskaya, Liubov Gregory, Melissa K. Shafer-Weaver, Kimberly A. Vahanian, Nicholas Link, Charles J. TI Assay development and testing of a reference population of normal healthy volunteers used for immunomonitoring of an anti-cancer vaccine clinical trial SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Rossi, Gnbriela R.; Vahanian, Nicholas; Link, Charles J.] Tumor Immunol New Link Genet, Ames, IA USA. [Morris, John C.] NCI, Metab Branch, NIH, Bethesda, MD USA. [Malyguine, Anatoli M.; Strobl, Susan L.; Zaritskaya, Liubov; Gregory, Melissa K.; Shafer-Weaver, Kimberly A.; Vahanian, Nicholas] LCMI, SAIC, NCI, NIH, Frederick, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 864 EP 864 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700039 ER PT J AU Walsh, MP Kim, SY Krauss, A Davis, JP Azizz, N Guimond, M Mackall, CL Fry, TJ AF Walsh, Meghaan P. Kim, Su Young Krauss, Aviva Davis, Jessica P. Azizz, Nazneen Guimond, Martin Mackall, Crystal L. Fry, Terry J. TI PT-100 induces T cell-mediated MB49 tumor regression SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Walsh, Meghaan P.; Kim, Su Young; Krauss, Aviva; Davis, Jessica P.; Guimond, Martin; Mackall, Crystal L.; Fry, Terry J.] NIH, NCI, Pediat Oncol Branch, CCR, Bethlehem, PA USA. [Azizz, Nazneen] Point Therapeut, Boston, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 865 EP 866 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700043 ER PT J AU Sportes, C Hakim, F Nemon, S Fry, TJ Cui, K Gress, R Mackall, CL AF Sportes, Claude Hakim, Frances Nemon, Sarfraz Fry, Terry J. Cui, Karen Gress, Ron Mackall, Crystal L. TI Interleukin-7 therapy in humans: Proof-of-principle SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Fry, Terry J.; Cui, Karen; Mackall, Crystal L.] Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA. [Sportes, Claude; Hakim, Frances; Nemon, Sarfraz; Gress, Ron] Natl Canc Inst, Expt Transplantat & Immunol Branch, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 876 EP 876 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700079 ER PT J AU Hallett, WH Barao, I Redelman, D Sayers, T Taylor, PA Blazar, BR Murphy, WJ AF Hallett, William H. Barao, Isabel Redelman, Douglas Sayers, Thomas Taylor, Patricia A. Blazar, Bruce R. Murphy, William J. TI Promotion of natural killer cell-mediated anti-tumor effects by removal of tregs in combination with interleukin-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Hallett, William H.; Barao, Isabel; Redelman, Douglas; Murphy, William J.] Univ Nevada, Reno, NV USA. [Sayers, Thomas] Natl Canc Inst, Ctr Canc Res, Basic Sci Program, Frederick, MD USA. [Taylor, Patricia A.; Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 879 EP 879 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700087 ER PT J AU Morris, JC Gwynne, S Rossi, GR Janik, JE Harold, N Pittaluga, S Malyguine, AM Strobl, SL Tennant, L Vahanian, N Link, CJ AF Morris, John C. Gwynne, Schoonmaker Rossi, Gabriela R. Janik, John E. Harold, Nancy Pittaluga, Stefania Malyguine, Anatoli M. Strobl, Susan L. Tennant, Lucinda Vahanian, Nicholas Link, Charles J. TI Phase I study of antitumor vaccination with genetically modified lung cancer cells expressing murine alpha(1,3)galactosyltransferase (alpha GT) in patients with advanced refractory non-small cell lung cancer (NSCLC) SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Morris, John C.; Gwynne, Schoonmaker; Janik, John E.; Harold, Nancy] Natl Canc Inst, Metab Branch, Bethesda, MD USA. [Rossi, Gabriela R.; Tennant, Lucinda; Vahanian, Nicholas; Link, Charles J.] NewLink Genet Corp, Tumor Immunol Sect, Ames, IA USA. [Pittaluga, Stefania] Natl Canc Inst, Pathol Lab, Bethesda, MD USA. [Malyguine, Anatoli M.; Strobl, Susan L.] SAIC Frederick Inc, Cellular Immunol Lab, Frederick, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 898 EP 899 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700151 ER PT J AU Rossi, GR Vahanian, N Morris, JC Malyguine, AM Strobl, SL Zaritskaya, L Gregory, MK Shafer-Weaver, KA Tennant, L Link, CJ AF Rossi, Gabriela R. Vahanian, Nicholas Morris, John C. Malyguine, Anatoli M. Strobl, Susan L. Zaritskaya, Liubov Gregory, Melissa K. Shafer-Weaver, Kimberly A. Tennant, Lucinda Link, Charles J. TI Immunological findings in a phase I study of anti-tumor vaccination using allogeneic lung cancer cells genetically modified to express alpha(1,3) galactosyltransferase (alpha GT) in patients with advanced non-small cell lung cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Rossi, Gabriela R.; Vahanian, Nicholas; Tennant, Lucinda; Link, Charles J.] NewLink Genet, Ames, IA USA. [Morris, John C.] NIH, Metab Branch, NCI, Bethesda, MD 20892 USA. [Malyguine, Anatoli M.; Strobl, Susan L.; Zaritskaya, Liubov; Gregory, Melissa K.; Shafer-Weaver, Kimberly A.] NIH, NCI, LCMI, SAIC, Frederick, MD 21701 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 901 EP 901 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700160 ER PT J AU Darnell, MER Plant, EP Watanabe, H Byrum, R Claire, MS Ward, JM Taylor, DR AF Darnell, Miriam E. R. Plant, Ewan P. Watanabe, Hisayoshi Byrum, Russ Claire, Marisa St. Ward, Jerrold M. Taylor, Deborah R. TI Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PROTECTIVE IMMUNITY; NEUTRALIZING ANTIBODY; SPIKE GLYCOPROTEIN; SARS VACCINE; VIRUS; MICE; IMMUNIZATION; REPLICATION; DISEASES; TRACT AB Background. Development of vaccines to prevent severe acute respiratory syndrome (SARS) is limited by the lack of well-characterized animal models. Previous vaccine reports have noted robust neutralizing antibody and inflammatory responses in ferrets, resulting in enhanced hepatitis. Methods. We evaluated the humoral immune response and pathological end points in ferrets challenged with the Urbani strain of SARS-associated coronavirus (SARS-CoV) after having received formalin-inactivated whole-virus vaccine or mock vaccine. Results. Humoral responses were observed in ferrets that received an inactivated virus vaccine. Histopathological findings in lungs showed that infection of ferrets produced residual lung lesions not seen in both mock and vaccinated ferrets. SARS-CoV infection demonstrated bronchial and bronchiolar hyperplasia and perivascular cuffing in ferret lung tissue, as seen previously in infected mice. No evidence of enhanced disease was observed in any of the ferrets. All of the ferrets cleared the virus by day 14, 1 week earlier if vaccinated. Conclusions. The vaccine provided mild immune protection to the ferrets after challenge; however, there was no evidence of enhanced liver or lung disease induced by the inactivated whole-virus vaccine. The ferret may provide another useful model for evaluating SARS vaccine safety and efficacy. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Lab Hepatitis & Related Em, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD USA. Bioqual Inc, Rockville, MD USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Lab Hepatitis & Related Em, 8800 Rockville Pike,HFM-310,NIH Bldg 29A,1C-14, Bethesda, MD 20892 USA. EM Deborah.Taylor@FDA.HHS.gov OI Plant, Ewan/0000-0003-0166-5939 FU Intramural NIH HHS NR 28 TC 25 Z9 26 U1 0 U2 1 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 NOV 1 PY 2007 VL 196 IS 9 BP 1329 EP 1338 DI 10.1086/522431 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 218JC UT WOS:000250010800011 PM 17922397 ER PT J AU Gropman, AL Summar, M Leonard, JV AF Gropman, A. L. Summar, M. Leonard, J. V. TI Neurological implications of urea cycle disorders SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Review ID ORNITHINE-TRANSCARBAMYLASE DEFICIENCY; ACUTE LIVER-FAILURE; CARBAMOYL TRANSFERASE DEFICIENCY; MAGNETIC-RESONANCE-SPECTROSCOPY; TRAUMATIC BRAIN-INJURY; MILD SYSTEMIC HYPOTHERMIA; HYPERAMMONEMIC RAT-BRAIN; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; SPARSE-FUR MUTATION AB The urea cycle disorders constitute a group of rare congenital disorders caused by a deficiency of the enzymes or transport proteins required to remove ammonia from the body. Via a series of biochemical steps, nitrogen, the waste product of protein metabolism, is removed from the blood and converted into urea. A consequence of these disorders is hyperammonaemia, resulting in central nervous system dysfunction with mental status changes, brain oedema, seizures, coma, and potentially death. Both acute and chronic hyperammonaemia result in alterations of neurotransmitter systems. In acute hyperammonaemia, activation of the NMDA receptor leads to excitotoxic cell death, changes in energy metabolism and alterations in protein expression of the astrocyte that affect volume regulation and contribute to oedema. Neuropathological evaluation demonstrates alterations in the astrocyte morphology. Imaging studies, in particular H-1 MRS, can reveal markers of impaired metabolism such as elevations of glutamine and reduction of myoinositol. In contrast, chronic hyperammonaemia leads to adaptive responses in the NMDA receptor and impairments in the glutamate-nitric oxide-cGMP pathway, leading to alterations in cognition and learning. Therapy of acute hyperammonaemia has relied on ammonia-lowering agents but in recent years there has been considerable interest in neuroprotective strategies. Recent studies have suggested restoration of learning abilities by pharmacological manipulation of brain cGMP with phosphodiesterase inhibitors. Thus, both strategies are intriguing areas for potential investigation in human urea cycle disorders. C1 George Washington Univ Hlth Sci, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Genet & Metab, Nashville, TN USA. Inst Child Hlth, London, England. RP Gropman, AL (reprint author), George Washington Univ Hlth Sci, Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM agropman@cnmc.org FU NCRR NIH HHS [K12RR17613, K12 RR017613, U54 RR019453]; NICHD NIH HHS [U54 HD061221] NR 145 TC 62 Z9 63 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD NOV PY 2007 VL 30 IS 6 BP 865 EP 879 DI 10.1007/s10545-007-0709-5 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 238CY UT WOS:000251426100004 PM 18038189 ER PT J AU Wang, R Wang, J Han, G Song, L Chen, G Xu, R Yu, M Qian, J Shen, B Li, Y AF Wang, R. Wang, J. Han, G. Song, L. Chen, G. Xu, R. Yu, M. Qian, J. Shen, B. Li, Y. TI Mechanisms underlying B-cell tolerance induction by antigen-immunoglobulin G gene transfer SO JOURNAL OF INTERNATIONAL MEDICAL RESEARCH LA English DT Article DE non-obese diabetic mice; tolerence; B-cell; CD40; CD40 ligand; diabetes ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PREVENTS ACUTE REJECTION; SOLUBLE CD40 LIGAND; REGULATORY T-CELLS; COSTIMULATORY BLOCKADE; MONOCLONAL-ANTIBODY; PROLONGED SURVIVAL; DONOR SPLENOCYTES; PRESENTING CELLS AB Previous studies on the mechanisms underlying tolerance induction in diabetes have mainly focused on T cells, however B cells also have an important role in diabetes. Based on our previous studies that splenocytes, transduced with glutamic acid decarboxylase (GAD) 65 fused to immunoglobulin (Ig) G carrier, reduced antibody-mediated response in non-obese diabetic (NOD) mice, here we examined the mechanisms underlying B-cell tolerance in this system. We found that GAD-IgG-transduced splenocytes did not reduce CD40 expression on B cells in NOD mice, but they did downregulate CD40 ligand (CD40L) expression. Furthermore, anti-CD40L injection reduced autoantibody levels in NOD mice and in vitro experiments demonstrated that CD40L blockade reduced the antigen-presenting capability of B-cells. In conclusion, the results of this study suggest that downregulation of CD40L may be one mechanism underlying the induction of B-cell tolerance in GAD-IgG-treated NOD mice. C1 Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. NCI, NIH, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Inst Basic Med Sci, Dept Mol Immunol, 27 Taiping Rd, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 38 TC 0 Z9 0 U1 0 U2 4 PU FIELD HOUSE PUBLISHING LLP PI WORTHING PA 6 SOMPTING AVENUE, WORTHING, BN14 8HN, ENGLAND SN 0300-0605 J9 J INT MED RES JI J. Int. Med. Res. PD NOV-DEC PY 2007 VL 35 IS 6 BP 781 EP 789 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 237NV UT WOS:000251382700006 PM 18034991 ER PT J AU Buechau, AS Hassan, M Kukova, G Lewerenz, V Kellermann, S Wuerthner, JU Wolf, R Walz, M Gallo, RL Ruzicka, T AF Buechau, Amanda S. Hassan, Mohamed Kukova, Gabriela Lewerenz, Virginia Kellermann, Sabine Wuerthner, Jens U. Wolf, Ronald Walz, Markus Gallo, Richard L. Ruzicka, Thomas TI S100A15, an antimicrobial protein of the skin: Regulation by E-coli through toll-like receptor 4 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NF-KAPPA-B; HUMAN EPIDERMAL-KERATINOCYTES; SIGNALING PATHWAY; GENE-EXPRESSION; INNATE IMMUNITY; CALGRANULIN C; CELL-GROWTH; FAMILY; PSORIASIN; LIPOPOLYSACCHARIDE AB E. coli is a Gram-negative bacterium rarely found on human skin. We investigated whether direct interaction of E. coli with keratinocytes might induce an innate immune response through recognition by pattern recognition receptors. The capacity of E. coli to activate innate immune responses and IL-8 induction was investigated. We found that E. coli significantly induced human S100A7 and S100A15 transcript abundance and IL-8 release in cultured primary human keratinocytes. S100A15 is a member of the S100 protein family with previously unknown function. E. coli induced effects could be inhibited by neutralizing Toll-like receptor 4 (TLR4) antibodies, suggesting that E. coli-induced IL-8 and S100A15 expression in human keratinocytes are TLR4 dependent. TLR4(-/-) mice lacked elevated mS100A15 expression after infection with E. coli in contrast to wildtype mice. In vitro, human S100A15 displayed antimicrobial activity against E. coli. Our findings suggest that E. coli modulates S100A15 and IL-8 expression of keratinocytes by recognition through TLR4. C1 Univ Calif San Diego, Div Dermatol, San Diego, CA 92307 USA. Univ Dusseldorf, Dept Dermatol, D-4000 Dusseldorf, Germany. VA San Diego Healthcare Syst, San Diego, CA USA. Univ Dusseldorf, Dept Med Microbiol, D-4000 Dusseldorf, Germany. NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. RP Buechau, AS (reprint author), Univ Calif San Diego, Div Dermatol, San Diego, CA 92307 USA. EM asbuchau@ucsd.edu RI Gallo, Richard/A-8931-2009 NR 50 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2007 VL 127 IS 11 BP 2596 EP 2604 DI 10.1038/sj.jid.5700946 PG 9 WC Dermatology SC Dermatology GA 221KS UT WOS:000250226800016 ER PT J AU Westbroek, W Adams, D Huizing, M Koshoffer, A Dorward, H Tinloy, B Parkes, J Helip-Wooley, A Kleta, R Tsilou, E Duvernay, P Digre, KB Creel, DJ White, JG Boissy, RE Gahl, WA AF Westbroek, Wendy Adams, David Huizing, Marjan Koshoffer, Amy Dorward, Heidi Tinloy, Bradford Parkes, Jennifer Helip-Wooley, Amanda Kleta, Robert Tsilou, Ekaterina Duvernay, Patrice Digre, Kathleen B. Creel, Donnell J. White, James G. Boissy, Raymond E. Gahl, William A. TI Cellular defects in Chediak-Higashi syndrome correlate with the molecular genotype and clinical phenotype SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID IDENTIFICATION; DISORDERS; PLATELETS; LYSOSOMES; PROTEINS; GRANULES; MUTATION; DOMAIN; BEIGE; LYST C1 NIH, NHGRI, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD USA. Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH USA. NIH, Off Rare Dis, Intramural Program, Bethesda, MD USA. NIH, NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD USA. Univ Utah, Dept Neurol, Intermt Hlth Care, Salt Lake City, UT USA. Univ Utah, Dept Neurol, Salt Lake City, UT USA. Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA. Univ Utah, John Moran Eye Ctr, Dept Visual Sci, Salt Lake City, UT USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Westbroek, W (reprint author), NIH, NHGRI, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD USA. EM wwestbro@mail.nih.gov RI Koshoffer, Amy/N-2278-2014; OI Koshoffer, Amy/0000-0001-8130-103X; Creel, Donnell Joseph/0000-0003-2882-3845 FU Intramural NIH HHS NR 18 TC 27 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2007 VL 127 IS 11 BP 2674 EP 2677 DI 10.1038/sj.jid.5700899 PG 4 WC Dermatology SC Dermatology GA 221KS UT WOS:000250226800027 PM 17554367 ER PT J AU Lyons, JG Patel, V Gutkind, JS AF Lyons, J. G. Patel, V. Gutkind, J. S. TI Snail transcription factors down-regulate keratinocyte differentiation genes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 3RD ANNUAL MEETING OF THE AUSTRALASIAN-SOCIETY-FOR-DERMATOLOGY-RESEARCH CY MAY 13, 2006 CL Melbourne, AUSTRALIA C1 Univ Sydney, Dermatol Res Labs, Camperdown, NSW, Australia. RPA Hosp, Sydney Head & Neck Canc Inst, Camperdown, NSW, Australia. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2007 VL 127 IS 11 BP 2688 EP 2688 PG 1 WC Dermatology SC Dermatology GA 221KS UT WOS:000250226800061 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI Macrophages, apoptotic cells and cholesterol - strategies for survival: an interview with Dr. Ira Tabas SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID ATHEROSCLEROSIS C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2007 VL 82 IS 5 BP 1051 EP 1052 DI 10.1189/jlb.1307192 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225JT UT WOS:000250514900004 ER PT J AU Buono, C Li, YF Waldo, SW Kruth, HS AF Buono, Chiara Li, Yifu Waldo, Stephen W. Kruth, Howard S. TI Liver X receptors inhibit human monocyte-derived macrophage foam cell formation by inhibiting fluid-phase pinocytosis of LDL SO JOURNAL OF LIPID RESEARCH LA English DT Article DE atherosclerosis; cholesterol; endocytosis ID LOW-DENSITY-LIPOPROTEIN; CHOLESTEROL EFFLUX; LIPID-METABOLISM; PPAR-ALPHA; ATHEROSCLEROSIS; LXR; MACROPINOCYTOSIS; EXPRESSION; GENE; MICE AB Liver X receptors ( LXRs) are ligand-activated transcription factors involved in the control of lipid metabolism and inflammation. Several studies have recently shown that LXRs promote reverse cholesterol transport and inhibit atherosclerosis. Our study investigated whether LXRs affect macrophage uptake of LDL by human monocyte-derived macrophages. We have previously shown that human monocytes differentiated into macrophages with macrophage-colony-stimulating factor ( M-CSF) constitutively take up large amounts of native LDL by receptor-independent, fluid-phase pinocytosis. In the research reported here, human monocytes were differentiated to macrophages in the presence of M-CSF with or without the LXR agonists T0901317 or 22(R)-hydroxycholesterol. Then, macrophages were incubated with native I-125-LDL to determine LDL uptake. T0901317 and 22(R)-hydroxycholesterol inhibited I-125-LDL uptake by 68 +/- 1% and 69 +/- 2%, respectively, and decreased pinocytotic vacuoles in the macrophages. I-125-BSA uptake, a measure of fluid-phase pinocytosis, and I-125-LDL uptake were the same, and T0901317 treatment inhibited uptake of both to the same degree. T0901317 did not affect receptor-mediated uptake of acetylated LDL, showing that the LXR effect is specific for fluid-phase pinocytosis of lipoproteins. Our results show that LXRs downregulate macrophage pinocytosis of LDL. The findings reveal an additional new mechanism by which LXR agonists may inhibit macrophage cholesterol accumulation and atherosclerosis, namely, by inhibiting macrophage uptake of LDL. C1 NIH, NHLBI, Expt Atherosclerosis Sect, Bethesda, MD 20892 USA. NIMH, Howard Hughes Med Inst, Res Sch Program, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NIH, NHLBI, Expt Atherosclerosis Sect, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU Intramural NIH HHS NR 39 TC 18 Z9 21 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2007 VL 48 IS 11 BP 2411 EP 2418 DI 10.1194/jlr.M700170-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220HT UT WOS:000250148500009 PM 17693624 ER PT J AU Igarashi, M Ma, KZ Chang, L Bell, JM Rapoport, SI AF Igarashi, Miki Ma, Kaizong Chang, Lisa Bell, Jane M. Rapoport, Stanley I. TI Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain SO JOURNAL OF LIPID RESEARCH LA English DT Article DE beta-oxidation; diet; docosahexaenoic acid; alpha-linolenic acid; polyunsaturated fatty acid ID ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; PROLIFERATOR-ACTIVATED RECEPTORS; ELEMENT-BINDING PROTEIN-1; DOCOSAHEXAENOIC ACID; NUTRITIONAL DEPRIVATION; GENE-EXPRESSION; DELTA-6 DESATURASE; OXIDATION ENZYMES; LEARNING-TASKS AB Fifteen weeks of dietary n-3 PUFA deprivation increases coefficients of conversion of circulating alpha-linolenic acid (alpha-LNA; 18:3n-3) to docosahexaenoic acid ( DHA; 22:6n-3) in rat liver but not brain. To determine whether these increases reflect organ differences in enzymatic activities, we examined brain and liver expression of converting enzymes and of two of their transcription factors, peroxisome proliferator-activated receptor a ( PPAR alpha) and sterol-regulatory element binding protein-1 (SREBP-1), in rats fed an n-3 PUFA "adequate" ( 4.6% alpha-LNA of total fatty acid, no DHA) or "deficient" ( 0.2% alpha-LNA, no DHA) diet for 15 weeks after weaning. In rats fed the deficient compared with the adequate diet, mRNA and activity levels of Delta 5 and Delta 6 desaturases and elongases 2 and 5 were upregulated in liver but not brain, but liver PPAR alpha and SREBP-1 mRNA levels were unchanged. In rats fed the adequate diet, enzyme activities generally were higher in liver than brain. Thus, differences in conversion enzyme expression explain why the liver has a greater capacity to synthesize DHA from circulating alpha-LNA than does the brain in animals on an adequate n-3 PUFA diet and why liver synthesis capacity is increased by dietary deprivation. These data suggest that liver n-3 PUFA metabolism determines DHA availability to the brain when DHA is absent from the diet. C1 NIH, NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. RP Igarashi, M (reprint author), NIH, NIA, Brain Physiol & Metab Sect, Bldg 10, Bethesda, MD 20892 USA. EM mikii@mail.nih.gov RI Igarashi, Miki/B-1085-2017 FU Intramural NIH HHS NR 73 TC 91 Z9 93 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2007 VL 48 IS 11 BP 2463 EP 2470 DI 10.1194/jlr.M700315-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220HT UT WOS:000250148500014 PM 17715424 ER PT J AU Stark, KD Lim, SY Salem, N AF Stark, Ken D. Lim, Sun-Young Salem, Norman, Jr. TI Artificial rearing with docosahexaenoic acid and n-6 docosapentaenoic acid alters rat tissue fatty acid composition SO JOURNAL OF LIPID RESEARCH LA English DT Article DE brain; heart; plasma; erythrocytes; liver; adipose; kidney; muscle; testes; gas chromatography ID SCHIZOCHYTRIUM SP; LINOLENIC ACID; FISH-OIL; LIPIDS; METABOLISM; DEFICIENT; WOMEN; BRAIN; LIVER; SUPPLEMENTATION AB Docosahexaenoic acid (DHA; 22:6n-3) and n-6 docosapentaenoic acid (DPAn-6; 22:5n-6) are components of enriched animal feed and oil derived from Schizochytrium species microalgae. A one generation, artificial rearing model from day 2 after birth onward ( AR) and a dam-reared control group (DAM) were used to examine DPAn-6 feeding on the fatty acid composition of various rat tissues at 15 weeks of age. Four AR diets were based on an n-3 fatty acid-deficient, 18:2n-6-based artificial milk with 22:6n-3 and/or 22:5n-6 added: AR-LA, AR-DHA, AR-DPAn-6, and AR-DHA+DPAn-6. The 22:6n-3 levels for the DAM,AR-DHA, and AR-DHA+DPAn-6 groups tended to be similar and higher than in the AR- LA and AR- DPAn-6 groups. The levels of 22:5n-6 tended to be higher only in the absence of dietary 22:6n-3. Adipose levels of 22:5n-6 was the only exception, as 22:5n-6 was significantly higher in AR-DHA+DPAn-6 than was observed in either the DAM or the AR- DHA group. There were no differences in 20:4n-6 levels within the tissues examined. In conclusion, 22:5n-6 replaces 22:6n-3 in the absence of 22:6n-3 only and does not appear to compete with 22:6n-3 in the presence of dietary 22:6n-3, suggesting that oils containing 22:5n-6 and 22:6n-3 may be a good dietary source of 22:6n-3. C1 Univ Waterloo, Dept Kinesiol, Nutr Lab & Nutraceut Res, Waterloo, ON N2L 3G1, Canada. Korea Maritime Univ, Div Marine Environm & Biosci, Pusan 606791, South Korea. NIH, NIAAA, Div Intramural Clin & Biol Res, Biochim Membranes Lab & Biophys, Bethesda, MD 20892 USA. RP Salem, N (reprint author), Univ Waterloo, Dept Kinesiol, Nutr Lab & Nutraceut Res, Waterloo, ON N2L 3G1, Canada. EM nsalem@niaaa.nih.gov RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 FU Intramural NIH HHS NR 35 TC 16 Z9 16 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2007 VL 48 IS 11 BP 2471 EP 2477 DI 10.1194/jlr.M700317-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220HT UT WOS:000250148500015 PM 17703057 ER PT J AU Komlosh, ME Horkay, F Freldlin, RZ Nevo, U Assaf, Y Basser, PJ AF Komlosh, M. E. Horkay, F. Freldlin, R. Z. Nevo, U. Assaf, Y. Basser, P. J. TI Detection of microscopic anisotropy in gray matter and in a novel tissue phantom using double Pulsed Gradient Spin Echo MR SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE pulsed gradient; spin echo; diffusion; MR; anisotropic; isotropic; microscopic; macroscopic; restriction; brain; gray matter; phantom ID DIFFUSION TENSOR; MAGNETIC-SUSCEPTIBILITY; SELF-DIFFUSION; FIELD-GRADIENT; PGSE NMR; SYSTEM; MOTION; WATER; SLOW AB A double Pulsed Gradient Spin Echo (d-PGSE) MR experiment was used to measure and assess the degree of local diffusion anisotropy in brain gray matter, and in a novel "gray matter" phantom that consists of randomly oriented tubes filled with water. In both samples, isotropic diffusion was observed at a macroscopic scale while anisotropic diffusion was observed at a microscopic scale, however, the nature of the resulting echo attenuation profiles were qualitatively different. Gray matter, which contains multiple cell types and fibers, exhibits a more complicated echo attenuation profile than the phantom. Since microscopic anisotropy was observed in both samples in the low q regime comparable to that achievable in clinical scanner, it may offer a new potential contrast mechanism for characterizing gray matter microstructure in medical and biological applications. (C) 2007 Published by Elsevier Inc. C1 NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. NIH, Comp Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Levie Edersheim Gitter Inst Human Brain Mapping, IL-69978 Tel Aviv, Israel. RP Komlosh, ME (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. EM michalk@mail.nih.gov RI Basser, Peter/H-5477-2011 FU Intramural NIH HHS NR 25 TC 55 Z9 55 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2007 VL 189 IS 1 BP 38 EP 45 DI 10.1016/jjmr.2007.07.003 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 233CP UT WOS:000251068300005 PM 17869147 ER PT J AU Gai, ND Zur, Y AF Gai, Neville D. Zur, Yuval TI Design and optimization for variable rate selective excitation using an analytic RF scaling function SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE SAR reduction; analytic RF scaling function; constant pulse width; constant contrast ID FLIP ANGLE; SEQUENCES; INVERSION; POWER AB At higher B-0 fields, specific absorption rate (SAR) deposition increases. Due to maximum SAR limitation, slice coverage decreases and/or scan time increases. Conventional selective RF pulses are played out in conjunction with a time independent field gradient. Variable rate selective excitation (VERSE) is a technique that modifies the original RF and gradient waveforms such that slice profile is unchanged. The drawback is that the slice profile for off-resonance spins is distorted. A new VERSE algorithm based on modeling the scaled waveforms as a Fermi function is introduced. It ensures that system related constraints of maximum gradient amplitude and slew rate are not exceeded. The algorithm can be used to preserve the original RF pulse duration while minimizing SAR and peak b1 or to minimize the RF pulse duration. The design is general and can be applied to any symmetrical or asymmetrical RF waveform. The algorithm is demonstrated by using it to (a) minimize the SAR of a linear phase RF pulse, (b) minimize SAR of a hyperbolic secant RF pulse, and (c) minimize the duration of a linear phase RF pulse. Images with a T1-FLAIR (T1 FLuid Attenuated Inversion Recovery) sequence using a conventional and VERSE adiabatic inversion RF pulse are presented. Comparison of images and scan parameters for different anatomies and coils shows increased scan coverage and decreased SAR with the VERSE inversion RF pulse, while image quality is preserved. (C) 2007 Elsevier Inc. All rights reserved. C1 GE Healthcare, Waukesha, WI USA. GE Healthcare, Tirat Carmel, Israel. RP Gai, ND (reprint author), NIH, DRD CC IN242, 10 Ctr Dr, Bethesda, MD 20892 USA. EM gaind@mail.nih.gov NR 14 TC 8 Z9 8 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2007 VL 189 IS 1 BP 78 EP 89 DI 10.1016/j.jmr.2007.08.017 PG 12 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 233CP UT WOS:000251068300008 PM 17889579 ER PT J AU Wang, J Walsh, JD Kuszewski, J Wang, YX AF Wang, Jinbu Walsh, Joseph D. Kuszewski, John Wang, Yun-Xing TI Periodicity, planarity, and pixel (3P): A program using the intrinsic residual dipolar coupling periodicity-to-peptide plane correlation and phi/psi angles to derive protein backbone structures SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE residual dipolar coupling; RDC wave; peptide plane; RDC-PP correlation ID MOLECULAR FRAGMENT REPLACEMENT; ALIGNMENT TENSOR; ORIENTED MACROMOLECULES; CHEMICAL-SHIFT; NUCLEIC-ACIDS; NMR MAPS; DYNAMICS; MOTION; WAVES; ORIENTATIONS AB We present a detailed description of a theory and a program called 3P. "3P" stands for periodicity, planarity, and pixel. The 3P program is based on the intrinsic periodic correlations between residual dipolar couplings (RDCs) and in-plane internuclear vectors, and between RDCs and the orientation of peptide planes relative to an alignment tensor. The program extracts accurate rhombic, axial components of the alignment tensor without explicit coordinates, and discrete peptide plane orientations, which are utilized in combination with readily available phi/psi angles to determine the three-dimensional backbone structures of proteins, The 3P program uses one alignment tensor. We demonstrate the utility and robustness of the program, using both experimental and synthetic data sets, which were added with different levels of noise or were incomplete. The program is interfaced to Xplor-NIH via a "3P" module and is available to the public. The limitations and differences between our program and existing methods are also discussed. Published by Elsevier Inc. C1 NCI Frederick, Prot Nucle Interact Sect, Struct Biophys Lab, NIH, Ft Detrick, MD 21702 USA. NIH, Imaging Sci Lab, Div Computat Biol, CIT, Bethesda, MD 20892 USA. RP Wang, YX (reprint author), NCI Frederick, Prot Nucle Interact Sect, Struct Biophys Lab, NIH, Ft Detrick, MD 21702 USA. EM wangyu@ncifcrf.gov FU Intramural NIH HHS NR 45 TC 17 Z9 17 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2007 VL 189 IS 1 BP 90 EP 103 DI 10.1016/jjmr.2007.08.018 PG 14 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 233CP UT WOS:000251068300009 PM 17892961 ER PT J AU Akca, IB Ferhanoglu, O Yeung, CJ Guney, S Tasci, TO Atalar, E AF Akca, Imran B. Ferhanoglu, Onur Yeung, Christopher J. Guney, Sevin Tasci, T. Onur Atalar, Ergin TI Measuring local RF heating in MRI: Simulating perfusion in a perfusionless phantom SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE RF heating; MRI safety; interventional MRI; metallic implants; perfusion; bioheat equation ID LOOPLESS CATHETER ANTENNA; INTERVENTIONAL MRI; CARDIAC-PACEMAKERS; MAGNETIC-FIELD; BLOOD-FLOW; IN-VITRO; MICROSPHERES; IMPLANTS; ENERGY; WIRES AB Purpose: To overcome conflicting methods of local RF heating measurements by proposing a simple technique for predicting in vivo temperature rise by using a gel phantom experiment. Materials and Methods: In vivo temperature measurements are difficult to conduct reproducibly; fluid phantoms introduce convection, and gel phantom lacks perfusion. In the proposed method the local temperature rise is measured in a gel phantom at a timepoint that the phantom temperature would be equal to the per-fused body steady-state temperature value. The idea comes from the fact that the steady-state temperature rise in a perfused body is smaller than the steady-state temperature increase in a perfusionless phantom. Therefore, when measuring the temperature on a phantom there will be the timepoint that corresponds to the perfusion time constant of the body part. Results: The proposed method was tested with several phantom and in vivo experiments. Instead, an overall average of 30.8% error can be given as the amount of underestimation with the proposed method. This error is within the variability of in vivo experiments (45%). Conclusion: With the aid of this reliable temperature rise prediction the amount of power delivered by the scanner can be controlled, enabling safe MRI examinations of patients with implants. C1 Bilkent Univ, Dept Elect & Elect Engn, TR-06800 Ankara, Turkey. NHLBI, Div Intramural Res, Natl Inst Hlth, Bethesda, MD 20892 USA. Gazi Univ, Dept Physiol, Inst Hlth Sci, Ankara, Turkey. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP Atalar, E (reprint author), Bilkent Univ, Dept Elect & Elect Engn, TR-06800 Ankara, Turkey. EM ergin@ee.bilkent.edu.tr RI Atalar, Ergin/D-3184-2012; Ferhanoglu, Onur/I-9348-2014 OI Atalar, Ergin/0000-0002-6874-6103; Ferhanoglu, Onur/0000-0002-5381-533X FU NCRR NIH HHS [R01 RR15396] NR 34 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2007 VL 26 IS 5 BP 1228 EP 1235 DI 10.1002/jmri.21161 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 225SR UT WOS:000250538300012 PM 17969180 ER PT J AU Szewczuk, LM Saldanha, SA Ganguly, S Bowers, EM Javoroncov, M Karanam, B Culhane, JC Holbert, MA Klein, DC Abagyan, R Cole, PA AF Szewczuk, Lawrence M. Saldanha, S. Adrian Ganguly, Surajit Bowers, Erin M. Javoroncov, Margarita Karanam, Balasubramanyam Culhane, Jeffrey C. Holbert, Marc A. Klein, David C. Abagyan, Ruben Cole, Philip A. TI De novo discovery of serotonin N-acetyltransferase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MELATONIN RHYTHM ENZYME; PINEAL-GLAND; HISTONE ACETYLTRANSFERASE; CATALYTIC MECHANISM; ANGSTROM RESOLUTION; BISUBSTRATE ANALOG; CRYSTAL-STRUCTURE; COENZYME-A; SUBSTRATE; DOCKING AB Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) is a member of the GCN5 N-acetyltransferase (GNAT) superfamily and catalyzes the penultimate step in the biosynthesis of melatonin; a large daily rhythm in AANAT activity drives the daily rhythm in circulating melatonin. We have used a structure-based computational approach to identify the first druglike and selective inhibitors of AANAT. Approximately 1.2 million compounds were virtually screened by 3D high-throughput docking into the active site of X-ray structures for AANAT, and in total 241 compounds were tested as inhibitors. One compound class, containing a rhodanine scaffold, exhibited low micromolar competitive inhibition against acetyl-CoA (AcCoA) and proved to be effective in blocking melatonin production in pineal cells. Compounds from this class are predicted to bind as bisubstrate inhibitors through interactions with the AcCoA and serotonin binding sites. Overall, this study demonstrates the feasibility of using virtual screening to identify small molecules that are selective inhibitors of AANAT. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NICHHD, NIH, Sect Neuroendocrinol, Bethesda, MD 20892 USA. RP Abagyan, R (reprint author), Scripps Res Inst, Dept Mol Biol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM abagyan@scripps.edu; pcole@jhmi.edu FU NIA NIH HHS [R01 AG019186-08, R01 AG019186]; NIGMS NIH HHS [R01 GM062437, R01 GM062437-08] NR 62 TC 17 Z9 17 U1 4 U2 12 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 NOV 1 PY 2007 VL 50 IS 22 BP 5330 EP 5338 DI 10.1021/jm0706463 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 225ZO UT WOS:000250557100011 PM 17924613 ER PT J AU Sharifi, N Lechleider, RJ Farrar, WL AF Sharifi, Nima Lechleider, Robert J. Farrar, William L. TI Transforming growth factor-beta receptor III downregulation in prostate cancer: is inhibin B a tumor suppressor in prostate? SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Editorial Material ID EXPRESSION; GENE; PROGRESSION; BETAGLYCAN; ALPHA; MICE AB The transforming growth factor-beta (TGF-beta) pathway plays dual roles in cancer, inhibiting epithelial cell growth under normal physiologic conditions, but promoting invasion and metastasis once growth inhibitory responses are lost. Two recent papers show that TGF-beta receptor III is the most common TGF-beta pathway component downregulated in prostate cancer. Here, we discuss the implications of these findings and what it may mean about the biology of this disease. C1 [Sharifi, Nima; Farrar, William L.] Natl Canc Inst Frederick, Ctr Canc Res, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD 21702 USA. [Sharifi, Nima; Lechleider, Robert J.] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. RP Sharifi, N (reprint author), Natl Canc Inst Frederick, Ctr Canc Res, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD 21702 USA. EM nima.sharifi@nih.gov FU Intramural NIH HHS NR 22 TC 17 Z9 18 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD NOV-DEC PY 2007 VL 39 IS 5-6 BP 329 EP 332 DI 10.1677/JME-07-0084 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247QE UT WOS:000252093600001 PM 17975259 ER PT J AU Nguyen, TL Panchal, RG Topol, IA Lane, D Kenny, T Burnett, JC Hermone, AR McGrath, C Burt, SK Gussio, R Bavari, S AF Nguyen, Tam Luong Panchal, Rekha G. Topol, Igor A. Lane, Douglas Kenny, Tara Burnett, James C. Hermone, Ann R. McGrath, Connor Burt, Stanley K. Gussio, Rick Bavari, Sina TI A theoretical study of anthrax lethal factor inhibition by a set of novel carbamimidolyl-aryl-vinyl-carboxamidines: A possible mechanism involving zinc-ligation by amidine SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE three-dimensional search query; density functional theory; docking study; molecular dynamics; zinc coordination ID CRYSTAL-STRUCTURE; FACTOR PROTEASE; GUANIDINE; AMINOGLYCOSIDES; DERIVATIVES; REACTIVITY; HYDRATION; COMPLEX; LIGAND AB A congeneric set of carbamimidolyl-aryl-vinyl-carboxamidines from the National Cancer Institute (NCI) open chemical repository were identified as potent inhibitors of anthrax lethal factor (LF), a zinc-dependent metalloprotease that plays a critical role in potentiating Bacillus anthracis infection. Surprisingly, these compounds exhibited no differential change in activity with concentration. Docking studies revealed that the indole-attached amidine substituents of these inhibitors were positioned in close proximity to the biological zinc atom and could potentially function as transition-state mimetics. This broaches the stunning possibility that the dose independence of these inhibitors is linked to zinc-ligation. Because the amidine functionality is highly basic and cationic, it is generally not considered a viable zinc-binding motif. However, quantum chemical calculations on small-molecule models predicted a marked decrease in the pK(a) of the amidine functionality when it is in close proximity to zinc, thus allowing for the formation of a robust zinc-amidine bond. Published by Elsevier B.V. C1 USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, Target Struct Based Drug Discovery Grp, Informat Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. EM sina.bavari@amedd.army.mil NR 28 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD NOV 1 PY 2007 VL 821 IS 1-3 BP 139 EP 144 DI 10.1016/j.theochem.2007.07.009 PG 6 WC Chemistry, Physical SC Chemistry GA 227JF UT WOS:000250652300018 ER PT J AU Plaza, A Gustchina, E Baker, HL Kelly, M Bewley, CA AF Plaza, Alberto Gustchina, Elena Baker, Heather L. Kelly, Michelle Bewley, Carole A. TI Mirabamides A-D, depsipeptides from the sponge siliquariaspongia mirabilis that inhibit HIV-1 fusion SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PAPUA-NEW-GUINEA; BIOACTIVE MARINE METABOLITES; CALLIPELTIN-A; THEONELLA-SWINHOEI; STEREOSELECTIVE SYNTHESIS; ABSOLUTE-CONFIGURATION; ASYMMETRIC-SYNTHESIS; NATURAL-PRODUCTS; (2R,3R,4S)-3-HYDROXY-2,4,6-TRIMETHYLHEPTANOIC ACID; BETA-METHOXYTYROSINE AB Four new cyclic depsipeptides termed mirabamides A-D (1-4) have been isolated from the marine sponge Siliquariaspongia mirabilis and shown to potently inhibit HIV- 1 fusion. Their structures were elucidated by NMR and ESIMS, and absolute stereochemistry of the amino acids was determined using advanced Marfey's methods and NMR. Mirabamides contain two new entities, including 4-chlorohomoproline in 1-3 and an unusual glycosylated amino acid, beta-methoxytyrosine 4'-O-alpha-L-rhamnopyranoside (in 1, 2, and 4), along with a rare N-terminal aliphatic hydroxy acid. These elements proved to be useful for anti-HIV structure-activity relationship studies. Mirabamide A inhibited HIV-1 in neutralization and fusion assays with IC50 values between 40 and 140 nM, as did mirabamides C and D (IC50 values between 140 nM and 1.3 mu M for 3 and 190 nM and 3.9,mu M for 4), indicating that these peptides can act at the early stages of HIV- I entry. The potent activity of depsipeptides containing the glycosylated beta-OMe Tyr unit demonstrates that beta-OMe Tyr itself is not critical for activity. Mirabamides A-C inhibited the growth of B. subtilis and C. albicans at 1-5 mu g/disk in disk diffusion assays. C1 NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NIDDK, Natl Inst Hlth, Chem Phys Lab, Bethesda, MD 20892 USA. Aquat Biodivers & Biosecur, Natl Inst Water & Atmospher Res, Auckland, New Zealand. RP Bewley, CA (reprint author), NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU Intramural NIH HHS NR 35 TC 61 Z9 62 U1 3 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2007 VL 70 IS 11 BP 1753 EP 1760 DI 10.1021/np070306k PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 234QO UT WOS:000251179000011 PM 17963357 ER PT J AU Mameza, MG Lockard, JM Zamora, E Hillefors, M Lavina, ZS Kaplan, BB AF Mameza, Marie Germaine Lockard, Jon M. Zamora, Eduardo Hillefors, Mi Lavina, Zeno Scotto Kaplan, Barry B. TI Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE axonal localization; lipoprotein; mRNA; sympathetic neurons; yeast two hybrid screen ID AUTOSOMAL RECESSIVE HYPERCHOLESTEROLEMIA; DENSITY-LIPOPROTEIN RECEPTOR; LONG-TERM FACILITATION; GABA(A) RECEPTOR; MESSENGER-RNAS; APOLIPOPROTEIN-E; NERVOUS-SYSTEM; GROWTH CONES; GABARAP; SYNAPSE AB Previously, pA134 was identified as one of the mRNAs present in the squid giant axon. Comparative sequence analyses revealed that the pA134 gene product manifested significant similarity to the mammalian lipoprotein receptor adaptor protein also known as ARH (autosomal recessive hypercholesterolemia). ARH mRNA and protein displayed very similar pattern of expression throughout the mouse brain. Significant levels of expression were observed in cells with a predominantly neuronal profile in the cerebellum, brainstem, olfactory bulb, hippocampus, and cortex. A yeast two hybrid screen for ARH protein interactions in mouse brain identified the following binders: amyloid precursor-like protein 1, low density lipoprotein receptor-related protein (LRP) 1, LRP8, and GABA receptor-associated protein-like 1. The interactions of ARH with LRP1 and GABA receptor-associated protein-like 1 were subsequently verified by co-immunoprecipitation of the protein complexes from transfected human embryonic kidney cells. The presence of ARH mRNA in axon of primary sympathetic neurons was established by RT-PCR analyses and confirmed by in situ hybridization. Taken together, our data suggest that ARH is a multifunctional protein whose spectrum of function in the brain goes beyond the traditionally known metabolism of lipoproteins, and that ARH may be locally synthesized in the axon. C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM barry.kaplan@nih.gov FU Intramural NIH HHS NR 50 TC 6 Z9 6 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 3 BP 927 EP 941 DI 10.1111/j.1471-4159.2007.04854.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 221ZS UT WOS:000250266500008 PM 17727637 ER PT J AU Ni, YC Malarkey, EB Parpura, V AF Ni, Yingchun Malarkey, Erik B. Parpura, Vladimir TI Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE exocytosis; intracellular Ca2+ dynamics; synaptic transmission; tripartite synapse ID CULTURED HIPPOCAMPAL-NEURONS; IN-SITU; SYNAPTIC-TRANSMISSION; GLIAL-CELLS; CALCIUM WAVES; NMDA RECEPTORS; ENDOPLASMIC-RETICULUM; EXOCYTOTIC RELEASE; MODULATION; ACTIVATION AB The major excitatory neurotransmitter in the CNS, glutamate, can be released exocytotically by neurons and astrocytes. Glutamate released from neurons can affect adjacent astrocytes by changing their intracellular Ca2+ dynamics and, vice versa, glutamate released from astrocytes can cause a variety of responses in neurons such as: an elevation of [Ca2+](i), a slow inward current, an increase of excitability, modulation of synaptic transmission, synchronization of synaptic events, or some combination of these. This astrocyte-neuron signaling pathway might be a widespread phenomenon throughout the brain with astrocytes possessing the means to be active participants in many functions of the CNS. Thus, it appears that the vesicular release of glutamate can serve as a common denominator for two of the major cellular components of the CNS, astrocytes and neurons, in brain function. C1 Univ Alabama, Ctr Glial Biol Med, Civitan Int Res Ctr, Birmingham, AL 35294 USA. NICHHD, NIH, Bethesda, MD USA. RP Parpura, V (reprint author), Univ Alabama, Ctr Glial Biol Med, Civitan Int Res Ctr, 1719 6th Ave S,CIRC 429, Birmingham, AL 35294 USA. EM vlad@uab.edu RI Parpura, Vladimir/A-1242-2010 OI Parpura, Vladimir/0000-0002-4643-2197 FU NIMH NIH HHS [MH 069791] NR 78 TC 59 Z9 59 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 4 BP 1273 EP 1284 DI 10.1111/j.1471-4159.2007.04864.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223WH UT WOS:000250403500001 PM 17727631 ER PT J AU Rissman, RA De Blas, AL Armstrong, DM AF Rissman, Robert A. De Blas, Angel L. Armstrong, David M. TI GABA(A) receptors in aging and Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE age; aging; Alzheimer's disease; benzodiazepine receptor; GABA; GABA(A) receptor; inhibitory neurotransmission; receptor subunits ID AMINOBUTYRIC ACID(A) RECEPTORS; BENZODIAZEPINE BINDING-SITES; HUMAN HIPPOCAMPAL-FORMATION; SUBUNIT EXPRESSION CHANGES; RAT CEREBRAL-CORTEX; AGE-RELATED-CHANGES; IMMUNOCYTOCHEMICAL LOCALIZATION; NEUROPATHOLOGIC CHANGES; ALPHA(6) SUBUNITS; SENILE DEMENTIA AB In this article we present a comprehensive review of relevant research and reports on the GABA(A) receptor in the aged and Alzheimer's disease (AD) brain. In comparison to glutamatergic and cholinergic systems, the GABAergic system is relatively spared in AD, but the precise mechanisms underlying differential vulnerability are not well understood. Using several methods, investigations demonstrate that despite resistance of the GABAergic system to neurodegeneration, particular subunits of the GABA(A) receptor are altered with age and AD, which can induce compensatory increases in GABA(A) receptor subunits within surrounding cells. We conclude that although aging- and disease-related changes in GABA(A) receptor subunits may be modest, the mechanisms that compensate for these changes may alter the pharmacokinetic and physiological properties of the receptor. It is therefore crucial to understand the subunit composition of individual GABA(A) receptors in the diseased brain when developing therapeutics that act at these receptors. C1 Salk Inst Biol Studies, Neuronal Struct & Funct Lab, La Jolla, CA 92037 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Dept Neurobiol & Physiol, Storrs, CT USA. Lanknau Inst Med Res, Lab Neuronal Vulnerab, Philadelphia, PA USA. RP Rissman, RA (reprint author), Salk Inst Biol Studies, Neuronal Struct & Funct Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM rrissman@salk.edu FU NIDDK NIH HHS [DK026741] NR 79 TC 85 Z9 89 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 4 BP 1285 EP 1292 DI 10.1111/j.1471-4159.2007.04832.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223WH UT WOS:000250403500002 PM 17714455 ER PT J AU Dienel, GA Schmidt, KC Cruz, NF AF Dienel, Gerald A. Schmidt, Kathleen C. Cruz, Nancy F. TI Astrocyte activation in vivo during graded photic stimulation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE acetate; astrocyte; deoxyglucose; glucose; oxidative metabolism; sensory stimulation ID CEREBRAL GLUCOSE-UTILIZATION; ACID-CYCLE METABOLISM; MAGNETIC-RESONANCE-SPECTROSCOPY; BOUND ACETYL ADENYLATE; BLOOD-BRAIN-BARRIER; INTACT RAT-BRAIN; AMINO-ACIDS; ENERGY-METABOLISM; OXIDATIVE-METABOLISM; SYNTHETASE REACTION AB Astrocytes have important roles in control of extracellular environment, de novo synthesis of neurotransmitters, and regulation of neurotransmission and blood flow. All of these functions require energy, suggesting that astrocytic metabolism should rise and fall with changes in neuronal activity and that brain imaging can be used to visualize and quantify astrocytic activation in vivo. A unilateral photic stimulation paradigm was used to test the hypothesis that graded sensory stimuli cause progressive increases in the uptake coefficient of [2-C-14]acetate, a substrate preferentially oxidized by astrocytes. The acetate uptake coefficient fell in deafferented visual structures and it rose in intact tissue during photic stimulation of conscious rats; the increase was highest in structures with monosynaptic input from the eye and was much smaller in magnitude than the change in glucose utilization (CMRglc) by all cells. The acetate uptake coefficient was not proportional to stimulus rate and did not correlate with CMRglc in resting or activated structures. Simulation studies support the conclusions that acetate uptake coefficients represent mainly metabolism and respond to changes in metabolism rate, with a lower response at high rates. A model portraying regulation of acetate oxidation illustrates complex relationships among functional activation, cation levels, and astrocytic metabolism. C1 Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. NIMH, Cerebral Metab Lab, Bethesda, MD USA. RP Dienel, GA (reprint author), Univ Arkansas Med Sci, Dept Neurol, 4301 W Markham St,Shorey Bldg,Rm 715,Slot 830, Little Rock, AR 72205 USA. EM gadienel@uams.edu FU Intramural NIH HHS; NICHD NIH HHS [HD16596]; NINDS NIH HHS [R01 NS036728, NS36728, NS38230, R01 NS038230] NR 89 TC 20 Z9 21 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 4 BP 1506 EP 1522 DI 10.1111/j.1471-4159.2007.04859.x PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223WH UT WOS:000250403500022 PM 17725580 ER PT J AU Yang, HYT Mitchell, K Keller, JM Iadarola, MJ AF Yang, Hsiu-Ying T. Mitchell, Kendall Keller, Jason M. Iadarola, Michael J. TI Peripheral inflammation increases Scya2 expression in sensory ganglia and cytokine and endothelial related gene expression in inflamed tissue SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cytokine microarray; dorsal root ganglia; monocyte chemoattractant protein-1; pain; peripheral inflammation; Scya2 ID NECROSIS-FACTOR-ALPHA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; DORSAL-ROOT GANGLIA; PRIMARY AFFERENT NEURONS; CHEMOKINE RECEPTOR 4; NEUROPATHIC PAIN; CHRONIC COMPRESSION; LUMBAR GANGLIA; RAT; HYPERALGESIA AB The sensation of pain (nociception) is a critical factor in host defense during tissue injury and inflammation and is initiated at the site of injury by activation of primary afferent C-fiber and A-partial derivative nerve endings. Inflammation induces tissue alterations that sensitize these nociceptive nerve terminals, contributing to persistent pain. To understand this ' algesic tissue environment' and peripheral nervous signaling to the CNS and immune system, we examined cytokine and endothelial-related gene expression profiles in inflamed rat tissues and corresponding dorsal root ganglia (DRG) by microarray and RT-PCR following hind paw injection of carrageenan. In inflamed tissue, forty-two cytokine and endothelial-related genes exhibited elevated expression. In contrast, in DRG, only Scya2 (chemokine C-C motif ligand 2) mRNA was up-regulated, leading to an increase in its gene product monocyte chemoattractant protein-1. Scya2 mRNA was localized by in situ hybridization-immunocytochemical double-labeling to a subpopulation of vanilloid receptor-1 ( transient receptor potential vanilloid subtype 1) containing neurons, and its expression was increased by direct transient receptor potential vanilloid subtype 1 stimulation with the vanilloid agonist resiniferatoxin, indicating sensitivity to nociceptive afferent activity. Our results are consistent with the idea that monocyte chemoattractant protein-1 at the site of peripheral injury and/ or in DRG is involved in inflammatory hyperalgesia. C1 NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bethesda, MD 20892 USA. RP Yang, HYT (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Bldg 49,Room 1A07,49 Convent Dr,MSC 4410, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 44 TC 30 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 4 BP 1628 EP 1643 DI 10.1111/j.1471-4159.2007.04874.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223WH UT WOS:000250403500032 PM 17883394 ER PT J AU Logan, SM Partridge, JG Matta, JA Buonanno, A Vicini, S AF Logan, Stephen M. Partridge, John G. Matta, Jose A. Buonanno, Andres Vicini, Stefano TI Long-lasting NMDA receptor-mediated EPSCs in mouse striatal medium spiny neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID METHYL-D-ASPARTATE; SUBUNIT MESSENGER-RNAS; BASAL GANGLIA; POSTNATAL-DEVELOPMENT; TERM POTENTIATION; NR2D SUBUNITS; DEVELOPMENTAL-CHANGES; FUNCTIONAL-PROPERTIES; HUNTINGTON-DISEASE; PROJECTION NEURONS AB Excitatory postsynaptic currents (EPSCs) from dorsolateral medium spiny neurons (MSNs) were recorded in cortico-striatal slice preparations from postnatal day 6-8 (P6-8) and >P12 wild-type mice and mice that were lacking either the NR2A or the NR2C subunit of the N-methyl-D- aspartate (NMDA) receptor. EPSCs were elicited by stimulation of the excitatory afferents and the NMDA and non-NMDA receptor-mediated components were pharmacologically isolated. The ratio of these components decreased with development and was significantly reduced only between age-matched +/+ and NR2A -/- neurons. In many MSNs, the NMDA-EPSC decay was characterized by the presence of a slow exponential component with a time constant lasting >1 s regardless of genotype or age. In the NR2A -/-, no developmental increase in the decay time (Tw) of the NMDA-EPSCs was observed although it was almost twofold longer than in +/+ MSNs. NR1/NR2B antagonists were ineffective in reducing the slow NMDA-EPSCs at all ages. Input-output studies revealed differences in stimulation threshold sensitivity of MSNs based on stimulus location. High- threshold responders were preferentially identified with stimulation from intracortical locations that produced considerably faster NMDA-EPSCs, whereas low-threshold responders were mainly elicited with stimulation more proximal to the striatum and exhibited slower NMDA-EPSCs. A low-affinity competitive antagonist of NMDA receptors failed to alter the decay of NMDA-EPSCs elicited from either location, suggesting that glutamate spillover is not responsible for the long-lasting NMDA-EPSCs. Our data are consistent with the expression of a unique NMDA receptor complex in MSNs with very slow deactivation kinetics. C1 Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. NICHHD, Mol Neurobiol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Vicini, S (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, BSB225,3900 Reservoir Rd, Washington, DC 20007 USA. EM svicin01@georgetown.edu FU NINDS NIH HHS [T32NS041218, NS-047700] NR 62 TC 26 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2007 VL 98 IS 5 BP 2693 EP 2704 DI 10.1152/jn.00462.2007 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 230UB UT WOS:000250900300019 PM 17804581 ER PT J AU Williams, MA McAllister, JP Walker, ML Kranz, DA Bergsneider, M Del Bigio, MR Fleming, L Frim, DM Gwinn, K Kestle, JRW Luciano, MG Madsen, JR Oster-Granite, ML Spinella, G AF Williams, Michael A. McAllister, James P. Walker, Marion L. Kranz, Dory A. Bergsneider, Marvin Del Bigio, Marc R. Fleming, Laurel Frim, Davm M. Gwinn, Katrina Kestle, John R. W. Luciano, Mark G. Madsen, Joseph R. Oster-Granite, Mary Lou Spinella, Giovanna TI Priorities for hydrocephalus research: report from a National Institutes of Health-sponsored workshop SO JOURNAL OF NEUROSURGERY LA English DT Review DE adult; basic biomedical research; children; clinical research; diagnostic criteria; hydrocephalus; infant; National Institutes of Health; neurosurgical education; normal pressure hydrocephalus pediatric neurosurgery; therapeutic intervention ID NORMAL-PRESSURE HYDROCEPHALUS; H-TX RAT; KAOLIN-INDUCED HYDROCEPHALUS; CEREBROSPINAL-FLUID OUTFLOW; CEREBRAL-BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; SHUNT VALVE DESIGN; LONG-TERM OUTCOMES; INTRACRANIAL-PRESSURE; CONGENITAL HYDROCEPHALUS AB Object. Treatment for hydrocephalus has not advanced appreciably since the advent of cerebrospinal fluid (CSF) shunts more than 50 years ago. Many questions remain that clinical and basic research could address, which in turn could improve therapeutic options. To clarify the main issues facing hydrocephalus research and to identify critical advances necessary to improve outcomes for patients with hydrocephalus, the National Institutes of Health (NIH) sponsored a workshop titled "Hydrocephalus: Myths, New Facts, and Clear Directions." The purpose of this paper is to report on the recommendations that resulted from that workshop. Methods. The workshop convened from September 29 to October 1, 2005, in Bethesda, Maryland. Among the 150 attendees was an international group of participants, including experts in pediatric and adult hydrocephalus as well as scientists working in related fields, neurosurgeons, laboratory-based neuroscientists, neurologists, patient advocates, individuals with hydrocephalus, parents, and NIH program and intramural staff. Plenary and breakout sessions covered injury and recovery mechanisms, modeling, biomechanics, diagnosis, current treatment and outcomes, complications, quality of life, future treatments, medical devices, development of research networks and information sharing, and education and career development. Results. The conclusions were as follows: 1) current methods of diagnosis, treatment, and outcomes monitoring need improvement; 2) frequent complications, poor rate of shunt survival, and poor quality of life for patients lead to unsatisfactory outcomes; 3) investigators and caregivers need additional methods to monitor neurocognitive function and control of CSF variables such as pressure, flow, or pulsatility; 4) research warrants novel interdisciplinary approaches; 5) understanding of the pathophysiological and recovery mechanisms of neuronal function in hydrocephalus is poor, warranting further investigation; and 6) both basic and clinical aspects warrant expanded and innovative training programs. Conclusions. The research priorities of this workshop provide critical guidance for future research in hydrocephalus, which should result in advances in knowledge, and ultimately in the treatment for this important disorder and improved outcomes in patients of all ages. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. Adult Hydrocephalus Ctr, Life Bridge Hlth Brain & Spine Inst, Baltimore, MD USA. Wayne State Univ, Dept Neurosurg, Detroit, MI USA. Univ Utah, Dept Neurosurg, Salt Lake City, UT USA. Hydrocephalus Assoc, San Francisco, CA USA. Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. Univ Manitoba, Dept Pathol, Winnipeg, MB R3T 2N2, Canada. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Chicago, Dept Neurosurg, Chicago, IL 60637 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA. NICHHD, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP McAllister, JP (reprint author), Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. EM pat.mcallister@hsc.utah.edu RI Gwinn, Katrina/C-2508-2009; OI Del Bigio, Marc/0000-0001-8366-0394; Gwinn, Katrina/0000-0002-8277-651X NR 189 TC 40 Z9 41 U1 2 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2007 VL 107 IS 5 SU S BP 345 EP 357 DI 10.3171/PED-07/11/345 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 233GT UT WOS:000251079200001 PM 18459897 ER PT J AU Jung, CS Oldfield, EH Harvey-White, J Espey, MG Zimmermann, M Seifert, V Pluta, RM AF Jung, Carla S. Oldfield, Edward H. Harvey-White, Judith Espey, Michael G. Zimmermann, Michael Seifert, Volker Pluta, Ryszard M. TI Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE asymmetric dimethyl-L-arginine; nitric oxide; nitric oxide synthase inhibitor; subarachnoid hemorrhage; vasospasm ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIMETHYL-L-ARGININE; CEREBROSPINAL-FLUID; HUMAN PLASMA; PRIMATE MODEL; ASYMMETRIC DIMETHYLARGININE; INTRACRANIAL ANEURYSMS; ENDOTHELIAL DYSFUNCTION; SODIUM-NITROPRUSSIDE; ALZHEIMERS-DISEASE AB Object. Delayed cerebral vasospasm after subarachnoid hemorrhage (SAH) may be evoked by the decreased availability of nitric oxide (NO). Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO synthase (NOS), have been associated with the course and degree of cerebral vasospasm in a primate model of SAH. In this study, the authors sought to determine if similar changes in CSF ADMA levels are observed in patients with SAH, and whether these changes are associated with NO and NOS metabolite levels in the CSF and the presence of cerebral vasospasm. Methods. Asymmetric dimethyl-L-arginine, L-arginine, L-Citrulline, and nitrite levels were measured in CSF and serum samples collected during the 21-day period after a single aneurysmal SAH in 18 consecutive patients. Samples were also obtained in a control group consisting of seven patients with Chiari malformation Type I and five patients with spontaneous intracerebral hemorrhage without SAH. Vasospasm, defined as a greater than 11% reduction in the anterior circulation vessel diameter ratio compared with the ratio calculated from the initial arteriogram, was assessed on cerebral arteriography performed around Day 7. Results. In 13 patients with SAH, arteriographic cerebral vasospasm developed. Cerebrospinal fluid ADMA levels in patients with SAH were higher than in those in the control group (p < 0.001). The CSF ADMA level remained unchanged in the five patients with SAH without vasospasm, but was significantly increased in patients with vasospasm after Day 3 (6.2 +/- 1.7 mu M) peaking during Days 7 through 9 (13.3 +/- 6.7 mu M; p < 0.001) and then gradually decreasing between Days 12 and 21 (8.8 +/- 3.2 mu M; p < 0.05). Nitrite levels in the CSF were lower in patients with vasospasm compared to patients without vasospasm (p < 0.03). Cerebrospinal fluid ADMA levels positively correlated with the degree of vasospasm (correlation coefficient [CC] = 0.88, p = 0.0001; 95% confidence interval [CI] 0.74-0.95) and negatively correlated with CSF nitrite levels (CC = -0.55; p = 0.017; 95% CI -0.8 1 to -0.12). Conclusions. These results support the hypothesis that ADMA is involved in the progression of cerebral vasospasm. Asymmetric dimethyl-L-arginine and its metabolizing enzymes may be a future target for treatment of cerebral vasospasm after SAH. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Physiol Studies, Bethesda, MD USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Dept Neurosurg, D-6000 Frankfurt, Germany. RP Jung, CS (reprint author), Natl Inst Neurol Dis, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 56 TC 35 Z9 35 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2007 VL 107 IS 5 BP 945 EP 950 DI 10.3171/JNS-07/11/0945 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 230LN UT WOS:000250878100007 PM 17977265 ER PT J AU Dixon, LB Subar, AF Peters, U Weissfeld, JL Bresalier, RS Risch, A Schatzkin, A Hayes, RB AF Dixon, L. Beth Subar, Amy F. Peters, Ulrike Weissfeld, Joel L. Bresalier, Robert S. Risch, Adam Schatzkin, Arthur Hayes, Richard B. TI Adherence to the USDA food guide, DASH eating plan, and Mediterranean dietary pattern reduces risk of colorectal adenoma SO JOURNAL OF NUTRITION LA English DT Article ID MAJOR CHRONIC DISEASE; FREQUENCY QUESTIONNAIRES; FOR-AMERICANS; CANCER RISK; DIVERSITY; PREVENTION; INTERVENTION; VALIDATION; NUTRITION; CHOICES AB The 2005 Dietary Guidelines for Americans include quantitative recommendations for 2 eating patterns, the USDA Food Guide and the Dietary Approaches to Stop Hypertension (DASH) Eating Plan, to promote optimal health and reduce disease risk. A Mediterranean dietary pattern has also been promoted for health benefits. Our objective was to determine whether adherence to the USDA Food Guide recommendations, the DASH Eating Plan, or a Mediterranean dietary pattern is associated with reduced risk of distal colorectal adenoma. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, men and women aged 55-74 y were screened for colorectal cancer by sigmoidoscopy at 10 centers in the U.S. After adjusting for potential confounders, men who most complied with the USDA Food Guide recommendations had a 26% reduced risk of colorectal adenoma compared with men who least complied with the recommendations (OR USDA score >= 5 vs. <= 2 = 0.74, 95% Cl = 0.64-0.85; P-trend < 0.001). Comparable results were found for men who had intakes most similar to the DASH Eating Plan or a Mediterranean dietary pattern. Women who most complied with the USDA Food Guide recommendations had an 18% reduced risk for colorectal adenoma, but subgroup analyses revealed protective associations only for current smokers (OR USDA score >= 5 vs. <= 2 0.52, 95% Cl - 0.31-0.89; P-trend < 0.01) or normal-weight women (OR USDA score >= 5 vs. <= 2 = 0.74, 95% Cl = 0.55-0.99, P-trend = 0.08). Following the current U.S. dietary recommendations or a Mediterranean dietary pattern is associated with reduced risk of colorectal adenoma, especially in men. C1 NYU, Dept Nutr Food Studies & Publ Hlth, New York, NY 10012 USA. NCI, Div Canc Prevent & Populat Sci, Bethesda, MD 20892 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15232 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Informat Management Syst Inc, Silver Spring, MD 20904 USA. NCI, Div Can Epidemiol & Genet, Bethesda, MD 20892 USA. RP Dixon, LB (reprint author), NYU, Dept Nutr Food Studies & Publ Hlth, 550 1St Ave, New York, NY 10012 USA. EM beth.dixon@nyu.edu FU Intramural NIH HHS NR 38 TC 56 Z9 56 U1 2 U2 11 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2007 VL 137 IS 11 BP 2443 EP 2450 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 224YX UT WOS:000250485400018 PM 17951483 ER PT J AU Kant, AK Graubard, BI AF Kant, Ashima K. Graubard, Barry I. TI Ethnicity is an independent correlate of biomarkers of micronutrient intake and status in American adults SO JOURNAL OF NUTRITION LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; UNITED-STATES; US POPULATION; ALPHA-TOCOPHEROL; SERUM; RACE; DETERMINANTS; ISSUES; FOLATE AB Diet may be among the factors that mediate the acknowledged ethnicity and socioeconomic differentials in health. Biomarkers of nutritional exposure avoid reliance on biased self-reports of diet and allow an objective assessment of dietary differentials associated with ethnicity and socioeconomic position. We used data from the NHANES III (n = 13113) and NHANES 1999-2002 (n = 7246) to examine ethnic, education, and income differentials in serum concentrations of nutrients of putative public health importance (vitamins C, D, and E, folate, carotenoids, selenium, and ferritin) in U.S. adults. Multiple regression methods were used to adjust for covariates and complex survey design to examine these associations. The serum beta-cryptoxanthin and lutein + zeaxanthin concentrations, adjusted for education and income, were higher in non-whites (P < 0.0001) relative to non-Hispanic whites. Non-Hispanic blacks had lower serum vitamins C and D, folate, and selenium concentrations relative to non-Hispanic-whites. The biomarker profile (except vitamin D, and folate and ferritin in women) of Mexican-Americans was comparable or better relative to non-Hispanic-whites. Ethnicity associations with mean biomarker concentrations generally paralleled these associations with the proportion of the population at risk of marginal concentrations. Education was an independent positive predictor of serum concentrations of several carotenoids and vitamin C (P <= 0.01). Both education and income were independent inverse predictors of risk of marginal vitamin C concentration in men (P <= 0.003). Relative to income, ethnicity and education were stronger independent predictors of several outcomes. Ethnic differences in status of several micronutrients persisted after adjustment for education and income, suggesting the importance of ethnicity-specific nutrition interventions. C1 CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. EM ashima.kant@qc.cuny.edu FU Intramural NIH HHS; NCI NIH HHS [CA108274] NR 37 TC 43 Z9 45 U1 1 U2 5 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2007 VL 137 IS 11 BP 2456 EP 2463 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 224YX UT WOS:000250485400020 PM 17951485 ER PT J AU Dwyer, JT AF Dwyer, Johanna T. TI Do functional components in foods have a role in helping to solve current health issues? SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 5th ORAFTI Research Conference on Inulin and Oligofructose - Proven Health Benefits and Claims CY SEP 28-29, 2006 CL Harvard Med Sch, Boston, MA SP ORAFTI HO Harvard Med Sch ID CLAIMS AB Functional foods and ingredients that are safe and efficacious have the potential for a positive impact on health. Current regulations in the United States governing claims about foods and dietary supplements, including functional foods and ingredients, are briefly reviewed. Research and communications challenges necessary to bring such products to the market are discussed. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Dwyer, JT (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. EM dwyerj1@od.nih.gov NR 15 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2007 VL 137 IS 11 SU S BP 2489S EP 2492S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 226NL UT WOS:000250595700001 PM 17951491 ER PT J AU Kim, YS Milner, JA AF Kim, Young S. Milner, John A. TI Dietary modulation of colon cancer risk SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 5th ORAFTI Research Conference on Inulin and Oligofructose - Proven Health Benefits and Claims CY SEP 28-29, 2006 CL Harvard Med Sch, Boston, MA SP ORAFTI HO Harvard Med Sch ID COLORECTAL-CANCER; GENE-EXPRESSION; INHIBITION; BUTYRATE; FIBER; CHEMOPREVENTION; CARCINOGENESIS; CALCIUM; FOLATE; CELLS AB Colon cancer remains a significant global health concern. The impact of specific dietary components on colon tissue likely depends on a host of genomic processes that influence the growth, development, and differentiation of the epithelial cells at the colon crypt surface, where the balance between proliferation and differentiation is maintained possibly through the Wnt (beta-catenin/T-cell factor) signaling pathway. A loss of balance caused by either genetic mutations or environmental factors such as dietary habits can modulate the risk for the formation of aberrant crypt foci and ultimately the development of colon cancer. Evidence exists that butyrate reduces the number and the size of aberrant crypt foci in the colon. Butyrate is a natural his tone deacetylase inhibitor as well as a molecule involved with enhanced TGF-,beta-induced SMAD3 phosphorylation, increased IFN-gamma-mediated apoptosis, and altered expression of the intestinal muc2 gene that is responsible for mucin synthesis. Other dietary components, such as vitamin D and (n-3) fatty acids, may regulate proliferative properties of colon progenitor cells as well as the differentiation of subcellular lineages. Although these findings are intriguing, there are uncertainties that remain to be resolved including the optimal exposure needed to bring about an effect, the appropriate timing of administration, and if nutrient-nutrient and nutrient-gene interactions determine the overall response. The expanded use of high-throughput technologies, knowledge about the expression of genes and protein fingerprints, and metabolomic profiling will assist in addressing these issues and ultimately in determining the physiological significance of bioactive food components as cancer protectants. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Kim, YS (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. EM yk47s@nih.gov NR 21 TC 60 Z9 62 U1 1 U2 11 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2007 VL 137 IS 11 SU S BP 2576S EP 2579S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 226NL UT WOS:000250595700016 PM 17951506 ER PT J AU Stratakis, CA AF Stratakis, Constantine A. TI Dan F. Gunther (1958-2007): Dedicated pediatric endocrinologist, astute clinician and exceptional person SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Biographical-Item ID GROWTH ATTENUATION C1 [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, PDEGEN, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHHD, Inter Inst Pediat Endocrinol Training Program, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, PDEGEN, NIH, Bldg 10 CRC E,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2007 VL 20 IS 11 BP 1157 EP 1159 PG 3 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 240LO UT WOS:000251589300001 ER PT J AU Inge, TH Zeller, M Harmon, C Helmrath, M Bean, J Modi, A Horlick, M Kalra, M Xanthakos, S Miller, R Akers, R Courcoulas, A AF Inge, Thomas H. Zeller, Meg Harmon, Carroll Helmrath, Michael Bean, Judy Modi, Avani Horlick, Mary Kalra, Maninder Xanthakos, Stavra Miller, Rosemary Akers, Rachel Courcoulas, Anita TI Teen-Longitudinal Assessment of Bariatric Surgery: methodological features of the first prospective multicenter study of adolescent bariatric surgery SO JOURNAL OF PEDIATRIC SURGERY LA English DT Letter C1 [Inge, Thomas H.; Zeller, Meg; Bean, Judy; Modi, Avani; Kalra, Maninder; Xanthakos, Stavra; Miller, Rosemary; Akers, Rachel] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Harmon, Carroll] Univ Alabama, Dept Surg, Birmingham, AL 35233 USA. [Harmon, Carroll] Univ Alabama, Div Pediat Surg, Birmingham, AL 35233 USA. [Helmrath, Michael] Texas Childrens Hosp, Baylor Coll Med, Div Pediat Surg, Houston, TX 77030 USA. [Horlick, Mary] NIDDKD, Bethesda, MD 20817 USA. [Courcoulas, Anita] Univ Pittsburgh, Dept Surg, Med Ctr, Pittsburgh, PA 15213 USA. RP Inge, TH (reprint author), Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. EM thomas.inge@cchmc.org RI Xanthakos, Stavra/B-1012-2009 FU NCATS NIH HHS [UL1 TR000005]; NIDDK NIH HHS [(U01 DK072493-01A1, U01 DK072493, U01 DK072493-01A1] NR 5 TC 55 Z9 56 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD NOV PY 2007 VL 42 IS 11 BP 1969 EP 1971 DI 10.1016/j.jpedsurg.2007.08.010 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 239XN UT WOS:000251551700034 PM 18022459 ER PT J AU Broitman, E Ambalavanan, N Higgins, RD Vohr, BR Das, A Bhaskar, B Murray, K Hintz, SR Carlo, WA AF Broitman, Eduardo Ambalavanan, Namasivayam Higgins, Rosemary D. Vohr, Betty R. Das, Abhik Bhaskar, Brinda Murray, Kennan Hintz, Susan R. Carlo, Waldemar A. CA Natl I Child Hlth Human Dev Neonatal Res Network TI Clinical data predict neurodevelopmental outcome better than head ultrasound in extremely low birth weight infants SO JOURNAL OF PEDIATRICS LA English DT Article ID TRANSIENT PERIVENTRICULAR ECHODENSITIES; NEONATAL INTENSIVE-CARE; PRETERM INFANTS; CRANIAL ULTRASOUND; WHITE-MATTER; INTRAVENTRICULAR HEMORRHAGE; DEVELOPMENTAL-DISABILITY; CEREBRAL-PALSY; CHILDREN; MORTALITY AB Objective To determine the relative contribution of clinical data versus head ultrasound scanning (HUS) in predicting neurodevelopmental impairment (NDI) in extremely low birth weight infants. Study design A total of 2103 extremely low birth weight infants (< 1000 g) admitted to a National Institute of Child Health and Human Development Neonatal Research Net-work center who underwent HUS within the first 28 days. a repeat one around 36 weeks' postmenstrual age, and neurodevelopmental assessment at 18 to 22 months corrected age were selected. Multivariate logistic regression models were developed with clinical or HUS variables. The primary outcome was the predictive abilities of the HUS performed before 28 days after birth and closer to 36 weeks postmenstrual age, either alone or in combination with '' Early '' and "Late-clinical variables. Results Models with clinical variables alone predicted NDI better than models with only HUS variables at both 28 days and 36 weeks (both P < .001), and the addition of the HUS data did not improve prediction. NDI was absent in 30% and 28% of, the infants with grade IV intracranial hemorrhage or periventricular leukomalacia, respectively, but was present in 39% of the infants with a normal HUS result. Conclusions Clinical models were better than HUS models in predicting neuro-development. C1 Univ Alabama, Birmingham, AL 35294 USA. NICHHD, Bethesda, MD 20892 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. RTI Int, Res Triangle Pk, NC USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Broitman, E (reprint author), Univ Alabama, Birmingham, AL 35294 USA. FU BHP HRSA HHS [U10DH27881]; NICHD NIH HHS [U10 HD021385, U10 HD027851, U10 HD027853, U10 HD027871, U10 HD027880, U10 HD034216-04, U10 HD040461, U10 HD040498, U10 HD040689, U10HD21385, U10HD21415, U10HD27851, U10HD27853, U10HD27871, U10HD27880, U10HD40498, U10HD40689, U10HD27856, U10 HD021364, U10 HD021373, U10 HD021397, U10 HD027856, U10 HD027904, U10 HD034216, U10 HD040521, U10 HD34216, U10HD21364, U10HD21373, U10HD21397, U10HD27904, U10HD40521, U10HD40461] NR 43 TC 39 Z9 39 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2007 VL 151 IS 5 BP 500 EP 505 DI 10.1016/j.jpeds.2007.04.013 PG 6 WC Pediatrics SC Pediatrics GA 229PG UT WOS:000250815900013 PM 17961693 ER PT J AU Bakalov, VK Shawker, T Cenicefros, I Bondy, CA AF Bakalov, Vladimir K. Shawker, Thomas Cenicefros, Irene Bondy, Carolyn A. TI Uterine development in Turner syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID GROWTH-HORMONE THERAPY; ESTROGEN REPLACEMENT; OOCYTE DONATION; WOMEN; INDUCTION; PUBERTY; GIRLS AB Objective To evaluate uterine development of women with Turner syndrome (TS) receiving conventional medical care. Study design in a cross-sectional study we used ultrasonography for uterine evaluation in 86 women with TS 18 to 45.,cars of age participating in an intramural NIH study, and who had abnormal karyotypes in > 70% of white blood cells. Outcomes were uterine dimensions and shape. Information on hormone treatment was obtained by personal interview. Results Twenty-five percent had a mature in size and shape uterus, and 31% had an immature uterus, with the remainder in a transitional category. Twenty percent of all participants were not taking hormone replacement therapy (HRT) in the preceding year. The majority on treatment were taking conjugated estrogens (CE) or oral contraceptives (OC). Factors associated with uterine maturity were history of spontaneous puberty and duration and type of HRT, with estradiol-based treatment being the most effective. The age at starting HRT was not a critical factor. Conclusions Women with TS may develop a normal uterus even at a late start of HRT given adequate duration of treatment and regardless of karyotype. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. RP Bakalov, VK (reprint author), NICHHD, Dev Endocrinol Branch, 10 Ctr Dr,CRC I-3330, Bethesda, MD 20892 USA. EM bakalov@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 15 TC 24 Z9 24 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2007 VL 151 IS 5 BP 528 EP 531 DI 10.1016/j.jpeds.2007.04.031 PG 4 WC Pediatrics SC Pediatrics GA 229PG UT WOS:000250815900018 PM 17961700 ER PT J AU Steffen, KM Cooper, ME Shi, M Caprau, D Simhan, HN Dagle, JM Marazita, ML Murray, JC AF Steffen, K. M. Cooper, M. E. Shi, M. Caprau, D. Simhan, H. N. Dagle, J. M. Marazita, M. L. Murray, J. C. TI Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery SO JOURNAL OF PERINATOLOGY LA English DT Article DE prematurity; cholesterol; preterm delivery; birth weight ID GROWTH-RESTRICTED PREGNANCIES; DENSITY-LIPOPROTEIN; UNIFIED APPROACH; BIRTH; POPULATION; DISEASE; POLYMORPHISM; NUTRITION; DESIGN; TRIADS AB Objective: To examine the contribution of variants in fetal and maternal cholesterol metabolism genes in preterm delivery ( PTD). Study Design: A total of 40 single-nucleotide polymorphisms ( SNPs) in 16 genes related to cholesterol metabolism were examined for 414 preterm infants ( gestational ages 22 to 36 weeks; comprising 305 singletons and 109 twins) and at least 1 parent. Fetal effects were assessed using the transmission disequilibrium test ( TDT) for each SNP, followed by a log linear model-based approach to utilize families with missing parental genotypes for those SNPs showing significance under TDT. Genetic variant effects were examined for a role in PTD, gestational age and birth weight. Maternal effects were estimated using a log linear model-based approach. Result: Among singleton gestations, suggestive association ( P< 0.01 without adjusting for multiple comparisons) was found between birth weight and fetal DHCR7 gene/SNP combinations ( rs1630498, P = 0.002 and rs2002064, P = 0.003). Among all gestations, suggestive associations were found between PTD and fetal HMGCR ( rs2303152, P = 0.002) and APOA1 (rs 5070, P = 0.004). The result for HMGCR was further supported by the log linear model-based test in the single births ( P = 0.007) and in all births ( P = 0.006). New associations ( APOE and ABCA1) were observed when birth weight was normalized for gestational age suggesting independent effects of variants on birth weight separate from effects on PTD. Testing for maternally mediated genetic effects has identified suggestive association between ABCA1 ( rs4149313, P = 0.004) and decreased gestational age. Conclusion: Variants in maternal and fetal genes for cholesterol metabolism were associated with PTD and decreased birth weight or gestational age in this study. Genetic markers may serve as one mechanism to identify high-risk mothers and fetuses for targeted nutritional treatment and/or prevention of low birth weight or PTD. C1 Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Iowa City, IA USA. Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, S Grand Ave,2182 ML, Iowa City, IA 52242 USA. EM jeff-murray@uiowa.edu FU NCRR NIH HHS [M01 RR000059, M01 RR000059-466795]; NICHD NIH HHS [R01 HD052953, R01 HD052953-01, R01 HD052953-03, HD052953, R01 HD052953-02] NR 44 TC 38 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD NOV PY 2007 VL 27 IS 11 BP 672 EP 680 DI 10.1038/sj.jp.7211806 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 224JY UT WOS:000250444500002 PM 17855807 ER PT J AU Gasior, M White, NA Rogawski, MA AF Gasior, Maciej White, Natalie A. Rogawski, Michael A. TI Prolonged attenuation of amygdala-kindled seizure measures in rats by convection-enhanced delivery of the n-type calcium channel antagonists omega-conotoxin GVIA and omega-conotoxin MVIIA SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOCKS SYNAPTIC TRANSMISSION; ELECTRICAL STIMULATION; BRAIN-STEM; HIPPOCAMPUS; INFUSION; EPILEPSY; CONOPEPTIDES; INHIBITION; INVITRO; ANTICONVULSANT AB Convection- enhanced delivery (CED) permits the homogeneous distribution of therapeutic agents throughout localized regions of the brain parenchyma without causing tissue damage as occurs with bolus injection. Here, we examined whether CED infusion of the N- type calcium channel antagonists w- conotoxin GVIA ( w- CTX- G) and w- conotoxin MVIIA ( w- CTX- M) can attenuate kindling measures in fully amygdala-kindled rats. Rats were implanted with a combination infusion cannula- stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received infusions of vehicle, w- CTX- G ( 0.005, 0.05, and 0.5 nmol), w- CTX- M ( 0.05, 0.15, and 0.5 nmol), proteolytically inactivated w- CTX- M ( 0.5 nmol), or carbamazepine ( 500 nmol) into the stimulation site. CED of w- CTX- G and w- CTX- M over a 20- min period resulted in a dose- dependent increase in the afterdischarge threshold and a decrease in the afterdischarge duration and behavioral seizure score and duration during a period of 20 min to 1 week after the infusion, indicating an inhibitory effect on the triggering and expression of kindled seizures. The protective effects of w- conotoxins reached a maximum at 48 h postinfusion, and then they gradually resolved over the next 5 days. In contrast, carbamazepine was active at 20 min but not at 24 h after the infusion, whereas CED of vehicle or inactivated w- CTX- M had no effect. Except for transient tremor in some rats receiving the highest toxin doses, no adverse effects were observed. These results indicate that local CED of high- molecular- weight presynaptic N- type calcium channel blockers can produce long- lasting inhibition of brain excitability and that they may provide prolonged seizure protection in focal seizure disorders. C1 Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Natl Inst Hlth, Natl Inst Neurol Disorder & Stoke, Epilepsy Res Sect, Bethesda, MD USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. EM rogawski@ucdavis.edu RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS [Z01 NS002877-15] NR 42 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2007 VL 323 IS 2 BP 458 EP 468 DI 10.1124/jpet.107.125047 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222ZO UT WOS:000250338400006 PM 17717191 ER PT J AU Oz, M Yang, KH Dinc, M Shippenberg, TS AF Oz, Murat Yang, Keun-Hang Dinc, Meral Shippenberg, Toni S. TI The endogenous cannabinoid anandamide inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus Oocytes SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RECEPTOR-MEDIATED RESPONSES; GLYCINE RECEPTORS; DELAYED RECTIFIER; CYTOSOLIC CA2+; ATP CHANNELS; ION CHANNELS; CELLS; NEURONS; MATURATION; LIPIDS AB The effect of the endogenous cannabinoid anandamide on K+ currents activated by the ATP-sensitive potassium (K-ATP) channel opener cromakalim was investigated in follicle-enclosed Xenopus oocytes using the two-electrode voltage-clamp technique. Anandamide (1 - 90 mu M) reversibly inhibited cromakaliminduced K+ currents, with an IC50 value of 8.1 +/- 2 mu M. Inhibition was noncompetitive and independent of membrane potential. Coapplication of anandamide with the cannabinoid type 1 (CB1) receptor antagonist N-(piperidin-1-yl)-5-(4chlorophenyl)- 1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3carboximide hydrochloride (SR 141716A) (1 mu M), the CB2 receptor antagonist N-[(1S) endo-1,3,3-trimethyl bicyclo heptan2- yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3carboxamide (SR144528) (1 mu M), or pertussis toxin (5 mu g/ml) did not alter the inhibitory effect of anandamide, suggesting that known cannabinoid receptors are not involved in anandamide inhibition of K+ currents. Similarly, neither the amidohydrolase inhibitor phenylmethylsulfonyl fluoride ( 0.2 mM) nor the cyclooxygenase inhibitor indomethacin ( 5 mu M) affected anandamide inhibition of K+ currents, suggesting that the effects of anandamide are not mediated by its metabolic products. In radioligand binding studies, anandamide inhibited the specific binding of the K-ATP ligand [H-3] glibenclamide in the oocyte microsomal fractions, with an IC50 value of 6.3 +/- 0.4 mu M. Gonadotropin- induced oocyte maturation and the cromakalim- acceleration of progesterone- induced oocyte maturation were significantly inhibited in the presence of 10 mu M anandamide. Collectively, these results indicate that cromakalim- activated K+ currents in follicular cells of Xenopus oocytes are modulated by anandamide via a cannabinoid receptor- independent mechanism and that the inhibition of these channels by anandamide alters the responsiveness of oocytes to gonadotropin and progesterone. C1 Natl Inst Drug Abuse, Natl Inst Hlth, Dept Hlth & Human Serv, Intramural Res Program,Integat Neurosi Sect, Baltimore, MD USA. Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Sect Dev Neurobiol, Lab Neural Control, Baltimore, MD USA. Oncol Training & Res Hosp, Dept Pulm Dis, Ankara, Turkey. RP Oz, M (reprint author), NIDA, Intramural Res Program, Integat Neurosi Sect, 333 Casell Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 FU Intramural NIH HHS NR 41 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2007 VL 323 IS 2 BP 547 EP 554 DI 10.1124/jpet.107.125336 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222ZO UT WOS:000250338400015 PM 17682128 ER PT J AU Gay, EA Yakel, JL AF Gay, Elaine A. Yakel, Jerrel L. TI Gating of nicotinic ACh receptors; new insights into structural transitions triggered by agonist binding that induce channel opening SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID NORMAL-MODE ANALYSIS; CYS-LOOP RECEPTORS; GATED ION-CHANNEL; ACETYLCHOLINE-RECEPTOR; EXTRACELLULAR DOMAIN; LIGAND-BINDING; CONFORMATIONAL-CHANGE; CRYSTAL-STRUCTURE; CHARGED RESIDUES; GABA(A) RECEPTOR AB Nicotinic acetylcholine receptors (nAChRs) are in the superfamily of Cys-loop ligand-gated ion channels, and are pentameric assemblies of five subunits, with each subunit arranged around the central ion-conducting pore. The binding of ACh to the extracellular interface between two subunits induces channel opening. With the recent 4 angstrom resolution of the Torpedo nAChR, and the crystal structure of the related molluscan ACh binding protein, much has been learned about the structure of the ligand binding domain and the channel pore, as well as major structural rearrangements that may confer channel opening. For example, the putative pathway coupling agonist binding to channel gating may include a major rearrangement of the C-loop within the ligand binding pocket, and the disruption of a salt bridge between an arginine residue at the end of the beta 10 strand and a glutamate residue in the beta 1-beta 2 linker. Here we will review and discuss the latest structural findings aiming to further refine the transduction pathway linking binding to gating for the nAChR channels, and discuss similarities and differences among the different members of this Cys-loop superfamily of receptors. C1 NIEHS, NIH, Dept Hlth & Human Serv, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural NIH HHS NR 40 TC 30 Z9 31 U1 3 U2 6 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 NOV 1 PY 2007 VL 584 IS 3 BP 727 EP 733 DI 10.1113/jphysiol.2007.142554 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 234AD UT WOS:000251132100004 PM 17823204 ER PT J AU Yu, LR Zhu, ZY Chan, KC Issaq, HJ Dimitrov, DS Veenstra, TD AF Yu, Li-Rong Zhu, Zhongyu Chan, King C. Issaq, Haleem J. Dimitrov, Dimiter S. Veenstra, Timothy D. TI Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE phosphoproteomics; titanium dioxide; phosphopeptide enrichment; HeLa cells; tandem mass; spectrometry; neutral loss scan ID METAL-AFFINITY-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; TYROSINE PHOSPHORYLATION SITES; PHOSPHOPROTEOMIC ANALYSIS; PROTEIN-PHOSPHORYLATION; IN-VIVO; SINGLE PHOSPHORYLATION; TAG APPROACH; QUANTITATIVE PHOSPHOPROTEOMICS; MULTISITE PHOSPHORYLATION AB Enrichment is essential for phosphoproteome analysis because phosphorylated proteins are usually present in cells in low abundance. Recently, titanium dioxide (TiO2) has been demonstrated to enrich phosphopeptides from simple peptide mixtures with high specificity; however, the technology has not been optimized. In the present study, significant non-specific bindings were observed when proteome samples were applied to TiO2 columns. Column wash with an NH(4)Glu solution after loading peptide mixtures significantly increased the efficiency of TiO2 phosphopeptide enrichment with a recovery of up to 84%. Also, for proteome samples, more than a 2-fold increase in unique phosphopeptide identifications has been achieved. The use of NH(4)Glu for a TiO2 column wash does not significantly reduce the phosphopeptide recovery. A total of 858 phosphopeptides corresponding to 1034 distinct phosphosites has been identified from HeLa cells using the improved TiO2 enrichment procedure in combination with data-dependent neutral loss nano-RPLC-MS2-MS3 analysis. While 41 and 35% of the phosphopeptides were identified only by MS2 and MS3, respectively, 24% was identified by both MS2 and MS3. Cross-validation of the phosphopeptide assignment by MS2 and MS3 scans resulted in the highest confidence in identification (99.5%). Many phosphosites identified in this study appear to be novel, including sites from antigen Ki-67, nucleolar phosphoprotein p130, and Treacle protein. The study also indicates that evaluation of confidence levels for phosphopeptide identification via the reversed sequence database searching strategy might underestimate the false positive rate. C1 NCI, Lab Proteom & Anal Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Nanobiol Program, Frederick, MD 21702 USA. RP Yu, LR (reprint author), NCI, Lab Proteom & Anal Technol, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM lyu@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 76 TC 100 Z9 278 U1 5 U2 59 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 NOV PY 2007 VL 6 IS 11 BP 4150 EP 4162 DI 10.1021/pr070152u PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 228GU UT WOS:000250718700010 PM 17924679 ER PT J AU Fontana, S Alessandro, R Barranca, M Giordano, M Corrado, C Zanella-Cleon, I Becchi, M Kohn, EC De Leo, G AF Fontana, Simona Alessandro, Riccardo Barranca, Marilisa Giordano, Margherita Corrado, Chiara Zanella-Cleon, Isabelle Becchi, Michel Kohn, Elise C. De Leo, Giacomo TI Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE chronic myelogenous leukemia cell lines; proteome profiling; tumor invasion; drug resistance. ID CHRONIC MYELOID-LEUKEMIA; HUMAN LUNG-CANCER; 2-DIMENSIONAL GEL-ELECTROPHORESIS; METASTASIS-ASSOCIATED PROTEINS; ACUTE LYMPHOBLASTIC-LEUKEMIA; GLUTATHIONE-S-TRANSFERASE; TYROSINE KINASE-ACTIVITY; COLORECTAL-CANCER; BREAST-CANCER; CARBONIC-ANHYDRASE AB The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment. C1 Univ Palermo, Sez Biol & Genet, Dipartimento Biopatol & Metodol, I-90133 Palermo, Italy. Univ Lyon, IFR 128, CNRS,UMR 5086, Inst Biol & Chim Prot, Lyon, France. NCI, Ctr Canc Res, Med Oncol Branch, Mol Signaling Sect, Bethesda, MD 20892 USA. RP Alessandro, R (reprint author), Univ Palermo, Sez Biol & Genet, Dipartimento Biopatol & Metodol, Via Divisi 83, I-90133 Palermo, Italy. EM ricale@unipa.it OI Fontana, Simona/0000-0003-4681-2170 NR 106 TC 18 Z9 18 U1 1 U2 3 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 NOV PY 2007 VL 6 IS 11 BP 4330 EP 4342 DI 10.1021/pr0704128 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 228GU UT WOS:000250718700026 PM 17935311 ER PT J AU Sun, YN An, SH Henrich, VC Sun, XP Song, QS AF Sun, Yaning An, Shiheng Henrich, Vincent C. Sun, Xiaoping Song, Qisheng TI Proteornic identification of PKC-mediated expression of 20E-induced protein in drosophila melanogaster SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE nuclear receptor; protein expression; protein kinase; inhibitor ID STEROID-HORMONE RECEPTORS; LIGAND-INDEPENDENT ACTIVATION; KINASE-C; ECDYSTEROID RECEPTOR; SIGNALING PATHWAYS; ECDYSONE RECEPTOR; SCAFFOLD PROTEIN; GENE-EXPRESSION; BETA-SUBUNIT; CROSS-TALK AB Ecdysone receptor (EcR) and its heterodimeric partner, ultraspiracle protein (USP), are nuclear receptors that mediate the action of the insect molting hormone 20-hydroxyecdysone (20E). There is evidence that the activity of both receptors is affected by phosphorylation. Using a proteomic approach, we have shown that protein kinase C (PKC) activity is necessary for. mediating 20E-induced expression of 14 specific proteins, including three previously reported 20E responsive proteins, and is also responsible for the intracellular localization of EcR and USP in larval salivary glands of Drosophila melanogaster. The 20E-dependent expression of the proteins was verified using real-time PCR and/or Western blot analysis. For some genes, inhibition of PKC activity reduced 20E-dependent transcriptional activity rapidly, raising the possibility that these are direct gene targets of EcR and USP. The data further indicate that PKC-mediated phosphorylation is also required for genes regulated indirectly by 20E-induced changes in the larval salivary gland. C1 Univ Missouri, Div Plant Sci, Columbia, MO 65211 USA. Univ N Carolina, Ctr Biotechnol Genom & Hlth Res, Greensboro, NC 27402 USA. NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Song, QS (reprint author), Univ Missouri, Div Plant Sci, 1-31 Agr Bldg, Columbia, MO 65211 USA. EM SongQ@missouri.edu NR 38 TC 15 Z9 18 U1 0 U2 2 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 NOV PY 2007 VL 6 IS 11 BP 4478 EP 4488 DI 10.1021/pr0705183 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 228GU UT WOS:000250718700040 PM 17924685 ER PT J AU Cook, IA Balasubramani, GK Eng, H Friedman, E Young, EA Martin, J Nay, WT Ritz, L Rush, AJ Stegman, D Warden, D Trivedi, MH Wisniewski, SR AF Cook, Ian A. Balasubramani, G. K. Eng, Heather Friedman, Edward Young, Elizabeth A. Martin, Jeff Nay, William T. Ritz, Louise Rush, A. John Stegman, Diane Warden, Diane Trivedi, Madhukar H. Wisniewski, Stephen R. TI Electronic source materials in clinical research: Acceptability and validity of symptom self-rating in major depressive disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; computer; assessment; clinical trial; acceptability; informatics ID SEQUENCED TREATMENT ALTERNATIVES; STAR-ASTERISK-D; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; SCALE; IDS; QUESTIONNAIRE; RATIONALE AB Objectives: Clinical research projects gather large amounts of data. Typically, information is captured on paper source documents for later transcription to an electronic format, where responses can be checked, and errors, omissions, and inconsistencies can be resolved. These steps contribute delays, cost, and complexity to clinical research, particularly in large-scale multi-site investigations. To address these issues, we used a mobile computing device with a touch-screen display ("tablet PC") to capture clinical data from depressed patients directly into electronic format. We then examined ease of use, the equivalence of responses between paper and electronic methods, and the acceptability of the tablet PC for this clinical population. Settings: Outpatient clinics at four medical centers. Methods: 80 adults with major depressive disorder (MDD) completed the 16-item Quick Inventory of Depressive Symptomatology Self-Rated (QIDS-SR16), using both traditional paper forms and an electronic representation of the same questions; participants also completed a survey to evaluate their experience. Results: QIDS-SR16 responses from paper and electronic versions were highly correlated (mean total: 15.3 (SD = 5.2) electronic vs. 15.1 (SD = 5.2) paper format), and showed high inter-rating reliability for overall score (intra-class correlation 0.987 (with a 95%CI [0.979,0.992])) and high degree of association for individual symptom items. Participants found both methods acceptable and overall found the electronic implementation easier to use. Conclusions: QIDS-SR16 values collected electronically from research participants were equivalent to those collected using traditional paper self-assessment forms. Participants with MDD found the tablet PC version to be acceptable and easier to use than the paper forms. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA. NIMH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75216 USA. RP Cook, IA (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM icook@ucla.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01 MH 90003] NR 28 TC 16 Z9 17 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2007 VL 41 IS 9 BP 737 EP 743 DI 10.1016/j.jpsychires.2006.07.015 PG 7 WC Psychiatry SC Psychiatry GA 173NK UT WOS:000246879600003 PM 17275840 ER PT J AU Nelson, DE Reynolds, JH Luke, DA Mueller, NB Eischen, MH Jordan, J Lancaster, RB Marcus, SE Vallone, D AF Nelson, David E. Reynolds, Jennifer H. Luke, Douglas A. Mueller, Nancy B. Eischen, Monica H. Jordan, Jerelyn Lancaster, R. Brick Marcus, Stephen E. Vallone, Donna TI Successfully maintaining program funding during trying times: Lessons from tobacco control programs in five states SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE health promotion; public health; tobacco AB Despite negative financial conditions in recent years, several states were able to successfully maintain funding for tobacco prevention and control, which provided an opportunity to understand the factors associated with success. One explanation may be the level of long-term program sustainability in some states, According to a model developed by Saint Louis University researchers, the five elements critical to tobacco control sustainability are state political and financial climate; community awareness and capacity; program structure and administration; funding stability and planning; and surveillance and evaluation. Five states (Nebraska, New York, Indiana, Virginia, and Colorado) maintained funding for their tobacco control programs. Four of these states gained additional legislative appropriations or prevented a massive reduction; Colorado used a statewide ballot initiative to increase funding. On the basis of the sustainability framework, case studies, and prior research, the major lessons learned for maintaining funding were the importance of (1) strong and experienced leadership, (2) broad and deep organizational and community ties, (3) coordinated efforts, (4) strategic use of surveillance and evaluation data, (5) active dissemination of information about program successes, and (6) policy maker champions. The sustainability framework and lessons learned may provide valuable insights for other public health programs facing funding threats. C1 Ctr Dis Control & Prevent, Off Smoking & Hlth, Atlanta, GA 30341 USA. St Louis Univ, Sch Publ Hlth, Ctr Tobacco Policy Res, St Louis, MO 63103 USA. Natl Canc Inst, Bethesda, MD USA. Amer Legacy Fdn, Washington, DC USA. RP Nelson, DE (reprint author), Ctr Dis Control & Prevent, Off Smoking & Hlth, 4770 Buford Highway,NE Mailstop K-50, Atlanta, GA 30341 USA. EM den2@cdc.gov OI Luke, Douglas/0000-0003-1332-8569 NR 18 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD NOV-DEC PY 2007 VL 13 IS 6 BP 612 EP 620 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223DD UT WOS:000250348900013 PM 17984716 ER PT J AU Farley, JH Harlan, LC Clegg, LX Larsen, WI Trimble, EL AF Farley, John H. Harlan, Linda C. Clegg, Limin X. Larsen, Wilma I. Trimble, Edward L. TI Patterns of care for cervical cancer patients treated in the US military health care system SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE cervix cancer; chemotherapy; National Institutes of Health; radiotherapy ID CONCURRENT CHEMOTHERAPY; RADIATION-THERAPY; CARCINOMA; SURVIVAL; CHEMORADIOTHERAPY; CHEMORADIATION; CISPLATIN AB OBJECTIVE: To determine whether women diagnosed with cervical cancer within the U.S. Department of Defense (DOD) Military Health Care System received treatment within standard guidelines and whether survival was influenced by Implementation of these guidelines. STUDY DESIGN: We identified 621 women treated from 1994 to 2002. Guideline therapy was defined as hysterectomy or radiation for FIGO stage <= IB, and hysterectomy or chemoradiation for advanced localized FIGO stage > IB. Survival analysis was performed using Cox Proportional Hazards models. RESULTS: Of those 621 women, 25% received no surgery, while 41 % received radiation therapy. 6 % of all patients received chemoradiation therapy prior to the Clinical Announcement received versus 26% of patients after the announcement. Variables associated with significant increased risk of death were advanced age, advanced stage and poorly differentiated lesions, p < 0.01. The lack of guideline therapy was associated with an increased risk of death, p < 0.005. Those patients who did not receive guideline therapy were twice as likely to die (HR 2.11, p = 0.005). CONCLUSION: Our study suggests that chemoradiation was rapidly introduced in the DOD care system after the 1999 National Cancer Institute's Clinical Announcement. However, some patients did not receive guideline therapy. C1 Tripler Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Dept Clin Invest, Div Gynecol Oncol, Honolulu, HI 96859 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Farley, JH (reprint author), Tripler Army Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 1 Jarrett White Rd, Honolulu, HI 96859 USA. EM john.farley@amedd.army.mil NR 15 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD NOV PY 2007 VL 52 IS 11 BP 1040 EP 1045 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 235HE UT WOS:000251223500011 PM 18161403 ER PT J AU Hu, PQ Hurwitz, AA Oppenheim, MJ AF Hu, Paul Q. Hurwitz, Arthur A. Oppenheim, Joost J. TI Immunization with DNA topoisomerase I induces autoimmune responses but not scleroderma-like pathologies in mice SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE DNA topoisomerase I; antibody; autoimmunity; skin; systemic sclerosis ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TIGHT-SKIN MOUSE; T-CELLS; RHEUMATOID-ARTHRITIS; SCLEROSIS SCLERODERMA; ANTIBODY-LEVELS; MURINE LUPUS; AUTOANTIBODIES; SERUM; EPITOPES AB Objective. Anti-DNA topoisomerase I (anti-topo-I) antibody is a marker of systemic sclerosis (SSc). Anti-topo-I antibody levels are positively correlated with both disease severity and activity. However, its pathogenic role in SSc remains unclear. We investigated whether induction of an autoreactive antibody response is directly pathogenic in mice. Methods. Autoimmune responses were induced in mice immunized with human recombinant topo-I (rhutopo-I). Both Immoral and T cell-mediated autoimmune responses were assessed. Necropsy analyses were performed to determine pathologic changes in immunized mice. Results. Autoimmune prone SJL and non-obese diabetic mice developed higher Immoral autoreactive responses against mouse topo-I than did BALB/c and C56BL/6 mice. Splenic T cells also showed proliferative responses and interferon-gamma secretion in response to rhutopo-I. However, serum anti-topo-I antibody levels declined 2 months after the initial immunization. Neither weight loss nor dermal thickening was observed in mice during a followup period of 9 months. Whole-body necropsy analyses, including skin, lung, heart, kidney, gastrointestinal tract, and joints, showed no typical findings of human SSc. Coadministration of anti-CD25 and anti-CTLA-4 antibody with the initial immunization resulted in higher titers of anti-topo-I antibody, but these mice also did not develop SSc-like pathologic features. Development of an anti-topo-I response was not associated with acceleration of the recognized abnormalities in tight-skin mice. Conclusion. Although tolerance was broken and anti-topo-I antibody was induced by immunization with rhutopo-I in mice, induction of this antibody was not sufficient to induce SSc-like disease. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Oppenheim, MJ (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick Canc Res & Dev Ctr, Bldg 560,Room 21-89, Frederick, MD 21702 USA. FU Intramural NIH HHS NR 46 TC 7 Z9 8 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2007 VL 34 IS 11 BP 2243 EP 2252 PG 10 WC Rheumatology SC Rheumatology GA 228WT UT WOS:000250764000021 PM 17937466 ER PT J AU Dasgupta, A Self, SG Gupta, SD AF Dasgupta, Abhijit Self, Steven G. Gupta, Somesh Das TI Non-identifiable parametric probability models and reparametrization SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE parametric identifiability; reparametrization; statistical inference; mixture model AB Identifiability is a primary assumption in virtually all classical statistical theory. However, such an assumption may be violated in a variety of statistical models. We consider parametric models where the assumption of identifiability is violated, but otherwise satisfy standard assumptions. We propose an analytic method for constructing new parameters under which the model will be at least locally identifiable. This method is based on solving a system of linear partial differential equations involving the Fisher information matrix. Some consequences and valid inference procedures under non-identifiability have been discussed. The method of reparametrization is illustrated with an example. (C) 2007 Elsevier B.V. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Indian Natl Sci Acad, New Delhi, India. RP Dasgupta, A (reprint author), 6120 Execut Blvd,Room 8044, Bethesda, MD 20892 USA. EM Abhijit.Dasgupta@mail.jci.tju.edu NR 34 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV 1 PY 2007 VL 137 IS 11 BP 3380 EP 3393 DI 10.1016/j.jspi.2007.03.018 PG 14 WC Statistics & Probability SC Mathematics GA 205UM UT WOS:000249140100017 ER PT J AU Zanuy, D Rodriguez-Ropero, F Nussinov, R Aleman, C AF Zanuy, David Rodriguez-Ropero, Francisco Nussinov, Ruth Aleman, Carlos TI Testing beta-helix terminal coils stability by targeted substitutions with non-proteogenic amino acids: A molecular dynamics study SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE beta-helix proteins; beta-sheet conformation; structural motifs; unnatural synthetic amino acids; nanotechnological applications; Oligopeptides; molecular dynamics; peptide nanotubes ID PROTEIN BUILDING-BLOCKS; NANOSTRUCTURE DESIGN; ALPHA-AMINO; CONFORMATION; PEPTIDES; RESIDUES; DEHYDROALANINE; DIPEPTIDES; ENERGIES; HAIRPIN AB The search for new building block templates useful for nanostructures design, targets protein motifs with a wide range of structures. Stabilizing these building blocks when extracted from their natural environment becomes a fundamental goal in order to successfully control their assembly. Targeted replacements of natural residues by conformationally constrained amino acids were shown to be a successful strategy to achieve such stabilization. In this work, the effect of replacing natural amino acids by non-proteogenic residues in a Phelix building block has been evaluated using extensive molecular dynamics simulations. Here, we focus on systematic substitutions of valine residues present in P-sheet segments of a beta-helical building block excised from Escherichia coli galactoside acetyltransferase, residues 131-165. Four different types of non-proteogenic amino acids have been considered for substitution: (i) one dehydroamino acid, (ii) two beta-amino acids, (iii) one P-amino acid and (iv) two alpha,alpha-dialkylamino acids. Our results indicate that the ability of non-proteogenic amino acids to stabilize small building block motifs is site-dependent. We conclude that if the replacement does not alter the energy balance between attractive non-covalent interactions and steric hindrance, synthetic residues are suitable candidates to nucleate P-helix formation. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Politecn Cataluna, ETS Eng Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain. NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. RP Zanuy, D (reprint author), Univ Politecn Cataluna, ETS Eng Ind Barcelona, Dept Engn Quim, Diagonal 647, E-08028 Barcelona, Spain. RI Rodriguez-Ropero, Francisco/F-2458-2011; Zanuy, David/G-3930-2014 OI Rodriguez-Ropero, Francisco/0000-0001-7435-8986; Zanuy, David/0000-0001-7704-2178 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 39 TC 7 Z9 7 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD NOV PY 2007 VL 160 IS 2 BP 177 EP 189 DI 10.1016/j.jsb.2007.07.014 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 224OM UT WOS:000250456300007 PM 17897839 ER PT J AU Novak, MF Kenney, C Suomi, SJ Ruppenthal, GC AF Novak, Matthew Fsx Kenney, Caroline Suomi, Stephen J. Ruppenthal, Gerald C. TI Use of animal-operated folding perches by rhesus macaques (Macaca mulatta) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID ENVIRONMENTAL ENRICHMENT; CORTISOL RESPONSES; BONNET MACAQUES; PUZZLE FEEDERS; MONKEYS; MIRRORS; CHIMPANZEES; MOTIVATION; BEHAVIOR AB Providing captive or laboratory animals with the best possible living conditions has led to many ideas about how caging environments can be enhanced and the animals' lives can be enriched. This study focused primarily on 2 issues: more efficient use of existing caging and providing animals with a measure of control over their environments. We designed a new spring-loaded folding perching apparatus that, when modified for size, could be added to almost any caging system. Experiment 1 measured usage by animals in standard laboratory caging for rhesus macaque monkeys (Macaca mulatta). Experiment 2 measured usage by this same species in social groups in a 5-acre outdoor-indoor field setting, where several other forms of enrichment were available to the animals. Results indicated that the folding perches were used in both environments. Animals quickly learned to fold down the devices to use as a place to perch, even in the presence of permanent fixed perches. The folding perches did not significantly affect existing behavioral repertoires, but they altered how the animal used the cage. Increased animal presence near folding perches during experiment 2 suggests that these devices actually were preferred. The preference results can only partially be explained by novelty. The folding perches afforded animals a measure of control over their immediate environment without interfering in research or animal care efforts. Including at least 1 folding perch per cage satisfies both the letter and the spirit of regulations on environmental enhancement for captive primates. C1 [Novak, Matthew Fsx; Kenney, Caroline; Suomi, Stephen J.; Ruppenthal, Gerald C.] NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20839 USA. RP Novak, MF (reprint author), NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20839 USA. EM novakm@mail.nih.gov FU Intramural NIH HHS NR 37 TC 1 Z9 1 U1 3 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2007 VL 46 IS 6 BP 35 EP 43 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 258IX UT WOS:000252862700005 PM 17994671 ER PT J AU Tanumihardjo, SA Anderson, C Kalifer-Horwitz, M Bode, L Emenaker, NJ Haqq, AM Satia, JA Silver, HJ Stadler, DD AF Tanumihardjo, Sherry A. Anderson, Cheryl Kalifer-Horwitz, Martha Bode, Lars Emenaker, Nancy J. Haqq, Andrea M. Satia, Jessie A. Silver, Heidi J. Stadler, Diane D. TI Poverty, obesity, and malnutrition: An international perspective recognizing the paradox SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Review ID VITAMIN-A STATUS; FOOD INSECURITY; IRON SUPPLEMENTATION; ENERGY DENSITY; UNITED-STATES; NUTRITION; CHILDREN; INCOME; WOMEN; PREVALENCE AB In the year 2000, multiple global health agencies and stakeholders convened and established eight tenets that, if followed. would make our world a vastly better place. These tenets are called the Millennium Development Goals. Most of these goals are either directly or indirectly related to nutrition. The United Nations has led an evaluation team to monitor and assess the progress toward achieving these goals until 2015. We are midway between when the goals were set and the year 2015. The first goal is to "eradicate extreme poverty and hunger." Our greatest responsibility as nutrition professionals is to understand the ramifications of poverty, chronic hunger, and food insecurity. Food insecurity is complex, and the paradox is that not only can it lead to undernutrition and recurring hunger, but also to overnutrition, which can lead to overweight and obesity. It is estimated that by the year 201.5 noncommunicable diseases associated with overnutrition will surpass undernutrition as the leading causes of death in low-income communities. Therefore, we need to take heed of the double burden of malnutrition caused by poverty, hunger, and food insecurity. Informing current practitioners, educators, and policymakers and passing this information on to future generations of nutrition students is of paramount importance. C1 Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Fdn Mexicana Salud, Mexico City, DF, Mexico. Burnham Inst Med Res, La Jolla, CA USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Dept Nutr & Epidemiol, Chapel Hill, NC USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Tanumihardjo, SA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA. EM sherry@nutrisci.wisc.edu RI Kaufer-Horwitz, Martha/A-3789-2015; OI Kaufer-Horwitz, Martha/0000-0003-3489-6899; Stadler, Diane/0000-0002-4718-2054 FU NCRR NIH HHS [K23 RR 021979-03]; NHLBI NIH HHS [K01 HL092595] NR 49 TC 92 Z9 97 U1 4 U2 55 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2007 VL 107 IS 11 BP 1966 EP 1972 DI 10.1016/j.jada.2007.08.007 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 227IU UT WOS:000250651200019 PM 17964317 ER PT J AU Alley, DE Crimmins, E Bandeen-Roche, K Guralnik, J Ferrucci, L AF Alley, Dawn E. Crimmins, Eileen Bandeen-Roche, Karen Guralnik, Jack Ferrucci, Luigi TI Three-year change in inflammatory markers in elderly people and mortality: The Invecchiare in Chianti study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; epidemiology; interleukins ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; OLDER PERSONS; CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATION; PHYSICAL-ACTIVITY; SERUM-LEVELS; HEALTH; RISK; VARIABILITY AB OBJECTIVES: To describe changes in interleukin-6 (IL-6) and C-reactive protein (CRP) and to determine how changes are related to mortality in elderly people. DESIGN: Prospective cohort study. SETTING: Two communities in the Tuscany region of Italy. PARTICIPANTS: Randomly selected residents aged 65 and older who participated in the first two waves of data collection (N=736). MEASUREMENTS: Two serum measurements of IL-6 and CRP taken 3 years apart. Mortality was observed for the 3 years after the second measurement; 79 deaths were observed in 2,079 person-years. RESULTS: Correlations indicated marginal to moderate stability in IL-6 and CRP, with clinical categories remaining relatively stable over time. Baseline levels were not related to mortality between follow-up Years 3 and 6, but increases in IL-6 and CRP predicted 3- to 6-year mortality. Controlling for follow-up IL-6 and CRP attenuated the relationship between inflammatory changes and mortality, but increases in CRP continued to increase odds of mortality. After controlling for sociodemographic characteristics, biological risk factors, health behaviors, and disease at both times, increases in CRP, but not IL-6, were related to mortality. Odds of death were more than three times as great in subjects in whom any CRP increase was observed (odds ratio=3.10, 95% confidence interval=1.25-7.68) as in subjects with stable or declining CRP. CONCLUSION: CRP and IL-6 levels within individuals vary over time, and increases in CRP are associated with greater mortality risk. Three-year changes in inflammatory markers are better predictors of mortality than baseline measures. C1 Univ Penn, Robert Wood Johnson Fdn Hlth & Soc Scholars Progr, Philadelphia, PA 19104 USA. Univ So Calif, Davis Sch Gerontol, Los Angeles, CA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Alley, DE (reprint author), Univ Penn, Robert Wood Johnson Fdn Hlth & Soc Scholars Progr, 3641 Locust Walk,Suite 302, Philadelphia, PA 19104 USA. EM alley@wharton.upenn.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [P30 AG017265, T32AG00037, T32 AG000037, N01-AG-821336, N01-AG-916413, P30AG17265]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 33 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2007 VL 55 IS 11 BP 1801 EP 1807 DI 10.1111/j.1532-5415.2007.01390.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 225YB UT WOS:000250553100014 PM 17727645 ER PT J AU Lang, IA Guralnik, JM Melzer, D AF Lang, Iain A. Guralnik, Jack M. Melzer, David TI Physical activity in middle-aged adults reduces risks of functional impairment independent of its effect on weight SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE exercise; excess body weight; mobility; Short Physical Performance Battery; middle-aged ID LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; PERFORMANCE BATTERY; ELDERLY-PEOPLE; SELF-REPORT; DISABILITY; MORTALITY; HEALTH; EXERCISE; WOMEN AB OBJECTIVES: To assess the association between physical activity and subsequent physical functioning in middle-aged adults across a range of body mass index (BMI) categories. DESIGN: Prospective nationally representative cohort studies. SETTING: The United States and England. PARTICIPANTS: Eight thousand seven hundred two individuals in the United States and 1,507 in England aged 50 to 69 and free of impairment at baseline, followed up for 6 years. MEASUREMENTS: Self-reported and measured BMI and self-reported level of physical activity. Outcome measures were score on a physical performance battery and self-reported mobility impairment. RESULTS: In both studies, being overweight and being obese were associated with greater risk of impairment (than being of recommended weight). In all weight categories and both countries, higher levels of physical activity were associated with lower risks of mobility impairment. For example, U.S. respondents of recommended weight (BMI 20-25) who were active on 3 or more days per week had a relative risk (RR) of incident mobility difficulties, compared with those who were less active, of 0.56 (95% confidence interval (CI)=0.40-0.78); for those who were obese (BMI >= 30) the corresponding RR was 0.59 (95% CI=0.45-0.76). CONCLUSION: Excess bodyweight is a risk factor for impaired physical function in middle-aged and older people. Physical activity is protective of impaired physical functioning in this age group in subjects with recommended weight, overweight, and obesity. Older adults should be encouraged to engage in appropriate levels of physical activity irrespective of their weight. C1 Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter EX2 5DW, Devon, England. NIA, Bethesda, MD 20892 USA. RP Lang, IA (reprint author), Peninsula Med Sch, Epidemiol & Publ Hlth Grp, RD&E Hosp Site,Barrack Rd, Exeter EX2 5DW, Devon, England. EM iain.lang@pms.ac.uk RI Lang, Iain/B-8255-2008; OI Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS; NIA NIH HHS [R03-AG022912-01] NR 30 TC 42 Z9 42 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2007 VL 55 IS 11 BP 1836 EP 1841 DI 10.1111/j.1532-5415.2007.01426.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 225YB UT WOS:000250553100019 PM 17979901 ER PT J AU Sneiderman, CA Demner-Fushman, D Fiszman, M Ide, NC Rindflesch, TC AF Sneiderman, Charles A. Demner-Fushman, Dina Fiszman, Marcelo Ide, Nicholas C. Rindflesch, Thomas C. TI Knowledge-based methods to help clinicians find answers in MEDLINE SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID MEDICAL LITERATURE; BIOMEDICAL TEXT; USERS GUIDES; PRIMARY-CARE; QUESTIONS; INFORMATION; RELEVANCE; FEEDBACK; ACCESS AB Objectives: Large databases of published medical research can support clinical decision making by providing physicians with the best available evidence. The time required to obtain optimal results from these databases using traditional systems often makes accessing the databases impractical for clinicians. This article explores whether a hybrid approach of augmenting traditional information retrieval with knowledge-based methods facilitates finding practical clinical advice in the research literature. Design: Three experimental systems were evaluated for their ability to find MEDLINE citations providing answers to clinical questions of different complexity. The systems (SemRep, Essie, and CQA-1.0), which rely on domain knowledge and semantic processing to varying extents, were evaluated separately and in combination. Fifteen therapy and prevention questions in three categories (general, intermediate, and specific questions) were searched. The first 10 citations retrieved by each system were randomized, anonymized, and evaluated on a three-point scale. The reasons for ratings were documented. Measurements: Metrics evaluating the overall performance of a system (mean average precision, binary preference) and metrics evaluating the number of relevant documents in the first several presented to a physician were used. Results: Scores (mean average precision = 0.57, binary preference = 0.71) for fusion of the retrieval results of the three systems are significantly (p < 0.01) better than those for any individual system. All three systems present three to four relevant citations in the first five for any question type. Conclusion: The improvements in finding relevant MEDLINE citations clue to knowledge-based processing show promise in assisting physicians to answer questions in clinical practice. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. Univ Tennessee, Grad Sch Med, Knoxville, TN USA. RP Sneiderman, CA (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM charlie@nlm.nih.gov FU Intramural NIH HHS NR 55 TC 17 Z9 17 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 772 EP 780 DI 10.1197/jamia.M2407 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 237ME UT WOS:000251377300012 PM 17712086 ER PT J AU Hauser, SE Demner-Fushman, D Jacobs, JL Humphrey, SM Ford, G Thoma, GR AF Hauser, Susan E. Demner-Fushman, Dina Jacobs, Joshua L. Humphrey, Susanne M. Ford, Glenn Thoma, George R. TI Using wireless handheld computers to seek information at the point of care: An evaluation by clinicians SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID SYSTEM; PDAS AB Objective: To evaluate: (1) the effectiveness of wireless handheld computers for online information retrieval in clinical settings; (2) the role of MEDLINE (R) in answering clinical questions raised at the point of care. Design: A prospective single-cohort study: accompanying medical teams on teaching rounds, five internal medicine residents used and evaluated MD on Tap, an application for handheld computers, to seek answers in real time to clinical questions arising at the point of care. Measurements: All transactions were stored by an intermediate server. Evaluators recorded clinical scenarios and questions, identified MEDLINE citations that answered the questions, and submitted daily and summative reports of their experience. A senior medical librarian corroborated the relevance of the selected citation to each scenario and question. Results: Evaluators answered 68% of 363 background and foreground clinical questions during rounding sessions using a variety of MD on Tap features in an average session length of less than four minutes. The evaluator, the number and quality of query terms, the total number of citations found for a query, and the use of auto-spellcheck significantly contributed to the probability of query success. Conclusion: Handheld computers with Internet access are useful tools for healthcare providers to access MEDLINE in real time. MEDLINE citations can answer specific clinical questions when several medical terms are used to form a query. The MD on Tap application is an effective interface to MEDLINE in clinical settings, allowing clinicians to quickly find relevant citations. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, DHHS, Bethesda, MD 20894 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Demner-Fushman, D (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, DHHS, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ddemner@mail.nih.gov FU Intramural NIH HHS NR 22 TC 16 Z9 16 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 807 EP 815 DI 10.1197/jamia.M2424 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 237ME UT WOS:000251377300016 PM 17712085 ER PT J AU McKenzie, LM Hendrickson, SL Briggs, WA Dart, RA Korbet, SM Mokrzycki, MH Kimmel, PL Ahuja, TS Berns, JS Simon, EE Smith, MC Trachtman, H Michel, DM Schelling, JR Cho, M Zhou, YC Binns-Roemer, E Kirk, GD Kopp, JB Winkler, CA AF McKenzie, Louise M. Hendrickson, Sher L. Briggs, William A. Dart, Richard A. Korbet, Stephen M. Mokrzycki, Michelle H. Kimmel, Paul L. Ahuja, Tejinder S. Berns, Jeffrey S. Simon, Eric E. Smith, Michael C. Trachtman, Howard Michel, Donna M. Schelling, Jeffrey R. Cho, Monique Zhou, Yu C. Binns-Roemer, Elizabeth Kirk, Gregory D. Kopp, Jeffrey B. Winkler, Cheryl A. TI NPHS2 variation in sporadic focal segmental glomerulosclerosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RESISTANT NEPHROTIC SYNDROME; STAGE RENAL-DISEASE; HAPLOTYPE RECONSTRUCTION; PODOCIN MUTATIONS; POPULATION; GENE; CHILDREN; R229Q AB Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3' untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR = 4.9, P = 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in European-Americans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR = 0.5, P = 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS. C1 NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Marshfield Clin Fdn Med Res & Educ, Dept Hypertens & Nephrol, Marshfield, WI 54449 USA. Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. Albert Einstein Coll Med, Div Nephrol, New York, NY USA. George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Washington, DC USA. Univ Texas, Med Branch, Dept Med, Div Nephrol, Galveston, TX 77550 USA. Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Tulane Univ, Sch Med, Nephrol Sect, New Orleans, LA 70112 USA. Univ Hosp Cleveland, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. Schneider Childrens Hosp N Shore Long Isl Jewish, New Hyde Pk, NY USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. NIDDK, NIH, Kidney Dis Sect, Dept Hlth & Human Serv, Bethesda, MD USA. Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Kopp, JB (reprint author), NCI, SAIC Frederick, Lab Genom Divers, Bldg 560, Frederick, MD 21702 USA. EM jeffreyk@intra.niddk.nih.gov; winkler@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; OI Trachtman, Howard/0000-0001-7447-9489; Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIDA NIH HHS [DA-04334, R01 DA004334, R37 DA004334, R56 DA004334] NR 29 TC 30 Z9 34 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2007 VL 18 IS 11 BP 2987 EP 2995 DI 10.1681/ASN.2007030319 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 228NW UT WOS:000250737600028 PM 17942957 ER PT J AU Unverzagt, FW Kasten, L Johnson, KE Rebok, GW Marsiske, M Koepke, KM Elias, JW Morris, JN Willis, SL Ball, K Rexroth, DF Smith, DM Wolinsky, FD Tennstedt, SL AF Unverzagt, Frederick W. Kasten, Linda Johnson, Kathy E. Rebok, George W. Marsiske, Michael Koepke, Kathy Mann Elias, Jeffrey W. Morris, John N. Willis, Sherry L. Ball, Karlene Rexroth, Daniel F. Smith, David M. Wolinsky, Fredric D. Tennstedt, Sharon L. TI Effect of memory impairment on training outcomes in ACTIVE SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE cognition; memory; mild cognitive impairment; aging; therapeutics; clinical trial; psychological technique ID MILD COGNITIVE IMPAIRMENT; OLDER-ADULTS; ALZHEIMER-DISEASE; PRIMARY-CARE; PREVALENCE; INTERVENTION; DEMENTIA; HEALTH; TRIAL; RISK AB Cognitive training improves mental abilities in older adults, but the trainability of persons with memory impairment is unclear. We conducted a subgroup analysis of subjects in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial to examine this issue. ACTIVE enrolled 2802 non-demented, community-dwelling adults aged 65 years and older and randomly assigned them to one of four groups: Memory training, reasoning training, speed-of-processing training, or no-contact control. For this study, participants were defined as memory-impaired if baseline Rey Auditory Verbal Learning Test (AVLT) sum recall score was 1.5 SD or more below predicted AVLT sum recall score from a regression-derived formula using age, education, ethnicity, and vocabulary from all subjects at baseline. Assessments were taken at baseline (BL), post-test, first annual (A1), and second annual (A2) follow-up. One hundred and ninety-three subjects were defined as memory-impaired and 2580 were memory-normal. Training gain as a function memory status (impaired vs. normal) was compared in a mixed effects model. Results indicated that memory-impaired participants failed to benefit from Memory training but did show normal training gains after reasoning and speed training. Memory function appears to mediate response to structured cognitive interventions in older adults. C1 Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. New England Res Inst, Watertown, MA 02172 USA. Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46205 USA. Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. NINR, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. Hebrew Senior Life, Boston, MA USA. Penn State Univ, Dept Human Dev & Family Studies, State Coll, PA USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Univ Iowa, Dept Hlth Management & Policy, Iowa City, IA USA. RP Unverzagt, FW (reprint author), Indiana Univ, Sch Med, Dept Psychiat, 1111 W 10th St,Suite PB 218A, Indianapolis, IN 46202 USA. EM funverza@iupi.edu RI Wolinsky, Fredric/F-9231-2011; OI Marsiske, Michael/0000-0001-5973-2116; Wolinsky, Fredric/0000-0002-0916-4955 FU NIA NIH HHS [R01 AG14282, R01 AG014276, R01 AG026096, R01 AG026096-04, R01 AG14260, R01 AG14263, R01 AG14289, U01 AG014260, U01 AG014263, U01 AG014276, U01 AG014282, U01 AG014289]; NINR NIH HHS [R01 NR04507, R01 NR04508, U01 NR004507, U01 NR004508, U01 NR004508-10] NR 33 TC 58 Z9 62 U1 3 U2 20 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2007 VL 13 IS 6 BP 953 EP 960 DI 10.1017/S1355617707071512 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 227GK UT WOS:000250645000005 PM 17942013 ER PT J AU Espinoza, J Hassan, SS Gotsch, F Kusanovic, JP Lee, W Erez, O Goncalves, LF Schoen, ML Romero, R AF Espinoza, Jimmy Hassan, Sonia S. Gotsch, Francesca Kusanovic, Juan Pedro Lee, Wesley Erez, Offer Goncalves, Luis F. Schoen, Mary Lou Romero, Roberto TI A systematic approach to the use of the multiplanar display in evaluation of abnormal vascular connections to the fetal heart using 4-dimensional ultrasonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE congenital heart disease; fetal echocardiography; prenatal diagnosis; spatiotemporal; spatiotemporal image correlation; vascular connections ID SPATIOTEMPORAL IMAGE CORRELATION; POWER DOPPLER ULTRASONOGRAPHY; 3-DIMENSIONAL ULTRASONOGRAPHY; B-FLOW; PULMONARY-ARTERIES; INVERSION MODE; CORONARY-SINUS; ECHOCARDIOGRAPHY; DEFECTS; ANATOMY AB Objective. The multiplanar display is a modality that allows the simultaneous visualization of 3 orthogonal planes from volume data sets obtained with 3- and 4-climensional ultrasonography, Simultaneous display of standard views used in fetal echocardiography and their orthogonal planes may provide novel ultrasonographic views for examination of the fetal heart and its vascular connections. This study was designed to determine the clinical utility of the multiplanar display in the examination of abnormal vascular connections to the fetal heart. Methods. We reviewed 4-climensional volume data sets, acquired with the spatiotemporal image correlation technique, from patients with abnormal vascular connections to the fetal heart. Multiplanar views of the fetal heart were used to simultaneously display standard planes used in fetal echocardiography and their corresponding orthogonal planes. Results. This study included 4 volume data sets from fetuses with confirmed abnormal vascular connections to the heart, including: (1) an interrupted inferior vena cava with azygos or hemiazygos vein continuation; (2) a persistent left superior vena cava draining into a dilated coronary sinus; and (3) a dilated superior vena cava associated with a thoracic lymphangionna. Simultaneous visualization of orthogonal planes displaying abnormal vascular connections to the fetal heart facilitated identification of the abnormal vessels and their spatial relationships with other vascular structures. Conclusions. Multiplanar imaging can be used to assess abnormal vascular connections to the fetal heart and may provide novel ultrasonographic planes for fetal echocardiography using 3- and 4-dimensional ultrasonography. C1 Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS,Dept Hlth & Human Serv, Detroit, MI 48201 USA. NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. RP Espinoza, J (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD NIH DHHS,Dept Hlth & Human Serv, 3990 John R,Box 4, Detroit, MI 48201 USA. EM jespinoz@med.wayne.edu FU Intramural NIH HHS [Z01 HD002401-15] NR 35 TC 10 Z9 10 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2007 VL 26 IS 11 BP 1461 EP 1467 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 227EH UT WOS:000250639500001 PM 17957040 ER PT J AU Santolaya-Forgas, J Schoff, P Romero, R AF Santolaya-Forgas, Joaquin Schoff, Patrick Romero, Roberto TI Visual display of prenatal ultrasonographic examinations SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Letter ID UTEROPLACENTAL BLOOD-FLOW; FETAL C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Fetal Med & Prenatal Genet, Boston, MA 02115 USA. NICHHD, NIH, Perinatol Res Branch, Dept Hlth & Human Serv, Detroit, MI USA. RP Santolaya-Forgas, J (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Fetal Med & Prenatal Genet, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2007 VL 26 IS 11 BP 1633 EP 1634 PG 2 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 227EH UT WOS:000250639500021 PM 17957060 ER PT J AU Johnson, TM Burrows, PK Kusek, JW Nyberg, LM Tenover, JL Lepor, H Roehrborn, CG AF Johnson, Theodore M., II Burrows, Pamela K. Kusek, John W. Nyberg, Leroy M. Tenover, J. Lisa Lepor, Herbert Roehrborn, Claus G. CA Med Therapy Prostatic Symptoms Res TI The effect of doxazosin, Finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia SO JOURNAL OF UROLOGY LA English DT Article DE nocturia; prostatic hyperplasia; adrenergic alpha-antagonists; finasteride ID URINARY-TRACT SYMPTOMS; ELDERLY-MEN; TRIAL; TAMSULOSIN; TERAZOSIN; EFFICACY AB Purpose: We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Materials and Methods: A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. Results: Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at I year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p < 0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p < 0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p < 0.05). Conclusions: Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride. C1 Atlanta Vet Affairs Med Ctr, Birmingham Atlanta Geriat Res Educ & Clin Ctr, Decatur, GA 30033 USA. Emory Univ, Div Geriatr Med & Gerontol, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Emory Univ Ctr Hlth Aging, Atlanta, GA 30322 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. NIDDK, NIH, Bethesda, MD USA. NYU, Med Ctr, Dept Urol, New York, NY 10016 USA. NYU, Med Ctr, Dept Pharmacol, New York, NY 10016 USA. Univ Texas SW, Dept Urol, Dallas, TX USA. RP Johnson, TM (reprint author), Atlanta Vet Affairs Med Ctr, Birmingham Atlanta Geriat Res Educ & Clin Ctr, 508-11B,1670 Clarimont Rd, Decatur, GA 30033 USA. FU NIDDK NIH HHS [U01 DK49960, U01 DK41418, U01 DK46416, U01 DK46429, U01 DK46431, U01 DK46437, U01 DK46468, U01 DK46472, U01 DK49880, U01 DK49912, U01 DK49951, U01 DK49954, U01 DK49963, U01 DK49971, U01 DK49977]; PHS HHS [U01 49980] NR 20 TC 40 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2007 VL 178 IS 5 BP 2045 EP 2050 DI 10.1016/j.juro.2007.07.013 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 220WC UT WOS:000250187000061 PM 17869295 ER PT J AU Farci, P Chessa, L Balestrieri, C Serra, G Lai, ME AF Farci, P. Chessa, L. Balestrieri, C. Serra, G. Lai, M. E. TI Treatment of chronic hepatitis D SO JOURNAL OF VIRAL HEPATITIS LA English DT Article; Proceedings Paper CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan-Amer Soc Clin Virol, European Soc Clin Virol DE chronic hepatitis D; hepatitis B virus; hepatitis D virus; nucleoside analogues; pegylated interferon-alpha; quantification; of HDV RNA; standard interferon-alpha; treatment ID CHRONIC DELTA-HEPATITIS; RANDOMIZED CONTROLLED TRIAL; POLYMERASE-CHAIN-REACTION; D VIRUS-INFECTION; PEGYLATED INTERFERON-ALPHA-2B; COMBINATION THERAPY; 12-MONTH COURSE; SELF-CLEAVAGE; RNA; LAMIVUDINE AB Despite recent advances in the treatment of chronic viral hepatitis, therapy of chronic hepatitis D is not yet satisfactory. The only option currently available is interferon-alpha (IFN), whose efficacy is related to the dose and duration of treatment, However, the rate of sustained hepatitis D virus (HDV) clearance after a 1-year course with high doses of standard IFN is low. Better results have recently been reported with pegylated IFN both in IFN-naive and in previous nonresponders to standard IFN, suggesting the use of pegylated IFN as a first-line therapy in chronic hepatitis D. Nucleoside analogues that inhibit hepatitis B virus (HBV) are ineffective against HDV and combination therapy with lamivudine or ribavirin has not shown significant advantages over monotherapy with either standard or pegylatcd IFN. Because the ultimate goal of treatment is eradication of both HDV and HBV, in responders IFN therapy should be continued as long as possible until the loss of hepatitis B surface antigen, adjusting the dose to patient tolerance. However, because side-effects are common, continuous monitoring is mandatory. Although the first results obtained with pegylated IFN have been encouraging, the rate of sustained virological response is still low and the rate of relapse high, emphasizing the need for developing novel classes of antivirals specifically interfering with the life cycle of this unique virus. C1 Univ Cagliari, Policlin Univ, Dept Med Sci, Cagliari, Italy. RP Farci, P (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Bldg 50,Rm 6529, Bethesda, MD 20892 USA. EM pfarci@niaid.nih.gov RI Chessa, Luchino/H-7561-2012 OI Chessa, Luchino/0000-0002-9474-0995 NR 49 TC 20 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD NOV PY 2007 VL 14 SU 1 BP 58 EP 63 DI 10.1111/j.1365-2893.2007.00917.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 229SN UT WOS:000250824700011 PM 17958644 ER PT J AU Negrete, A Kotin, RM AF Negrete, Alejandro Kotin, Robert M. TI Production of recombinant adeno-associated vectors using two bioreactor configurations at different scales SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE adeno-associated vectors; large-scale production; stirred tank bioreactor; Wave (TM) bioreactor; gene therapy ID INSECT CELLS; WILD-TYPE; VIRUS; PURIFICATION; EXPRESSION; CULTURE AB The conventional methods for producing recombinant adeno-associated virus (rAAV) rely on transient transfection of adherent mammalian cells. To gain acceptance and achieve current good manufacturing process (cGMP) compliance, clinical grade rAAV production process should have the following qualities: simplicity, consistency, cost effectiveness, and scalability. Currently, the only viable method for producing rAAV in large-scale, e.g. >= 10(16) particles per production run, utilizes baculovirus expression vectors (BEVs) and insect cells suspension cultures. The previously described rAAV production in 40 L culture using a stirred tank bioreactor requires special conditions for implementation and operation not available in all laboratories. Alternatives to producing rAAV in stirred tank bioreactors are single-use, disposable bioreactors, e.g. Wave(TM). The disposable bags are purchased pre-sterilized thereby eliminating the need for end-user sterilization and also avoiding cleaning steps between production runs thus facilitating the production process. In this study, rAAV production in stirred tank and Wave(TM) bioreactors was compared. The working volumes were 10 L and 40 L for the stirred tank bioreactors and 5 L and 20 L for the Wave(TM) bioreactors. Comparable yields of rAAV, similar to 2E+13 particles per liter of cell culture were obtained in all volumes and configurations. These results demonstrate that producing rAAV in large scale using BEVs is reproducible, scalable, and independent of the bioreactor configuration. Published by Elsevier B.V. C1 NHLBI, US Natl Inst Hlth, Lab Biochem Genet, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 7D05, Bethesda, MD 20892 USA. EM kotinr@mail.nih.gov RI kotin, robert/B-8954-2008 FU Intramural NIH HHS [Z01 HL002237-13] NR 20 TC 23 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2007 VL 145 IS 2 BP 155 EP 161 DI 10.1016/j.jviromet.2007.05.020 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 216RP UT WOS:000249897000008 PM 17606302 ER PT J AU DiNapoli, JM Yang, LJ Suguitan, A Elankumaran, S Dorward, DW Murphy, BR Samal, SK Collins, PL Bukreyev, A AF DiNapoli, Joshua M. Yang, Lijuan Suguitan, Amorsolo, Jr. Elankumaran, Subbiah Dorward, David W. Murphy, Brian R. Samal, Siba K. Collins, Peter L. Bukreyev, Alexander TI Immunization of primates with a newcastle disease virus-vectored vaccine via the respiratory tract induces a high titer of serum neutralizing antibodies against highly pathogenic avian influenza virus SO JOURNAL OF VIROLOGY LA English DT Article ID A/DUCK/SINGAPORE/97 H5N3 VACCINE; MF59-ADJUVANTED INFLUENZA; PROTECTS CHICKENS; LETHAL CHALLENGE; AFRICAN-GREEN; MONKEYS; REPLICATION; REACTIVITY; INFECTION; INFANTS AB The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV in birds, the incidence of transmission to humans with a resulting high mortality rate, and the possibility of a human pandemic warrant the development of effective human vaccines against HPAIV. We developed an experimental live-attenuated vaccine for direct inoculation of the respiratory tract based on recombinant avian Newcastle disease virus (NDV) expressing the hemagglutinin (HA) glycoprotein of H5N1 HPAIV (NDV-HA). Expression of the HPAIV HA gene slightly reduced NDV virulence, as evidenced by the increased mean embryo death time and reduced replication in chickens. NDV-RA was administered to African green monkeys in two doses of 2 x 10(7) infectious units each with a 28-day interval to evaluate the systemic and local antibody responses specific to H5N1 HPAIV. The virus was shed only at low titers from the monkeys, indicative of safety. Two doses of NDV-HA induced a high titer of H5N1 HPAIV-neutralizing serum antibodies in all of the immunized monkeys. Moreover, a substantial mucosal immunoglobulin A response was induced in the respiratory tract after one and two doses. The titers of neutralizing antibodies achieved in this study suggest that the vaccine would be likely to prevent mortality and reduce morbidity caused by the H5N1 HPAIV. In addition, induction of a local immune response in the respiratory tract is an important advantage that is likely to reduce or prevent transmission of the virus during an outbreak or a pandemic. This vaccine is a candidate for clinical evaluation in humans. C1 NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NIAID, Res Technol Sect, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Bukreyev, A (reprint author), NIAID, NIH, Infect Dis Lab, 50 S Dr,Rm 6505, Bethesda, MD 20892 USA. EM abl76v@nih.gov RI Subbiah, Elankumaran/E-9277-2010 OI Subbiah, Elankumaran/0000-0003-4135-9477 FU Intramural NIH HHS NR 28 TC 62 Z9 66 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 21 BP 11560 EP 11568 DI 10.1128/JVI.00713-07 PG 9 WC Virology SC Virology GA 224AM UT WOS:000250417400002 PM 17715243 ER PT J AU Boasso, A Vaccari, M Hryniewicz, A Fuchs, D Nacsa, J Cecchinato, V Andersson, J Franchini, G Shearer, GM Chougnet, C AF Boasso, Adriano Vaccari, Monica Hryniewicz, Anna Fuchs, Dietmar Nacsa, Janos Cecchinato, Valentina Andersson, Jan Franchini, Genoveffa Shearer, Gene M. Chougnet, Claire TI Regulatory T-Cell markers, indoleamine 2,3-dioxygenase, and virus levels in spleen and gut during progressive simian immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; STANDING SIVMAC251 INFECTION; HIV-1 INFECTION; GASTROINTESTINAL-TRACT; TRYPTOPHAN CATABOLISM; IN-VITRO; IMMUNOLOGICAL-TOLERANCE; IMMUNE ACTIVATION; DENDRITIC CELLS; LYMPHOID-TISSUE AB High levels of viral replication occur in gut-associated lymphoid tissue (GALT) and other lymphoid tissues (LT) since the early phase of human/simian immunodeficiency virus (HIV/SIV) infection. Regulatory T cells (T-reg), a subset of immunosuppressive T cells expressing CTLA-4 and the FoxP3 transcription factor, accumulate in LT during HIV/SIV infection. Here we show that FoxP3 and CTLA-4 mRNA are increased in leukocytes from the spleens, lymph nodes (LN), and mucosal sites of chronically SIV-infected macaques with high viremia (SIVHI,) compared to animals with low viremia (SIVLO). FoxP3 and CTLA-4 correlated with SIV RNA levels in tissues; SIV virus levels in the spleen, inguinal LN, mesenteric LN, colon, and jejunum directly correlated with the plasma virus level. Importantly, CTLA-4 and FoxP3 mRNA were predominantly increased in the CD25(-) subpopulation of leukocytes from SIVHI, further challenging the classical definition of T-reg as CD4(+) CD25(+) T cells. Similar to CTLA-4 and FoxP3, expression of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme induced by T-V in antigen-presenting cells, was increased in the spleens, mesenteric LN, colons, and jejuna from SIVHI compared to SIVLO, and directly correlated to SIV RNA in the same tissues. Accordingly, plasma kynurenine/tryptophan, a marker for IDO enzymatic activity, was significantly higher in SIVHI compared to SIVLO and correlated with plasma viral levels. Increased Treg and IDO in LT of SIV-infected macaques may be the consequence of increased tissue inflammation and/or may favor virus replication during the chronic phase of SIV infection. C1 NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, NIH, Anim Models & Retrovial Vacc Sect, Bethesda, MD 20892 USA. Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. Innsbruk Med Univ, Div Biol Chem Bioctr, Ludwig Boltzmann Inst AIDS Res, Innsbruck, Austria. Karolinska Univ Hosp, Div Infect Dis, Karolinska Inst, Ctr Infect Med, Stockholm, Sweden. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH USA. RP Boasso, A (reprint author), NCI, NIH, Expt Immunol Branch, 10 Ctr Dr,Bldg 10,Rm4b36, Bethesda, MD 20892 USA. EM boassoa@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS; NIAID NIH HHS [AI 068524, R01 AI068524] NR 49 TC 66 Z9 70 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 21 BP 11593 EP 11603 DI 10.1128/JVI.00760-07 PG 11 WC Virology SC Virology GA 224AM UT WOS:000250417400006 PM 17715231 ER PT J AU Sacha, JB Chung, C Reed, J Jonas, AK Bean, AT Spencer, SP Lee, W Vojnov, L Rudersdorfl, R Friedrich, TC Wilson, NA Lifson, JD Watkins, DI AF Sacha, Jonah B. Chung, Chungwon Reed, Jason Jonas, Anna K. Bean, Alexander T. Spencer, Sean P. Lee, Wonhee Vojnov, Lara Rudersdorfl, Richard Friedrich, Thomas C. Wilson, Nancy A. Lifson, Jeffrey D. Watkins, David I. TI Pol-specific CD8(+) T cells recognize simian immunodeficiency virus-infected cells prior to nef-mediated major histocompatibility complex class I Downregulation SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; TYPE-1 NEF; ANTIGEN PRESENTATION; CUTTING EDGE; HIV-1; REPLICATION; LYMPHOCYTES; PROTEIN; EXPRESSION; AIDS AB Effective, vaccine-induced CD8(+) T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8(+) T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD+ T cells do not recognize infected cells until much later in infection. However, it remains unknown when other proteins present in the viral particle are presented to CD8(+) T cells after infection. To address this issue, we explored CD8(+) T-cell recognition of epitopes derived from two other relatively large virion proteins, Pol and Nef. Surprisingly, infected cells efficiently presented CD8(+) T-cell epitopes from virion-derived Pol proteins within 2 h of infection. In contrast, Nef-specific CD8(+) T cells did not recognize infected cells until 12 h postinfection. Additionally, we show that SIVmac239 Nef downregulated surface major histocompatibility complex class I (MHC-I) molecules beginning at 12 h postinfection, concomitant with presentation of Nef-derived CD8(+) T-cell epitopes. Finally, Pol-specific CD8(+) T cells eliminated infected cells as early as 6 h postinfection, well before MHC-1 downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8(+) T cells. C1 Univ Wisconsin, Dept Lab Med & Pathol, Madison, WI 53711 USA. NCI, Sci Applicat Int Corp, AIDS Vac Program, Frederick, MD 21702 USA. Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. RP Watkins, DI (reprint author), Univ Wisconsin, Dept Lab Med & Pathol, 555 Sci Dr, Madison, WI 53711 USA. EM watkins@primate.wisc.edu OI Friedrich, Thomas/0000-0001-9831-6895 FU NCI NIH HHS [N01 CO 12400, N01CO12400]; NCRR NIH HHS [RR 020141-01, C06 RR015459, C06 RR020141, P51 RR 000167, P51 RR000167, R24 RR 015371, R24 RR015371, RR 15459-01]; NIAID NIH HHS [R01 AI 049120, R01 AI 052056, R01 AI049120, R01 AI052056] NR 50 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 21 BP 11703 EP 11712 DI 10.1128/JVI.00926-07 PG 10 WC Virology SC Virology GA 224AM UT WOS:000250417400017 PM 17699580 ER PT J AU Oliphant, T Nybakken, GE Austin, SK Xu, Q Bramson, J Loeb, M Throsby, M Fremont, DH Pierson, TC Diamond, MS AF Oliphant, Theodore Nybakken, Grant E. Austin, S. Kyle Xu, Qing Bramson, Jonathan Loeb, Mark Throsby, Mark Fremont, Daved H. Pierson, Theodore C. Diamond, Michael S. TI Induction of epitope-specific neutralizing antibodies against west nile virus SO JOURNAL OF VIROLOGY LA English DT Article ID FLAVIVIRUS ENVELOPE GLYCOPROTEIN; HUMANIZED MONOCLONAL-ANTIBODY; DENGUE VIRUS; DOMAIN-III; MEDIATED NEUTRALIZATION; MOUSE NEUROINVASIVENESS; COMPLEMENT ACTIVATION; LETHAL ENCEPHALITIS; GERMINAL-CENTERS; IMMUNE-RESPONSE AB Previous studies have established that an epitope on the lateral ridge of domain III (DIII-lr) of West Nile virus (WNV) envelope (E) protein is recognized by strongly neutralizing type-specific antibodies. In contrast, an epitope against the fusion loop in domain II (DII-fl) is recognized by flavivirus cross-reactive antibodies with less neutralizing potential. Using gain- and loss-of-function E proteins and wild-type and variant WNV reporter virus particles, we evaluated the expression pattern and activity of antibodies against the DIII-lr and DII-fl epitopes in mouse and human serum after WNV infection. In mice, immunoglobulin M (IgM) antibodies to the DIII-Ir epitope were detected at low levels at day 6 after infection. However, compared to IgG responses against other epitopes in DI and DII, which were readily detected at day 8, the development of IgG against DIII-lr epitope was delayed and did not appear consistently until day 15. This late time point is notable since almost all death after VVNV infection in mice occurs by day 12. Nonetheless, at later time points, DIII-lr antibodies accumulated and comprised a significant fraction of the DIII-specific IgG response. In sera from infected humans, DIII-lr antibodies were detected at low levels and did not correlate with clinical outcome. In contrast, antibodies to the DII-fl were detected in all human serum samples and encompassed a significant percentage of the anti-E protein response. Our experiments suggest that the highly neutralizing DIII-lr IgG antibodies have little significant role in primary infection and that the antibody response of humans may be skewed toward the induction of cross-reactive, less-neutralizing antibodies. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bethesda, MD 20892 USA. McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada. Crucell Holland BV, Leiden, Netherlands. RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, 600 S Euclid Ave,Box 8051, St Louis, MO 63110 USA. EM diamond@borcim.wustl.edu FU Intramural NIH HHS; NIAID NIH HHS [AI 061373, U01 AI061373, U54 AI 057160, U54 AI057160] NR 61 TC 111 Z9 117 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 21 BP 11828 EP 11839 DI 10.1128/JVI.00643-07 PG 12 WC Virology SC Virology GA 224AM UT WOS:000250417400030 PM 17715236 ER PT J AU Ambrose, Z Palmer, S Boltz, VF Kearney, M Larsen, K Polacino, P Flanary, L Oswald, K Piatak, M Smedley, J Shao, W Bischofberger, N Maldarelli, F Kimata, JT Mellors, JW Hu, SL Coffin, JM Lifson, JD KewalRamani, VN AF Ambrose, Zandrea Palmer, Sarah Boltz, Valerie F. Kearney, Mary Larsen, Kay Polacino, Patricia Flanary, Leon Oswald, Kelli Piatak, Michael, Jr. Smedley, Jerem Shao, Wei Bischofberger, Norbert Maldarelli, Frank Kimata, Jason T. Mellors, John W. Hu, Shiu-Lok Coffin, John M. Lifson, Jeffrey D. KewalRamani, Vineet N. TI Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for Antiretroviral therapy SO JOURNAL OF VIROLOGY LA English DT Article ID TO-CHILD TRANSMISSION; SINGLE-DOSE NEVIRAPINE; DYNAMICS IN-VIVO; STRUCTURED TREATMENT INTERRUPTIONS; REVERSE-TRANSCRIPTASE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; EXPERIENCED PATIENTS; RHESUS MACAQUES; HIV-1 VARIANTS; NVP RESISTANCE AB Antiretroviral therapy (ART) in human immunodeficiency virus type 1 (HIV-1)-infected patients does not clear the infection and can select for drug resistance over time. Not only is drug-resistant HIV-1 a concern for infected individuals on continual therapy, but it is an emerging problem in resource-limited settings where, in efforts to stem mother-to-child-transmission of HIV-1, transient nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy given during labor can select for NNRTI resistance in both mother and child. Questions of HIV-1 persistence and drug resistance are highly amenable to exploration within animals models, where therapy manipulation is less constrained. We examined a pigtail macaque infection model responsive to anti-HIV-1 therapy to study the development of resistance. Pigtail macaques were infected with a pathogenic simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT-SHIV) to examine the impact of prior exposure to a NNRTI on subsequent ART comprised of a NNRTI and two nucleoside RT inhibitors. K103N resistance-conferring mutations in RT rapidly accumulated in 2/3 infected animals after NNRTI monotherapy and contributed to virologic failure during ART in 113 animals. By contrast, ART effectively suppressed RT-SHIV in 5/6 animals. These data indicate that suboptimal therapy facilitates HIV-1 drug resistance and suggest that this model can be used to investigate persisting viral reservoirs. C1 [Ambrose, Zandrea; Palmer, Sarah; Boltz, Valerie F.; Kearney, Mary; Shao, Wei; Maldarelli, Frank; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Mellors, John W.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Kimata, Jason T.] Baylor Coll Med, Dept Virol & Mol Microbiol, Houston, TX 77030 USA. [Bischofberger, Norbert] Gilead Sci Inc, Foster City, CA 94404 USA. [Smedley, Jerem; Lifson, Jeffrey D.] NCI, SAIC Frederick Inc, Lab Anim Sci, Bethesda, MD 20892 USA. [Oswald, Kelli; Piatak, Michael, Jr.] NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. [Larsen, Kay; Polacino, Patricia; Flanary, Leon; Hu, Shiu-Lok] Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. RP KewalRamani, VN (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 123, Frederick, MD 21702 USA. EM ambrosez@dom.pitt.edu; vineet@ncifcrf.gov RI Hu, Shiu-Lok/A-3196-2008; OI Hu, Shiu-Lok/0000-0003-4336-7964; Smedley, Jeremy/0000-0003-3369-4662 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI047725] NR 61 TC 35 Z9 35 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12145 EP 12155 DI 10.1128/JVI.01301-07 PG 11 WC Virology SC Virology GA 275IP UT WOS:000254065400006 PM 17855539 ER PT J AU Kumar, M Jayaram, H Carpio, RVD Jiang, X Taraporewala, ZF Jacobson, RH Patton, JT Prasad, BVV AF Kumar, Mukesh Jayaram, Hariharan Carpio, Rodrigo Vasquez-Del Jiang, Xiaofang Taraporewala, Zenobia F. Jacobson, Raymond H. Patton, John T. Prasad, B. V. Venkataram TI Crystallographic and biochemical analysis of rotavirus NSP2 with nucleotides reveals a nucleoside diphosphate kinase-like activity SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEIN NSP2; VIRUS-REPLICATION COMPLEXES; HISTIDINE TRIAD SUPERFAMILY; VIRAL-RNA SYNTHESIS; GENOME REPLICATION; VIROPLASM; PHOSPHORYLATION; MECHANISM; IDENTIFICATION; LOCALIZATION AB Rotavirus, the major pathogen of infantile gastroenteritis, carries a nonstructural protein, NSP2, essential for viroplasm formation and genome replication/packaging. In addition to RNA-binding and helix-destabilizing properties, NSP2 exhibits nucleoside triphosphatase activity. A conserved histidine (H225) functions as the catalytic residue for this enzymatic activity, and mutation of this residue abrogates genomic double-stranded RNA synthesis without affecting viroplasm formation. To understand the structural basis of the phosphatase activity of NSP2, we performed crystallographic analyses of native NSP2 and a functionally defective H225A mutant in the presence of nucleotides. These studies showed that nucleotides bind inside a cleft between the two domains of NSP2 in a region that exhibits structural similarity to ubiquitous cellular HIT (histidine triad) proteins. Only minor conformational alterations were observed in the cleft upon nucleotide binding and hydrolysis. This hydrolysis involved the formation of a stable phosphohistidine intermediate. These observations, reminiscent of cellular nucleoside diphosphate (NDP) kinases, prompted us to investigate whether NSP2 exhibits phosphoryl-transfer activity. Bioluminometric assay showed that NSP2 exhibits an NDP kinase-like activity that transfers the bound phosphate to NDPs. However, NSP2 is distinct from the highly conserved cellular NDP kinases in both its structure and catalytic mechanism, thus making NSP2 a potential target for antiviral drug design. With structural similarities to HIT proteins, which are not known to exhibit NDP kinase activity, NSP2 represents a unique example among structure-activity relationships. The newly observed phosphoryl-transfer activity of NSP2 may be utilized for homeostasis of nucleotide pools in viroplasms during genome replication. C1 [Kumar, Mukesh; Jayaram, Hariharan; Jiang, Xiaofang; Prasad, B. V. Venkataram] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Jacobson, Raymond H.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Carpio, Rodrigo Vasquez-Del; Taraporewala, Zenobia F.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Prasad, BVV (reprint author), Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM vprasad@bcm.tmc.edu RI Kumar, Mukesh/A-1876-2011; Patton, John/P-1390-2014 OI Kumar, Mukesh/0000-0002-3392-7481; FU Intramural NIH HHS; NIAID NIH HHS [AI36040, R01 AI036040, R37 AI036040]; NIGMS NIH HHS [GM069769, R01 GM069769] NR 47 TC 23 Z9 26 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12272 EP 12284 DI 10.1128/JVI.00984-07 PG 13 WC Virology SC Virology GA 275IP UT WOS:000254065400018 PM 17804496 ER PT J AU Letvin, NL Rao, SS Dang, V Buzby, AP Korioth-Schmitz, B Dombagoda, D Parvani, JG Clarke, RH Bar, L Carlson, KR Kozlowski, PA Hirsch, VM Mascola, JR Nabel, GJ AF Letvin, Norman L. Rao, Srini S. Dang, Vi Buzby, Adam P. Korioth-Schmitz, Birgit Dombagoda, Dilani Parvani, Jenny G. Clarke, Ryon H. Bar, Liat Carlson, Kevin R. Kozlowski, Pamela A. Hirsch, Vanessa M. Mascola, John R. Nabel, Gary J. TI No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC T-LYMPHOCYTES; COMMERCIAL SEX WORKERS; HIV-1 INFECTION; CELL RESPONSES; MUCOSAL; NAIROBI; PROSTITUTES; VACCINIA; IGA AB Defining the immune correlates of the protection against human immunodeficiency virus type 1 (HIV-1) acquisition in individuals who are exposed to HIV-1 but do not become infected may provide important direction for the creation of an HIV-1 vaccine. We have employed the simian immunodeficiency virus (SIV)/ rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protection from infection can be identified in uninfected monkeys. Five of 18 rhesus monkeys exposed 18 times by intrarectal inoculation to SIVmac251 or SIVsmE660 were resistant to infection, indicating that the exposed/uninfected phenotype can be reproduced in a nonhuman primate AIDS model. However, routine peripheral blood lymphocyte gamma interferon enzyme-linked immunospot (ELISPOT), tetramer, and intracellular cytokine staining assays, as well as cytokine-augmented ELISPOT and peptide-stimulated tetramer assays, failed to define a systemic antigen-specific cellular immune correlate to this protection. Further, local cell-mediated immunity could not be demonstrated by tetramer assays of these protected monkeys, and local Immoral immunity was not associated with protection against acquisition of virus in another cohort of mucosally exposed monkeys. Therefore, resistance to mucosal infection in these monkeys may not be mediated by adaptive virus-specific immune mechanisms. Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys. C1 [Letvin, Norman L.; Buzby, Adam P.; Korioth-Schmitz, Birgit; Dombagoda, Dilani; Parvani, Jenny G.; Clarke, Ryon H.; Bar, Liat; Carlson, Kevin R.] Harvard Univ, Sch Med, Div Viral Pathogenesis, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Letvin, Norman L.; Rao, Srini S.; Dang, Vi; Mascola, John R.; Nabel, Gary J.] NIH, Vaccine Res Ctr, NIAID, Bethesda, MD 20892 USA. [Kozlowski, Pamela A.] Harvard Univ, Sch Med, Div Gastroenterol, Dept Med,Childrens Hosp, Boston, MA 02115 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Div Viral Pathogenesis, Dept Med,Beth Israel Deaconess Med Ctr, RE113 POB 15732, Boston, MA 02115 USA. EM nletvin@bidmc.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU Intramural NIH HHS; NIAID NIH HHS [AI058896, R01 AI058896, P30 AI060354, AI060354] NR 24 TC 48 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12368 EP 12374 DI 10.1128/JVI.00822-07 PG 7 WC Virology SC Virology GA 275IP UT WOS:000254065400027 PM 17686853 ER PT J AU Vanpouille, C Bioncotto, A Lisco, A Brichacek, B AF Vanpouille, Christophe Bioncotto, Angelique Lisco, Andrea Brichacek, Beda TI Interactions between human immunodeficiency virus type 1 and vaccinia virus in human lymphoid tissue ex vivo SO JOURNAL OF VIROLOGY LA English DT Article ID CXCR4-TROPIC HIV-1; CHEMOKINE ACTIVITY; MEASLES-VIRUS; T-CELLS; INFECTION; REPLICATION; INHIBITION; SMALLPOX; TROPISM; HUMAN-HERPESVIRUS-6 AB Vaccinia virus (VACV) has been attracting attention recently not only as a vector for various vaccines but also as an immunization tool against smallpox because of its potential use as a bioterrorism agent. It has become evident that in spite of a long history of studies of VACV, its tissue pathogenesis remains to be fully understood. Here, we investigated the pathogenesis of VACV and its interactions with human immunodeficiency virus type 1 (HIV-1) in the context of human lymphoid tissues. We found that ex vivo-cultured tonsillar tissue supports productive infection by the New York City Board of Health strain, the VACV strain of the Dryvax vaccine. VACV readily infected both T and non-T (B) lymphocytes and depleted cells of both of these subsets equally over a 12-day period postinfection. Among T lymphocytes, CD8(+) cells are preferentially depleted in accordance with their preferential infection: the probability that a CD8(+) T cell will be productively infected is almost six times higher than for a CD4(+) T cell. T cells expressing CCR5 and the activation markers CD25, CD38, and HLA-DR are other major targets for infection by VACV in lymphoid tissue. As a consequence, VACV predominantly inhibits the replication of the R5(SF162) phenotype of HIV-1 in coinfected tissues, as R5-tropic HIV-1 requires activated CCR5(+) CD4(+) cells for productive infection. Human lymphoid tissue infected ex vivo by VACV can be used to investigate interactions of VACV with other viruses, in particular HIV-1, and to evaluate various VACV vectors for the purpose of recombinant vaccine development. C1 [Vanpouille, Christophe; Bioncotto, Angelique; Lisco, Andrea; Brichacek, Beda] Natl Inst Child Hlth & Human Dev, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. [Vanpouille, Christophe; Brichacek, Beda] George Washington Univ, Med Ctr, Washington, DC 20037 USA. RP Vanpouille, C (reprint author), 10 Ctr Dr NIH,Bldg 10 Room 9D58, Bethesda, MD 20892 USA. EM vanpouic@mail.nih.gov FU Intramural NIH HHS NR 36 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12458 EP 12464 DI 10.1128/JVI.00326-07 PG 7 WC Virology SC Virology GA 275IP UT WOS:000254065400036 PM 17804502 ER PT J AU Jukic, AMZ Weinberg, CR Baird, DD Wilcox, AJ AF Jukic, Anne Marie Zaura Weinberg, Clarice R. Baird, Donna D. Wilcox, Allen J. TI Lifestyle and reproductive factors associated with follicular phase length SO JOURNAL OF WOMENS HEALTH LA English DT Article ID MENSTRUAL-CYCLE CHARACTERISTICS; ORAL-CONTRACEPTIVE USE; STIMULATING-HORMONE; PROGESTERONE METABOLITES; PREMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; CIGARETTE-SMOKING; MARIJUANA SMOKING; URINARY ESTROGEN; FERTILITY AB Purpose: Variability in menstrual cycle length, largely determined by variation in follicular phase length, is related to several health outcomes, yet the causes of this variability are incompletely understood. We sought to identify characteristics associated with follicular phase length. Methods: We used the North Carolina Early Pregnancy Study to describe factors correlated with timing of ovulation ( follicular phase length). Women collected daily urine specimens and recorded vaginal bleeding. Specimens were assayed for estrone 3-glucuronide and pregnanediol 3-glucuronide, which in turn were used to estimate the day of ovulation. All other variables were assessed through interview. Associations with follicular phase length were evaluated using a multiple regression model. Results: We determined follicular phase length for the first cycles of 201 women. Women with a history of miscarriage tended to have shorter follicular phases (2.2 days). Longer duration of oral contraceptive (OC) use and recent OC use (in the last 90 days) were both correlated with longer follicular phase. Occasional marijuana users ( up to three times in the last 3 months) had a longer follicular phase than nonusers (3.5 days); the follicular phase in frequent users (more than three times) was almost 2 days longer than that of nonusers. Conclusions: The association between marijuana use and longer follicular phase is consistent with prior rhesus monkey research that shows ovulatory delay or inhibition. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Jukic, AMZ (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM jukica@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS [Z99 ES999999] NR 51 TC 13 Z9 16 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2007 VL 16 IS 9 BP 1340 EP 1347 DI 10.1089/jwh.2007.0354 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 234PB UT WOS:000251174900012 PM 18001191 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Gail, MH AF Flegal, Katherine M. Graubard, Barry I. Williamson, David F. Gail, Mitchell H. TI Weight-associated deaths in the United States SO JOURNAL OF WOMENS HEALTH LA English DT Letter ID OBESITY; POPULATION; MORTALITY; UNDERWEIGHT; OVERWEIGHT; FRACTIONS; MEN C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd, Hyattsville, MD 20782 USA. EM kflegal@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 11 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2007 VL 16 IS 9 BP 1368 EP 1370 DI 10.1089/jwh.2007.0547 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 234PB UT WOS:000251174900016 PM 18001195 ER PT J AU Espeland, MA Gill, TM Guralnik, J Miller, ME Fielding, R Newman, AB Pahor, M AF Espeland, Mark A. Gill, Thomas M. Guralnik, Jack Miller, Michael E. Fielding, Roger Newman, Anne B. Pahor, Marco CA Lifestyle Interventions Indepe TI Designing clinical trials of interventions for mobility disability: Results from the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) trial SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; OLDER-ADULTS; KNEE OSTEOARTHRITIS; POPULATION; MORTALITY; ARTHRITIS; EXERCISE; HEALTH; ASSOCIATION AB Background. Clinical trials to assess interventions for mobility disability are critically needed; however, data for efficiently designing such trials are lacking. Methods. Results are described from a pilot clinical trial in which 424 volunteers aged 70-89 years were randomly assigned to one of two interventions-physical activity or a healthy aging education program-and followed for a planned minimum of 12 months. We evaluated the longitudinal distributions of four standardized outcomes to contrast how they may serve as primary outcomes of future clinical trials: ability to walk 400 meters, ability to walk 4 meters in <= 10 seconds, a physical performance battery, and a questionnaire focused on physical function. Results. Changes in all four outcomes were interrelated over time. The ability to walk 400 meters as a dichotomous outcome provided the smallest sample size projections (i.e., appeared to be the most efficient outcome). It loaded most heavily on the underlying latent variable in structural equation modeling with a weight of 80%. A 4-year trial based on the outcome of the 400-meter walk is projected to require N = 962-2234 to detect an intervention effect of 30%-20% with 90% power. Conclusions. Future clinical trials of interventions designed to influence mobility disability may have greater efficiency if they adopt the ability to complete a 400-meter walk as their primary outcome. C1 [Espeland, Mark A.; Miller, Michael E.] Wake Forest Univ, Med Ctr, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. [Gill, Thomas M.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Guralnik, Jack] NIA, Epidemiol & Demog Sec, Bethesda, MD 20892 USA. [Fielding, Roger] Jean Mayer USDA Human Nutr Res Ctr, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol & Med, Pittsburgh, PA 15260 USA. [Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. RP Espeland, MA (reprint author), Wake Forest Univ, Med Ctr, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. EM mespelan@wfubmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NCATS NIH HHS [UL1 TR000064]; NCRR NIH HHS [UL1 RR029890]; NIA NIH HHS [1P30AG21332, K24 AG021507, P30 AG021332, P30 AG028740, U01 AG022376, U01 AG022376-04, U01AG22376] NR 31 TC 33 Z9 33 U1 1 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2007 VL 62 IS 11 BP 1237 EP 1243 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AH UT WOS:000253829300007 PM 18000143 ER PT J AU Fitzpatrick, AL Buchanan, CK Nahin, RL DeKosky, ST Atkinson, HH Carlson, MC Williamson, JD AF Fitzpatrick, Annette L. Buchanan, Catherine K. Nahin, Richard L. DeKosky, Steven T. Atkinson, Hal H. Carlson, Michelle C. Williamson, Jeff D. CA GEM Study Investigators TI Associations of gait speed and other measures of physical function with cognition in a healthy cohort of elderly persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID NURSING-HOME ADMISSION; BASE-LINE DATA; EXECUTIVE FUNCTION; INCIDENT DEMENTIA; GINKGO EVALUATION; OLDER-PEOPLE; PERFORMANCE-MEASURES; INITIATIVE MEMORY; ALZHEIMER-DISEASE; FOLLOW-UP AB Background. Recent evidence suggests that physical decline and slower gait may be associated with early signs of dementia, but more information on healthy older adults is needed. Methods. We determined associations between cognitive function, gait speed, and self-reported measures of physical function in 3035 healthy mobile participants of the Ginkgo Evaluation of Memory Study evaluated in 2000-2001. Gait speed was measured over a 15-foot course with participants walking at both their usual and rapid pace. Self-reported difficulties with Activities of Daily Living (ADLs) and other physical function tasks were also collected. Results of the Modified Mini-Mental State Examination (3MSE) determined cognitive function. Results. The average age of the cohort was 78.6 years (standard deviation [SD] 3.3), and 53.9% of participants were men. Mean gait speed was 0.95 (SD 0.23) m/s at a usual pace and 1.35 (SD 0.58) m/s at a rapid pace. More than three-fourths of participants had 3MSE scores > 90. In multiple logistic models adjusted for demographics and comorbidities, risk of low cognition (defined as 3MSE score of 80-85) was almost twice as great for participants in the slowest quartile of the rapid-paced walking task than for the fastest walkers (odds ratio: 1.96, 95% confidence interval, 1.25-3.08). Associations between cognition and usual-paced walking were borderline, and no relationships were found with self-reported measures of physical function, including ADLs. Conclusions. In very healthy older adults, performance -based measures better predict early cognitive decline than do subjective measures, and tasks requiring greater functional reserve, such as fast-paced walking, appear to be the most sensitive in assessing these relationships. C1 [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98115 USA. [Buchanan, Catherine K.; Atkinson, Hal H.; Williamson, Jeff D.] Wake Forest Sch Med, Sticht Ctr Aging, Kulynych Ctr Memory & Cognit Res, Winston Salem, NC USA. [Buchanan, Catherine K.; Atkinson, Hal H.; Williamson, Jeff D.] Wake Forest Sch Med, Sticht Ctr Aging, Claude D Pepper Older Amer Independence Ctr, Winston Salem, NC USA. [DeKosky, Steven T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Nahin, Richard L.] Natl Ctr Complementary & Alternat Med, Natl Inst Hlth, Bethesda, MD USA. [Carlson, Michelle C.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. RP Fitzpatrick, AL (reprint author), Univ Washington, Dept Epidemiol, Collaborat Hlth Studies Coordinating Ctr, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98115 USA. EM fitzpal@u.washington.edu FU NCCIH NIH HHS [5 U01 AT000162] NR 44 TC 88 Z9 90 U1 0 U2 17 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2007 VL 62 IS 11 BP 1244 EP 1251 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AH UT WOS:000253829300008 PM 18000144 ER PT J AU Knepper, MA Pisitkun, T AF Knepper, M. A. Pisitkun, T. TI Exosomes in urine: Who would have thought.? SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID IDENTIFICATION AB Normal urine contains thousands of proteins, largely due to the presence of 'exosomes,'tiny vesicles secreted into the urine by renal epithelial cells. These exosomes, demonstrated by Keller and colleagues to be also retrievable from amniotic fluid, offer great promise for future disease biomarker discovery studies. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 11 TC 32 Z9 32 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2007 VL 72 IS 9 BP 1043 EP 1045 DI 10.1038/sj.ki.5002510 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 221KT UT WOS:000250226900002 PM 17943150 ER PT J AU Portnoy, L Bur, M AF Portnoy, Lisa Bur, Monica TI Concur with covelli SO LAB ANIMAL LA English DT Editorial Material C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Portnoy, L (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2007 VL 36 IS 10 BP 13 EP 14 DI 10.1038/laban1107-13b PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 229LF UT WOS:000250803800002 PM 17957170 ER PT J AU Foltz, C Carbone, L DeLong, D Rollin, BE Van Loo, P Whitaker, J Wolff, A AF Foltz, Charmalne Carbone, Larry DeLong, David Rollin, Bernard E. Van Loo, Pascalle Whitaker, Julia Wolff, Axel TI Considerations for determining optimal mouse caging density SO LAB ANIMAL LA English DT Editorial Material ID CAGE POPULATION-DENSITY; LABORATORY MICE; ENVIRONMENTAL ENRICHMENT; HOUSING DENSITY; FLOOR SPACE; NESTING MATERIAL; WEIGHT-GAIN; BODY-WEIGHT; BEHAVIOR; STRESS AB At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal wellbeing should be the measure of interest in evaluating housing density and that well-being includes not only physical health, but also animals' behavior, productivity and preference. C1 NIH, Div Vet Resources, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Vet Med Unit, Minneapolis, MN USA. Colorado State Univ, Ft Collins, CO 80523 USA. Univ Utrecht, NL-3508 TC Utrecht, Netherlands. Univ N Carolina, Dept Pathol & Lab Med, Div Lab Anim Med, Chapel Hill, NC USA. NIH, Div Compliance Oversight, Bethesda, MD 20892 USA. RP Foltz, C (reprint author), NIH, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. EM foltzc@mail.nih.gov NR 46 TC 8 Z9 8 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2007 VL 36 IS 10 BP 40 EP 49 DI 10.1038/laban1107-40 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA 229LF UT WOS:000250803800009 PM 17957179 ER PT J AU Linehan, WM AF Linehan, W. Marston TI Targeting VEGF receptors in kidney cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID ALPHA; GENE C1 Natl Canc Inst, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), Natl Canc Inst, Urol Oncol Branch, Bethesda, MD 20892 USA. EM WML@nih.gov NR 10 TC 14 Z9 14 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2007 VL 8 IS 11 BP 956 EP 957 DI 10.1016/S1470-2045(07)70322-4 PG 2 WC Oncology SC Oncology GA 230WP UT WOS:000250907300003 PM 17976606 ER PT J AU Iqbal, J Greiner, TC Patel, K Dave, BJ Smith, L Ji, J Wright, G Sanger, WG Pickering, DL Jain, S Horsman, DE Shen, Y Fu, K Weisenburger, DD Hans, CP Campo, E Gascoyne, RD Rosenwald, A Jaffe, ES Delabie, J Rimsza, L Ott, G Muller-Hermelink, HK Connors, JM Vose, JM McKeithan, T Staudt, LM Chan, WC AF Iqbal, J. Greiner, T. C. Patel, K. Dave, B. J. Smith, L. Ji, J. Wright, G. Sanger, W. G. Pickering, D. L. Jain, S. Horsman, D. E. Shen, Y. Fu, K. Weisenburger, D. D. Hans, C. P. Campo, E. Gascoyne, R. D. Rosenwald, A. Jaffe, E. S. Delabie, J. Rimsza, L. Ott, G. Mueller-Hermelink, H. K. Connors, J. M. Vose, J. M. McKeithan, T. Staudt, L. M. Chan, W. C. CA LLMPP TI Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma SO LEUKEMIA LA English DT Article DE BCL6; mutation; translocation; protein expression; gene expression profiling; diffuse large B-cell lymphoma ID NON-HODGKINS-LYMPHOMA; REGULATORY REGION; TRANSCRIPTIONAL REPRESSOR; SOMATIC HYPERMUTATION; FOLLICULAR LYMPHOMAS; TISSUE MICROARRAY; FINGER PROTEIN; GENE FUSION; GRADE 3B; EXPRESSION AB Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed biologically and prognostically distinct subgroups: germinal center B-cell-like (GCB), activated B-celllike (ABC) and primary mediastinal (PM) DLBCL. The BCL6 gene is often translocated and/ or mutated in DLBCL. Therefore, we examined the BCL6 molecular alterations in these DLBCL subgroups, and their impact on BCL6 expression and BCL6 target gene repression. BCL6 translocations at the major breakpoint region (MBR) were detected in 25 (18.8%) of 133 DLBCL cases, with a higher frequency in the PM (33%) and ABC (24%) subgroups than in the GCB (10%) subgroup. Translocations at the alternative breakpoint region (ABR) were detected in five (6.4%) of 78 DLBCL cases, with three cases in ABC and one case each in the GCB and the unclassifiable subgroups. The translocated cases involved IgH and non-IgH partners in about equal frequency and were not associated with different levels of BCL6 mRNA and protein expression. BCL6 mutations were detected in 61% of DLBCL cases, with a significantly higher frequency in the GCB and PM subgroups (470%) than in the ABC subgroup (44%). Exon-1 mutations were mostly observed in the GCB subgroup. The repression of known BCL6 target genes correlated with the level of BCL6 mRNA and protein expression in GCB and ABC subgroups but not with BCL6 translocation and intronic mutations. No clear inverse correlation between BCL6 expression and p53 expression was observed. Patients with higher BCL6 mRNA or protein expression had a significantly better overall survival. The biological role of BCL6 in translocated cases where repression of known target genes is not demonstrated is intriguing and warrants further investigation. C1 Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Metab Branch & Lab Pathol, Bethesda, MD USA. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC, Canada. Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain. Univ Wurzburg, Dept Pathol, Wurzburg, Germany. Univ Arizona, Dept Pathol, Tucson, AZ USA. RP Chan, WC (reprint author), Univ Nebraska Med Ctr, Ctr Lymphona & Leukemia Res, Dept Pathol & Microbiol, Omaha, NE 68198 USA. EM jchan@unmc.edu OI McKeithan, Timothy/0000-0003-2242-3074; Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [U01 CA114778-03, CA36727, CA84967, P30 CA036727, U01 CA084967, U01 CA114778-01] NR 55 TC 100 Z9 106 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2007 VL 21 IS 11 BP 2332 EP 2343 DI 10.1038/sj.leu.2404856 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 223OU UT WOS:000250382100014 PM 17625604 ER PT J AU Liepold, L Anderson, S Willits, D Oltrogge, L Frank, JA Douglas, T Young, M AF Liepold, Lars Anderson, Stasia Willits, Deborah Oltrogge, Luke Frank, Joseph A. Douglas, Trevor Young, Mark TI Viral capsids as MRI contrast agents SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; contrast agent; viral capsids; cowpea chlorotic mottle virus; gadolinium ID CHLOROTIC MOTTLE VIRUS; PROTEIN CAGE ARCHITECTURE; NUCLEAR-MAGNETIC-RESONANCE; COAT PROTEIN; 500 MHZ; NANOPARTICLES; GADOLINIUM; DYNAMICS; BINDING; SPECTROSCOPY AB Viral capsids have the potential for combined cell/tissue targeting, drug delivery, and imaging. Described here is the development of a viral capsid as an efficient and potentially relevant MRI contrast agent. Two approaches are outlined to fuse high affinity Gd3+ chelating moieties to the surface of the cowpea chlorotic mottle virus (CCMV) capsid. In the first approach, a metal binding peptide has been genetically engineered into the subunit of CCMV. In a second approach gadolinium-tetraazacyclododecane tetraacetic acid (GdDOTA) was attached to CCMV by reactions with endogenous lysine residues on the surface of the viral capsid. T-1 and T-2 ionic relaxivity rates for the genetic fusion particle were R1 = 210 and R2 = 402 mM(-1)s(-1) (R2 at 56 MHz) and for CCMV functionalized with GdDOTA were R1 = 46 and R2 = 142 mM(-1)s(-1) at 61 MHz. The relaxivities per intact capsid for the genetic fusion were RI = 36,120 and R2 = 69,144 mM(-1)s(-1) (R2 at 56 MHz) and for the GdDOTA CCMV construct were R1 = 2,806 and R2 = 8,662 mM(-1)s(-1) at 61 MHz. The combination of high relaxivity, stable Gd3+ binding, and large Gd3+ payloads indicates the potential of viral capsids as high-performance contrast agents. C1 Montana State Univ, Ctr BioInspired Nanomat, Bozeman, MT 59717 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Montana State Univ, Dept Plant Sci, Bozeman, MT 59717 USA. Natl Inst Hlth, Expt Neuroimaging Sect, Ctr Clin, Bethesda, MD USA. RP Douglas, T (reprint author), Montana State Univ, Ctr BioInspired Nanomat, Bozeman, MT 59717 USA. EM tdouglas@chemistry.montana.edu RI Douglas, Trevor/F-2748-2011 FU NIBIB NIH HHS [R01 EB00432, R21EB005364] NR 39 TC 87 Z9 87 U1 1 U2 27 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2007 VL 58 IS 5 BP 871 EP 879 DI 10.1002/mrm.21307 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 226AQ UT WOS:000250560000003 PM 17969126 ER PT J AU Driehuys, B Walker, J Pollaro, J Cofer, GP Mistry, N Schwartz, D Johnson, GA AF Driehuys, Bastiaan Walker, Julia Pollaro, Jim Cofer, Gary P. Mistry, Nilesh Schwartz, David Johnson, G. Allan TI He-3 MRI in mouse models of asthma SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE murine; asthma; airways hyperresponsiveness; broncho-constriction; hyperpolarized He-3 ID MAGNETIC-RESONANCE MICROSCOPY; HYPERPOLARIZED HE-3; LUNG VENTILATION; PROJECTION RECONSTRUCTION; CHALLENGE; METHACHOLINE; MICE; BRONCHOCONSTRICTION; RELAXATION; MORPHOLOGY AB In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) He-3 MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such He-3 imaging of MCh response in mice, where voxels must be similar to 3000 times smaller than in humans and He-3 diffusion becomes an impediment to resolving the airways. We show three-dimensional (313) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 mu m(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 mu m(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of He-3 MRI to mouse models should make it a valuable translational tool in asthma research. C1 Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Durham, NC 27710 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Driehuys, B (reprint author), Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Box 3302, Durham, NC 27710 USA. EM driehuys@orion.duhs.duke.edu OI Johnson, G.Allan/0000-0002-7606-5447 FU NCI NIH HHS [R24 CA092656-06, R24 CA092656]; NCRR NIH HHS [P41 RR005959, P41 RR005959-18]; NHLBI NIH HHS [R01 HL055348, R01 HL055348-07] NR 38 TC 42 Z9 42 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2007 VL 58 IS 5 BP 893 EP 900 DI 10.1002/mrm.21306 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 226AQ UT WOS:000250560000006 PM 17969115 ER PT J AU Yeung, CJ Karmarkar, P McVeigh, ER AF Yeung, Christopher J. Karmarkar, Parag McVeigh, Elliot R. TI Minimizing RF heating of conducting wires in MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; safety; RF heating; interventional MRI; guidewires; catheters; MRI-guided surgery; moment method; conductive wires ID INTERVENTIONAL MRI; CATHETERS AB Performing interventions using long conducting wires in MRI introduces the risk of focal RF heating at the wire tip. Comprehensive EM simulations are combined with carefully measured experimental data to show that method-of-moments EM field modeling coupled with heat transfer modeling can adequately predict RF heating with wires partially inserted into the patient-mimicking phantom. The effects of total wire length, inserted length, wire position in the phantom, phantom position in the scanner, and phantom size are examined. Increasing phantom size can shift a wire's length of maximum tip heating from about a half wave toward a quarter wave. In any event, with wires parallel to the scanner bore, wire tip heating is minimized by keeping the patient and wires as close as possible to the central axis of the scanner bore. At 1.5T, heating is minimized if bare wires are shorter than 0.6 m or between approximate to 2.4 m and approximate to 3.0 m. Heating is further minimized if wire insertion into phantoms equivalent to most aqueous soft tissues is less than 13 cm or greater than 40 cm (longer for fatty tissues, bone, and lung). The methods demonstrated can be used to estimate the absolute amount of heating in order to set RF power safety thresholds. C1 NHLBI, Cardiac Energet Lab, Natl Inst Hlth, Div Intramural Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RP McVeigh, ER (reprint author), NHLBI, Cardiac Energet Lab, Natl Inst Hlth, Div Intramural Res, 10 Ctr Dr,MSC 1061, Bethesda, MD 20892 USA. EM mcveighe@mail.nih.gov NR 14 TC 26 Z9 26 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2007 VL 58 IS 5 BP 1028 EP 1034 DI 10.1002/mrm.21410 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 226AQ UT WOS:000250560000021 PM 17969097 ER PT J AU Brazhnik, P Kohn, KW AF Brazhnik, Paul Kohn, Kurt W. TI HAUSP-regulated switch from auto- to p53 ubiquitination by Mdm2 (in silico discovery) SO MATHEMATICAL BIOSCIENCES LA English DT Article DE p53 ubiquitination; HAUSP; mathematical models; Mdm2; stress response ID TUMOR-SUPPRESSOR PROTEIN; DNA-DAMAGE; DOWN-REGULATION; POSTTRANSLATIONAL MODIFICATIONS; CELL-CYCLE; DEGRADATION; NUCLEAR; PHOSPHORYLATION; ACTIVATION; STABILITY AB Stability of the 'guardian of the genome' tumor suppressor protein p53 is regulated predominantly through its ubiquitination. The ubiquitin-specific protease HAUSP plays an important role in this process. Recent experiments showed that p53 demonstrates a differential response to changes in HAUSP which nature and significance are not understood yet. Here a data-driven mathematical model of the Mdm2-mediated p53 ubiquitination network is presented which offers an explanation for the cause of such a response. The model predicts existence of the HAUSP-regulated switch from auto- to p53 ubiquitination by Mdm2. This switch suggests a potential role of HAUSP as a downstream target of stress signals in cells. The model accounts for a significant amount of experimental data, makes predictions for some rate constants, and can serve as a building block for the larger model describing a complex dynamic response of p53 to cellular stresses. (c) 2007 Elsevier Inc. All rights reserved. C1 Virginia Tech, Dept Sci Biol, Blacksburg, VA 24061 USA. NIH, NCI, Bethesda, MD 20892 USA. RP Brazhnik, P (reprint author), Virginia Tech, Dept Sci Biol, Blacksburg, VA 24061 USA. EM brazhnik@vt.edu NR 92 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD NOV PY 2007 VL 210 IS 1 BP 60 EP 77 DI 10.1016/j.mbs.2007.05.005 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 233MU UT WOS:000251095800004 PM 17585950 ER PT J AU Rosenfeld, S AF Rosenfeld, Simon TI Stochastic cooperativity in non-linear dynamics of genetic regulatory networks SO MATHEMATICAL BIOSCIENCES LA English DT Article DE non-linear dynainics; stochastic processes; gene expression; biochernical networks; S-functions ID BIOCHEMICAL SYSTEMS-ANALYSIS; POWER-LAW APPROXIMATION; ESCHERICHIA-COLI; EXPRESSION; TRANSCRIPTION; NOISE; CELLS; TIME; FLOW AB Two major approaches are known in the field of stochastic dynamics of genetic regulatory networks (GRN). The first one, referred here to as the Markov Process Paradigm (MPP), places the focus of attention on the fact that many biochemical constituents vitally important for the network functionality are present only in small quantities within the cell, and therefore the regulatory process is essentially discrete and prone to relatively big fluctuations. The Master Equation of Markov Processes is an appropriate tool for the description of this kind of stochasticity. The second approach, the Non-linear Dynamics Paradigm (NDP), treats the regulatory process as essentially continuous. A natural tool for the description of such processes are deterministic differential equations. According to NDP, stochasticity in such systems occurs due to possible bistability and oscillatory motion within the limit cycles. The goal of this paper is to outline a third scenario of stochasticity in the regulatory process. This scenario is only conceivable in high-dimensional, highly non-linear systems, and thus represents an adequate framework for conceptually modeling the GRN. We refer to this framework as the Stochastic Cooperativity Paradigm (SCP). In this approach, the focus of attention is placed on the fact that in systems with the size and link density of GRN (similar to 25000 and similar to 100, respectively), the confluence of all the factors which are necessary for gene expression is a comparatively rare event, and only massive redundancy makes such events sufficiently frequent. An immediate consequence of this rareness is 'burstiness' in mRNA and protein concentrations, a well known effect in intracellular dynamics. We demonstrate that a high-dimensional nonlinear system, despite the absence of explicit mechanisms for suppressing inherent instability, may nevertheless reside in a state of stationary pseudo-random fluctuations which for all practical purposes may be regarded as a stochastic process. This type of stochastic behavior is an inherent property of such systems and requires neither an external random force as in the Langevin approach, nor the discreteness of the process as in MPP, nor highly specialized conditions of bistability as in NDP, nor bifurcations with transition to chaos as in low-dimensional chaotic maps. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Bethesda, MD 20892 USA. RP Rosenfeld, S (reprint author), NCI, EPN 3108,6130 Execut Bldg, Bethesda, MD 20892 USA. EM sr2l2a@nih.gov NR 70 TC 2 Z9 2 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 EI 1879-3134 J9 MATH BIOSCI JI Math. Biosci. PD NOV PY 2007 VL 210 IS 1 BP 121 EP 142 DI 10.1016/j.mbs.2007.05.006 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 233MU UT WOS:000251095800007 PM 17617426 ER PT J AU Pereira, M Mason, P Szczesny, RJ Maddukuri, L Dziwura, S Jedrzejczak, R Paul, E Wojcik, A Dybczynska, L Tudek, B Bartnik, E Klysik, J Bohr, VA Stepien, PP AF Pereira, Mandy Mason, Penelope Szczesny, Roman J. Maddukuri, Leena Dziwura, Sylwia Jedrzejczak, Robert Paul, Erin Wojcik, Andrzej Dybczynska, Lien Tudek, Barbara Bartnik, Ewa Klysik, Jan Bohr, Vilhelm A. Stepien, Piotr P. TI Interaction of human SUV3 RNA/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE SUV3; helicase; WRN; BLM; mouse; SCE ID BLOOMS-SYNDROME HELICASE; RNA HELICASE; HOMOLOGOUS RECOMBINATION; GENOMIC STABILITY; REPLICATION FORK; RECQ HELICASES; DNA HELICASES; PROTEIN; PREDISPOSITION; METABOLISM AB The SUV3 gene is present in all eukaryotes and encodes an RNA/DNA helicase which operates both in mitochondria and cell nuclei. To assess its function in mammals we generated a mouse mutant strain in which the 3' part of the SUV3 gene is disrupted. The mutated allele is a hypomorph transmitted from one generation to another at a frequency about 35% lower than expected while mice homozygous for the mutation die in utero before midgestation. Using ELISA binding assays we show that human SUV3 protein interacts with human WRN and BLM helicases. The binding to BLM protein was 10-fold stronger (with a K-d of 0.5 nM) than to WRN protein (Kd of 5 nM). Silencing of the SUV3 gene in the human cell line HeLa resulted in elevation of homologous recombination as measured by the frequency of sister chromatid exchange during mitotic cell division. These results indicate that the SUV3 protein is required in mammalian development and in somatic cells participates in genome maintenance through interaction with other genome fidelity housekeepers. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Szczesny, Roman J.; Maddukuri, Leena; Tudek, Barbara; Bartnik, Ewa; Stepien, Piotr P.] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. [Pereira, Mandy; Paul, Erin; Klysik, Jan] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Mason, Penelope; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, IRP, Natl Inst Hlth, Baltimore, MD 21224 USA. [Dziwura, Sylwia; Dybczynska, Lien; Tudek, Barbara; Bartnik, Ewa; Stepien, Piotr P.] Warsaw Univ, Dept Genet & Biotechnol, Warsaw, Poland. [Wojcik, Andrzej] Inst Nucl Chem & Technol, PL-03195 Warsaw, Poland. RP Stepien, PP (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. EM stepien@ibb.waw.pl FU Intramural NIH HHS; NCRR NIH HHS [5P20RR015578-07] NR 41 TC 18 Z9 23 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV-DEC PY 2007 VL 128 IS 11-12 BP 609 EP 617 DI 10.1016/j.mad.2007.09.001 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 261KV UT WOS:000253078400004 PM 17961633 ER PT J AU Vaitiekunaite, R Butkiewicz, D Krzesniak, M Przybylek, M Gryc, A Snietura, M Benedyk, M Harris, CC Rusin, M AF Vaitiekunaite, Rasa Butkiewicz, Dorota Krzesniak, Malgorzata Przybylek, Malgorzata Gryc, Agata Snietura, Miroslaw Benedyk, Malgorzata Harris, Curtis C. Rusin, Marek TI Expression and localization of Werner syndrome protein is modulated by SIRT1 and PML SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE WRN; BLM; PML; SIRT1; helicase; senescence; aggresomes ID DNA-DAMAGE; FUNCTIONAL INTERACTION; PREMATURE SENESCENCE; NUCLEAR-STRUCTURE; RECQ HELICASES; CELLS; P53; TRANSCRIPTION; ACETYLATION; COLOCALIZES AB Mutations in genes for WRN and BLM RecQ family helicases cause cancer prone syndromes. Werner syndrome, resulting from WRN mutation, is a segmental progeria. Endogenous WRN and BLM proteins localize in nucleoli and in nuclear PML bodies defined by isoforms of the PML protein, which is a key regulator of cellular senescence. We further characterized WRN and BLM localization using labeling with monomeric red fluorescence protein (mRFP). When ectopically expressed, mRFP-WRN (or untagged WRN) forms nuclear bodies, which are donut-shaped in some cells. We identified PML isoforms associating with the nuclear bodies. Interestingly, mRFP-WRN relocalizes from nucleoli to the nucleoplasm, frequently showing conspicuous nucleolar exclusion as well as a decrease in frequency of mRFP-WRN nuclear bodies in response to overexpression of wild-type and deacetylase mutant (H363Y) SIRT1 proteins. Similar nucleolar relocalization in response to wild-type SIRT1 was detected for mRFP-labeled BLM. Moreover, increased SIRT1 expression was associated with the downregulation of endogenous WRN and a decreased frequency of cells with BRCA1 foci. Our data indicate for the first time that SIRT1 protein may be functionally associated with WRN and BLM helicases and that some major SIRT1 functions may not require its deacetylase activity. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Vaitiekunaite, Rasa; Butkiewicz, Dorota; Krzesniak, Malgorzata; Przybylek, Malgorzata; Gryc, Agata; Benedyk, Malgorzata; Rusin, Marek] Marie Sklodowska Curie Mem Canc Ctr, Dept Tumor Biol, PL-44101 Gliwice, Poland. [Vaitiekunaite, Rasa; Butkiewicz, Dorota; Krzesniak, Malgorzata; Przybylek, Malgorzata; Gryc, Agata; Snietura, Miroslaw; Harris, Curtis C.; Rusin, Marek] Inst Oncol, Gilwice Branch, PL-44101 Gliwice, Poland. [Snietura, Miroslaw] Marie Sklodowska Curie Mem Canc Ctr, Dept Pathol, PL-44101 Gliwice, Poland. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rusin, M (reprint author), Marie Sklodowska Curie Mem Canc Ctr, Dept Tumor Biol, Ul Wybrzeze Armii Krajowej 15, PL-44101 Gliwice, Poland. EM rusinm@rocketmail.com NR 47 TC 24 Z9 27 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV-DEC PY 2007 VL 128 IS 11-12 BP 650 EP 661 DI 10.1016/j.mad.2007.09.004 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 261KV UT WOS:000253078400008 PM 17996922 ER PT J AU Badano, A Kyprianou, IS Jennings, RJ Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Jennings, Robert J. Sempau, Josep TI Anisotropic imaging performance in breast tomosynthesis SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo simulation; digital imaging; phosphor screen; cesium iodide; point response function; Swank factor ID MONTE-CARLO-SIMULATION; CESIUM IODIDE SCINTILLATORS; RAY FLUORESCENT SCREENS; POINT-SPREAD FUNCTION; X-RAY; DIGITAL MAMMOGRAPHY; CODE PENELOPE; COLUMNAR PHOSPHORS; ELECTRON; EFFICIENCY AB We describe the anisotropy in imaging performance caused by oblique x-ray incidence in indirect detectors for breast tomosynthesis based on columnar scintillator screens. We use MANTIS, a freely available combined x-ray, electron, and optical Monte Carlo transport package which models the indirect detection processes in columnar screens, interaction by interaction. The code has been previously validated against published optical distributions. In this article, initial validation results are provided concerning the blur for particular designs of phosphor screens for which some details with respect to the columnar geometry are available from scanning electron microscopy. The poly-energetic x-ray spectrum utilized comes from a database of experimental data for three different anode/filter/kVp combinations: Mo/Mo at 28 kVp, Rh/Rh at 28 kVp, and W/A1 at 42 kVp. The x-ray spectra were then filtered with breast tissue (3, 4, and 6 cm thickness), compression paddle, and support base, according to the oblique paths determined by the incidence angle. The composition of the breast tissue was 50% /50% adipose/glandular tissue mass ratio. Results are reported on the pulse-height statistics of the light output and on spatial blur, expressed as the response of the detector to a pencil beam with a certain incidence angle. Results suggest that the response is nonsymmetrical and that the resolution properties of a tomosynthesis system vary significantly with the angle of x-ray incidence. In contrast, it is found that the noise due to the variability in the number of light photons detected per primary x-ray interaction changes only a few percent. The anisotropy in the response is not less in screens with absorptive backings while the noise introduced by variations in the depth-dependent light output and optical transport is larger. The results suggest that anisotropic imaging performance across the detector area can be incorporated into reconstruction algorithms for improving the image quality of breast tomosynthesis. This study also demonstrates that the assessment of image quality of breast tomosynthesis systems requires a more complete description of the detector response beyond local, center measurements of resolution and noise that assume some degree of symmetry in the detector performance. (C) 2007 American Association of Physicists in Medicine. C1 US FDA, CDRH NIBIB Lab Anal Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. Univ Politecn Cataluna, Inst Tecn Energet, E-08028 Barcelona, Spain. RP Badano, A (reprint author), US FDA, CDRH NIBIB Lab Anal Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 FU Intramural NIH HHS NR 40 TC 25 Z9 25 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2007 VL 34 IS 11 BP 4076 EP 4091 DI 10.1118/1.2779943 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234FK UT WOS:000251145900002 PM 18074617 ER PT J AU Romagnoli, R Baraldi, PG Remusat, V Carrion, MD Cara, CL Cruz-Lopez, O Preti, D Fruttarolo, F Tabrizi, MA Balzarini, J Hamel, E AF Romagnoli, Romeo Baraldi, Pier Giovanni Remusat, Vincent Carrion, Maria Dora Cara, Carlota Lopez Cruz-Lopez, Olga Preti, Delia Fruttarolo, Francesca Tabrizi, Mojgan Aghazadeh Balzarini, Jan Hamel, Ernest TI Synthesis and biological evaluation of 2-amino-3-(3 ',4 ',5 '-trimethoxyphenyisulfonyl)-5-aryl thiophenes as a new class of antitubulin agents SO MEDICINAL CHEMISTRY LA English DT Article DE microtubule; combretastatin A-4; bioisoster; 2-aminothiophene ID ANTIMITOTIC NATURAL-PRODUCTS; ANTINEOPLASTIC AGENTS; COMBRETASTATIN A-4; DRUG DESIGN; TUBULIN; PHOSPHATE; POLYMERIZATION; BIOISOSTERISM; PROTEINS; A4 AB Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. Bioisosteres are substituents or groups that have chemical or physical similarities and that produce broadly similar biological effects. The sulfone moiety is recognized as a nonclassical bioisostere for replacement of the carbonyl group. When sulfonyl derivatives 5a-e were compared with carbonyl compounds 4a-e, the sulfone substitution dramatically decreased the antiproliferative activity of the series. C1 Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. Katholieke Univ Leuven, Rega Inst Med Res, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium. NCI, 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, Via Fossato Mortara 17-19, 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; Cruz-Lopez, Olga /F-3060-2017 OI LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; Carrion, M. Dora/0000-0002-6794-3949; preti, delia/0000-0002-1075-3781; NR 25 TC 3 Z9 3 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 J9 MED CHEM JI Med. Chem. PD NOV PY 2007 VL 3 IS 6 BP 507 EP 512 DI 10.2174/157340607782360380 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 225BF UT WOS:000250491400001 PM 18045199 ER PT J AU Shiotani, K Miyazaki, A Li, T Tsuda, Y Yokoi, T Arnbo, A Sasaki, Y Bryant, SD Jinsmaa, Y Lazarus, LH Okada, Y AF Shiotani, Kimitaka Miyazaki, Anna Li, Tingyou Tsuda, Yuko Yokoi, Toshio Arnbo, Akihiro Sasaki, Yusuke Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. Okada, Yoshio TI Synthesis of opioidmimetics, 3-[H-Dmt-NH(CH2)(m)]-6-[H-Dmt-NH(CH2)(n)]2(1H)-pyrazinones, and studies on structure-activity relationships SO MEDICINAL CHEMISTRY LA English DT Article DE opioidmimetic; 2 ',6 '-dimethyl-L-tyrosin (Dmt); pyrazinone platform; Dmt-dimerization; opioid receptor affinity; mu-agonism; delta-antagonism; structure-activity relationship ID OPIOID RECEPTOR ANTAGONISTS; DELTA-OPIATE RECEPTOR; CATALYTIC-HYDROGENATION; IMMEDIATE DEAMINATION; ENDOGENOUS AGONIST; MEDIATED ANALGESIA; BETA-LIPOTROPIN; POTENT; PEPTIDES; ANALOGS AB Opioidmimetics containing 3-[H-Dmt-NH-(CH2)(m)]-6-[H-Dmt-NH-(CH2)(n)]-2(1H)-pyrazinone symmetric (m = n, 1-4) (1 - 4) and asymmetric (m, n = 1 - 4) aliphatic chains (5 - 16) were synthesized using dipeptidyl chloromethylketone intermediates. They had high mu-affinity (K-i mu = 0.021 - 2.94 nM), delta-affinity (K-i delta = 1.06 - 152.6 nM), and mu selectivity (K-i delta/K-i mu = 14 - 3,126). The opioidmimetics (1 - 16) exhibited mu agonism, in proportion to their mu-receptor affinity. Agonism was essentially lacking in the compounds except (4) and (16), and (1) and (2) indicated weak 8 antagonism (pA(2) = 6.47 and 6.56, respectively). The data verify that a specific length of aliphatic linker is required between the Dint pharmacophore and the pyrazinone ring to produce unique t-opioid receptor ligands. C1 Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. Tohoku Pharmaceut Univ, Sendai, Miyagi 9818558, Japan. Natl Inst Environm Hlth Sci, LPC, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS NR 45 TC 1 Z9 1 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 J9 MED CHEM JI Med. Chem. PD NOV PY 2007 VL 3 IS 6 BP 583 EP 598 DI 10.2174/157340607782360272 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 225BF UT WOS:000250491400011 PM 18045209 ER PT J AU Kriska, AM Brach, JS Jarvis, BJ Everhart, JE Fabio, A Richardson, CR Howard, BV AF Kriska, Andrea M. Brach, Jennifer S. Jarvis, Betty J. Everhart, James E. Fabio, Anthony Richardson, Caroline R. Howard, Barbara V. TI Physical activity and gallbladder disease determined by ultrasonography SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE gallstones; exercise; American Indians; gallbladder ultrasonography ID PIMA-INDIANS; OBESITY; ASSOCIATION; PREVENTION; PREVALENCE; EXERCISE; WOMEN; RISK AB Purpose: Several prospective studies have suggested that physical activity may decrease the risk for symptomatic gallbladder disease. None of these studies were able to include subjects with asymptomatic gallstones in their case group. Methods: This investigation examined the relationship between physical activity levels and the development of gallbladder disease determined by ultrasonography in a population-based cohort of 3143 men and women, 45-74 yr of age, from 13 American Indian communities. Participants were examined at baseline (1989-1992), at which time physical activity levels, age, body mass index, waist circumference, smoking status, and diabetes status were determined. Gallbladder disease status was assessed in the entire cohort at follow-up (1993-1995) by ultrasonography. Results: Individuals who reported at baseline that they had gallbladder surgery or that a physician had told them that they had gallbladder disease were removed from the analyses. Out of the 2130 remaining, 650 individuals (403 women and 247 men) were found to have gallbladder disease according to ultrasound or reported surgery by the follow-up clinic visit. After adjusting for potential confounders including body mass index, increased activity levels were inversely related to gallbladder disease status. These findings were maintained when the data were stratified by sex, but they were only significant in individuals without diabetes (not in those with diabetes). Conclusions: Physical activity seems to be significantly and inversely related to the development of gallbladder disease as assessed by ultrasonography in a population at high risk for gallbladder disease. These findings add to the evidence supporting a causal link between physical activity levels and a decreased risk of gallbladder disease, and they provide yet another reason to encourage the achievement and maintenance of a physically active lifestyle. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Hlth & Rehabilitat Sci, Pittsburgh, PA USA. Medstat Res Inst, Phoenix, AZ USA. Medstat Res Inst, Hyattsville, MD USA. NIDDK, Bethesda, MD USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Michigan, VA Med Ctr, Ann Arbor, MI USA. RP Kriska, AM (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM aky@pitt.edu OI Kriska, Andrea/0000-0002-3522-0869; Fabio, Anthony/0000-0002-6808-4939 FU NHLBI NIH HHS [U01 HL41652, U01 HL4164, U01 HL41642]; NIMHD NIH HHS [MD-000-207-03]; PHS HHS [P60] NR 19 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2007 VL 39 IS 11 BP 1927 EP 1932 DI 10.1249/mss.0b013e3181484d0e PG 6 WC Sport Sciences SC Sport Sciences GA 230VB UT WOS:000250903100006 PM 17986899 ER PT J AU Taylor, GA Feng, CG Sher, A AF Taylor, Gregory A. Feng, Carl G. Sher, Alan TI Control of IFN-gamma-mediated host resistance to intracellular pathogens by immunity-related GTPases (p47 GTPases) SO MICROBES AND INFECTION LA English DT Article DE interferon; GTPase; innate immunity ID INDUCIBLY EXPRESSED GTPASE; TOXOPLASMA-GONDII; INTERFERON-GAMMA; ENDOPLASMIC-RETICULUM; BINDING PROTEIN; MICE DEFICIENT; 47-KDA GTPASE; INFECTION; LRG-47; IGTP AB IRG proteins (also known as p47 GTPases) are key mediators of interferon-gamma-induced resistance to pathogens. Absence of certain IRG proteins leads to profound susceptibility to protozoa and bacteria in mice. Underlying their roles in host resistance, IRG proteins regulate the processing of pathogen-containing vacuoles in host cells, and regulate hernatopoiesis following infection. Published by Elsevier Masson SAS. C1 [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Div Geriatr,Dept Med, Durham, NC 27705 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Div Geriatr,Dept Mol Genet, Durham, NC 27705 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Div Geriatr,Dept Microbiol, Durham, NC 27705 USA. [Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Div Geriatr,Dept Immunol, Durham, NC 27705 USA. [Taylor, Gregory A.] Vet Adm Med Ctr, GRECC, Durham, NC 27705 USA. [Feng, Carl G.; Sher, Alan] NIAID, Parasit Dis Lab, Immunol Sect, Bethesda, MD 20892 USA. RP Taylor, GA (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Div Geriatr,Dept Med, 508 Fulton St,Room N3008, Durham, NC 27705 USA. EM gregory.taylor@duke.edu; asher@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI57831, R01 AI057831] NR 40 TC 58 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD NOV-DEC PY 2007 VL 9 IS 14-15 BP 1644 EP 1651 DI 10.1016/j.micinf.2007.09.004 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 250WX UT WOS:000252333100018 PM 18023232 ER PT J AU Yin, JJ Pollock, C Tracy, K Chock, M Martin, P Oberst, M Kelly, K AF Yin, JuanJuan Pollock, Claire Tracy, Kirsten Chock, Monika Martin, Philip Oberst, Michael Kelly, Kathleen TI Activation of the RaIGEF/ral pathway promotes prostate cancer metastasis to bone SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BREAST-CANCER; RAL-GTPASES; CELL-TRANSFORMATION; PRIMARY TUMORS; SOLID TUMORS; PROGRESSION; KINASE; GROWTH; GENES; ANGIOGENESIS AB A hallmark of metastasis is organ specificity; however, little is known about the underlying signaling pathways responsible for the colonization and growth of tumor cells in target organs. Since tyrosine kinase receptor activation is frequently associated with prostate cancer progression, we have investigated the role of a common signaling intermediary, activated Ras, in prostate cancer metastasis. Three effector pathways downstream of Ras, Raf/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase, and Ral guanine nucleotide exchange factors (RaIGEFs), were assayed for their ability to promote the metastasis of a tumorigenic, nonmetastatic human prostate cancer cell line, DU145. Oncogenic Ras promoted the metastasis of DU145 to multiple organs, including bone and brain. Activation of the Raf/ERK pathway stimulated metastatic colonization of the brain, while activation of the RaIGEF pathway led to bone metastases, the most common organ site for prostate cancer metastasis. In addition, loss of RaIA in the metastatic PC3 cell line inhibited bone metastasis but did not affect subcutaneous tumor growth. Loss of RaI appeared to suppress expansive growth of prostate cancer cells in bone, whereas homing and initial colonization were less affected. These data extend our understanding of the functional roles of the RaI pathway and begin to identify signaling pathways relevant for organ-specific metastasis. C1 NCI, Ctr Canc Res, Cell & Canc Bil Branch, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), NCI, Ctr Canc Res, Cell & Canc Bil Branch, 37 Convert Dr,Rm 1068, Bethesda, MD 20892 USA. EM kellyka@mail.nih.gov FU Intramural NIH HHS NR 43 TC 57 Z9 60 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2007 VL 27 IS 21 BP 7538 EP 7550 DI 10.1128/MCB.00955-07 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 223LK UT WOS:000250371600016 PM 17709381 ER PT J AU Das, M Scappini, E Martin, NP Wong, KA Dunn, S Chen, YJ Miller, SLH Domin, J O'Bryan, JP AF Das, Margaret Scappini, Erica Martin, Negin P. Wong, Katy A. Dunn, Sara Chen, Yun-Ju Miller, Stephanie L. H. Domin, Jan O'Bryan, John P. TI Regulation of neuron survival through an intersectin-phosphoinositide 3'-kinase C2 beta-AKT pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOCYTIC PROTEIN INTERSECTIN; BIMOLECULAR FLUORESCENCE COMPLEMENTATION; DENDRITIC SPINE DEVELOPMENT; GROWTH-FACTOR RECEPTOR; ADAPTER PROTEIN; CLATHRIN; CDC42; CELLS; RAS; NETWORK AB While endocytosis attenuates signals from plasma membrane receptors, recent studies suggest that endocytosis also serves as a platform for the compartmentalized activation of cellular signaling pathways. Intersectin (ITSN) is a multidomain scaffolding protein that regulates endocytosis and has the potential to regulate various biochemical pathways through its multiple, modular domains. To address the biological importance of ITSN in regulating cellular signaling pathways versus in endocytosis, we have stably silenced ITSN expression in neuronal cells by using short hairpin RNAs. Decreasing ITSN expression dramatically increased apoptosis in both neuroblastoma cells and primary cortical neurons. Surprisingly, the loss of ITSN did not lead to major defects in the endocytic pathway. Yeast two-hybrid analysis identified class II phosphoinositide 3 '-kinase C2 beta PI3K-C2 beta as an ITSN binding protein, suggesting that ITSN may regulate a PI3K-C2 beta-AKT survival pathway. ITSN associated with PI3K-C2 beta on a subset of endomembrane vesicles and enhanced both basal and growth factor-stimulated PI3K-C2 beta activity, resulting in AKT activation. The use of pharmacological inhibitors, dominant negatives, and rescue experiments revealed that PI3K-C2 beta and AKT were epistatic to ITSN. This study represents the first demonstration that ITSN, independent of its role in endocytosis, regulates a critical cellular signaling pathway necessary for cell survival. C1 Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. US Dept HHS, Lab Signal Transduct, Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. US Dept HHS, Neurobiol Lab, Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Dept Biomed Engn, Chapel Hill, NC 27599 USA. Imperial Coll Sch Med, Div Med, London W12 0NN, England. RP O'Bryan, JP (reprint author), Univ Illinois, Coll Med, Dept Pharmacol, 835 S Wolcott,E403 M-C 868, Chicago, IL 60612 USA. EM obryanj@uic.edu FU Intramural NIH HHS; Medical Research Council [G0500936] NR 36 TC 48 Z9 57 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2007 VL 27 IS 22 BP 7906 EP 7917 DI 10.1128/MCB.01369-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229KD UT WOS:000250800900015 PM 17875942 ER PT J AU Huang, S Li, X Yusufzai, TM Qiu, Y Felsenfeld, G AF Huang, Suming Li, Xingguo Yusufzai, Timur M. Qiu, Yi Felsenfeld, Gary TI USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FAMILIAL COMBINED HYPERLIPIDEMIA; H3 LYSINE-27 METHYLATION; TRANSCRIPTION FACTOR USF; BETA-GLOBIN LOCUS; PROTEIN METHYLTRANSFERASE; HEMATOPOIETIC EXPRESSION; EPIGENETIC CONTROL; ENHANCER BLOCKING; RECEPTOR FUNCTION; GENE-EXPRESSION AB The insulator element at the 5 ' end of the chicken beta-globin locus acts as a barrier, protecting transgenes against silencing effects of adjacent heterochromatin. We showed earlier that the transcription factor USF1 binds within the insulator and that this site is important for generating in adjacent nucleosomes histone modifications associated with active chromatin and, by inference, with barrier function. To understand the mechanism of USF1 action, we have characterized USF1-containing complexes. USF1 interacts directly with the histone H4R3-specific methyltransferase PRMT1. USF1, PRMT1, and the histone acetyltransferases (HATS) PCAF and SRC-1 form a complex with both H4R3 histone methyltransferase and HAT activities. Small interfering RNA downregulation of USF1 results in localized loss of H4R3 methylation, and other histone modifications associated with euchromatin, at the insulator. A dominant negative peptide that interferes with USF1 binding to DNA causes silencing of an insulated reporter construct, indicating abolition of barrier function. These results show that USF1 plays a direct role in maintaining the barrier, supporting a model in which the insulator works as a barrier by maintaining a local environment of active chromatin. C1 Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32611 USA. RP Huang, S (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM sumingh@ufl.edu; Gary.felsenfeld@nih.gov FU Intramural NIH HHS NR 46 TC 81 Z9 85 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2007 VL 27 IS 22 BP 7991 EP 8002 DI 10.1128/MCB.01326-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229KD UT WOS:000250800900022 PM 17846119 ER PT J AU Vogt, DL Gray, CD Young, W Orellana, SA Malouf, AT AF Vogt, D. L. Gray, C. D. Young, Ws., III Orellana, S. A. Malouf, A. T. TI ARHGAP4 is a novel RhoGAP that mediates inhibition of cell motility and axon outgrowth SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID GTPASE-ACTIVATING PROTEINS; GROWTH CONE; ACTIN; GUIDANCE; KINASE; COMPLEXES; DOMAIN; CDC42; GENE; MICROTUBULES AB This report examines the structure and function of ARHGAP4, a novel RhoGAP whose structural features make it ideally suited to regulate the cvtoskeletal dvnamics that control cell motility and axon outgrowth. Our studies show that ARHGAP4 inhibits the migration of NIH/3T3 cells and the outgrowth of hippocampal axons. ARHGAP4 contains an N-terminal FCH domain, a central GTPase activating (GAP) domain and a C-terminal SH3 domain. Our structure/function analyses show that the FCH domain appears to be important for spatially localizing ARHGAP4 to the leading edges of migrating NIH/3T3 cells and to axon growth cones. Our analyses also show that the GAP domain and C-terminus are necessary for APHGAP4-mediated inhibition of cell and axon motility. These observations suggest that ARHGAP4 can act as a potent inhibitor of cell and axon motility when it is localized to the leading edge of motile cells and axons. (c) 2007 Elsevier Inc. All rights reserved. C1 Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. RP Malouf, AT (reprint author), Case Western Reserve Univ, Dept Pediat, 11100 Euclid Ave,MS 6040, Cleveland, OH 44106 USA. EM alfred.malouf@case.edu RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; Vogt, Daniel/0000-0003-1876-5936 FU Intramural NIH HHS; NIGMS NIH HHS [T32 GM007250]; NIMH NIH HHS [Z01 MH002498]; NINDS NIH HHS [NS 41383, R01 NS041383, R01 NS041383-04] NR 33 TC 23 Z9 24 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2007 VL 36 IS 3 BP 332 EP 342 DI 10.1016/j.mcn.2007.07.004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 230RX UT WOS:000250894700003 PM 17804252 ER PT J AU Zheng, J Rogozin, IB Koonin, EV Przytycka, TM AF Zheng, Jie Rogozin, Igor B. Koonin, Eugene V. Przytycka, Teresa M. TI Support for the coelomata clade of animals from a rigorous analysis of the pattern of intron conservation SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE intron loss; intron conservation; phylogenetic analysis; coelomata; ecdysozoa ID LONG-BRANCH ATTRACTION; PHYLOGENETIC ANALYSIS; MODEL ORGANISMS; GENE-SEQUENCES; GENOME TREES; EVOLUTION; ECDYSOZOA; RECONSTRUCTION; ARTHROPODS; ARTIFACTS AB Many intron positions are conserved in varying subsets of eukaryotic genomes and, consequently, comprise a potentially informative class of phylogenetic characters. Roy and Gilbert developed a method of phylogenetic reconstruction using the patterns of intron presence-absence in eukaryotic genes and, applying this method to the analysis of animal phylogeny, obtained support for an Ecdysozoa clade (Roy SW, Gilbert W. 2005. Resolution of a deep animal divergence by the pattern of intron conservation. Proc Natl Acad Sci USA. 102:4403-4408). The critical assumption in the method was the independence of intron loss in different branches of the phylogenetic tree. Here, this assumption is refuted by showing that the branch-specific intron loss rates are strongly correlated. We show that different tree topologies are obtained, in each case with a significant statistical support, when different subsets of intron positions are analyzed. The analysis of the conserved intron positions supports the Coelomata topology, that is, a clade comprised of arthropods and chordates, whereas the analysis of more variable intron positions favors the Ecdysozoa topology, that is, a clade of arthropods and nematodes. We show, however, that the support for Ecdysozoa is fully explained by parallel loss of introns in nematodes and arthropods, a factor that does not contribute to the analysis of the conserved introns. The developed procedure for the identification and analysis of conserved introns and other characters with minimal or no homoplasy is expected to be useful for resolving many hard phylogenetic problems. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM przytyck@mail.nih.edu RI Zheng, Jie/C-1356-2011 OI Zheng, Jie/0000-0001-6774-9786 FU Intramural NIH HHS NR 63 TC 31 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 2007 VL 24 IS 11 BP 2583 EP 2592 DI 10.1093/molbev/msm207 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 227UI UT WOS:000250682900024 PM 17893400 ER PT J AU Yoshikawa, H Matsubara, K Zhou, X Okamura, S Kubo, T Murase, Y Shikauchi, Y Esteller, M Herman, JG Wang, XW Harris, CC AF Yoshikawa, Hirohide Matsubara, Kenichi Zhou, Xiaoling Okamura, Shu Kubo, Takahiko Murase, Yaeko Shikauchi, Yuko Esteller, Manel Herman, James G. Wang, Xin Wei Harris, Curtis C. TI WNT10B functional dualism: beta-Catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; GENE FAMILY; PROTOONCOGENE INT-1; C-MYC; TRANSCRIPTIONAL ACTIVATION; NEGATIVE REGULATOR; COLORECTAL-CANCER; SIGNALING PATHWAY; COLON-CARCINOMA; MAMMARY-GLAND AB We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator. C1 NCI, Natl Inst Hlth, Human Carcinogenesis Lab, Bethesda, MD 20896 USA. Japanese Fdn Canc Res, Inst Canc, Dept Epigenet Carcinogenesis, Tokyo 1358550, Japan. DNA Chip Res Inc, Kanagawa 2300045, Japan. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21231 USA. RP Harris, CC (reprint author), NCI, Natl Inst Hlth, Human Carcinogenesis Lab, Bethesda, MD 20896 USA. EM curtis_harris@nih.gov RI Wang, Xin/B-6162-2009; Esteller, Manel/L-5956-2014 OI Esteller, Manel/0000-0003-4490-6093 FU Intramural NIH HHS; NCI NIH HHS [P50 CA058184, P50 CA58184] NR 78 TC 17 Z9 23 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2007 VL 18 IS 11 BP 4292 EP 4303 DI 10.1091/mbc.E06-10-0889 PG 12 WC Cell Biology SC Cell Biology GA 228OT UT WOS:000250740000008 PM 17761539 ER PT J AU Li, CC Chiang, TC Wu, TS Pacheco-Rodriguez, G Moss, J Lee, FJS AF Li, Chun-Chun Chiang, Tsai-Chen Wu, Tsung-Sheng Pacheco-Rodriguez, Gustavo Moss, Joel Lee, Fang-Jen S. TI ARL4D recruits cytohesin-2/ARNO to modulate actin remodeling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GUANINE-NUCLEOTIDE-EXCHANGE; ADP-RIBOSYLATION FACTOR; PLECKSTRIN-HOMOLOGY DOMAINS; GTP-BINDING PROTEINS; PLASMA-MEMBRANE; SEC7 DOMAIN; FACTOR ARNO; PH DOMAIN; ARF GTPASES; ACTIVATION AB ARL4D is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. Although the primary structure of ARL4D is very similar to that of other ARF/ARL molecules, its function remains unclear. Cytohesin-2/ARF nucleotide-binding-site opener (ARNO) is a guanine nucleotide-exchange factor (GEF) for ARE, and, at the plasma membrane, it can activate ARF6 to regulate actin reorganization and membrane ruffling. We show here that ARL4D interacts with the C-terminal pleckstrin homology (PH) and polybasic c domains of cytohesin-2/ARNO in a GTP-dependent manner. Localization of ARL4D at the plasma membrane is GTP- and N-terminal myristoylation-dependent. ARL4D(Q80L), a putative active form of ARL4D, induced accumulation of cytohesin-2/ARNO at the plasma membrane. Consistent with a known action of cytohesin-2/ARNO, ARL4D(Q80L) increased GTP-bound ARF6 and induced disassembly of actin stress fibers. Expression of inactive cytohesin-2/ARNO(E156K) or small interfering RNA knockdown of cytohesin-2/ARNO blocked ARL4D-mediated disassembly of actin stress fibers. Similar to the results with cytohesin-2/ARNO or ARF6, reduction of ARL4D suppressed cell migration activity. Furthermore, ARL4D-induced translocation of cytohesin-2/ARNO did not require phosphoinositide 3-kinase activation. Together, these data demonstrate that ARL4D acts as a novel upstream regulator of cytohesin-2/ARNO to promote ARF6 activation and modulate actin remodeling. C1 Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Med Res, Taipei 100, Taiwan. NHLBI, NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. RP Lee, FJS (reprint author), Natl Taiwan Univ, Coll Med, Inst Mol Med, Taipei, Taiwan. EM fangjen@ha.mc.ntu.edu.tw OI LEE, FANG-JEN/0000-0002-2167-2426 FU Intramural NIH HHS NR 80 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2007 VL 18 IS 11 BP 4420 EP 4437 DI 10.1091/mbc.E07-02-0149 PG 18 WC Cell Biology SC Cell Biology GA 228OT UT WOS:000250740000019 PM 17804820 ER PT J AU Xiao, L Rao, JN Zou, TT Liu, L Marasa, BS Chen, J Turner, DJ Zhou, HP Gorospe, M Wang, JY AF Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Marasa, Bernard S. Chen, Jie Turner, Douglas J. Zhou, Huiping Gorospe, Myriam Wang, Jian-Ying TI Polyamines regulate the stability of activating transcription factor-2 mRNA through RNA-binding protein HuR in intestinal epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID C-JUN; ORNITHINE DECARBOXYLASE; MUCOSAL GROWTH; APOPTOSIS; DEPLETION; EXPRESSION; PHOSPHORYLATION; STABILIZATION; PROLIFERATION; METABOLISM AB Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR. Here, we show that polyamines negatively regulate ATF-2 expression posttranscriptionally and that polyamine depletion stabilizes ATF-2 mRNA by enhancing the interaction of the 3'-untranslated region (UTR) of ATF-2 with cytoplasmic HuR. Decreasing cellular polyamines by inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine increased the levels of ATF-2 mRNA and protein, whereas increasing polyamines by ectopic ODC overexpression repressed ATF-2 expression. Polyamine depletion did not alter transcription via the ATF-2 gene promoter but increased the stability of ATF-2 mRNA. Increased cytoplasmic HuR in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous ATF-2 mRNA and specifically bound to 3'-UTR of ATF-2 mRNA on multiple nonoverlapping 3'-UTR segments. Adenovirus-mediated HuR overexpression elevated ATF-2 mRNA and protein levels, whereas HuR silencing rendered the ATF-2 mRNA unstable and prevented increases in ATF-2 mRNA and protein. Furthermore, inhibition of ATF-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-a and cycloheximide. These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis. C1 Univ Maryland, Sch Med, Cell Biol Grp, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wang, JY (reprint author), Univ Maryland, Sch Med, Cell Biol Grp, Dept Surg, Baltimore, MD 21201 USA. EM jwang@smail.umaryland.edu FU Intramural NIH HHS; NCCIH NIH HHS [AT-4148, R01 AT004148]; NIAID NIH HHS [AI-68432, R21 AI068432]; NIDDK NIH HHS [DK-61972, R01 DK061972, DK-68491, R01 DK057819, R01 DK068491, DK-57819] NR 63 TC 47 Z9 51 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2007 VL 18 IS 11 BP 4579 EP 4590 DI 10.1091/mbc.E07-07-0675 PG 12 WC Cell Biology SC Cell Biology GA 228OT UT WOS:000250740000032 PM 17804813 ER PT J AU Jollivet, F Raposo, GA Dimitrov, A Sougrat, R Goud, B Perez, F AF Jollivet, Florence Raposo, Gra A. Dimitrov, Ariane Sougrat, Rachid Goud, Bruno Perez, Franck TI Analysis of de novo golgi complex formation after enzyme-based inactivation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ENDOPLASMIC-RETICULUM; RECYCLING ENDOSOMES; MAMMALIAN-CELLS; SNARE COMPLEX; TRANSPORT; APPARATUS; PROTEIN; VESICLES; INHERITANCE; ANTEROGRADE AB The Golgi complex is characterized by its unique morphology of closely apposed flattened cisternae that persists despite the large quantity of lipids and proteins that transit bidirectionally. Whether such a structure is maintained through endoplasmic reticulum (ER)-based recycling and auto-organization or whether it depends on a permanent Golgi structure is strongly debated. To further study Golgi maintenance in interphase cells, we developed a method allowing for a drug-free inactivation of Golgi dynamics and function in living cells. After Golgi inactivation, a new Golgi-like structure, containing only certain Golgi markers and newly synthesized cargos, was produced. However, this structure did not acquire a normal Golgi architecture and was unable to ensure a normal trafficking activity. This suggests an integrative model for Golgi maintenance in interphase where the ER is able to autonomously produce Golgi-like structures that need pre-existing Golgi complexes to be organized as morphologically normal and active Golgi elements. C1 CNRS, Unite Mixte Rech 144, F-75248 Paris 05, France. Inst Curie, F-75248 Paris, France. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Perez, F (reprint author), CNRS, Unite Mixte Rech 144, F-75248 Paris 05, France. EM Franck.Perez@curie.fr OI Sougrat, Rachid/0000-0001-6476-1886; Perez, Franck/0000-0002-9129-9401 NR 48 TC 6 Z9 7 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2007 VL 18 IS 11 BP 4637 EP 4647 DI 10.1091/mbc.E07-08-0799 PG 11 WC Cell Biology SC Cell Biology GA 228OT UT WOS:000250740000037 PM 17855505 ER PT J AU Varricchio, L Migliaccio, A Castoria, G Yamaguchi, H de Falco, A Di Domenico, M Giovannelli, P Farrar, W Appella, E Auricchio, F AF Varricchio, Lilian Migliaccio, Antimo Castoria, Gabriella Yamaguchi, Hiroshi de Falco, Antonietta Di Domenico, Marina Giovannelli, Pia Farrar, William Appella, Ettore Auricchio, Ferdinando TI Inhibition of estradiol receptor/Src association and cell growth by an estradiol receptor alpha tyrosine-phosphorylated peptide SO MOLECULAR CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR; BREAST-CANCER; MCF-7 CELLS; PATHWAY ACTIVATION; ANDROGEN RECEPTOR; DNA-SYNTHESIS; KINASE; PROTEIN; SRC; COMPLEX AB This report offers direct evidence that association of the estradiol receptor (ER) with Src triggered by steroid agonists or growth factors controls breast and prostate cancer cell growth. This association is abolished in whole cells and in vitro by a six-amino-acid peptide that mimics the sequence around the phosphotyrosine residue in position 537 of the human ER alpha. The phosphorylated peptide, at nanomolar concentrations, is taken up by MCF-7 and LNCaP cells derived from human mammary and prostate cancers, respectively. In addition, to block the ER/Src interaction, the phosphopeptide inhibits Src/Erk pathway, cyclin D1 expression, and DNA synthesis induced by estradiol or androgen or triggered by epidermal growth factor. In contrast, no inhibition of the Src-mediated epidermal growth factor action on DNA synthesis is detectable in human mammary cancer cells that do not express ER (MDA-MB231), indicating that the peptide specifically targets the ER-associated Src. Remarkably, the peptide, in contrast with classic steroid antagonists, does not interfere in ER- or androgen receptor-dependent transcriptional activity. Nevertheless, it markedly inhibits the growth of MCF-7 cell xenografts induced in immunodepressed and estradiol-treated mice. The present report suggests that inhibition of association of steroid receptors with Src or other signaling effectors may have therapeutic applications for patients with ER-positive tumors. C1 Univ Naples 2, Dept Gen Pathol, I-80138 Naples, Italy. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, NCI, Frederick, MD USA. RP Auricchio, F (reprint author), Univ Naples 2, Dept Gen Pathol, Via L De Crecchio 7, I-80138 Naples, Italy. EM ferdinando.auricchio@unina2.it OI Di Domenico, Marina/0000-0002-6201-4200; Castoria, Gabriella/0000-0002-0576-4494 FU Intramural NIH HHS NR 26 TC 52 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2007 VL 5 IS 11 BP 1213 EP 1221 DI 10.1158/1541-7786.MCR-07-0150 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 233NH UT WOS:000251097100010 PM 18025264 ER PT J AU Jewett, MW Byram, R Bestor, A Tilly, K Lawrence, K Burtnick, MN Gherardini, F Rosa, PA AF Jewett, Mollie W. Byram, Rebecca Bestor, Aaron Tilly, Kit Lawrence, Kevin Burtnick, Mary N. Gherardini, Frank Rosa, Patricia A. TI Genetic basis for retention of a critical virulence plasmid of Borrelia burgdorferi SO MOLECULAR MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; CIRCULAR PLASMID; OUTER-SURFACE; STRAIN B31; INFECTIOUS CYCLE; MAMMALIAN HOST; SENSU-STRICTO; CELL-SURFACE; TICK VECTOR; OSPC GENE AB The genome of Borrelia burgdorferi is composed of one linear chromosome and approximately 20 linear and circular plasmids. Although some plasmids are required by B. burgdorferi in vivo, most plasmids are dispensable for growth in vitro. However, circular plasmid (cp) 26 is present in all natural isolates and has never been lost during in vitro growth. This plasmid carries ospC, which is critical for mammalian infection. We previously showed that cp26 encodes essential functions, including the telomere resolvase, ResT, and hence cannot be displaced. Here we identify two additional essential genes on cp26, bbb26 and bbb27, through a systematic attempt to inactivate each open reading frame (ORF). Furthermore, an incompatible plasmid carrying resT, bbb26 and bbb27 could displace cp26. Computational and experimental analyses suggested that both BBB26 and BBB27 are membrane-associated, periplasmic proteins. These data indicate that bbb26 and bbb27 encode essential but possibly redundant functions and that one or the other of these cp26 genes, in addition to resT, is required for bacterial viability. We conclude that the genetic linkage of critical physiological and virulence functions on cp26 is pertinent to its stable maintenance throughout the evolution of B. burgdorferi. C1 NIH, NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. Univ Wyoming, Dept Mol Biol, Laramie, WY 82701 USA. RP Rosa, PA (reprint author), NIH, NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. EM prosa@nih.gov FU Intramural NIH HHS NR 66 TC 41 Z9 41 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2007 VL 66 IS 4 BP 975 EP 990 DI 10.1111/j.1365-2958.2007.05969.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 227HM UT WOS:000250647800011 PM 17919281 ER PT J AU Srivastava, P Chattoraj, DK AF Srivastava, Preeti Chattoraj, Dhruba K. TI Selective chromosome amplification in Vibrio cholerae SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; DIFFERENT GROWTH-RATES; COPY NUMBER CONTROL; CELL-CYCLE; DNA-REPLICATION; BACTERIAL CHROMOSOME; PLASMID REPLICATION; FLOW-CYTOMETRY; SEQA PROTEIN; SEGREGATION AB Most bacteria have one chromosome but some have more than one, as is common in eukaryotes. How multiple chromosomes are maintained in bacteria remains largely obscure. Here we have examined the behaviour of the two Vibrio cholerae chromosomes as a function of growth rate. At slow growth rates, both chromosomes were maintained at copy numbers of one to two per cell. Increasing the growth rate by nutritional shift-up amplified the origin-proximal DNA of the larger chromosome (chrI) to four copies per cell, but not that of the smaller chrII. The latter was amplified when its specific initiator was supplied in excess or a specific negative regulator was deleted. The growth rate-insensitive behaviour of chrII, whose origin is similar to origins of members of a major class of plasmids, was shared by some but not all of several representative plasmids tested in V. cholerae. Also, unlike plasmid replication, chrII replication is known to be initiated at a specific stage of the cell cycle. Raising chrII copy number decreased growth rate, suggesting that this chromosome might serve as a repository for necessary but potentially deleterious genes. C1 NIH, NCI, Ctr Canc Res, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NIH, NCI, Ctr Canc Res, Biochem & Mol Biol Lab, Bldg 10, Bethesda, MD 20892 USA. EM chattoraj@nih.gov FU Intramural NIH HHS NR 61 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2007 VL 66 IS 4 BP 1016 EP 1028 DI 10.1111/j.1365-2958.2007.05973.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 227HM UT WOS:000250647800014 PM 17944831 ER PT J AU Hashimoto, R Hashimoto, H Shintani, N Chiba, S Hattori, S Okada, T Nakajima, M Tanaka, K Kawagishi, N Nemoto, K Mori, T Ohnishi, T Noguchi, H Hori, H Suzuki, T Iwata, N Ozaki, N Nakabayashi, T Saitoh, O Kosuga, A Tatsumi, M Kamijima, K Weinberger, DR Kunugi, H Baba, A AF Hashimoto, R. Hashimoto, H. Shintani, N. Chiba, S. Hattori, S. Okada, T. Nakajima, M. Tanaka, K. Kawagishi, N. Nemoto, K. Mori, T. Ohnishi, T. Noguchi, H. Hori, H. Suzuki, T. Iwata, N. Ozaki, N. Nakabayashi, T. Saitoh, O. Kosuga, A. Tatsumi, M. Kamijima, K. Weinberger, D. R. Kunugi, H. Baba, A. TI Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; PACAP; SNP; hippocampus; memory; PPI ID PREPULSE INHIBITION; PACAP; MICE; GENE; DISORDERS; INSIGHTS; DEFICITS; CORTEX; MEMORY AB Pituitary adenylate cyclase- activating polypeptide (PACAP, ADCYAP1: adenylate cyclaseactivating polypeptide 1), a neuropeptide with neurotransmission modulating activity, is a promising schizophrenia candidate gene. Here, we provide evidence that genetic variants of the genes encoding PACAP and its receptor, PAC1, are associated with schizophrenia. We studied the effects of the associated polymorphism in the PACAP gene on neurobiological traits related to risk for schizophrenia. This allele of the PACAP gene, which is overrepresented in schizophrenia patients, was associated with reduced hippocampal volume and poorer memory performance. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition of the startle response, were reversed by treatment with an atypical antipsychotic, risperidone. These convergent data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia. C1 Osaka Univ, Grad Sch Med, Osaka Hamamatsu Joint Res, Ctr Child & Mental Dev, Suita, Osaka 565, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Kodaira, Tokyo 187, Japan. Osaka Univ, Grad Sch Pharmaceut Sci, Osaka Hamamatsu Joint Res, Lab Mol Neuropharmacol, Suita, Osaka 565, Japan. Natl Ctr Hosp Mental Nervous & Muscular Disorders, Natl Ctr Neurol & Psychiat, Dept Radiol, Kodaira, Tokyo, Japan. Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. Nagoya Univ, Grad Sch Med, Dept Psychiat, Nagoya, Aichi, Japan. Natl Ctr Neurol & Psychiat, Natl Ctr Hosp Mental Nervous & Muscular Disorders, Dept Psychiat, Kodaira, Tokyo, Japan. Showa Univ, Sch Med, Dept Psychiat, Shinagawa Ku, Tokyo 142, Japan. NIH, NIMH, Clin Brain Disorders Branch, Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Hashimoto, R (reprint author), Osaka Univ, Grad Sch Med, Osaka Hamamatsu Joint Res, Ctr Child & Mental Dev, D3,2-2,Yamadaoka, Suita, Osaka 565, Japan. EM hashimor@psy.med.osaka-u.ac.jp RI Hashimoto, Hitoshi/D-1209-2010; Shintani, Norihito/D-5860-2014; Hashimoto, Ryota/P-8572-2014; Ozaki, Norio/M-8908-2014; OI Hashimoto, Hitoshi/0000-0001-6548-4016; Shintani, Norihito/0000-0002-7850-9064; Hashimoto, Ryota/0000-0002-5941-4238; Ozaki, Norio/0000-0002-7360-4898; Kunugi, Hiroshi/0000-0002-7209-3790 NR 26 TC 83 Z9 87 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2007 VL 12 IS 11 BP 1026 EP 1032 DI 10.1038/sj.mp.4001982 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 223YS UT WOS:000250412700009 PM 17387318 ER PT J AU Edwan, JH McFarland, H Bielekova, B AF Edwan, J. H. McFarland, H. Bielekova, B. TI NK cells inhibit T cell expansion and Th17 priming SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 12th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY MAY 30-JUN 02, 2007 CL Washington, DC SP Americas Comm Treatment & Res Multiple Sclerosis, Univ Maryland Sch Med, Natl Multiple Sclerosis Soc DE dendritic cells; IL-17; IL-17 cells; NK cells; T cells; Tsh17 cells C1 Univ Cincinnati, Waddell Ctr MS, Dept Neurol, Cincinnati, OH 45221 USA. NIH, NINDS, Neuroimmunol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD NOV PY 2007 VL 13 IS 9 MA P26 BP 1235 EP 1235 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 238KU UT WOS:000251447300058 ER PT J AU Chikova, AK Schaaper, RM AF Chikova, Anna K. Schaaper, Roel M. TI The bacteriophage P1 hot gene, encoding a homolog of the E-coli DNA polymerase III theta subunit, is expressed during both lysogenic and lytic growth stages SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE DNA polymerase III; theta subunit; bacteriophage P1; P1 hot protein; mutator effects ID MUTATIONAL ANALYSIS; HOLOENZYME; EPSILON; PROTEIN; PRODUCT; MUTANT AB The bacteriophage P1 hot gene product is a homolog of the theta subunit of E. coli DNA polymerase III. Previous studies with hot cloned on a plasmid have shown that Hot protein can substitute for theta, as evidenced by its stabilizing effect on certain dnaQ mutator mutants carrying an unstable pol III proofreading subunit (epsilon subunit). These results are consistent with Hot, like theta, being a replication protein involved in stabilizing the intrinsically unstable epsilon proofreading function. However, the function of hot for the viral life cycle is less clear. In the present study, we show that the hot gene is not essential. Based on its promoter structure, hot has been previously classified as a "late" phage gene, a property that is not easily reconciled with a presumed replication function. Here, we clarify this issue by demonstrating that P1 hot is actively expressed both during the lysogenic state and in the early stages of a lytic induction, in addition to its expression in the late stage of phage development. The results indicate that P1 hot has a complex expression pattern, compatible with a model in which Hot may affect the host replication machinery to benefit overall phage replication. Published by Elsevier B.V. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Russian Acad Med Sci, DI Ivanovskii Virol Inst, Moscow 123098, Russia. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065088-12] NR 25 TC 3 Z9 3 U1 2 U2 4 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 NOV 1 PY 2007 VL 624 IS 1-2 BP 1 EP 8 DI 10.1016/j.mrfmmm.2007.01.014 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 233MR UT WOS:000251095500001 PM 17482649 ER PT J AU Pratt, MM Sirajuddin, P Poirier, MC Schiffman, M Glass, AG Scott, DR Rush, BB Olivero, OA Castle, PE AF Pratt, M. Margaret Sirajuddin, Paul Poirier, Miriam C. Schiffman, Mark Glass, Andrew G. Scott, David R. Rush, Brenda B. Olivero, Ofelia A. Castle, Philip E. TI Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Automated Cellular Imaging System; BPDE-DNA antiserum; smoking; chemiluminescence immunoassay; human keratinocytes ID WHITE BLOOD-CELLS; SMOKING; CANCER; NONSMOKERS; SMOKERS; IDENTIFICATION; CONSUMPTION; EPITHELIUM; NEOPLASIA; TOBACCO AB Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331 mu M BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N-2 deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10(8) nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10(8) nucleotides, with a median of 75/10(8) nucleotides. PAH-DNA adduct values above 150/10(8) nucleotides were found in eight C1 NIH, NCI, Canc Res Ctr, LCBG,Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA. NIH, NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. NW Kaiser Permanente, Portland, OR USA. RP Pratt, MM (reprint author), NIH, NCI, Bldg 37,Rm 4032,37 Convent Dr, Bethesda, MD 20892 USA. EM prattm@mail.nih.gov FU Intramural NIH HHS [Z01 BC005177-26, NIH0011402708] NR 30 TC 13 Z9 14 U1 3 U2 4 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 NOV 1 PY 2007 VL 624 IS 1-2 BP 114 EP 123 DI 10.1016/j.mrfmmm.2007.04.008 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 233MR UT WOS:000251095500012 PM 17583755 ER PT J AU Hosgood, HD Berndt, SI Lan, Q AF Hosgood, H. Dean, III Berndt, Sonja I. Lan, Qing TI GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: A meta-analysis SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE coal; heating and cooking; non-smoking lung cancer; GSTM1; GSTT1; GSTP1 ID POLYCYCLIC AROMATIC-HYDROCARBONS; COAL COMBUSTION EMISSIONS; S-TRANSFERASE GENOTYPES; GENETIC POLYMORPHISMS; XUAN-WEI; CHINESE POPULATION; NONSMOKING WOMEN; RISK-FACTORS; DNA-ADDUCTS; HONG-KONG AB About half of the world's population is exposed to smoke from heating or cooking with coal, wood, or biomass. These exposures, and fumes from cooking oil use, have been associated with increased lung cancer risk. Glutathione S-transferases play an important role in the detoxification of a wide range of human carcinogens in these exposures. Functional polymorphisms have been identified in the GSTM1, GSTT1, and GSTP1 genes, which may alter the risk of lung cancer among individuals exposed to coal, wood, and biomass smoke, and cooking oil fumes. We performed a meta-analysis of 6 published studies (912 cases; 1063 controls) from regions in Asia where indoor air pollution makes a substantial contribution to lung cancer risk, and evaluated the association between the GSTM1 null, GSTT1 null, and GSTP1 105Val polymorphisms and lung cancer risk. Using a random effects model, we found that carriers of the GSTM1 null genotype had a borderline significant increased lung cancer risk (odds ratio (OR), 1.31; 95% confidence interval (CI), 0.95-1.79; p = 0.10), which was particularly evident in the summary risk estimate for the four studies carried out in regions of Asia that use coal for heating and cooking (OR, 1.64; 95% Cl, 1.25-2.14; p, = 0.0003). The GSTT1 null genotype was also associated with an increased lung cancer risk (OR, 1.49; 95% CI, 1.17-1.89; p = 0.001), but no association was observed for the GSTP1 105Val allele. Previous meta- and pooled-analyses suggest at most a small association between the GSTM1 null genotype and lung cancer risk in populations where the vast majority of lung cancer is attributed to tobacco, and where indoor air pollution from domestic heating and cooking is much less than in developing Asian countries. Our results suggest that the GSTM1 null genotype may be associated with a more substantial risk of lung cancer in populations with coal exposure. (C) 2007 Elsevier B.V. All rights reserved. C1 [Hosgood, H. Dean, III; Berndt, Sonja I.; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8118,MCS 7240, Bethesda, MD 20892 USA. EM hosgoodd@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 64 TC 43 Z9 45 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD NOV-DEC PY 2007 VL 636 IS 1-3 BP 134 EP 143 DI 10.1016/j.mrrev.2007.02.002 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 245HK UT WOS:000251925500006 PM 17428724 ER PT J AU Bennett, JW Kans, JA AF Bennett, J. W. Kans, J. A. TI Edward Garber, 1918-2004 SO MYCOLOGIA LA English DT Biographical-Item C1 [Bennett, J. W.] Rutgers State Univ, Piscataway, NJ 08855 USA. [Kans, J. A.] Natl Inst Hlth, Bethesda, MD USA. RP Bennett, JW (reprint author), Rutgers State Univ, Piscataway, NJ 08855 USA. EM profmycogirl@yahoo.com NR 1 TC 0 Z9 0 U1 0 U2 1 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD NOV-DEC PY 2007 VL 99 IS 6 BP 958 EP 960 DI 10.3852/mycologia.99.6.958 PG 3 WC Mycology SC Mycology GA 261LP UT WOS:000253080600016 ER PT J AU Abrams, J Goldberg, J AF Abrams, Jeffrey Goldberg, Jacquelyn TI Ethics reviews can be centralized without delays SO NATURE LA English DT Letter C1 NCI, Cent Inst Rev Board Initiat, Bethesda, MD 20892 USA. RP Abrams, J (reprint author), NCI, Cent Inst Rev Board Initiat, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 1 PY 2007 VL 450 IS 7166 BP 27 EP 27 DI 10.1038/450027b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 226JR UT WOS:000250585800016 PM 17972859 ER PT J AU Okada, Y Scott, G Ray, MK Mishina, Y Zhang, Y AF Okada, Yuki Scott, Greg Ray, Manas K. Mishina, Yuji Zhang, Yi TI Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis SO NATURE LA English DT Article ID MICE; PROTEIN; SPERMIOGENESIS; CONDENSATION; METHYLATION; DOMAIN; MOUSE AB Recent studies indicate that, similar to other covalent modifications, histone lysine methylation is subject to enzyme-catalysed reversion(1,2). So far, LSD1 (also known as AOF2) and the jumonji C (JmjC)-domain-containing proteins have been shown to possess histone demethylase activity. LSD1 catalyses removal of H3K4me2/H3K4me1 through a flavin-adenine-dinucleotide-dependent oxidation reaction(3). In contrast, JmjC-domain-containing proteins remove methyl groups from histones through a hydroxylation reaction that requires alpha-ketoglutarate and Fe(II) as cofactors(4). Although an increasing number of histone demethylases have been identified and biochemically characterized(1,2), their biological functions, particularly in the context of an animal model, are poorly characterized. Here we use a loss-of-function approach to demonstrate that the mouse H3K9me2/1-specific demethylase JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) is essential for spermatogenesis. We show that Jhdm2a-deficient mice exhibit post-meiotic chromatin condensation defects, and that JHDM2A directly binds to and controls the expression of transition nuclear protein 1 (Tnp1) and protamine 1 (Prm1) genes, the products of which are required for packaging and condensation of sperm chromatin. Thus, our work uncovers a role for JHDM2A in spermatogenesis and reveals transition nuclear protein and protamine genes as direct targets of JHDM2A. C1 Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. NIH, Knock Out Core, Res Triangle Pk, NC 27709 USA. NIH, Mol Dev Biol Grp, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Zhang, Y (reprint author), Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu NR 23 TC 169 Z9 189 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 1 PY 2007 VL 450 IS 7166 BP 119 EP + DI 10.1038/nature06236 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 226JR UT WOS:000250585800049 PM 17943087 ER PT J AU Fleg, JL AF Fleg, Jerome L. TI Do patients with ACS aged 90 years or older receive the same standard of care as younger patients? SO NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE LA English DT Editorial Material DE acute coronary syndromes; CRUSADE registry; elderly ID ACUTE CORONARY SYNDROMES; MANAGEMENT C1 NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Bethesda, MD USA. RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Dis, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM flegj@nhlbi.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1743-4297 J9 NAT CLIN PRACT CARD JI Nat. Clin. Pract. Cardiovasc. Med. PD NOV PY 2007 VL 4 IS 11 BP 586 EP 587 DI 10.1038/ncpcardio0978 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 221NE UT WOS:000250233800003 PM 17712317 ER PT J AU Pacak, K Eisenhofer, G AF Pacak, Karel Eisenhofer, Graeme TI An assessment of biochemical tests for the diagnosis of pheochromocytoma SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE catecholamine; chromogranin A; diagnosis; metanephrine; pheochromocytoma ID PLASMA METANEPHRINES C1 NICHHD, Sect Med Neuroendocrinol, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Bldg 10,CRC,Rm 1E 1 3140 10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 6 TC 10 Z9 10 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2007 VL 3 IS 11 BP 744 EP 745 DI 10.1038/ncpendmet0615 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221NF UT WOS:000250233900007 PM 17684481 ER PT J AU Stratakis, CA Boikos, SA AF Stratakis, Constantine A. Boikos, Sosipatros A. TI Genetics of adrenal tumors associated with Cushing's syndrome: a new classification for bilateral adrenocortical hyperplasias SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE adrenal tumors; Cushing's syndrome; phosphodiesterases; protein kinase A; tumor-suppressor genes ID PROTEIN-KINASE-A; ALPHA REGULATORY SUBUNIT; LI-FRAUMENI-SYNDROME; CARNEY COMPLEX; PHOSPHODIESTERASE 11A; CANDIDATE GENES; HUMAN TISSUES; PRKAR1A GENE; EXPRESSION; MUTATIONS AB Adrenocortical causes of Cushing's syndrome include the following: common cortisol-producing adenomas, which are usually isolated (without associated tumors) and sporadic (without a family history); rare, but often clinically devastating, adrenocortical carcinomas; and a spectrum of adrenocorticotropin-independent, and almost always bilateral, hyperplasias, which are not rare, and are the most recently recognized cause. The majority of benign lesions of the adrenal cortex seem to be linked to abnormalities of the cyclic AMP signaling pathway, whereas cancer is linked to aberrant expression of insulin-like growth factor II, tumor protein p53 and related molecules. In this article, we propose a new clinical classification and nomenclature for the various forms of adrenocorticotropin-independent adrenocortical hyperplasias that is based on their histologic and genetic features. We also review the molecular genetics of adrenocortical tumors, including recent discoveries relating to the role of phosphodiesterase 11A. This is a timely Review because of recent advances in the clinical and molecular understanding of these diseases. C1 NICHD, NIH, Hertable Disorders Branch, Pediat Endocrinol Training Program, Bethesda, MD USA. Dev Endocrinol Branch, Sect Endocrinol Genet, Bethesda, MD USA. RP Stratakis, CA (reprint author), NICHHD, NIH, Clin Res Ctr, Dev Endocrinol Branch,Pediat Endocrinol Training, Bldg 10,Rm 1 3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS NR 68 TC 56 Z9 58 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2007 VL 3 IS 11 BP 748 EP 757 DI 10.1038/ncpendmet0648 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221NF UT WOS:000250233900009 PM 17955016 ER PT J AU Pouratian, N Asthagiri, A Jagannathan, J Shaffrey, ME Schiff, D AF Pouratian, Nader Asthagiri, Ashok Jagannathan, Jay Shaffrey, Mark E. Schiff, David TI Surgery insight: the role of surgery in the management of low-grade gliomas SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE astrocytoma; low-grade glioma; oligoastrocytoma; oligodendroglioma; surgical resection ID STEREOTACTIC BIOPSY; PROGNOSTIC-FACTORS; RADIATION-THERAPY; RANDOMIZED-TRIAL; ELECTROCORTICAL STIMULATION; OLIGODENDROGLIAL TUMORS; EUROPEAN-ORGANIZATION; CEREBRAL HEMISPHERES; CORTICAL STIMULATION; SURGICAL REMOVAL AB The benefits of surgery for the management of low-grade gliomas have been difficult to determine from the literature. This difficulty might be explained by the inconsistency of the published data, and also by advances in both neuroimaging and neurosurgical techniques, which have made surgical intervention a safer and more viable option than it has been in the past, making the earlier studies less applicable to modern care. In this article, we critically analyze the utility of surgery in the management of low-grade gliomas, including the value of observation without surgical intervention, the relative risks and benefits of biopsy versus craniotomy and resection, and recent advances that have made surgery safer and gross total resection a more realistic proposition. As we will discuss, the literature provides modest evidence that surgery leads to improved outcomes through a reduction in tumor burden. As a result of advances in surgical techniques, the time might now be right to effectively and accurately assess the influence of aggressive surgical resection on the prognosis of low-grade gliomas. C1 Univ Virginia Hlth Syst, Neurooncol Ctr, Charlottesville, VA 22908 USA. NIH, Bethesda, MD 20892 USA. RP Schiff, D (reprint author), Univ Virginia Hlth Syst, Neurooncol Ctr, POB 800432, Charlottesville, VA 22908 USA. EM davidschiff@virginia.edu NR 75 TC 38 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD NOV PY 2007 VL 3 IS 11 BP 628 EP 639 DI 10.1038/ncpneuro0634 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 225JA UT WOS:000250513000011 PM 17982433 ER PT J AU Yabroff, KR Warren, JL Brown, ML AF Yabroff, K. Robin Warren, Joan L. Brown, Martin L. TI Costs of cancer care in the USA: a descriptive review SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE cost and cost analysis; economics; health-care costs; health-services research; neoplasms ID HEALTH MAINTENANCE ORGANIZATION; CELL LUNG-CANCER; STAGE BREAST-CANCER; SEER-MEDICARE DATA; ECONOMIC BURDEN; COLORECTAL-CANCER; PROSTATE-CANCER; RADICAL PROSTATECTOMY; RETROSPECTIVE ANALYSIS; PANCREATIC-CANCER AB Although many studies assesing the cost of cancer care have been conducted in the US, to date, these studies and the underlying methods used to estimate costs have not been reviewed systematically. We conducted a descriptive review of the published literature on the cost of cancer care in the US, and identified 60 papers published between 1995 and 2006 pertinent to our study methods. We found heterogenecity across the studies in terms of the settings, populations studied, measurement of costs, and study methods. We also identified limitations in the generalizability of findings, the misclassification of patient groups and costs, and concerns with the study methods. Among studies that reported costs of cancer care in multiple phases of care and for multiple tumor sites, costs were generally highest in the initial year following diagnosis and the last year of life and lower in the continuing phase (i.e. the period between the initial and last year of life phase), following a 'u-shaped' curve. Within phase of care, costs for lung and colorectal cancer care were generally higher than those for breast and prostate cancer care, however, the long-term of lifetime costs for each type of cancer were more similar, reflecting the differences in survival and costs in each phase between the different disease types. C1 NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Executive Pl N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 79 TC 45 Z9 48 U1 4 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2007 VL 4 IS 11 BP 643 EP 656 DI 10.1038/ncponc0978 PG 14 WC Oncology SC Oncology GA 227FL UT WOS:000250642500023 PM 17965642 ER PT J AU Levy-Clarke, G Gangaputra, S Nussenblatt, R AF Levy-Clarke, Grace Gangaputra, Sapna Nussenblatt, Robert TI Treatment with TNF inhibitors for uveitis associated with juvenile idiopathic arthritis SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material DE etanercept; infliximab; juvenile idiopathic arthritis; TNF; uveitis ID ETANERCEPT C1 NEI, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Levy-Clarke, G (reprint author), NEI, Immunol Lab, Natl Inst Hlth, Bldg 10,Room 10N 112,10 Ctr Dr,MSC-1857, Bethesda, MD 20892 USA. EM clarkeg@nei.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD NOV PY 2007 VL 3 IS 11 BP 608 EP 609 DI 10.1038/ncprheum0630 PG 2 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 225WU UT WOS:000250549700007 PM 17895875 ER PT J AU Valencia, X Lipsky, PE AF Valencia, Xavier Lipsky, Peter E. TI CD4(+) CD25(+) FoxP3(+) regulatory T cells in autoimmune diseases SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE CD4(+) CD25(+) FoxP3(+) regulatory T cells; rheumatoid arthritis; Sjogren's syndrome; systemic lupus erythematosus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR FOXP3; TNF-ALPHA THERAPY; RHEUMATOID-ARTHRITIS; TGF-BETA; MULTIPLE-SCLEROSIS; FUNCTIONAL DEFECT; MYASTHENIA-GRAVIS; PERIPHERAL-BLOOD; CYTOKINE MILIEU AB Maintenance of immune tolerance in the periphery can be envisioned as a balance between autoreactive lymphocytes and regulatory mechanisms that counteract them. The naturally occurring CD4(+) CD25(+) regulatory T cells (T-REGs) have a major role in modulating the activity of self- reactive cells. The identification of Forkhead box P3 transcription factor (FoxP3) as the critical determinant of T-REG development and function has provided new opportunities and generated expanded interest in studying the balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. The identification of both human and mouse diseases resulting from the lack of FoxP3 expression, and consequently the absence of T-REGs, has rapidly expanded knowledge of T-REG development and function during the past 5 years. Although it is still unclear how these regulatory cells function, they can inhibit the activation of potentially pathogenic T cells in vitro. Using in vitro functional assays and phenotypic analysis, T-REgs isolated from patients with a variety of autoimmune diseases have been shown to exhibit reduced regulatory function as compared with those isolated from healthy controls. This review will focus on the current state of knowledge on human T-REgs and their association with specific autoimmune diseases. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Valencia, X (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM xvalencia@mail.nih.gov NR 55 TC 87 Z9 93 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD NOV PY 2007 VL 3 IS 11 BP 619 EP 626 DI 10.1038/ncprheum0624 PG 8 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 225WU UT WOS:000250549700009 PM 17968332 ER PT J AU Newport, M Sirugo, G Lyons, E Vannberg, F Hill, AVS Bradbury, LA Farrar, C Pointon, JJ Wordsworth, P Brown, MA Franklyn, JA Heward, JM Simmonds, MJ Gough, SC Seal, S Stratton, MR Rahman, N Ban, M Goris, A Sawcer, SJ Compston, A Conway, D Jallow, M Newport, M Sirugo, G Rockett, KA Kwiatkowski, DP Bumpstead, SJ Chaney, A Downes, K Ghori, MJ Gwilliam, R Hunt, SE Inouye, M Keniry, A King, E McGinnis, R Potter, S Ravindrarajah, R Whittaker, P Widden, C Withers, D Deloukas, P Leung, HT Nutland, S Stevens, HE Walker, NM Todd, JA Easton, D Clayton, DG Burton, PR Tobin, MD Barrett, JC Evans, DM Morris, AP Cardon, LR Cardin, NJ Davison, D Ferreira, T Pereira-Gale, J Hallgrimsdottir, IB Howie, BN Marchini, JL Spencer, CC Su, Z Teo, YY Vukcevic, D Donnelly, P Bentley, D Brown, MA Cardon, LR Caulfield, M Clayton, DG Compston, A Craddock, N Deloukas, P Donnelly, P Farrall, M Barton, A Bruce, IN Donovan, H Eyre, S Gilbert, PD Hilder, SL Hinks, AM John, SL Potter, C Silman, AJ Symmons, DPM Thomson, W Worthington, J Gough, SC Hall, AS Hattersley, AT Hill, AVS Kwiatkowski, DP Matthew, CG McCarthy, MI Ouwehand, WH Parkes, M Pembrey, M Rahman, N Samani, NJ Stratton, MR Todd, JA Worthington, J Mitchell, SL Newby, PR Brand, OJ Carr-Smith, J Pearce, SHS Gough, SCL McGinnis, R Keniry, A Deloukas, P Reveille, JD Zhou, X Bradbury, LA Sims, AM Dowling, A Taylor, J Doan, T Cardon, LR Davis, JC Pointon, JJ Savage, L Ward, MM Learch, TL Weisman, MH Wordsworth, P Brown, MA AF Newport, Melanie Sirugo, Giorgio Lyons, Emily Vannberg, Fredrik Hill, Adrian V. S. Bradbury, Linda A. Farrar, Claire Pointon, Jennifer J. Wordsworth, Paul Brown, Matthew A. Franklyn, Jayne A. Heward, Joanne M. Simmonds, Matthew J. Gough, Stephen C. L. Seal, Sheila Stratton, Michael R. Rahman, Nazneen Ban, Maria Goris, An Sawcer, Stephen J. Compston, Alastair Conway, David Jallow, Muminatou Newport, Melanie Sirugo, Giorgio Rockett, Kirk A. Kwiatkowski, Dominic P. Bumpstead, Suzannah J. Chaney, Amy Downes, Kate Ghori, Mohammed J. R. Gwilliam, Rhian Hunt, Sarah E. Inouye, Michael Keniry, Andrew King, Emma McGinnis, Ralph Potter, Simon Ravindrarajah, Rathi Whittaker, Pamela Widden, Claire Withers, David Deloukas, Panos Leung, Hin-Tak Nutland, Sarah Stevens, Helen E. Walker, Neil M. Todd, John A. Easton, Doug Clayton, David G. Burton, Paul R. Tobin, Martin D. Barrett, Jeffrey C. Evans, David M. Morris, Andrew P. Cardon, Lon R. Cardin, Niall J. Davison, Dan Ferreira, Teresa Pereira-Gale, Joanne Hallgrimsdottir, Ingeleif B. Howie, Bryan N. Marchini, Jonathan L. Spencer, Chris C. A. Su, Zhan Teo, Yik Ying Vukcevic, Damjan Donnelly, Peter Bentley, David Brown, Matthew A. Cardon, Lon R. Caulfield, Mark Clayton, David G. Compston, Alastair Craddock, Nick Deloukas, Panos Donnelly, Peter Farrall, Martin Barton, Anne Bruce, Ian N. Donovan, Hannah Eyre, Steve Gilbert, Paul D. Hilder, Samantha L. Hinks, Anne M. John, Sally L. Potter, Catherine Silman, Alan J. Symmons, Deborah P. M. Thomson, Wendy Worthington, Jane Gough, Stephen C. L. Hall, Alistair S. Hattersley, Andrew T. Hill, Adrian V. S. Kwiatkowski, Dominic P. Matthew, Christopher G. McCarthy, Mark I. Ouwehand, Willem H. Parkes, Miles Pembrey, Marcus Rahman, Nazneen Samani, Nilesh J. Stratton, Michael R. Todd, John A. Worthington, Jane Mitchell, Sarah L. Newby, Paul R. Brand, Oliver J. Carr-Smith, Jackie Pearce, Simon H. S. Gough, Stephen C. L. McGinnis, R. Keniry, A. Deloukas, P. Reveille, John D. Zhou, Xiaodong Bradbury, Linda A. Sims, Anne-Marie Dowling, Alison Taylor, Jacqueline Doan, Tracy Cardon, Lon R. Davis, John C. Pointon, Jennifer J. Savage, Laurie Ward, Michael M. Learch, Thomas L. Weisman, Michael H. Wordsworth, Paul Brown, Matthew A. TI Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; GRAVES-DISEASE; CROHN-DISEASE; ANKYLOSING-SPONDYLITIS; POPULATION-STRUCTURE; GENETIC ASSOCIATION; SUSCEPTIBILITY LOCI; AMINOPEPTIDASE; RISK AB We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS), autoimmune thyroid disease (AITD), multiple sclerosis ( MS) and breast cancer ( BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major `seronegative' diseases. C1 Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester LE1 7RH, Leics, England. Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn Wellcome Trust Diabet & I, Cambridge CB2 0XY, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, Wales. Wellcome Trust Res Labs, London NW1 2BE, England. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England. Univ Cambridge, Dept Haematol, Cambridge CB2 2PT, England. Cambridge Ctr, Natl Hlth Serv Blood & Transplant, Cambridge CB2 2PT, England. Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England. Univ Oxford, Dept Stat, Oxford OX1 3TG, England. Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. Natl Hlth Serv Blood & Transplant, Sheffield Ctr, Sheffield S5 7JN, S Yorkshire, England. Natl Hlth Serv Blood & Transplant, Brentwood Ctr, Brentwood CM15 8DP, Essex, England. Scottish Natl Blood Transfus Serv, Edinburgh CB17 7QT, Midlothian, Scotland. Natl Hlth Serv Blood & Transplant, Southampton Ctr, Southampton SO16 5AF, Hants, England. Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 1TQ, Avon, England. St Georges Univ London, Div Community Hlth Serv, London SW17 0RE, England. UCL, Inst Child Hlth, London WC1N 1EH, England. Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. Univ Birmingham, Div Neurosci, Dept Psychiat, Birmingham B15 2QZ, W Midlands, England. Cardiff Univ, Sch Med, Dept Med Psychol, Cardiff CF14 4XN, Wales. Kings Coll London, Inst Psychiat, SGDP, London SE5 8AF, England. Royal Victoria Infirm, Sch Neurol Neurobiol & Psychiat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Univ Leeds, Fac Med & Hlth, LIGHT & LIMM Res Inst, Leeds LS1 3EX, W Yorkshire, England. Univ Cambridge, Addenbrookes Hosp, IBD Res Grp, Cambridge CB2 2QQ, England. Univ Edinburgh, Western Gen Hosp, Sch Mol & Clin Med, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Kings Coll London, Sch Med, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England. UCL, Hosp Trust, Inst Digest Dis, London NW1 2BU, England. Guys & St Thomas NHS Fdn Trust, Dept Gastroenterol, London SE1 7EH, England. Newcastle Univ, Royal Victoria Infirm, Dept Gastroenterol & Hepatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Univ Oxford, Radcliffe Infirm, Gastroenterol Unit, Oxford OX2 6HE, England. Aberdeen Royal Infirm, Aberdeen AB9 2ZB, Scotland. Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England. Univ Cambridge, Addenbrookes Hosp, Diabet & Inflammat Lab, Cambridge CB2 2QQ, England. Ctr Natl Genotypage, F-91057 Paris, France. Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland. Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London EC1M 6BQ, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Manchester, Arc Epidemiol Res Unit, Manchester M13 9PT, Lancs, England. Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England. Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DU, Devon, England. Barts & London Royal London Hosp, Ctr Diabet & Metab Med, London E1 1BB, England. Univ Newcastle, Sch Clin Med Sci, Diabet Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS2 8PR, Avon, England. MRC Labs, Fajara, Gambia. Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Woolloongabba, Qld 4102, Australia. Univ Oxford, Botnar Res Ctr, Oxford OX3 7BN, England. Univ Birmingham, Biomed Res Inst, Div Med Sci, Dept Med, Birmingham B15 2TT, W Midlands, England. Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. Illumina Cambridge, Saffron Walden CB10 1XL, Essex, England. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Newcastle, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. Univ Texas, Houston Med Sch, Houston, TX 77030 USA. Univ Queensland, Diamantina Inst Canc Immunol & Metab Med, St Lucia, Qld 4072, Australia. Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Calif San Francisco, Dept Rheumatol, San Francisco, CA 94143 USA. Spondylitis Assoc Amer, Sherman Oaks, CA 91403 USA. Univ Oxford, Botnar Res Ctr, Oxford OX3 7BN, England. NIAMSD, Natl Inst Hlth, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Dept Radiol, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Dept Rheumatol Med, Los Angeles, CA 90048 USA. RP Newport, M (reprint author), Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Adrian Bldg,Univ Rd, Leicester LE1 7RH, Leics, England. RI Rahman, Nazneen/D-2802-2013; HILL, Adrian/C-1306-2008; Todd, John/A-3542-2010; turton, miranda/F-4682-2011; Deloukas, Panos/B-2922-2013; Evans, David/H-6325-2013; Rahman, Nazneen/B-8890-2012; Worthington, Jane/M-9770-2014; Barton, Anne/N-2053-2014; Goris, An/F-2943-2010; Hinks, Anne/E-1853-2015; Burton, Paul/H-7527-2016; Newhouse, Stephen/C-9330-2011; Fox, Laura /C-6249-2016 OI Kwiatkowski, Dominic/0000-0002-5023-0176; Timpson, Nicholas/0000-0002-7141-9189; Dunger, Professor David/0000-0002-2566-9304; Symmons, Deborah/0000-0002-8625-1200; Pearce, Simon/0000-0001-8384-8063; Bishop, Tim/0000-0002-8752-8785; Thomson, Wendy/0000-0002-9022-5179; Wallace, Chris/0000-0001-9755-1703; Eyre, Stephen/0000-0002-1251-6974; Bruce, Ian/0000-0003-3047-500X; Prescott, Natalie/0000-0002-5901-7371; Evans, David/0000-0003-0663-4621; Walker, Neil/0000-0001-9796-7688; Rahman, Nazneen/0000-0003-4376-0440; Potter, Simon/0000-0003-4208-4102; Simmonds, Matt/0000-0003-3154-3510; O'Donovan, Michael/0000-0001-7073-2379; Hunt, Sarah/0000-0002-8350-1235; Brown, Matthew A/0000-0003-0538-8211; Zeggini, Eleftheria/0000-0003-4238-659X; King, Emma/0000-0003-3611-9647; Lango Allen, Hana/0000-0002-7803-8688; Deloukas, Panos/0000-0001-9251-070X; Worthington, Jane/0000-0003-0544-042X; Barton, Anne/0000-0003-3316-2527; Goris, An/0000-0002-1276-6682; Hinks, Anne/0000-0001-8843-3967; Newhouse, Stephen/0000-0002-1843-9842; NR 49 TC 782 Z9 793 U1 4 U2 61 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1329 EP 1337 DI 10.1038/ng.2007.17 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900017 ER PT J AU Pujana, MA Han, JDJ Starita, LM Stevens, KN Tewari, M Ahn, JS Rennert, G Moreno, V Kirchhoff, T Gold, B Assmann, V ElShamy, WM Rual, JF Levine, D Rozek, LS Gelman, RS Gunsalus, KC Greenberg, RA Sobhian, B Bertin, N Venkatesan, K Ayivi-Guedehoussou, N Sole, X Hernandez, P Lazaro, C Nathanson, KL Weber, BL Cusick, ME Hill, DE Offit, K Livingston, DM Gruber, SB Parvin, JD Vidal, M AF Pujana, Miguel Angel Han, Jing-Dong J. Starita, Lea M. Stevens, Kristen N. Tewari, Muneesh Ahn, Jin Sook Rennert, Gad Moreno, Victor Kirchhoff, Tomas Gold, Bert Assmann, Volker ElShamy, Wael M. Rual, Jean-Francois Levine, Douglas Rozek, Laura S. Gelman, Rebecca S. Gunsalus, Kristin C. Greenberg, Roger A. Sobhian, Bijan Bertin, Nicolas Venkatesan, Kavitha Ayivi-Guedehoussou, Nono Sole, Xavier Hernandez, Pilar Lazaro, Conxi Nathanson, Katherine L. Weber, Barbara L. Cusick, Michael E. Hill, David E. Offit, Kenneth Livingston, David M. Gruber, Stephen B. Parvin, Jeffrey D. Vidal, Marc TI Network modeling links breast cancer susceptibility and centrosome dysfunction SO NATURE GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; C-ELEGANS; GENETIC INSTABILITY; ZYG-9 FORM; PROTEIN; BRCA1; AMPLIFICATION; MUTATIONS; COMPLEX; TAC-1 AB Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic ( or `omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. C1 Harvard Univ, Sch Med, CCSB, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Carmel Hosp, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel. Technion, Bruce Rappaport Fac Med, IL-34362 Haifa, Israel. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. IDIBELL, Catalan Inst Oncol, Dept Epidemiol, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Canc Registry, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. Natl Canc Inst, Human Genet Sect, Lab Genome Divers, Frederick, MD 21702 USA. Univ Hamburg, Hosp Eppendorf, Inst Tumor Biol, Ctr Med Expt, D-20246 Hamburg, Germany. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Pujana, MA (reprint author), Harvard Univ, Sch Med, CCSB, Dept Genet, 44 Binney St, Boston, MA 02115 USA. RI Bertin, Nicolas/C-3025-2008; Moreno, Victor/A-1697-2010; Parvin, Jeffrey/C-8955-2009; Hill, David/B-6617-2011; pujana, Miguel Angel/N-3127-2014; OI Bertin, Nicolas/0000-0002-9835-9606; Moreno, Victor/0000-0002-2818-5487; pujana, Miguel Angel/0000-0003-3222-4044; Sole, Xavier/0000-0002-2197-3325; Rual, Jean-Francois/0000-0003-4465-8819; Nathanson, Katherine/0000-0002-6740-0901; Kirchhoff, Tomas/0000-0002-9055-2364 FU NCI NIH HHS [CA90281, P30 CA046592] NR 50 TC 315 Z9 335 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1338 EP 1349 DI 10.1038/ng.2007.2 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900018 PM 17922014 ER PT J AU Zampieri, CA Sullivan, NJ Nabel, GJ AF Zampieri, Carisa A. Sullivan, Nancy J. Nabel, Gary J. TI Immunopathology of highly virulent pathogens: insights from Ebola virus SO NATURE IMMUNOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; I INTERFERON RESPONSE; TUMOR-NECROSIS-FACTOR; HEMORRHAGIC-FEVER; DENDRITIC CELLS; MARBURG VIRUSES; VP35 PROTEIN; CYNOMOLGUS MACAQUES; ENDOTHELIAL-CELLS; INFECTED PATIENTS AB Ebola virus is a highly virulent pathogen capable of inducing a frequently lethal hemorrhagic fever syndrome. Accumulating evidence indicates that the virus actively subverts both innate and adaptive immune responses and triggers harmful inflammatory responses as it inflicts direct tissue damage. The host immune system is ultimately overwhelmed by a combination of inflammatory factors and virus-induced cell damage, particularly in the liver and vasculature, often leading to death from septic shock. We summarize the mechanisms of immune dysregulation and virus-mediated cell damage in Ebola virus-infected patients. Future approaches to prevention and treatment of infection will be guided by answers to unresolved questions about interspecies transmission, molecular mechanisms of pathogenesis, and protective adaptive and innate immune responses to Ebola virus. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 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 NR 67 TC 72 Z9 77 U1 0 U2 40 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2007 VL 8 IS 11 BP 1159 EP 1164 DI 10.1038/ni1519 PG 6 WC Immunology SC Immunology GA 222ZR UT WOS:000250338900005 PM 17952040 ER PT J AU Kaufmann, DE Kavanagh, DG Pereyra, F Zaunders, JJ Mackey, EW Miura, T Palmer, S Brockman, M Rathod, A Piechocka-Trocha, A Baker, B Zhu, B Le Gall, S Waring, MT Ahern, R Moss, K Kelleher, AD Coffin, JM Freeman, GJ Rosenberg, ES Walker, BD AF Kaufmann, Daniel E. Kavanagh, Daniel G. Pereyra, Florencia Zaunders, John J. Mackey, Elizabeth W. Miura, Toshiyuki Palmer, Sarah Brockman, Mark Rathod, Almas Piechocka-Trocha, Alicja Baker, Brett Zhu, Baogong Le Gall, Sylvie Waring, Michael T. Ahern, Ryan Moss, Kristin Kelleher, Anthony D. Coffin, John M. Freeman, Gordon J. Rosenberg, Eric S. Walker, Bruce D. TI Upregulation of CTLA-4 by HIV-specific CD4(+) T cells correlates with disease progression and defines a reversible immune dysfunction SO NATURE IMMUNOLOGY LA English DT Article ID INFECTED INDIVIDUALS; METASTATIC MELANOMA; ANTIGEN-4 BLOCKADE; TGF-BETA; IN-VITRO; EXPRESSION; RESPONSES; SUPPRESSION; PD-1; ACTIVATION AB In progressive viral infection, antiviral T cell function is impaired by poorly understood mechanisms. Here we report that the inhibitory immunoregulatory receptor CTLA-4 was selectively upregulated in human immunodeficiency virus (HIV)-specific CD4(+) T cells but not CD8(+) T cells in all categories of HIV-infected subjects evaluated, with the exception of rare people able to control viremia in the absence of antiretroviral therapy. CTLA-4 expression correlated positively with disease progression and negatively with the capacity of CD4(+) T cells to produce interleukin 2 in response to viral antigen. Most HIV-specific CD4(+) T cells coexpressed CTLA-4 and another inhibitory immunoregulatory receptor, PD-1. In vitro blockade of CTLA-4 augmented HIV-specific CD4(+) T cell function. These data, indicating a reversible immunoregulatory pathway selectively associated with CD4(+) T cell dysfunction, provide a potential target for immunotherapy in HIV-infected patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. St Vincents Hosp, Ctr Immunol, Darlinghurst, NSW 2010, Australia. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Kaufmann, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM dkaufmann@partners.org RI Zaunders, John/J-6553-2012 OI Zaunders, John/0000-0002-5912-5989 FU NHLBI NIH HHS [R01 HL092565]; NIAID NIH HHS [F32 AI058457, P30 AI060354] NR 46 TC 265 Z9 276 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2007 VL 8 IS 11 BP 1246 EP 1254 DI 10.1038/ni1515 PG 9 WC Immunology SC Immunology GA 222ZR UT WOS:000250338900017 PM 17906628 ER PT J AU Isermann, B Vinnikov, IA Madhusudhan, T Herzog, S Kashif, M Blautzik, J Corat, MAF Zeier, M Blessing, E Oh, J Gerlitz, B Berg, DT Grinnell, BW Chavakis, T Esmon, CT Weiler, H Bierhaus, A Nawroth, PP AF Isermann, Berend Vinnikov, Ilya A. Madhusudhan, Thati Herzog, Stefanie Kashif, Muhammed Blautzik, Janusch Corat, Marcus A. F. Zeier, Martin Blessing, Erwin Oh, Jun Gerlitz, Bruce Berg, David T. Grinnell, Brian W. Chavakis, Triantafyllos Esmon, Charles T. Weiler, Hartmut Bierhaus, Angelika Nawroth, Peter P. TI Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis SO NATURE MEDICINE LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; SEVERE SEPSIS; ANTICOAGULANT PATHWAY; CELL; THROMBOMODULIN; ALPHA; RECEPTOR-1; MOUSE; INFLAMMATION; DYSFUNCTION AB Data providing direct evidence for a causative link between endothelial dysfunction, microvascular disease and diabetic end-organ damage are scarce. Here we show that activated protein C (APC) formation, which is regulated by endothelial thrombomodulin, is reduced in diabetic mice and causally linked to nephropathy. Thrombomodulin-dependent APC formation mediates cytoprotection in diabetic nephropathy by inhibiting glomerular apoptosis. APC prevents glucose-induced apoptosis in endothelial cells and podocytes, the cellular components of the glomerular filtration barrier. APC modulates the mitochondrial apoptosis pathway via the protease-activated receptor PAR-1 and the endothelial protein C receptor EPCR in glucose-stressed cells. These experiments establish a new pathway, in which hyperglycemia impairs endothelial thrombomodulin-dependent APC formation. Loss of thrombomodulin-dependent APC formation interrupts cross-talk between the vascular compartment and podocytes, causing glomerular apoptosis and diabetic nephropathy. Conversely, maintaining high APC levels during long-term diabetes protects against diabetic nephropathy. C1 Univ Heidelberg, Dept Med & Clin Chem 1, D-69120 Heidelberg, Germany. Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53226 USA. Univ Heidelberg, Dept Med 1, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Med 3, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Pediat Nephrol, D-69120 Heidelberg, Germany. Lilly Res Labs, BioTechnol Discovery Res, Indianapolis, IN 46285 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA. Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. RP Isermann, B (reprint author), Univ Heidelberg, Dept Med & Clin Chem 1, INF 410, D-69120 Heidelberg, Germany. EM berend.isermann@med.uni-heidelberg.de RI Corat, Marcus/M-2301-2013; OI Corat, Marcus/0000-0002-8801-2318; Vinnikov, Ilya/0000-0003-0488-8484 NR 49 TC 201 Z9 207 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2007 VL 13 IS 11 BP 1349 EP 1358 DI 10.1038/nm1667 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 228NP UT WOS:000250736900028 PM 17982464 ER PT J AU Belkaid, Y AF Belkaid, Yasmine TI Regulatory T cells and infection: a dangerous necessity SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID LEISHMANIA-MAJOR INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; ANTIVIRAL IMMUNE-RESPONSE; HEPATITIS-C; IFN-GAMMA; TGF-BETA; DENDRITIC CELLS; CUTTING EDGE; IN-VITRO AB Surviving a given infection requires the generation of a controlled immune response. Failure to establish or restore homeostatic conditions during or following the onset of an infection can lead to tissue damage. Investigation of the immunoregulatory network that arises in response to the infectious process or that is induced by the pathogen itself should provide insight into therapeutic approaches for the control of infection and any subsequent immunopathology. In this Review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection. C1 NIAID, Parasit Dis Lab, Mucosal Immun Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Parasit Dis Lab, Mucosal Immun Unit, Natl Inst Hlth, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS NR 140 TC 439 Z9 455 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2007 VL 7 IS 11 BP 875 EP 888 DI 10.1038/nri2189 PG 14 WC Immunology SC Immunology GA 224KA UT WOS:000250444700014 PM 17948021 ER PT J AU Mulkidjanian, AY Makarova, KS Galperin, MY Koonin, EV AF Mulkidjanian, Armen Y. Makarova, Kira S. Galperin, Michael Y. Koonin, Eugene V. TI Inventing the dynamo machine: The evolution of the F-type and V-type ATPases SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID III SECRETION SYSTEMS; VACUOLAR H+-ATPASE; BACTERIAL CONJUGATION; ESCHERICHIA-COLI; CENTRAL STALK; SACCHAROMYCES-CEREVISIAE; THERMUS-THERMOPHILUS; BACTERIOPHAGE PHI-6; PHYSIOLOGICAL ROLES; ENTEROCOCCUS-HIRAE AB The rotary proton- and sodium-translocating ATPases are reversible molecular machines present in all cellular life forms that couple ion movement across membranes with ATP hydrolysis or synthesis. Sequence and structural comparisons of F- and V-type ATPases have revealed homology between their catalytic and membrane subunits, but not between the subunits of the central stalk that connects the catalytic and membrane components. Based on this pattern of homology, we propose that these ATPases originated from membrane protein translocases, which, themselves, evolved from RNA translocases. We suggest that in these ancestral translocases, the position of the central stalk was occupied by the translocated polymer. C1 Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. Moscow MV Lomonosov State Univ, Inst Phys Chem Biol, Moscow 119899, Russia. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de; koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Intramural NIH HHS NR 93 TC 74 Z9 78 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD NOV PY 2007 VL 5 IS 11 BP 892 EP 899 DI 10.1038/nrmicro1767 PG 8 WC Microbiology SC Microbiology GA 231NQ UT WOS:000250955800015 PM 17938630 ER PT J AU Basselin, M Villacreses, NE Lee, HJ Bell, JM Rapoport, SI AF Basselin, Mireille Villacreses, Nelly E. Lee, Ho-Joo Bell, Jane M. Rapoport, Stanley I. TI Flurbiprofen, a cyclooxygenase inhibitor, reduces the brain arachidonic acid signal in response to the cholinergic muscarinic agonist, arecoline, in awake rats SO NEUROCHEMICAL RESEARCH LA English DT Article DE arachidonic acid; cyclooxygenase; flurbiprofen; muscarinic receptors; cytosolic phospholipase A(2); prostaglandin E-2; thromboxane B-2; COX-1; COX-2; NSAID ID CYTOSOLIC PHOSPHOLIPASE A(2); UNANESTHETIZED RATS; ACETYLSALICYLIC-ACID; SELECTIVE-INHIBITION; PROSTAGLANDIN E-2; FATTY-ACIDS; RECEPTOR; ACTIVATION; COX-2; TRANSDUCTION AB Cholinergic muscarinic receptors, when stimulated by arecoline, can activate cytosolic phospholipase A(2) (cPLA(2)) to release arachidonic acid (AA) from membrane phospholipid. This signal can be imaged in the brain in vivo using quantitative autoradiography following the intravenous injection of radiolabeled AA, as an increment in a regional brain AA incorporation coefficient k*. Arecoline increases k* significantly in brain regions having muscarinic M-1,M-3,M-5 receptors in wild-type but not in cyclooxygenase (COX)-2 knockout mice. To further clarify the roles of COX enzymes in the AA signal, in this paper we imaged k* following arecoline (5 mg/kg i.p.) or saline in each of 81 brain regions of unanesthetized rats pretreated 6 h earlier with the non-selective COX inhibitor flurbiprofen (FB, 60 mg/kg s.c.) or with vehicle. Baseline values of k* were unaffected by FB treatment, which however reduced by 80% baseline brain concentrations of prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TXB2), eicosanoids preferentially derived from AA via COX-2 and COX-1, respectively. In vehicle-pretreated rats, arecoline increased the brain PGE(2) but not TXB2 concentration, as well as values for k* in 77 of the 81 brain regions. FB-pretreatment prevented these arecoline-provoked changes. These results and those reported in COX-2 knockout mice suggest that the AA released in brain following muscarinic receptor-mediated activation is lost via COX-2 to PGE(2) but not via COX-1 to TXB2, and that increments in k* following arecoline largely represent replacement by unesterified plasma AA of this loss. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,MSC 0947,9 Mem Dr, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov FU Intramural NIH HHS NR 75 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2007 VL 32 IS 11 BP 1857 EP 1867 DI 10.1007/s11064-007-9372-3 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 215FR UT WOS:000249794200006 PM 17562170 ER PT J AU Shmueli, K van Gelderen, P de Zwart, JA Horovitz, SG Fukunaga, M Jansma, JM Duyn, JH AF Shmueli, Karin van Gelderen, Peter de Zwart, Jacco A. Horovitz, Silvina G. Fukunaga, Masaki Jansma, J. Martijn Duyn, Jeff H. TI Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal SO NEUROIMAGE LA English DT Article ID PHYSIOLOGICAL ARTIFACTS; RETROSPECTIVE ESTIMATION; FUNCTIONAL CONNECTIVITY; 1.5 T; NOISE; MRI; OPTIMIZATION; OSCILLATIONS; EXTRACTION; IMPACT AB Heart rate fluctuations occur in the low-frequency range (<0.1 Hz) probed in functional magnetic resonance imaging (fMRI) studies of resting-state functional connectivity and most fMRI block paradigms and may be related to low-frequency blood-oxygenation-level-dependent (BOLD) signal fluctuations. To investigate this hypothesis, temporal correlations between cardiac rate and resting-state fMRI signal timecourses were assessed at 3 T. Resting-state BOLD fMRI and accompanying physiological data were acquired and analyzed using cross-correlation and regression. Time-shifted cardiac rate timecourses were included as regressors in addition to established physiological regressors (RETROICOR (Glover, G.H., Li, T.Q., Ress, D., 2000. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med 44, 162167) and respiration volume per unit time (Birn, R.M., Diamond, J.B., Smith, M.A., Bandettini, P.A., 2006b. Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. NeuroImage 31, 1536-1548). Significant correlations between the cardiac rate and BOLD signal timecourses were revealed, particularly negative correlations in gray matter at time shifts of 6-12 s and positive correlations at time shifts of 30-42 s (TR = 6 s). Regressors consisting of cardiac rate timecourses shifted by delays of between 0 and 24 s explained an additional 1% of the BOLD signal variance on average over the whole brain across 9 subjects, a similar additional variance to that explained by respiration volume per unit time and RETROICOR regressors, even when used in combination with these other physiological regressors. This suggests that including such time-shifted cardiac rate regressors will be beneficial for explaining physiological noise variance and will thereby improve the statistical power in future task-based and resting-state fMRI studies. Published by Elsevier Inc. C1 Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Adv MRI Sect, Bethesda, MD 20892 USA. RP Shmueli, K (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Adv MRI Sect, 10 Ctr Dr,Bldg 10,Rm B1D-728, Bethesda, MD 20892 USA. EM shmuelik@mail.nih.gov RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013; Shmueli, Karin/B-9432-2017 OI Fukunaga, Masaki/0000-0003-1010-2644; FU Intramural NIH HHS [Z01 NS002990-08, Z99 NS999999] NR 37 TC 244 Z9 246 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2007 VL 38 IS 2 BP 306 EP 320 DI 10.1016/j.neuroimage.2007.07.037 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 224EJ UT WOS:000250430000007 PM 17869543 ER PT J AU Asthagiri, AR Pouratian, N Sherman, J Ahmed, G Shaffrey, ME AF Asthagiri, Ashok R. Pouratian, Nader Sherman, Jonathan Ahmed, Galal Shaffrey, Mark E. TI Advances in brain tumor surgery SO NEUROLOGIC CLINICS LA English DT Review ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; CONTROLLED-RELEASE POLYMERS; LONG-TERM SURVIVAL; DIRECT CORTICAL STIMULATION; OPTICAL INTRINSIC SIGNALS; HUMAN VISUAL-CORTEX; LOW-GRADE GLIOMA; QUALITY-OF-LIFE; GLIOBLASTOMA-MULTIFORME AB Advances in the fields of molecular and translational research, oncology, and surgery have emboldened the medical community to believe that intrinsic brain tumors may be treatable. Intraoperative imaging and brain mapping allow operations adjacent to eloquent cortex and more radical resection of tumors with increased confidence and safety Despite these advances, the infiltrating edge of a neoplasm and distant microscopic satellite lesions will never be amendable to a surgical cure. Indeed, it is continued research into the delivery of an efficacious chemobiologic agent that will eventually allows us to manage this primary cause of treatment failure. C1 NIH, NINDS, Bethesda, MD 20892 USA. Univ Virginia, Dept Neurol Surg, Charlottesville, VA 22908 USA. RP Asthagiri, AR (reprint author), NIH, NINDS, Bethesda, MD 20892 USA. EM asthagiria@ninds.nih.gov OI Pouratian, Nader/0000-0002-0426-3241 NR 144 TC 32 Z9 44 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 975 EP + DI 10.1016/j.ncl.2007.07.006 PG 31 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500006 PM 17964023 ER PT J AU Asthagiri, AR Helm, GA Sheehan, JP AF Asthagiri, Ashok R. Helm, Gregory A. Sheehan, Jason P. TI Current concepts in management of meningiomas and schwannomas SO NEUROLOGIC CLINICS LA English DT Review ID GAMMA-KNIFE RADIOSURGERY; CAVERNOUS SINUS MENINGIOMAS; SKULL BASE MENINGIOMAS; NEUROMA VESTIBULAR SCHWANNOMA; NEUROFIBROMATOSIS TYPE-2 GENE; ACOUSTIC NEUROMA; INTRACRANIAL MENINGIOMAS; STEREOTACTIC RADIOSURGERY; FACIAL-NERVE; SURGICAL-MANAGEMENT AB Meningiomas and schwannomas are the two most common extra-axial intracranial tumors in adults. Since their initial discovery, these often-benign lesions have shared a parallel metamorphosis in their management. The goal of this article is to provide a review of the current literature surrounding the mainstays of therapy for these lesions. C1 NIH, NINDS, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol Surg, Charlottesville, VA 22908 USA. RP Asthagiri, AR (reprint author), NIH, NINDS, Bethesda, MD 20892 USA. EM asthagiria@ninds.nih.gov NR 128 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 1209 EP + DI 10.1016/j.ncl.2007.07.009 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500015 PM 17964032 ER PT J AU Xi, ZX Yang, Z Li, SJ Li, X Dillon, C Peng, XQ Spiller, K Gardner, EL AF Xi, Zheng-Xiong Yang, Zheng Li, Shi-Jiang Li, Xia Dillon, Christopher Peng, Xiao-Qing Spiller, Krista Gardner, Eliot L. TI Levo-tetrah dro almatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats SO NEUROPHARMACOLOGY LA English DT Article DE cocaine; levo-tetrahydropalmatine; dopamine; self-administration; brain reward; addiction ID DOPAMINE-RECEPTOR ANTAGONISTS; MEDICATION DEVELOPMENT; L-TETRAHYDROPALMATINE; NUCLEUS-ACCUMBENS; FOOD-DEPRIVATION; D-2 RECEPTORS; ANIMAL-MODELS; DRUG; D2; D1 AB It was recently reported that levo-tetrahydropalmatine (l-THP), a dopamine (DA) D-1 and D-2 receptor antagonist purified from the Chinese herb Stephanie, appears to be effective in attenuating cocaine self-administration, cocaine-triggered reinstatement and cocaine-induced conditioned place preference in preclinical animal models. The present study was designed to contrast l-THP's effects on cocaine self-administration under fixed-ratio (FR) and progressive-ratio (PR) reinforcement, and to study l-THP's effects on cocaine-enhanced brain stimulation reward (BSR). Systemic administration of l-THP produced dose-dependent, biphasic effects, i.e., low-to-moderate doses (1, 3, 10 mg/kg) increased, while a high dose (20 mg/kg) inhibited cocaine self-administration behavior under FR2 reinforcement. The increased cocaine self-administration is likely a compensatory response to a reduction in cocaine's rewarding effects, because the same low doses of l-THP dose-dependently attenuated cocaine self-administration under PR reinforcement and also attenuated cocaine-enhanced BSR. These attenuations of PR cocaine self-administration and cocaine-enhanced BSR are unlikely due to l-THP-induced sedation or locomotor inhibition, because only 10 mg/kg, but not 1-3 mg/kg, of l-THP inhibited locomotion, sucrose self-administration and asymptotic operant performance in the BSR paradigm. In vivo microdialysis demonstrated that l-THP slightly elevates extracellular nucleus accumbens DA by itself, but dose-dependently potentiates cocaine-augmented DA, suggesting that a postsynaptic, rather than presynaptic, DA receptor antagonism underlies l-THP's actions on cocaine reward. Together, the present data, combined with previous findings, support the potential use of l-THP for treatment of cocaine addiction. (C) 2007 Elsevier Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Beijing Inst Basic Med Sci, Beijing, Peoples R China. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 45 TC 26 Z9 35 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2007 VL 53 IS 6 BP 771 EP 782 DI 10.1016/j.neuropharm.2007.08.004 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 229IO UT WOS:000250796700007 PM 17888459 ER PT J AU Carriba, P Ortiz, O Patkar, K Justinova, Z Stroik, J Themann, A Muller, C Woods, AS Hope, BT Ciruela, F Casado, V Canela, EI Lluis, C Goldberg, SR Moratalla, R Franco, R Ferre, S AF Carriba, Paulina Ortiz, Oskar Patkar, Kshitij Justinova, Zuzana Stroik, Jessica Themann, Andrea Mueller, Christa Woods, Anima S. Hope, Bruce T. Ciruela, Francisco Casado, Vicent Canela, Enric I. Lluis, Carme Goldberg, Steven R. Moratalla, Rosario Franco, Rafael Ferre, Sergi TI Striatal adenosine A(2A) and Cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of Cannabinoids SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE adenosine A(2A) receptor; cannabinoid CB1 receptor; receptor heteromerization; striatum; cyclic AMP; motor activity ID BASAL GANGLIA; ULTRASTRUCTURAL-LOCALIZATION; DOPAMINE-D-2 RECEPTORS; RAT STRIATUM; NEURONS; OLIGOMERIZATION; PHARMACOLOGY; INVOLVEMENT; DERIVATIVES; ANTAGONISTS AB The mechanism of action responsible for the motor depressant effects of cannabinoids, which operate through centrally expressed cannabinoid CB1 receptors, is still a matter of debate. In the present study, we report that CB1 and adenosine A(2A) receptors form heteromeric complexes in co-transfected HEK-293T cells and rat striatum, where they colocalize in fibrilar structures. In a human neuroblastoma cell line, CB1 receptor signaling was found to be completely dependent on A(2A) receptor activation. Accordingly, blockade of A(2A) receptors counteracted the motor depressant effects produced by the intrastriatal administration of a cannabinoid CB1 receptor agonist. These biochemical and behavioral findings demonstrate that the profound motor effects of cannabinoids depend on physical and functional interactions between striatal A(2A) and CB1 receptors. C1 NIDA, Preclin Pharmacol Sect, Dept Hlth & Human Serv, IRP,NIH, Baltimore, MD 21224 USA. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. CSIC, Inst Cajal, E-28002 Madrid, Spain. NIDA, Prote Lab, Dept Hlth & Human Serv, Intramural Res Program,NIH, Baltimore, MD USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. Univ Bonn, Inst Pharmaceut, D-5300 Bonn, Germany. NIDA, Neurobiol Relapse Sect, Dept Hlth & Human Serv, IRP,NIH, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), NIDA, Preclin Pharmacol Sect, Dept Hlth & Human Serv, IRP,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; Justinova, Zuzana/A-9109-2011; Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Moratalla, Rosario/H-9280-2015; Casado, Vicent/K-1660-2014 OI Casado, Vicent/0000-0002-1764-3825; Hope, Bruce/0000-0001-5804-7061; Justinova, Zuzana/0000-0001-5793-7484; Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Moratalla, Rosario/0000-0002-7623-8010; FU Intramural NIH HHS NR 41 TC 123 Z9 127 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2007 VL 32 IS 11 BP 2249 EP 2259 DI 10.1038/sj.npp.1301375 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 221KL UT WOS:000250226000001 PM 17356572 ER PT J AU Cao, J Lotfipour, S Loughlin, SE Leslie, FM AF Cao, Junran Lotfipour, Shahrdad Loughlin, Sandra E. Leslie, Frances M. TI Adolescent maturation of cocaine-sensitive neural mechanisms SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE dopamine; caudate putamen; extended amygdala; c-fos; microdialysis; in situ hybridization ID EARLY GENE INDUCTION; DEVELOPING RAT-BRAIN; C-FOS; ADULT-RATS; EXTENDED AMYGDALA; STRIA TERMINALIS; BED NUCLEUS; AMPHETAMINE MICROINJECTIONS; CATECHOLAMINE INNERVATION; VENTROLATERAL STRIATUM AB Both clinical and animal studies have shown that adolescents undergo a late maturation of the central nervous system, which may underlie adolescent typical behaviors. In particular, decreased behavioral response to cocaine has been found in adolescents as compared to adults. In the present study, cocaine was used as a tool to explore adolescent brain maturation. Juvenile ( postnatal day ( P) 27), adolescent (P37), and adult (P90) male Sprague-Dawley rats were treated acutely with cocaine (750 mu g/kg/injection x 2,i.v.), and c-fos mRNA expression, a marker of neuronal activation, was evaluated by in situ hybridization. Cocaine-induced c-fos mRNA was similar across ages in the dorsal caudate putamen (CPu), nucleus accumbens, and lateral bed nucleus of the stria terminalis. In contrast, there was a diminished response in juvenile/adolescent ventral CPu and in juvenile central nucleus of the amygdala, and an increased response in juvenile/adolescent cortex. Further studies evaluated the mechanism of the late maturation of cocaine response in ventral CPu. No significant age differences were observed in regional dopamine (DA) transporter binding. Although striatal DA content was significantly reduced at P27 as compared to adult, there was no difference between dorsal and ventral subregions. In contrast, basal- and cocaine-induced extracellular DA overflow, as measured by in vivo microdialysis, was lower in juvenile ventral CPu than in the adults. This age difference was not observed in dorsal CPu. These findings suggest that impulse activity in DA afferents to ventral CPu is immature in adolescents. In conclusion, the present study showed that cocaine-sensitive neuronal circuits continue to mature during adolescence. C1 NIDA, Behave Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Calif Irvine, Sch Med, Dept Pharmacol, Irvine, CA 92717 USA. Univ Calif Irvine, Sch Med, Dept Anat & Neurobiol, Irvine, CA 92717 USA. RP Cao, J (reprint author), NIDA, Behave Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM caoju@mail.nih.gov RI Cao, Junran/E-7354-2013; Lotfipour, Shahrdad/K-8335-2014 OI Lotfipour, Shahrdad/0000-0002-2425-1096 FU NIDA NIH HHS [DA 19138] NR 71 TC 41 Z9 42 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2007 VL 32 IS 11 BP 2279 EP 2289 DI 10.1038/sj.npp.1301349 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 221KL UT WOS:000250226000004 PM 17299504 ER PT J AU Lule, D Diekmann, V Kassubek, J Kurt, A Birbaumer, N Ludolph, AC Kraft, E AF Lule, Dorothee Diekmann, Volker Kassubek, Jan Kurt, Anja Birbaumer, Niels Ludolph, Albert C. Kraft, Eduard TI Cortical plasticity in amyotrophic lateral sclerosis: Motor imagery and function SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE amyotrophic lateral sclerosis (ALS); cortical plasticity; motor imagery; fMRI; brain; computer interfaces ID POSITRON-EMISSION-TOMOGRAPHY; IMAGINED HAND MOVEMENTS; PARKINSONS-DISEASE; BAYESIAN-INFERENCE; NEURON DISEASE; BRAIN; REORGANIZATION; AREAS; FMRI; ACTIVATIONS AB Background. Cortical networks underlying motor imagery are functionally close to motor performance networks and can be activated by patients with severe motor disabilities. Objective. The aim of the study was to examine the longitudinal effect of progressive motoneuron degeneration on cortical representation of motor imagery and function in amyotrophic lateral sclerosis. Methods. The authors studied 14 amyotrophic lateral sclerosis patients and 15 healthy controls and a subgroup of 11 patients and 14 controls after 6 months with a grip force paradigm comprising imagery and execution tasks using functional magnetic resonance imaging. Results. Motor imagery activated similar neural networks as motor execution in amyotrophic lateral sclerosis patients and healthy subjects in the primary motor (BA 4), premotor, and supplementary motor (BA 6) cortex. Amyotrophic lateral sclerosis patients presented a stronger response within premotor and primary motor areas for imagery and execution compared to controls. After 6 months, these differences persisted with additional activity in the precentral gyrus in patients as well as in a frontoparietal network for motor imagery, in which activity increased with impairment. Conclusion. The findings suggest an ongoing compensatory process within the higher order motor-processing system of amyotrophic lateral sclerosis patients, probably to overcome loss of function in primary motor and motor imagery-specific networks. The increased activity in precentral and frontoparietal networks in motor imagery might be used to control brain-computer interfaces to drive communication and limb prosthetic devices in patients with loss of motor control such as severely disabled amyotrophic lateral sclerosis patients in a locked-in-like state. C1 Neurol Univ Klin Ulm, Sek Neurophysiol, D-89081 Ulm, Germany. Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. Human Cort Physiol, NINDS, Natl Inst Hlth, Bethesda, MD USA. RP Lule, D (reprint author), Neurol Univ Klin Ulm, Sek Neurophysiol, Albert Einstein Allee 47, D-89081 Ulm, Germany. EM dorothee.lule@uni-ulm.de RI Kassubek, Jan/F-2774-2015 NR 39 TC 29 Z9 30 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD NOV-DEC PY 2007 VL 21 IS 6 BP 518 EP 526 DI 10.1177/1545968307300698 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 223BR UT WOS:000250345100005 PM 17476000 ER PT J AU Calis, KA Pucino, F AF Calis, Karim Anton Pucino, Frank TI Zoledronic acid and secondary prevention of fractures SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HIP FRACTURE; OLDER-ADULTS C1 NIH, Dept Pharm, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. US Pharmacopeia, Endocrinol Expert Comm, Rockville, MD USA. RP Calis, KA (reprint author), NIH, Dept Pharm, Mark O Hatfield Clin Res Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 9 Z9 9 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 NOV 1 PY 2007 VL 357 IS 18 BP 1861 EP 1862 DI 10.1056/NEJMe078192 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 225OJ UT WOS:000250526900012 PM 17878150 ER PT J AU White, J Parascandola, M Bero, L AF White, Jenny Parascandola, Mark Bero, Lisa TI Tobacco industry research and protection of human subjects: A case study of R. J. Reynolds SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID AIR AB Companies that conduct research are under no obligation to follow guidelines regarding treatment of human subjects in clinical trials. By contrast, clinical researchers funded by federal agencies or under U.S. Food and Drug Administration authority are required to follow federal regulations, and academics must adhere to their institutions' standards. We examined how one tobacco company, R. J. Reynolds, treated human subjects in internal research conducted from 1985 to 2000. We then compared this treatment with standards of the time. We focused on R. J. Reynolds because the company conducted a significant amount of research using human subjects. Tobacco industry documents were retrieved from the UCSF/Legacy Tobacco Documents Library, Tobacco Documents Online, and industry Web sites. Materials from 73 research projects, including informed consent forms, were analyzed. The U.S. Code of Federal Regulations, Title 45 Part 46, Protection of Human Subjects (the Common Rule) was the primary source for human subjects research guidelines and standards. R. J. Reynolds formed a human subjects review committee in 1985. The committee's structure and procedures did not meet generally accepted practices of the time regarding community representation, written procedures for adverse events, and other factors. In all 73 studies, consent procedures failed to meet five or more human subjects research standards. Policymakers should consider expanding the scope of federal human subjects research regulations to cover research undertaken by private firms such as tobacco companies. C1 Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Bero, L (reprint author), Univ Calif San Francisco, Dept Clin Pharm, Suite 420,Box 0613,3333 Calf St, San Francisco, CA 94143 USA. EM berol@pharmacy.ucsf.edu NR 108 TC 2 Z9 2 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2007 VL 9 IS 11 BP 1213 EP 1225 DI 10.1080/14622200701648425 PG 13 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 236WS UT WOS:000251334700020 PM 17978997 ER PT J AU Paiva, FF Tannus, A Silva, AC AF Paiva, Fernando F. Tannus, Alberto Silva, Afonso C. TI Measurement of cerebral perfusion territories using arterial spin labelling SO NMR IN BIOMEDICINE LA English DT Review DE brain; cerebral blood flow; cerebrovascular diseases; MRI; vascular territory ID BRAIN PERFUSION; BLOOD-FLOW; IMAGING TECHNIQUES; FEEDING ARTERIES; MR ANGIOGRAPHY; INVERSION; PULSES; COIL; WATER; TIME AB The ability to assess the perfusion territories of major cerebral arteries can be a valuable asset to the diagnosis of a number of cerebrovascular diseases. Recently, several arterial spin labeling (ASL) techniques have been proposed for determining the cerebral perfusion territories of individual arteries by three different approaches: (1) using a dedicated labeling radio frequency (RF) coil; (2) applying selective inversion of spatially confined areas; (3) employing multidimensional RF pulses. Methods that use a separate labeling RF coil have high signal-to-noise ratio (SNR), low RF power deposition, and unrestricted three-dimensional coverage, but are mostly limited to separation of the left and right circulation, and do require extra hardware, which may limit their implementation in clinical systems. Alternatively, methods that utilize selective inversion have higher flexibility of implementation and higher arterial selectivity, but suffer from imaging artifacts resulting from interference between the labeling slab and the volume of interest. The goal of this review is to provide the reader with a critical survey of the different ASL approaches proposed to date for determining cerebral perfusion territories, by discussing the relative advantages and disadvantages of each technique, so as to serve as a guide for future refinement of this promising methodology. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 NIH, Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, Cerebral Microcirculat Unit, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Phys Sao Carlos, Lab Magnet Resonance Imaging, BR-13560970 Sao Carlos, SP, Brazil. RP Silva, AC (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, Cerebral Microcirculat Unit, 10 Ctr Dr MSC 1065,Bldg 10 Rm B1D106, Bethesda, MD 20892 USA. EM SilvaA@ninds.nih.gov RI Silva, Afonso/A-7129-2009; Paiva, Fernando/C-1429-2012; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; Tannus, Alberto/B-9821-2012 OI Paiva, Fernando/0000-0002-8989-9707; Tannus, Alberto/0000-0002-1675-1971 FU Intramural NIH HHS [Z01 NS003041-01] NR 49 TC 24 Z9 26 U1 3 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD NOV PY 2007 VL 20 IS 7 BP 633 EP 642 DI 10.1002/nbm.1177 PG 10 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 232GM UT WOS:000251006400001 PM 17503440 ER PT J AU Chen, Z Lewis, KA Shultzaberger, RK Lyakhov, IG Zheng, M Doan, B Storz, G Schneider, TD AF Chen, Zehua Lewis, Karen A. Shultzaberger, Ryan K. Lyakhov, Ilya G. Zheng, Ming Doan, Bernard Storz, Gisela Schneider, Thomas D. TI Discovery of Fur binding site clusters in Escherichia coli by information theory models SO NUCLEIC ACIDS RESEARCH LA English DT Article ID UPTAKE REGULATION PROTEIN; FERRIC UPTAKE REGULATOR; IRON HOMEOSTASIS; SEQUENCE LOGOS; SMALL RNA; TRANSCRIPTIONAL REGULATION; POLYAMINE STIMULATION; NUCLEOTIDE-SEQUENCES; MOLECULAR-MECHANISM; AEROBACTIN PROMOTER AB Fur is a DNA binding protein that represses bacterial iron uptake systems. Eleven footprinted Escherichia coli Fur binding sites were used to create an initial information theory model of Fur binding, which was then refined by adding 13 experimentally confirmed sites. When the refined model was scanned across all available footprinted sequences, sequence walkers, which are visual depictions of predicted binding sites, frequently appeared in clusters that fit the footprints (83 coverage). This indicated that the model can accurately predict Fur binding. Within the clusters, individual walkers were separated from their neighbors by exactly 3 or 6 bases, consistent with models in which Fur dimers bind on different faces of the DNA helix. When the E. coli genome was scanned, we found 363 unique clusters, which includes all known Fur-repressed genes that are involved in iron metabolism. In contrast, only a few of the known Fur-activated genes have predicted Fur binding sites at their promoters. These observations suggest that Fur is either a direct repressor or an indirect activator. The Pseudomonas aeruginosa and Bacillus subtilis Fur models are highly similar to the E. coli Fur model, suggesting that the FurDNA recognition mechanism may be conserved for even distantly related bacteria. C1 NCI, Ctr Canc Res Nanobiol Program, Ft Detrick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NIAID, Referral & Program Anal Branch, Div Extramural Activities, Bethesda, MD 20892 USA. RP Schneider, TD (reprint author), NCI, Ctr Canc Res Nanobiol Program, Ft Detrick, MD 21702 USA. EM toms@ncifcrf.gov RI Chen, Zehua/E-6356-2011; chen, zehua/H-1260-2011; OI Schneider, Thomas/0000-0002-9841-1531; Storz, Gisela/0000-0001-6698-1241 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 84 TC 44 Z9 46 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2007 VL 35 IS 20 BP 6762 EP 6777 DI 10.1093/nar/gkm631 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236XF UT WOS:000251336000012 PM 17921503 ER PT J AU Cruz, MLS Harris, DR Read, JS Mussi-Pinhata, MM Succi, RCM AF Cruz, Maria Leticia S. Harris, D. Robert Read, Jennifer S. Mussi-Pinhata, Marisa M. Succi, Regina C. M. CA Natl Inst Child Hlth & Human Dev TI Association of body mass index of HIV-1-infected pregnant women and infant birth weight, body mass index, length, and head circumference: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study SO NUTRITION RESEARCH LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-09, 2005 CL San Francisco, CA SP Infect Dis Soc Amer DE maternal BMI; low birth weight; preterm; HIV-exposed infants; HIV-infected pregnant women ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED WOMEN; NUTRITIONAL-STATUS; PRETERM BIRTH; PREDICTORS; MORTALITY; OUTCOMES; RISK; BORN; DETERMINANTS AB This study assessed the relationship between the body mass index (BMI) of HIV-1-infected women and their infants' perinatal outcomes. The study population was composed of women enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study, with data allowing calculation of their BMI adjusted for length of gestation (adjBMI), who delivered singleton infants. Outcome variables included infant growth parameters at birth (weight, BMI, length, and head circumference) and gestational age. Among the 697 women from Argentina, the Bahamas, Brazil, and Mexico who were included in the analysis, adjBMI was classified as underweight for 109 (15.6%), as normal for 418 (60.0%), as overweight for 88 (12.6%), and as obese for 82 (11.8%). Median infant birth weight, BMI, length, and head circumference differed significantly according to maternal adjBMI (P <= .0002). Mothers who were underweight gave birth to infants with lower weight, lower BMI, shorter length, and smaller head circumference, whereas infants born to mothers who were of normal weight, overweight, and obese were of similar characteristics. (c) 2007 Elsevier Inc. All rights reserved. C1 Hosp Servidores Estado, Serv Doencas Infecciosas & Parasitarias, BR-20221903 Rio De Janeiro, Brazil. Westat Corp, Rockville, MD 20850 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pediat, BR-14049900 Sao Paulo, Brazil. Univ Fed Sao Paulo, Div Pediat Infect Dis, BR-04049003 Sao Paulo, Brazil. RP Cruz, MLS (reprint author), Hosp Servidores Estado, Serv Doencas Infecciosas & Parasitarias, 4 Andar,Anexo 4, BR-20221903 Rio De Janeiro, Brazil. EM mleticia@diphse.com.br RI Mussi-Pinhata, Marisa/G-6568-2012 FU NICHD NIH HHS [N01 HD033345] NR 29 TC 3 Z9 3 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD NOV PY 2007 VL 27 IS 11 BP 685 EP 691 DI 10.1016/j.nutres.2007.09.005 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 236BC UT WOS:000251277000004 PM 19081829 ER PT J AU Pratt, CA Fernandez, ID Stevens, VJ AF Pratt, Charlotte A. Fernandez, Isabel Diana Stevens, Victor J. TI Formative research and baseline results of worksite studies on overweight and obesity control - Introduction and overview of worksite studies SO OBESITY LA English DT Editorial Material ID EPIDEMIC C1 [Pratt, Charlotte A.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Fernandez, Isabel Diana] Univ Rochester, Sch Med, Dept Community & Prevent Med, Rochester, NY USA. [Stevens, Victor J.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Pratt, CA (reprint author), NHLBI, Div Prevent & Populat Sci, 6701 Rockledge Dr,MSC 7936,Room 10118, Bethesda, MD 20892 USA. EM prattc@nhlbi.nih.gov FU NHLBI NIH HHS [R01 HL079509, R01 HL079511, R01 HL079546, R01 HL079478, R01 HL079491, R01 HL079483, R01 HL079505] NR 12 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2007 VL 15 SU 1 BP 1S EP 3S DI 10.1038/oby.2007.382 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 245ML UT WOS:000251939100001 PM 18073336 ER PT J AU Gorman, N Lackney, JA Rollings, K Huang, TTK AF Gorman, Nicholas Lackney, Jeffery A. Rollings, Kimberly Huang, Terry T. -K. TI Designer schools: The role of school space and architecture in obesity prevention SO OBESITY LA English DT Article DE childhood obesity; environmental factors; prevention; public health; energy balance ID HEALTH PROMOTION PROGRAMS; PHYSICAL-ENVIRONMENT; CHILDHOOD; CHILDREN; CENTERS; TRIAL; AIR AB Spatial features of obesogenic environments studied on a broad community level have been associated with childhood overweight and obesity, but little research has focused on the effects of the design of micro spaces, such as schools, on individual health behaviors. This article aims to generate thinking and research on the link between school space and architecture and obesity prevention by reviewing and synthesizing available literature in architecture, environmental psychology, and obesity research, in an effort to propose promising ideas for school space design and redesign. The school environment is defined through 5 dimensions: physical, legal, policy, social, and cultural domains. Theories underlying environmental interventions and documented associations between the environment and health behaviors and outcomes are reviewed to illustrate how existing environmental research could translate to obesity prevention. Design strategies aimed at promoting physical activity and healthful eating are proposed, with particular emphasis on the design of cafeterias, activity spaces, connectivity with the larger community, and student health centers. C1 [Gorman, Nicholas] Univ So Calif, Keck Sch Med, Inst Hlth Promot & Dis Prevent Res, Dept Prevent Med, Los Angeles, CA 90089 USA. [Lackney, Jeffery A.] Univ Wisconsin, Coll Engn, Sch Human Ecol, Dept Interior Design,Dept Engn Profess Dev, Madison, WI 53706 USA. [Rollings, Kimberly] Univ Wisconsin, Sch Architecture & Urban Plannning, Madison, WI 53706 USA. [Huang, Terry T. -K.] Natl Inst Hlth, Natl Inst Child Hlth & Human Dev, Ctr Res Mothers & Children, Endocrinol Nutr & Growth Branch, Bethesda, MD USA. RP Huang, TTK (reprint author), Natl Inst Child Hlth & Human Dev, 6100 Execut Blvd, Rockville, MD 20852 USA. EM huangter@mail.nih.gov RI Rollings, Kimberly/K-2393-2016 OI Rollings, Kimberly/0000-0002-3091-3340 NR 51 TC 15 Z9 15 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2007 VL 15 IS 11 BP 2521 EP 2530 DI 10.1038/oby.2007.300 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 243EX UT WOS:000251779000001 PM 18070739 ER PT J AU Saleem, S Reza, T McClure, EM Pasha, O Moss, N Rouse, DJ Bartz, J Goldenberg, RL AF Saleem, S. Reza, T. McClure, E. M. Pasha, O. Moss, N. Rouse, D. J. Bartz, J. Goldenberg, R. L. TI Chlorhexidine vaginal and neonatal wipes in home births in Pakistan - A Randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NEWBORN BABIES; MORTALITY; MORBIDITY; INTERVENTION; OUTCOMES AB Objective: To assess tolerance and safety of 0.6% chlorhexidine vaginal and neonatal wipes to improve perinatal outcomes in home deliveries in Pakistan and the ability of traditional birth attendants and project staff to perform a randomized trial of this intervention. Methods: Focus groups of pregnant and nonpregnant women and in-depth interviews of traditional birth attendants explored barriers to the use of chlorhexidine wipes. Then, a study was performed of women delivering at home attended by traditional birth attendants. Consenting women were randomly assigned to receive either 0.6% chlorhexidine or saline vaginal and neonatal wipes. Women and their infants were followed up on postpartum days 7, 14, and 28. Acceptability and tolerance of vaginal and neonatal wipes, as well as maternal and neonatal outcomes, were assessed. Results: The focus groups and interviews indicated that the chlorhexidine intervention would be acceptable to women and their providers. Of the 213 eligible pregnant women approached, 203 (950%) gave informed consent and were enrolled and allocated to groups. Traditional birth attendants had no difficulty administering chlorhexidine vaginal and neonatal wipes in a home setting. Of the 203 births, 103 (51%) of whom received 0.6% chlorhexidine, there were no allergic reactions, vaginal itching, burning, or requests for study termination. Follow-up at 28 days postpartum was more than 95%. Although this study was not powered to show significant differences in neonatal outcomes between treatment groups, the lower rates of some neonatal adverse clinical outcomes in the chlorhexidine group were encouraging. Conclusion: Use of 0.6% chlorhexidine vaginal and neonatal wipes for the prevention of neonatal infection is well-tolerated and seems safe. A trial of this intervention by traditional birth attendants in a home-delivery setting is feasible. C1 Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19102 USA. Aga Khan Univ, Karachi, Pakistan. RTI Int, Res Triangle Pk, NC USA. NICHHD, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RP Goldenberg, RL (reprint author), Drexel Univ, Coll Med, Dept Obstet & Gynecol, 245 N 15th St, Philadelphia, PA 19102 USA. EM rgoldenb@drexelmed.edu RI Sandall, Jane/D-4146-2009 OI Sandall, Jane/0000-0003-2000-743X FU NICHD NIH HHS [U01 HD040607, U01 HD040636] NR 17 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2007 VL 110 IS 5 BP 977 EP 985 DI 10.1097/01.AOG.0000285653.17869.26 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223HM UT WOS:000250360800004 PM 17978107 ER PT J AU Chi, BH Wang, L Read, JS Taha, TE Sinkala, M Brown, ER Valentine, M Martinson, F Goldenberg, RL AF Chi, Benjamin H. Wang, Lei Read, Jennifer S. Taha, Taha E. Sinkala, Moses Brown, Elizabeth R. Valentine, Megan Martinson, Francis Goldenberg, Robert L. TI Predictors of stillbirth in sub-saharan Africa SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PERINATAL HIV-1 TRANSMISSION; DEVELOPING-COUNTRIES; NEONATAL DEATHS; RISK FACTOR; CHORIOAMNIONITIS; SYPHILIS; ANTIBIOTICS; INFECTION; PREGNANCY; OUTCOMES AB Objective: To describe the incidence and predictors of stillbirth in a predominantly human immunodeficiency virus (HIV)-infected African cohort. Methods: Human Immunodeficiency Virus (HIV) Prevention Trials Network (HPTN) 024 was a randomized controlled trial of empiric antibiotics to reduce chorioam nionitis-related perinatal HIV transmission. A proportion of HIV-uninfected individuals were enrolled to reduce community-based stigma surrounding the trial. For this analysis, only women who gave birth to singleton infants were included. Results: Of 2,659 women enrolled, 2,434 (92%) motherchild pairs met inclusion criteria. Of these, 2,099 (86%) infants were born to HIV-infected women, and 335 (14%) were born to HIV-uninfected women. The overall stillbirth rate was 32.9 per 1,000 deliveries (95% confidence interval [CI] 26.1-40.7). In univariable analyses, predictors for stillbirth included previous stillbirth (odds ratio [OR] 2.3, 95% CI 1.2-4.3), antenatal hemorrhage (OR 14.4,95% CI 4.3-47.9), clinical chorioamnionitis (OR 20.9, 95% Cl 5.1-86.2), and marked polymorphonuclear infiltration on placental histology (OR 2.9, 95% CI 1.7-5.2). When compared with pregnancies longer than 37 weeks, those at 34-37 weeks (OR 1.7, 95% CI 0.8-3.4) and those at less than 34 weeks (OR 22.8, 95% CI 13.6-38.2) appeared more likely to result in stillborn delivery. Human immunodeficiency virus infection was not associated with a greater risk for stillbirth in either univariable (OR 1.5, 95% CI 0.7-3.0) or multivariable (adjusted OR 1.11, 95% Cl 0.38-3.26) analysis. Among HIV-infected women, however, decreasing CD4 cell count was inversely related to stillbirth risk (P=.009). Conclusion: In this large cohort, HIV infection was not associated with increased stillbirth risk. Further work is needed to elucidate the relationship between chorioamnionitis and stillbirth in African populations. C1 Ctr Infect Dis Res Zambia, Lusaka, Zambia. Univ Alabama, Sch Med, Birmingham, AL USA. SCHARP, Seattle, WA USA. NICHHD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Family Hlth Int, Durham, NC USA. UNC Project, Lilongwe, Malawi. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. RP Chi, BH (reprint author), Box 34681,Plot 5977 Benakale Rd, Lusaka, Zambia. EM bchi@cidrz.org RI Brown, Elizabeth/A-8984-2008 FU FIC NIH HHS [K01-TW06670]; NIAID NIH HHS [U01-AI-47972, N01-AI-35173, N01-AI-45200, N01-AI35173-117/412, U01-AI-48005, U01-AI048006] NR 27 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2007 VL 110 IS 5 BP 989 EP 997 DI 10.1097/01.AOG.0000281667.35113.a5 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223HM UT WOS:000250360800006 PM 17978109 ER PT J AU Stratton, P Turner, ML Childs, R Barrett, J Bishop, M Wayne, AS Pavletic, S AF Stratton, Pamela Turner, Maria L. Childs, Richard Barrett, John Bishop, Michael Wayne, Alan S. Pavletic, Steven TI Vulvovaginal chronic graft-versus-host disease with allogeneic hematopoietic stem cell transplantation SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Invest ID BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; HEMATOLOGIC MALIGNANCIES; CLINICAL-TRIALS; DIAGNOSIS; MANAGEMENT; LEUKEMIA; CRITERIA AB Objective: To describe the diagnosis and management of female genital chronic graft-versus-host (GVH) disease, a complication of hematopoietic stem cell transplantation. Methods: From 1999 to 2006, 33 women with vulvar symptoms or undergoing systematic evaluation for chronic GVH disease were referred 267 (median, range 29-6,117) days after transplantation for gynecologic evaluation. Pertinent histories, laboratory tests, and skin and genital area-directed examinations were performed. Vulvar disease was treated with superpotent topical glucocorticoids and topical estrogen. Sexually active, menopausal women used vaginal dilators, topical glucocorticoids and estrogen, and estrogen vaginal rings for vaginal synechiae. Results: At presentation, most patients complained of vulvar pain during urination and pain that prevented sexual intercourse. Twenty-nine of 33 presenting with vulvovaginal chronic GVH disease had vulvar erythema, with additional signs including vulvar vestibulitis syndrome (n=9), vulvar erosions (n=12), vulvar scarring (n=2), and vaginal scarring (n=6); over time, eight additional patients developed vaginal scarring. Topical glucocorticoids improved vulvar symptoms, and estrogen decreased vulvar mucosal friability. Eleven of 12 patients, who wanted to resume having intercourse, responded to nonsurgical treatment for vaginal synechiae. Conclusion: A combination of topical superpotent glucocorticoids and estrogen was effective in the treatment of vulvovaginal chronic GVH disease. In those with vaginal scarring, use of a vaginal dilator and estrogen ring was helpful. Early identification and treatment of vulvovaginal chronic GVH disease ameliorates vulvar pain by healing eroded vulvar mucosa and may prevent the need for surgery for hernatocolpos. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NICHD, Gynecol Consult Serv, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHD, Gynecol Consult Serv, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural NIH HHS NR 19 TC 30 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2007 VL 110 IS 5 BP 1041 EP 1049 DI 10.1097/01.AOG.0000285998.75450.86 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223HM UT WOS:000250360800015 PM 17978118 ER PT J AU Reddy, UM AF Reddy, Uma M. TI Prediction and prevention of recurrent stillbirth SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CHORIONIC-GONADOTROPIN CONCENTRATIONS; ANTEPARTUM FETAL DEATH; PLACENTAL ABRUPTION; ALPHA-FETOPROTEIN; ANTIPHOSPHOLIPID ANTIBODIES; SUBSEQUENT PREGNANCIES; CESAREAN-SECTION; GESTATIONAL-AGE; MATERNAL AGE; RISK AB Stillbirth is one of the most common adverse pregnancy outcomes in the United States, occurring in one out of every 200 pregnancies. There is a paucity of information on the outcome of pregnancies after stillbirth. Prior stillbirth is associated with a twofold to 10-fold increased risk of stillbirth in the future pregnancy. The risk depends on the etiology of the prior stillbirth, presence of fetal growth restriction, gestational age of the prior stillbirth, and race. Categorization of the cause of the initial stillbirth will allow better estimates of individual recurrence risk and guide management. A history of stillbirth also increases the risk of other adverse pregnancy outcomes in the subsequent pregnancy such as placental abruption, cesarean delivery, preterm delivery, and low birth weight infants. Prospective studies have revealed an increased risk of stillbirth with low pregnancy-associated plasma protein A, elevated maternal serum alpha fetoprotein, abnormal uterine artery Doppler studies, and antiphospholipid antibodies. However, the positive predictive value of these factors individually is poor. Because fetal growth restriction is associated with almost half of all stillbirths, the correct diagnosis of fetal growth restriction is essential. The use of individualized or customized growth standards will improve prediction of adverse pregnancy outcome by distinguishing growth-restricted fetuses from constitutionally small, healthy fetuses. Antepartum fetal surveillance and fetal movement counting are also mainstays of poststillbirth pregnancy management. C1 NICHD, Pregnancy & Perinatol Branch, NIH, Rockville, MD 20852 USA. RP Reddy, UM (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Rm 4B03,MSC 7510, Rockville, MD 20852 USA. EM reddyu@mail.nih.gov NR 68 TC 57 Z9 61 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2007 VL 110 IS 5 BP 1151 EP 1164 DI 10.1097/01.AOG.0000287616.71602.d0 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223HM UT WOS:000250360800029 PM 17978132 ER PT J AU Leske, MC Heijl, A Hyman, L Bengtsson, B Dong, LM Yang, ZM AF Leske, M. Cristina Heijl, Anders Hyman, Leslie Bengtsson, Boel Dong, LiMing Yang, Zhongming CA EMGT Grp TI Predictors of long-term progression in the early manifest glaucoma trial SO OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; INTRAOCULAR-PRESSURE; VISUAL-FIELD; BLOOD-PRESSURE; SYSTEMIC HYPERTENSION; OCULAR HYPERTENSION; RISK-FACTORS; EYE; POPULATION AB Purpose: To determine progression factors at the end of the Early Manifest Glaucoma Trial (EMGT) based on all EMGT patients and evaluate separately patients with higher and lower baseline intraocular pressure (IOP; median split). Design: Cohort of clinical trial participants. Participants: Patients with early open-angle glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no immediate treatment (n = 126), examined every 3 months for up to 11 years. Methods: Cox proportional hazard analyses, expressed by hazard ratios (HRs) and 95% confidence intervals (Cls). Main Outcome Measure: Time to progression, defined by perimetric and photographic disc criteria. Results: Overall progression was 67% when follow-up ended (median, 8 years). Treatment approximately halved progression risk (HR, 0.53; 95% Cl, 0.39-0.72); results were similar for patients with higher and lower baseline IOP (HRs, 0.41 and 0.55). Baseline progression factors (HRs, 1.51-2.12; P<0.01) were higher IOP, exfoliation, bilateral disease, and older age, as previously reported. New baseline predictors were lower ocular systolic perfusion pressure in all patients (<= 160 mmHg; HR, 1.42; 95% Cl, 1.04-1.94), cardiovascular disease history (HR, 2.75; 95% Cl, 1.44-5.26) in patients with higher baseline IOP, and lower systolic blood pressure (BP) (<= 125 mmHg; HR, 0.46; 95% Cl, 0.21-1.02) in patients with lower baseline IOP. Postbaseline progression factors were IOP levels at follow-up, with 12% to 13% average increase per millimeter of mercury in all patients (HRs, 1.12-1.13 per mmHg higher) and similar results in patients with higher and lower baseline IOP (HRs, 1.15 and 1.13 per mmHg higher). Disc hemorrhages (HR, 1.02; 95% Cl, 1.01-1.03 per percent higher frequency) also predicted progression. Thinner central corneal thickness (CCT) (HR, 1.25; 95% Cl, 1.01-1.55 per 40 mu m lower) was a new significant factor, a result observed in patients with higher baseline IOP (HR, 1.42; 95% Cl, 1.05-1.92 per 40 mu m lower) but not lower baseline IOP, with significant IOP-CCT interaction. Conclusions: Treatment and follow-up IOP continued to have a marked influence on progression, regardless of baseline IOP. Other significant factors were age, bilaterality, exfoliation, and disc hemorrhages, as previously determined. Lower systolic perfusion pressure, lower systolic BP, and cardiovascular disease history emerged as new predictors, suggesting a vascular role in glaucoma progression. Another new factor was thinner CCT, with results possibly indicating a preferential CCT effect with higher IOP. Ophthalmology 2007,114: 1965-1972 (C) 2007 by the American Academy of Ophthalmology. C1 SUNY Stony Brook, Ctr Med, Hlth Sci Ctr, Dept Prevent Med, Stony Brook, NY 11794 USA. Univ Lund Hosp, Dept Ophthalmol, Lund, Sweden. Helsingborg Hosp, Dept Ophthalmol, Helsingborg, Sweden. NEI, Natl Inst Hlth, Bethesda, MD USA. RP Leske, MC (reprint author), SUNY Stony Brook, Ctr Med, Hlth Sci Ctr, Dept Prevent Med, Stony Brook, NY 11794 USA. EM cleske@notes.cc.sunysb.edu NR 36 TC 496 Z9 505 U1 4 U2 43 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2007 VL 114 IS 11 BP 1965 EP 1972 DI 10.1016/j.ophtha.2007.03.016 PG 8 WC Ophthalmology SC Ophthalmology GA 230EF UT WOS:000250858100002 PM 17628686 ER PT J AU Lew, J Smith, JA AF Lew, J. Smith, J. A. TI Mucosal graft-vs-host disease SO ORAL DISEASES LA English DT Review DE mucosa; inflammatory disease; stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; CONSENSUS DEVELOPMENT PROJECT; AUTOLOGOUS SERUM TEARS; LOW-DOSE METHOTREXATE; WORKING GROUP-REPORT; TERM-FOLLOW-UP; SEVERE DRY EYE; RANDOMIZED-TRIAL AB Graft-vs-host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Indications for HSCT have greatly expanded, and more patients are undergoing HSCT today than ever before. In addition, the options for immunosuppressive therapy for both prevention and treatment of GVHD have also expanded. These changes have in turn altered the landscape of this disease. We have reviewed the current literature on this subject and presented an update on this disease with a particular emphasis on mucosal manifestations. C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Smith, JA (reprint author), NEI, Div Epidemiol & Clin Res, 10 Ctr Dr,MSC 1863,Bldg 10 Room 10S 227, Bethesda, MD 20892 USA. EM smithj@nei.nih.gov NR 101 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD NOV PY 2007 VL 13 IS 6 BP 519 EP 529 DI 10.1111/j.1601-0825.2007.01412.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 222DE UT WOS:000250275500005 PM 17944667 ER PT J AU Singleton, RJ Holman, RC Yorita, KL Holve, S Paisano, EL Steiner, CA Glass, RI Cheek, JE AF Singleton, Rosalyn J. Holman, Robert C. Yorita, Krista L. Holve, Steve Paisano, Edna L. Steiner, Claudia A. Glass, Roger I. Cheek, James E. TI Diarrhea-associated hospitalizations and outpatient visits among American Indian and Alaska native children younger than five years of age, 2000-2004 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE rotavirus; gastroenteritis; diarrhea; American Indian; Alaska Native; hospitalizations; outpatient visits; epidemiology; children; infants ID INFECTIOUS-DISEASE HOSPITALIZATIONS; UNITED-STATES; ROTAVIRUS; TRENDS; POPULATION; INFANTS; CANADA; COST AB Background: Diarrhea accounts for many hospitalizations and outpatient clinic visits among children. American Indian and Alaska Native (AI/AN) children have experienced a greater infectious disease burden compared with the general U.S. population of children, although diarrhea-associated hospitalization rates have declined among AI/AN children. Methods: Hospital discharge and outpatient visit records with a diagnosis indicating a diarrhea-associated diagnosis were evaluated for AI/AN children <5 years of age, using the 2000-2004 Indian Health Service Direct and Contract Health Service Inpatient Data and outpatient visit data from the Indian Health Service National Patient Information Reporting System, and for the general U.S. population of children <5 years of age using the Kids' Inpatient Database for 2003 and National Ambulatory data for 2000-2004. Results: For 2000-2004, the diarrhea-associated hospitalization rate was similar for AI/AN children and U.S. children <5 years of age (65.9 and 79.3 of 10,000, respectively), but the rate among AI/AN infants was nearly twice the rate among U.S. infants (262.6 and 154.7 of 10,000, respectively). The rate of diarrhea-associated outpatient visits among AI/AN children was higher than for U.S. children (2255.4 versus 1647.9 of 10,000, respectively), as a result of the high rate among AI/AN infants compared with U.S. infants (6103.5 and 2956.3 of 10,000, respectively). Conclusions: Although the diarrhea-associated hospitalization rate in AI/AN children <5 years old has declined to levels comparable with that of all U.S. children, the rate for AI/AN in infants remains higher than for U.S. infants. The diarrhea-associated outpatient visit rate for AI/AN children was higher than for U.S. children. Ongoing evaluation of hospitalization and outpatient data is important to understand the impact of rotavirus vaccine among AI/AN children. C1 USDHHS, CDC, CCID, AIP, Anchorage, AK 99508 USA. Alaska Native Tribal Hlth Consortium, Anchorage, AK USA. USDHHS, CDC, CCID, Div Viral & Rickettsial Dis, Atlanta, GA USA. Tuba City Reg Hlth Corp, Pediat Unit, Tuba City, AZ USA. USDHHS, Div Program Stat, Off Publ Hlth Support, Indian Hlth Serv, Rockville, MD USA. USDHHS, Ctr Delivery, Org & Markets Agcy Healthcare Res Delivery, Healthcare Cost & Utilizat Project, Rockville, MD USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. USDHHS, IHS, OPHS, Div Epidemiol, Albuquerque, NM USA. RP Singleton, RJ (reprint author), USDHHS, CDC, CCID, AIP, 4055 Tudor Ctr Dr, Anchorage, AK 99508 USA. EM ris2@cdc.gov NR 37 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2007 VL 26 IS 11 BP 1006 EP 1013 DI 10.1097/INF.0b013e3181256595 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 229QE UT WOS:000250818300006 PM 17984807 ER PT J AU Tanaka, G Faruque, ASG Luby, SP Malek, MA Glass, RI Parashar, UD AF Tanaka, Go Faruque, A. S. G. Luby, Stephen P. Malek, M. A. Glass, Roger I. Parashar, Umesh D. TI Deaths from rotavirus disease in Bangladeshi children - Estimates from hospital-based surveillance SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE rotavirus; Bangladeshi children; hospital-based surveillance; ICDDR,B; vaccine ID VACCINES; DIARRHEA AB Background: To assess the potential health benefits of introducing new rotavirus (RV) vaccines, we estimated mortality from RV gastroenteritis in Bangladeshi children <5 years of age. Methods: We examined data from ongoing diarrhea surveillance in a systematic 2% sample (4% until 1995) of patients visiting the International Centre for Diarrheal Disease Research, Bangladesh, Dhaka Hospital during 1993-2004 and all patients visiting the rural Matlab Hospital during 2000-2004. To estimate deaths from RV, we multiplied the proportion of diarrhea visits attributable to RV with 2004 estimates of diarrhea deaths in Bangladeshi children. Results: At Dhaka Hospital, RV was detected in 33% of 18,300 children with diarrhea. The proportion of diarrhea attributable to RV nearly doubled during 2002-2004 compared with 1993-1995 (42% versus 22%, P < 0.001). At Matlab Hospital, RV was detected in 35% of 4597 children with diarrhea. At both sites, most RV cases were among children age 3-24 months and the number of cases peaked during the cool and dry months from December through February. Of the 325,600 deaths among children <5 years that occur each year, we estimated 5600 to 9400 (2-3%) were attributable to RV. Thus, between 1 in 390 and 1 in 660 children born in Bangladesh each year die of RV infection by age 5. Conclusions: These data clearly demonstrate the tremendous health burden of RV gastroenteritis. The increasing proportion of severe diarrhea cases underscores the need for specific interventions against RV, such as vaccines, to further reduce diarrhea mortality and morbidity. C1 Gifu Prefectural Govt, Director Publ Hlth, Gifu 5008570, Japan. Gifu Prefectural Govt, Med Treatment Div, Gifu 5008570, Japan. Emory Univ, RSPH, HDGH, Atlanta, GA 30322 USA. Juntendo Univ, Sch Med, Dept Publ Hlth, Tokyo 113, Japan. ICDDR,B, Dhaka, Bangladesh. CDC, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Atlanta, GA USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Tanaka, G (reprint author), Gifu Prefectural Govt, Director Publ Hlth, 2-1-1 Yabuta Minami, Gifu 5008570, Japan. EM tanaka@umin.ac.jp NR 14 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2007 VL 26 IS 11 BP 1014 EP 1018 DI 10.1097/INF.0b013e318125721c PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 229QE UT WOS:000250818300007 PM 17984808 ER PT J AU Mussi-Pinhata, MM Aparecida, M Rego, MAC Freimanis, L Kakehasi, FM Machado, DM Cardoso, EM Read, JS AF Mussi-Pinhata, Marisa M. Aparecida, Maria Rego, Maria Aparecida C. Freimanis, Laura Kakehasi, Fabiana M. Machado, Daisy Maria Cardoso, Edmundo M. Read, Jennifer S. CA NISDI Perinatal Protocol Study Grp TI Maternal antiretrovirals and hepatic enzyme, Hematologic abnormalities among human immunodeficiency virus type 1-uninfected infants - The NISDI perinatal study SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE infant; pregnancy; transaminases; hematopoiesis; antiretrovirals; Latin America; Caribbean ID INFECTED PREGNANT-WOMEN; HIV-1-INFECTED MOTHERS; CELL COUNTS; ZIDOVUDINE; HEMATOPOIESIS; CHILDREN; THERAPY AB Objectives: To assess hepatic enzyme (HE) and hematologic abnormalities among human immunodeficiency virus-1-uninfected infants according to maternal antiretroviral regimen during pregnancy. Study Design: In a prospective cohort, HE and hematologic values of human immunodeficiency virus-1-uninfected, term infants with hospital discharge (HD) within 6 days after birth were evaluated. Maternal antiretroviral regimens were categorized as: 1 or 2 nucleoside reverse transcription inhibitors (NRTIs), highly active antiretroviral therapy (HAART)/protease inhibitor (PI), or HAART/non-NRTI. Results: Among 503 infants, 63% and 24% had HE and hemoglobin abnormalities, respectively, at HD. Most or all HE and hemoglobin abnormalities (96-100%) were grade 1 or 2. At HD, infants with maternal HAART/PI or HAART/non-NRTI were more likely to have elevated HE [adjusted odds ratio (AOR): 1.9, 2.4, respectively] compared with infants whose mothers received 1 or 2 NRTIs. Infants with maternal HAART/PI were less likely to have abnormal hemoglobin values at HD (AOR, 0.5) when compared with those whose mothers received 1 or 2 NRTIs. Persistently abnormal hemoglobin and HE values decreased with time, such that <10% of infants had abnormalities at 6 months of age. Conclusions: Maternal receipt of HAART regimens was associated with an increased risk of HE abnormalities, and maternal HAART/PI was associated with a lower risk of abnormal hemoglobin values, at HD. Abnormalities of HE and hemoglobin were generally mild and transient. C1 WESTAT Corp, Rockville, MD 20850 USA. Univ Sao Paulo, Dept Pediat, Sao Paulo, Brazil. Univ Fed Minas Gerais, Dept Pediat, Belo Horizonte, MG, Brazil. Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, Brazil. Na Sa Conceicao Hosp, Porto Alegre, RS, Brazil. NICHD, NIH, Dept Pediat Adolescent & Mat, AIDS Branch, Bethesda, MD USA. RP Mussi-Pinhata, MM (reprint author), FMRP USP, Dept Puericultura & Pediat, Avenida Bandeirantes 3900, BR-14049900 Ribeirao Preto, Brazil. EM mmmpinha@fmrp.usp.br RI Mussi-Pinhata, Marisa/G-6568-2012 NR 27 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2007 VL 26 IS 11 BP 1032 EP 1037 DI 10.1097/INF.0b013e31812f56ed PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 229QE UT WOS:000250818300010 PM 17984811 ER PT J AU Gea-Banacloche, JC Weinberg, GA AF Gea-Banacloche, Juan C. Weinberg, Geoffrey A. TI Monoclonal antibody therapeutics and risk for infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Editorial Material DE monoclonal antibodies; infecfious risks; therapeutic immunosuppression ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; LYMPHOPROLIFERATIVE DISORDERS; GRANULOMATOUS INFECTIONS; ALEMTUZUMAB; THERAPY; TRIAL; TRANSPLANTATION; MALIGNANCIES; NATALIZUMAB C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Bethesda, MD USA. RP Gea-Banacloche, JC (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 22 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2007 VL 26 IS 11 BP 1049 EP 1052 DI 10.1097/INF.0b11361815044f PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 229QE UT WOS:000250818300013 PM 17984814 ER PT J AU Ehn, NL Cooper, ME Orr, K Shi, M Johnson, MK Caprau, D Dagle, J Steffen, K Johnson, K Marazita, ML Merrill, D Murray, JC AF Ehn, Nicole L. Cooper, Margaret E. Orr, Kristin Shi, Min Johnson, Marla K. Caprau, Diana Dagle, John Steffen, Katherine Johnson, Karen Marazita, Mary L. Merrill, David Murray, Jeffrey C. TI Evaluation of fetal and maternal genetic variation in the progesterone receptor gene for contributions to preterm birth SO PEDIATRIC RESEARCH LA English DT Article ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; UNIFIED APPROACH; GESTATIONAL-AGE; DISEASE GENES; ASSOCIATION; DELIVERY; PREVENTION; PARTURITION; ISOFORM; RISK AB Progesterone plays a critical role in the maintenance of pregnancy and has been effectively used to prevent recurrences of preterm labor. We investigated the role of genetic variation in the progesterone receptor (PGR) gene in modulating risks for preterm labor by examining both maternal and fetal effects. Cases were infants delivered prematurely at the University of Iowa. DNA was collected from the mother, infant, and father. Seventeen single nucleotide polymorphisms (SNP) and an insertion deletion variant in PGR were studied in 415 families. Results were then analyzed using transmission disequilibrium tests and log-linear-model-based analysis. DNA sequencing of the PGR gene was also carried out in 92 mothers of preterm infants. We identified significant associations between SNP in the PGR for both mother and preterm infant. No etiologic sequence variants were found in the coding sequence of the PGR gene. This study suggests that genetic variation in the PGR gene of either the mother or the fetus may trigger preterm labor. C1 Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA 15219 USA. Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15219 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Bowman Gray Sch Med, Baptist Med Ctr, Winston Salem, NC 27157 USA. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, S Grand Ave,2182 ML, Iowa City, IA 52242 USA. EM jeff-murray@uiowa.edu FU NCRR NIH HHS [M01 RR000059, M01 RR000059-466795, M01-RR-59]; NICHD NIH HHS [HD052953, R01 HD052953, R01 HD052953-02, R01 HD052953-03]; PHS HHS [U50 CCU 713238] NR 40 TC 45 Z9 51 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2007 VL 62 IS 5 BP 630 EP 635 PG 6 WC Pediatrics SC Pediatrics GA 224WD UT WOS:000250477000022 PM 17805208 ER PT J AU Jean-Philippe, P Freedman, A Chang, MW Steinbergd, SP Gershon, AA LaRussa, PS Borkowsky, W AF Jean-Philippe, Patrick Freedman, Abigail Chang, Mary Wu Steinbergd, Sharon P. Gershon, Anne A. LaRussa, Philip S. Borkowsky, William TI Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction SO PEDIATRICS LA English DT Article DE varicella; vaccine adverse reaction; immunodeficiency ID ZOSTER-VIRUS-INFECTION; TRANSPLANT RECIPIENTS; HERPES-ZOSTER; UNITED-STATES; LIVE; LEUKEMIA; HEALTHY; EFFICACY; SAFETY; IMMUNOGENICITY AB In March 1995, the US Food and Drug Administration approved a live attenuated varicella vaccine for use in healthy children 12 months to 12 years old. We report here an 18-month-old girl with cell-mediated immunodeficiency who developed a severe vaccine-associated rash and clinical evidence of vaccine-associated pneumonia 1 month after inadvertent receipt of varicella vaccine. C1 NIAID, Jackson Fdn Adv Mil Med, Dept Def, Liason Off, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Pediat, New York, NY USA. NYU, Sch Med, Saul Krugman Div Infect Dis & Immunol, New York, NY USA. NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY USA. Columbia Univ, Med Ctr, Dept Pediat, Div Infect Dis, New York, NY USA. RP Jean-Philippe, P (reprint author), NIAID, Jackson Fdn Adv Mil Med, Dept Def, Liason Off, 3700 S Rockledge Dr,2nd Floor, Bethesda, MD 20892 USA. EM borkow01@gcrc.med.nyu.edu NR 43 TC 20 Z9 20 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2007 VL 120 IS 5 BP E1345 EP E1349 DI 10.1542/peds.2004-1681 PG 5 WC Pediatrics SC Pediatrics GA 226WJ UT WOS:000250618900070 PM 17974726 ER PT J AU Compton, C AF Compton, Carolyn TI The biospecimen as the key to personalizing medicine SO PERSONALIZED MEDICINE LA English DT Editorial Material C1 [Compton, Carolyn] NCI, Bethesda, MD 20892 USA. RP Compton, C (reprint author), NCI, Room 10A31,31 Ctr Dr, Bethesda, MD 20892 USA. EM comptcar@mail.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD NOV PY 2007 VL 4 IS 4 BP 385 EP 387 DI 10.2217/17410541.4.4.385 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 241EI UT WOS:000251639300001 ER PT J AU Ambudkar, IS Ong, HL AF Ambudkar, Indu S. Ong, Hwei Ling TI Organization and function of TRPC channelosomes SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE TRPC proteins; channelosomes; channel function ID OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CAPACITATIVE CALCIUM-ENTRY; PLASMA-MEMBRANE LOCALIZATION; PHOSPHOLIPASE-C-GAMMA; SALIVARY-GLAND CELLS; PAROTID ACINAR-CELLS; SMOOTH-MUSCLE-CELLS; EPITHELIAL-CELLS; POTENTIAL CHANNELS AB TRPC proteins constitute a family of conserved Ca(2+)-permeable cation channels which are activated in response to agonist-stimulated PIP(2) hydrolysis. These channels were initially proposed to be components of the store-operated calcium entry channel (SOC). Subsequent studies have provided substantial evidence that some TRPCs contribute to SOC activity. TRPC proteins have also been shown to form agonist-stimulated calcium entry channels that are not store-operated but are likely regulated by PIP(2) or diacylglycerol. Further, and consistent with the presently available data, selective homomeric or heteromeric interactions between TRPC monomers generate distinct agonist-stimulated cation permeable channels. We suggest that interaction between TRPC monomers, as well as the association of these channels with accessory proteins, determines their mode of regulation as well as their cellular localization and function. Currently identified accessory proteins include key Ca(2+)signaling proteins as well as proteins involved in vesicle trafficking, cytoskeletal interactions, and scaffolding. Studies reported until now demonstrate that TRPC proteins are segregated into specific Ca(2+) signaling complexes which can generate spatially and temporally controlled [Ca(2+)](i) signals. Thus, the functional organization of TRPC channelosomes dictates not only their regulation by extracellular stimuli but also serves as a platform to coordinate specific downstream cellular functions that are regulated as a consequence of Ca(2+)entry. This review will focus on the accessory proteins of TRPC channels and discuss the functional implications of TRPC channelosomes and their assembly in microdomains. C1 NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIH, Bldg 10,Room 1N-113,10 Ctr Dr, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov NR 134 TC 52 Z9 53 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD NOV PY 2007 VL 455 IS 2 BP 187 EP 200 DI 10.1007/s00424-007-0252-0 PG 14 WC Physiology SC Physiology GA 217UK UT WOS:000249972600001 PM 17486362 ER EF