FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bohlhalter, S Leon-Sarmiento, FE Hallett, M AF Bohlhalter, Stephan Leon-Sarmiento, Fidias E. Hallett, Mark TI Abnormality of motor cortex excitability in peripherally induced dystonia SO MOVEMENT DISORDERS LA English DT Article DE paired-pulse TMS; motor evoked potential; interstimulus interval; intracortical inhibition ID POSTTRAUMATIC CERVICAL DYSTONIA; TASK-SPECIFIC DYSTONIA; MOVEMENT-DISORDERS; TRAUMA; REPRESENTATION; BLEPHAROSPASM; INHIBITION; MONKEYS; INJURY; MODEL AB It is widely accepted that peripheral trauma such as soft tissue injuries can trigger dystonia, although little is known about the underlying mechanism. Because peripheral injury only rarely appears to elicit dystonia, a predisposing vulnerability in cortical motor areas might play a role. Using single and paired-pulse pulse transcranial magnetic stimulation, we evaluated motor cortex excitability of a hand muscle in a patient with peripherally induced foot dystonia, in her brother with craniocervical dystonia, and in her unaffected sister, and compared their results to those from a group of normal subjects. In the patient with peripherally induced dystonia, we found a paradoxical intracortical facilitation at short interstimulus intervals of 3 and 5 milliseconds, at which regular intracortical inhibition (ICI) occurred in healthy subjects. These findings suggest that the foot dystonia may have been precipitated as the result of a preexisting abnormality of motor cortex excitability. Furthermore, the abnormality of ICI in her brother and sister indicates that altered motor excitability may be a hereditary predisposition. The study demonstrates that the paired-pulse technique is a useful tool to assess individual vulnerability, which can be particularly relevant when the causal association between trauma and dystonia is less evident. (c) 2007 Movement Disorder Society. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Univ Nacl Colombia, Mediciencia Res Grp, Clin Neurol Sect, Fdn Santa Fe, Bogota, Colombia. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 24 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN 15 PY 2007 VL 22 IS 8 BP 1186 EP 1189 DI 10.1002/mds.21424 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 184GF UT WOS:000247628400022 PM 17415790 ER PT J AU Chanock, S Yeager, M AF Chanock, Stephen Yeager, Meredith TI The future of pediatric cancer and complex diseases: Aren't they all? SO PEDIATRIC BLOOD & CANCER LA English DT Review DE complex diseases; pediatric cancer; single nucleotide polymorphism ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN-GENOME; CANDIDATE GENES; THIOPURINE METHYLTRANSFERASE; LINKAGE DISEQUILIBRIUM; SEQUENCE VARIATION; CYSTIC-FIBROSIS; BREAST-CANCER; LUNG-DISEASE AB Over the past decade, the investigation of human genetics and disease has pursued both common and uncommon germ-line variation and shown that both can be associated with altered risk for cancer and its outcomes. This line of investigation has not only begun to generate markers for disease but also insights into the biological pathways that are altered in cancer. Already, there is emerging evidence that germ-line genetic variation can alter susceptibility to different types of cancers, including pediatric cancers. It is evident that common genetic variation has emerged as a key component of a comprehensive understanding of pediatric cancer and its outcome. Future studies should unravel the complex interaction between genes and the environment. Pediatr Blood Cancer 2007;48:719-722. (c) 2007 Wiley-Liss, Inc. C1 NCI, Pediat Oncol Branch, Sect Genom Variat, Ctr Adv Technol,Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, SAIC Frederisck, Core Genotyping Facil, Bethesda, MD USA. RP Chanock, S (reprint author), NCI, Pediat Oncol Branch, Sect Genom Variat, Ctr Adv Technol,Pediat Oncol Branch, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM sc83a@nih.gov NR 36 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 15 PY 2007 VL 48 IS 7 BP 719 EP 722 DI 10.1002/pbc.21115 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 164ND UT WOS:000246239900015 PM 17226845 ER PT J AU Kooperberg, C Cushman, M Hsia, J Robinson, JG Aragaki, AK Lynch, JK Baird, AE Johnson, KC Kuller, LH Beresford, SAA Rodriguez, B AF Kooperberg, Charles Cushman, Mary Hsia, Judith Robinson, Jennifer G. Aragaki, Aaron K. Lynch, John K. Baird, Alison E. Johnson, Karen C. Kuller, Lewis H. Beresford, Shirley A. A. Rodriguez, Beatriz TI Can biomarkers identify women at increased stroke risk? The women's health initiative hormone trials SO PLOS CLINICAL TRIALS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; C-REACTIVE PROTEIN; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; HEMOSTATIC MARKERS; EQUINE ESTROGEN; ISCHEMIC-STROKE; INTERLEUKIN-6 AB Objective: The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy ( HT). Design: The hormone trials were randomized, double-blind, and placebo controlled. Setting: The Women's Health Initiative trials were conducted at 40 clinical centers in the United States. Participants: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. Outcome Measures: Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. Results: No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin ( odds ratio 1.28) but were when assigned to placebo ( odds ratio 3.47; p for difference 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant ( p 0.03). Conclusions: Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Vermont, Coll Med, Burlington, VT USA. George Washington Univ, Dept Med, Washington, DC USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. NINDS, Stroke Neurosci Unit, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Kooperberg, C (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM clk@fhcrc.org NR 22 TC 20 Z9 21 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1555-5887 J9 PLOS CLIN TRIALS JI PLos Clin. Trials PD JUN 15 PY 2007 VL 2 IS 6 AR e28 DI 10.1371/journal.pctr.0020028 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 209OZ UT WOS:000249399200001 PM 17571161 ER PT J AU Womelsdorf, T Schoffelen, JM Oostenveld, R Singer, W Desimone, R Engel, AK Fries, P AF Womelsdorf, Thilo Schoffelen, Jan-Mathijs Oostenveld, Robert Singer, Wolf Desimone, Robert Engel, Andreas K. Fries, Pascal TI Modulation of neuronal interactions through neuronal synchronization SO SCIENCE LA English DT Article ID VISUAL-CORTEX; GAMMA-OSCILLATIONS; SYNAPTIC MODIFICATIONS; INTERNEURON NETWORKS; CORTICAL NEURON; BEHAVING RAT; COINCIDENCE; HIPPOCAMPUS; RESPONSES; MEMORY AB Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions. C1 Radboud Univ Nijmegen, FC Donders Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. Univ Frankfurt, Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. Univ Med Ctr Hamburg Eppendorf, Dept Neurophysiol & Pathophysiol, D-20246 Hamburg, Germany. Radboud Univ Nijmegen, Dept Biophys, NL-6525 EZ Nijmegen, Netherlands. RP Womelsdorf, T (reprint author), Radboud Univ Nijmegen, FC Donders Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. EM thilo.womelsdorf@tcdonders.ru.nl; jan.schoffelen@tcdonders.ru.nl RI Oostenveld, Robert/D-3259-2009; Fries, Pascal/E-3196-2010; Engel, Andreas/C-7781-2012; Singer, Wolf/D-6874-2012; schoffelen, jan mathijs/D-3716-2009; OI Oostenveld, Robert/0000-0002-1974-1293; Fries, Pascal/0000-0002-4270-1468; Engel, Andreas/0000-0003-4899-8466; schoffelen, jan mathijs/0000-0003-0923-6610; Womelsdorf, Thilo/0000-0001-6921-4187 FU NEI NIH HHS [R01EY017292] NR 28 TC 565 Z9 577 U1 6 U2 71 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 15 PY 2007 VL 316 IS 5831 BP 1609 EP 1612 DI 10.1126/science.1139597 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178SH UT WOS:000247239900039 PM 17569862 ER PT J AU Graubard, BI Flegal, KM Williamson, DF Gail, MH AF Graubard, Barry I. Flegal, Katherine M. Williamson, David F. Gail, Mitchell H. TI Estimation of attributable number of deaths and standard errors from simple and complex sampled cohorts SO STATISTICS IN MEDICINE LA English DT Article DE population attributable risk; influence function; survey sampling; Taylor deviate ID OBESITY; RISK AB Estimates of the attributable number of deaths (AD) from all causes can be obtained by first estimating population attributable risk (AR) adjusted for confounding covariates, and then multiplying the AR by the number of deaths determined from vital mortality statistics that occurred in the population for a specific time period. Proportional hazard regression estimates of adjusted relative hazards obtained from mortality follow-up data from a cohort is combined with a joint distribution of risk factor and confounders to compute an adjusted AR. Two estimators of adjusted AR are examined. These estimators differ according to which reference population is used to obtain the joint distribution of risk factor and confounders. Two types of reference populations were considered: (i) the population represented by the baseline cohort and (ii) a population that is external to the cohort. Methods used in survey sampling are applied to obtain estimates of the variance of the AD estimator. These variances can be applied to data that range from simple random samples to multistage stratified cluster samples, which are used in national household surveys. The variance estimation of AD is illustrated in an analysis of excess deaths due to having a non-ideal body mass index using the second National Health and Examination Survey (NHANES) Mortality Study and the 1999-2002 NHANES. These methods can also be used to estimate the attributable number of cause-specific deaths and their standard errors when the time period for the accrual of deaths is short. Published in 2006 by John Wiley & Sons, Ltd. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, 6120 Execut Blvd,Room 8024, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X FU Intramural NIH HHS NR 20 TC 13 Z9 13 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2007 VL 26 IS 13 BP 2639 EP 2649 DI 10.1002/sim.2734 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 175FL UT WOS:000246998300005 PM 17117403 ER PT J AU Li, Z Srivastava, S Mittal, S Yang, XR Sheng, LF Chan, C AF Li, Zheng Srivastava, Shireesh Mittal, Sheenu Yang, Xuerui Sheng, Lufang Chan, Christina TI A Three Stage Integrative Pathway Search (TIPS (c)) framework to identify toxicity relevant genes and pathways SO BMC BIOINFORMATICS LA English DT Article ID STEAROYL-COA DESATURASE; BIOCHEMICAL SYSTEMS-THEORY; PROTEIN PHOSPHATASE 2A; KAPPA-B ACTIVATION; RED-BLOOD-CELLS; REGULATORY NETWORKS; BAYESIAN NETWORKS; EXPRESSION DATA; HEPATOMA-CELLS; TNF-ALPHA AB Background: The ability to obtain profiles of gene expressions, proteins and metabolites with the advent of high throughput technologies has advanced the study of pathway and network reconstruction. Genome-wide network reconstruction requires either interaction measurements or large amount of perturbation data, often not available for mammalian cell systems. To overcome these shortcomings, we developed a Three Stage Integrative Pathway Search (TIPS (c)) approach to reconstruct context-specific active pathways involved in conferring a specific phenotype, from limited amount of perturbation data. The approach was tested on human liver cells to identify pathways that confer cytotoxicity. Results: This paper presents a systems approach that integrates gene expression and cytotoxicity profiles to identify a network of pathways involved in free fatty acid (FFA) and tumor necrosis factor-alpha (TNF-alpha) induced cytotoxicity in human hepatoblastoma cells (HepG2/C3A). Cytotoxicity relevant genes were first identified and then used to reconstruct a network using Bayesian network (BN) analysis. BN inference was used subsequently to predict the effects of perturbing a gene on the other genes in the network and on the cytotoxicity. These predictions were subsequently confirmed through the published literature and further experiments. Conclusion: The TIPS (c) approach is able to reconstruct active pathways that confer a particular phenotype by integrating gene expression and phenotypic profiles. A web-based version of TIPS (c) that performs the analysis described herein can be accessed at http://www.egr.msu.edu/tips. C1 Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Comp Sci & Engn, E Lansing, MI 48824 USA. MetagenX LLC, Okemos, MI 48864 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. NIAAA, NIH, Rockville, MD 20851 USA. RP Chan, C (reprint author), Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. EM lizheng1@gmail.com; srivas14@egr.msu.edu; mittalsh@msu.edu; yangxuer@egr.msu.edu; shenglufang@gmail.com; krischan@egr.msu.edu FU NIGMS NIH HHS [1R01GM079688-01, R01 GM079688] NR 63 TC 14 Z9 16 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 14 PY 2007 VL 8 AR 202 DI 10.1186/1471-2105-8-202 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 186QB UT WOS:000247792100001 PM 17570844 ER PT J AU Li, T Shiotani, K Miyazaki, A Tsuda, Y Ambo, A Sasaki, Y Jinsmaa, Y Marczak, E Bryant, SD Lazarus, LH Okada, Y AF Li, Tingyou Shiotani, Kimitaka Miyazaki, Anna Tsuda, Yuko Ambo, Akihiro Sasaki, Yusuke Jinsmaa, Yunden Marczak, Ewa Bryant, Sharon D. Lazarus, Lawrence H. Okada, Yoshio TI Bifunctional [2 ',6 '-Dimethyl-L-tyrosine(1)]endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BLOOD-BRAIN-BARRIER; PRO AMIDE BOND; ENDOMORPHIN-2 ANALOGS; RECEPTOR ANTAGONIST; MORPHINE-TOLERANCE; ANTINOCICEPTIVE ACTIVITY; CONFORMATIONAL-ANALYSIS; DELTA; PEPTIDES; DMP AB Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt(1)]EM-2 (Dmt = 2',6'-dimethyl-L-tyrosine) analogues, containing alkylated Phe(3) derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa(3)]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (K-i(delta) = 491-3451 nM). (ii) [Dmt(1),Xaa(3)]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (K-i(mu) = 0.069-0.32 nM; K-i(delta) = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 mu M in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50 mu = 0.12 and pA(2) = 8.15; for 6', IC50 mu = 0.21 nM and pA(2) = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50 mu = 0.17 nM; IC50 delta = 0.51 nM). 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, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Lazarus, LH (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM lazarus@niehs.nih.gov; okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS [Z01 ES100472-06, Z01 ES090053-20, Z99 ES999999] NR 67 TC 23 Z9 27 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 14 PY 2007 VL 50 IS 12 BP 2753 EP 2766 DI 10.1021/jm061238m PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 175SI UT WOS:000247033900001 PM 17497839 ER PT J AU La Regina, G Edler, MC Brancale, A Kandil, S Coluccia, A Piscitelli, F Hamel, E De Martino, G Matesanz, R Diaz, JF Scovassi, AI Prosperi, E Lavecchia, A Novellino, E Artico, M Silvestri, R AF La Regina, Giuseppe Edler, Michael C. Brancale, Andrea Kandil, Sahar Coluccia, Antonio Piscitelli, Francesco Hamel, Ernest De Martino, Gabriella Matesanz, Ruth Diaz, Jose Fernando Scovassi, Anna Ivana Prosperi, Ennio Lavecchia, Antonio Novellino, Ettore Artico, Marino Silvestri, Romano TI Arylthioindole inhibitors of tubulin polymerization. 3. Biological evaluation, structure-activity relationships and molecular modeling studies SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POTENT ANTITUBULIN AGENTS; ANTIMITOTIC AGENTS; COLCHICINE ANALOGS; BREAST-CANCER; RING-C; BINDING; MICROTUBULE; SITE; CYTOTOXICITY; DERIVATIVES AB The new arylthioindole (ATI) derivatives 10, 14-18, and 21-24, which bear a halogen atom or a small size ether group at position 5 of the indole moiety, were compared with the reference compounds colchicine and combretastatin A-4 for biological activity. Derivatives 10, 11, 16, and 21-24 inhibited MCF-7 cell growth with IC50 values < 50 nM. A halogen atom (14-17) at position 5 caused a significant reduction in the free energy of binding of compound to tubulin, with a concomitant reduction in cytotoxicity. In contrast, methyl (21) and methoxy (22) substituents at position 5 caused an increase in cytotoxicity. Compound 16, the most potent antitubulin agent, led to a large increase (56%) in HeLa cells in the G(2)/M phase at 24 h, and at 48 h, 26% of the cells were hyperploid. Molecular modeling studies showed that, despite the absence of the ester moiety present in the previously examined analogues, most of the compounds bind in the colchicine site in the same orientation as the previously studied ATIs. Binding to beta-tubulin involved formation of a hydrogen bond between the indole and Thr179 and positioning of the trimethoxy phenyl group in a hydrophobic pocket near Cys241. C1 Univ Rome, Dipartimento Studi Farmaceut, Fdn Cenci Bolognetti, Ist Pasteur, I-00185 Rome, Italy. Univ Cardiff Wales, Sch Pharm, Cardiff CF10 3XF, Wales. NIH, Natl Canc Inst, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. Univ Naples Federico 2, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy. Consejo Nazl Ric, Ctr Invest Biol, E-28040 Madrid, Spain. CNR, Ist Genet Mol, I-27100 Pavia, Italy. RP Silvestri, R (reprint author), Univ Rome, Dipartimento Studi Farmaceut, Fdn Cenci Bolognetti, Ist Pasteur, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM romano.silvestri@uniroma1.it RI scovassi, anna ivana/F-2458-2010; La Regina, Giuseppe/I-2161-2012; De Martino, Maria Gabriella/I-2357-2012; Brancale, Andrea/N-9445-2014; Kandil, Sahar/L-2458-2015; OI Silvestri, Romano/0000-0003-2489-0178; Scovassi, Anna Ivana/0000-0003-3484-9881; La Regina, Giuseppe/0000-0003-3252-1161; Brancale, Andrea/0000-0002-9728-3419; Kandil, Sahar/0000-0003-1806-9623; Prosperi, Ennio/0000-0001-5391-5157; /0000-0002-7940-8206; Diaz, J. Fernando/0000-0003-2743-3319 NR 35 TC 83 Z9 83 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 14 PY 2007 VL 50 IS 12 BP 2865 EP 2874 DI 10.1021/jm061479u PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 175SI UT WOS:000247033900011 PM 17497841 ER PT J AU Birney, E Stamatoyannopoulos, JA Dutta, A Guigo, R Gingeras, TR Margulies, EH Weng, ZP Snyder, M Dermitzakis, ET Stamatoyannopoulos, JA Thurman, RE Kuehn, MS Taylor, CM Neph, S Koch, CM Asthana, S Malhotra, A Adzhubei, I Greenbaum, JA Andrews, RM Flicek, P Boyle, PJ Cao, H Carter, NP Clelland, GK Davis, S Day, N Dhami, P Dillon, SC Dorschner, MO Fiegler, H Giresi, PG Goldy, J Hawrylycz, M Haydock, A Humbert, R James, KD Johnson, BE Johnson, EM Frum, TT Rosenzweig, ER Karnani, N Lee, K Lefebvre, GC Navas, PA Neri, F Parker, SCJ Sabo, PJ Sandstrom, R Shafer, A Vetrie, D Weaver, M Wilcox, S Yu, M Collins, FS Dekker, J Lieb, JD Tullius, TD Crawford, GE Sunyaev, S Noble, WS Dunham, I Dutta, A Guigo, R Denoeud, F Reymond, A Kapranov, P Rozowsky, J Zheng, DY Castelo, R Frankish, A Harrow, J Ghosh, S Sandelin, A Hofacker, IL Baertsch, R Keefe, D Flicek, P Dike, S Cheng, J Hirsch, HA Sekinger, EA Lagarde, J Abril, JF Shahab, A Flamm, C Fried, C Hackermuller, J Hertel, J Lindemeyer, M Missal, K Tanzer, A Washietl, S Korbel, J Emanuelsson, O Pedersen, JS Holroyd, N Taylor, R Swarbreck, D Matthews, N Dickson, MC Thomas, DJ Weirauch, MT Gilbert, J Drenkow, J Bell, I Zhao, X Srinivasan, KG Sung, WK Ooi, HS Chiu, KP Foissac, S Alioto, T Brent, M Pachter, L Tress, ML Valencia, A Choo, SW Choo, CY Ucla, C Manzano, C Wyss, C Cheung, E Clark, TG Brown, JB Ganesh, M Patel, S Tammana, H Chrast, J Henrichsen, CN Kai, C Kawai, J Nagalakshmi, U Wu, JQ Lian, Z Lian, J Newburger, P Zhang, XQ Bickel, P Mattick, JS Carninci, P Hayashizaki, Y Weissman, S Dermitzakis, ET Margulies, EH Hubbard, T Myers, RM Rogers, J Stadler, PF Lowe, TM Wei, CL Ruan, YJ Snyder, M Birney, E Struhl, K Gerstein, M Antonarakis, SE Gingeras, TR Brown, JB Flicek, P Fu, YT Keefe, D Birney, E Denoeud, F Gerstein, M Green, ED Kapranov, P Karaoz, U Myers, RM Noble, WS Reymond, A Rozowsky, J Struhl, K Siepel, A Stamatoyannopoulos, JA Taylor, CM Taylor, J Thurman, RE Tullius, TD Washietl, S Zheng, DY Liefer, LA Wetterstrand, KA Good, PJ Feingold, EA Guyer, MS Collins, FS Margulies, EH Cooper, GM Asimenos, G Thomas, DJ Dewey, CN Siepel, A Birney, E Keefe, D Hou, MM Taylor, J Nikolaev, S Montoya-Burgos, JI Loytynoja, A Whelan, S Pardi, F Massingham, T Brown, JB Huang, HY Zhang, NR Bickel, P Holmes, I Mullikin, JC Ureta-Vidal, A Paten, B Seringhaus, M Church, D Rosenbloom, K Kent, WJ Stone, EA Gerstein, M Antonarakis, SE Batzoglou, S Goldman, N Hardison, RC Haussler, D Miller, W Pachter, L Green, ED Sidow, A Weng, ZP Trinklein, ND Fu, YT Zhang, ZDD Karaoz, U Barrera, L Stuart, R Zheng, DY Ghosh, S Flicek, P King, DC Taylor, J Ameur, A Enroth, S Bieda, MC Koch, CM Hirsch, HA Wei, CL Cheng, J Kim, J Bhinge, AA Giresi, PG Jiang, N Liu, J Yao, F Sung, WK Chiu, KP Vega, VB Lee, CWH Ng, P Shahab, A Sekinger, EA Yang, A Moqtaderi, Z Zhu, Z Xu, XQ Squazzo, S Oberley, MJ Inman, D Singer, MA Richmond, TA Munn, KJ Rada-Iglesias, A Wallerman, O Komorowski, J Clelland, GK Wilcox, S Dillon, SC Andrews, RM Fowler, JC Couttet, P James, KD Lefebvre, GC Bruce, AW Dovey, OM Ellis, PD Dhami, P Langford, CF Carter, NP Vetrie, D Kapranov, P Nix, DA Bell, I Patel, S Rozowsky, J Euskirchen, G Hartman, S Lian, J Wu, JQ Urban, AE Kraus, P Van Calcar, S Heintzman, N Kim, TH Wang, K Qu, CX Hon, G Luna, R Glass, CK Rosenfeld, MG Aldred, SF Cooper, SJ Halees, A Lin, JM Shulha, HP Zhang, XL Xu, MS Haidar, JNS Yu, Y Birney, E Weissman, S Ruan, YJ Lieb, JD Iyer, VR Green, RD Gingeras, TR Wadelius, C Dunham, I Struhl, K Hardison, RC Gerstein, M Farnham, PJ Myers, RM Ren, B Snyder, M Thomas, DJ Rosenbloom, K Harte, RA Hinrichs, AS Trumbower, H Clawson, H Hillman-Jackson, J Zweig, AS Smith, K Thakkapallayil, A Barber, G Kuhn, RM Karolchik, D Haussler, D Kent, WJ Dermitzakis, ET Armengol, L Bird, CP Clark, TG Cooper, GM de Bakker, PIW Kern, AD Lopez-Bigas, N Martin, JD Stranger, BE Thomas, DJ Woodroffe, A Batzoglou, S Davydov, E Dimas, A Eyras, E Hallgrimsdottir, IB Hardison, RC Huppert, J Sidow, A Taylor, J Trumbower, H Zody, MC Guigo, R Mullikin, JC Abecasis, GR Estivill, X Birney, E Bouffard, GG Guan, XB Hansen, NF Idol, JR Maduro, VVB Maskeri, B McDowell, JC Park, M Thomas, PJ Young, AC Blakesley, RW Muzny, DM Sodergren, E Wheeler, DA Worley, KC Jiang, HY Weinstock, GM Gibbs, RA Graves, T Fulton, R Mardis, ER Wilson, RK Clamp, M Cuff, J Gnerre, S Jaffe, DB Chang, JL Lindblad-Toh, K Lander, ES Koriabine, M Nefedov, M Osoegawa, K Yoshinaga, Y Zhu, BL de Jong, PJ AF Birney, Ewan Stamatoyannopoulos, John A. 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CA ENCODE Project Consortium TI Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project SO NATURE LA English DT Review ID FACTOR-BINDING-SITES; POLYCOMB TARGET GENES; SEQUENCE TAG ANALYSIS; REGULATORY ELEMENTS; MAMMALIAN GENOMES; DNA-REPLICATION; HIGH-RESOLUTION; TILING ARRAYS; TRANSCRIPTIONAL PROMOTERS; ANTISENSE TRANSCRIPTION AB We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genomeas part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter-and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. 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Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. Univ Geneva, Fac Sci, Dept Zool & Anim Biol, CH-1205 Geneva, Switzerland. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Penn State Univ, HUck Inst Life Sci, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, HUman Genome Sequencing Ctr, Houston, TX 77030 USA. Washington Univ, Genom Sequencing Ctr, St Louis, MO 63108 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Childrens Hosp, Oakland Res Inst, BACPAC Resources, Oakland, CA 94609 USA. Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Uppsala Univ, Linnaeus Ctr Bioinformat, SE-75124 Uppsala, Sweden. Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. NimbleGen Syst Inc, Madison, WI 53711 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, SE-75185 Uppsala, Sweden. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Ctr Genom Regulat, Genes & Dis Program, Barcelona 08003, Spain. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Oxford, Dept Stat, Oxford OX1 3TG, England. RP Birney, E (reprint author), EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM birney@ebi.ac.uk; jstam@u.washington.edu; ad8q@virginia.edu; rguigo@imim.es; Tom_Gingeras@affymetrix.com; elliott@nhgri.nih.gov; zhiping@bu.edu; michael.snyder@yale.edu; md4@sanger.ac.uk RI Carninci, Piero/K-1568-2014; Sandelin, Albin/G-2881-2011; Eyras, Eduardo/L-1053-2014; Estivill, Xavier/A-3125-2013; Komorowski, Jan/M-2667-2013; Antonarakis, Stylianos/N-8866-2014; Brown, James/H-2971-2015; Hor, Charlotte/H-5908-2015; Guigo, Roderic/D-1303-2010; Lopez-Bigas, Nuria/F-6193-2011; Alioto, Tyler/K-7267-2015; Tanzer, Andrea/L-3147-2015; Abecasis, Goncalo/B-7840-2010; Tullius, Thomas/A-9685-2008; Komorowski, Jan/A-9175-2010; Cooper, Gregory/D-6914-2011; Ameur, Adam/E-6207-2011; Hubbard, Tim/C-2567-2008; Huppert, Julian/C-6664-2008; Enroth, Stefan/C-7396-2009; Pedersen, Jakob/C-4985-2009; Hardison, Ross/G-1142-2010; Dillon, Shane/A-2280-2011; Castelo, Robert/A-4679-2010; Whelan, Simon/A-6638-2011; Eyras, Eduardo/A-1560-2010; Valencia, Alfonso/I-3127-2015; Stadler, Peter F./L-7857-2015; Karnani, Neerja/G-2539-2012; Hackermuller, Jorg/F-2494-2016; Mattick, John/I-7789-2012; Kawai, Jun/A-6451-2016; Dutta, Anindya/P-3203-2016; Stone, Eric/Q-7840-2016; Gasull, Martina/A-6630-2013; Pedersen, Jakob/G-3382-2012; Frankish, Adam/G-6545-2011; Phelps, Steve/H-2263-2011; Choo, Siew Woh/E-3406-2010; Estivill, Xavier/E-2957-2012; Nikolaev, Sergey/F-3148-2012; Korbel, Jan/G-6470-2012; Malhotra, Ankit/I-3752-2012; Hofacker, Ivo/A-2378-2013; Zhang, Xiaoling/A-7132-2013; Taylor, James/F-1026-2011; Dermitzakis, Emmanouil/B-7687-2013; de Bakker, Paul/B-8730-2009; Abril Ferrando, Josep/B-3877-2014; Bruce, Alexander/H-4235-2014 OI Carninci, Piero/0000-0001-7202-7243; Sandelin, Albin/0000-0002-7109-7378; Eyras, Eduardo/0000-0003-0793-6218; Estivill, Xavier/0000-0002-0723-2256; Komorowski, Jan/0000-0002-0766-8789; Antonarakis, Stylianos/0000-0001-8907-5823; Hor, Charlotte/0000-0002-5361-2372; Guigo, Roderic/0000-0002-5738-4477; Lopez-Bigas, Nuria/0000-0003-4925-8988; Alioto, Tyler/0000-0002-2960-5420; Tanzer, Andrea/0000-0003-2873-4236; Tullius, Thomas/0000-0003-4425-796X; Cooper, Gregory/0000-0001-5509-9923; Hubbard, Tim/0000-0002-1767-9318; Huppert, Julian/0000-0001-5207-4886; Enroth, Stefan/0000-0002-5056-9137; Hardison, Ross/0000-0003-4084-7516; Castelo, Robert/0000-0003-2229-4508; Flamm, Christoph/0000-0001-5500-2415; Dutta, Anindya/0000-0002-4319-0073; Holmes, Ian/0000-0001-7639-5369; Flicek, Paul/0000-0002-3897-7955; Newburger, Peter/0000-0002-8615-673X; Birney, Ewan/0000-0001-8314-8497; Hinrichs, Angie/0000-0002-1697-1130; Koch, Christof/0000-0001-6482-8067; Stranger, Barbara/0000-0001-9021-7331; Rozowsky, Joel/0000-0002-3565-0762; Farnham, Peggy/0000-0003-4469-7914; Halees, Anason/0000-0001-5880-7067; Kim, Tae Hoon/0000-0003-3950-7557; Davis, Sean/0000-0002-8991-6458; Vetrie, David/0000-0003-2075-4662; Rada-Iglesias, Alvaro/0000-0001-7137-1341; Zheng, Deyou/0000-0003-4354-5337; Goldman, Nick/0000-0001-8486-2211; Siepel, Adam/0000-0002-3557-7219; Dunham, Ian/0000-0003-2525-5598; Ameur, Adam/0000-0001-6085-6749; Foissac, Sylvain/0000-0002-2631-5356; Reiche, Kristin/0000-0002-4452-4872; Abecasis, Goncalo/0000-0003-1509-1825; Valencia, Alfonso/0000-0002-8937-6789; Stadler, Peter F./0000-0002-5016-5191; Hackermuller, Jorg/0000-0003-4920-7072; Mattick, John/0000-0002-7680-7527; Pedersen, Jakob/0000-0002-7236-4001; Gingeras, Thomas/0000-0001-9106-3573; Wallerman, Ola/0000-0003-1037-7904; Loytynoja, Ari/0000-0001-5389-6611; Korbel, Jan/0000-0002-2798-3794; Hofacker, Ivo/0000-0001-7132-0800; Taylor, James/0000-0001-5079-840X; de Bakker, Paul/0000-0001-7735-7858; Abril Ferrando, Josep/0000-0001-7793-589X; Bruce, Alexander/0000-0003-4297-4412 NR 128 TC 2639 Z9 2755 U1 33 U2 346 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 14 PY 2007 VL 447 IS 7146 BP 799 EP 816 DI 10.1038/nature05874 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178FV UT WOS:000247207500034 ER PT J AU Pandey, UB Nie, ZP Batlevi, Y McCray, BA Ritson, GP Nedelsky, NB Schwartz, SL DiProspero, NA Knight, MA Schuldiner, O Padmanabhan, R Hild, M Berry, DL Garza, D Hubbert, CC Yao, TP Baehrecke, EH Taylor, JP AF Pandey, Udai Bhan Nie, Zhiping Batlevi, Yakup McCray, Brett A. Ritson, Gillian P. Nedelsky, Natalia B. Schwartz, Stephanie L. DiProspero, Nicholas A. Knight, Melanie A. Schuldiner, Oren Padmanabhan, Ranjani Hild, Marc Berry, Deborah L. Garza, Dan Hubbert, Charlotte C. Yao, Tso-Pang Baehrecke, Eric H. Taylor, J. Paul TI HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS SO NATURE LA English DT Article ID UBIQUITIN-PROTEASOME SYSTEM; ANDROGEN RECEPTOR; PROTEIN; DISEASE; DEGRADATION; DROSOPHILA; ACETYLATION; INCLUSIONS; TOXICITY; PATHWAYS AB A prominent feature of late-onset neurodegenerative diseases is accumulation of misfolded protein in vulnerable neurons(1). When levels of misfolded protein overwhelm degradative pathways, the result is cellular toxicity and neurodegeneration(2). Cellular mechanisms for degrading misfolded protein include the ubiquitin-proteasome system ( UPS), the main non-lysosomal degradative pathway for ubiquitinated proteins, and autophagy, a lysosome-mediated degradative pathway(3). The UPS and autophagy have long been viewed as complementary degradation systems with no point of intersection(4,5). This view has been challenged by two observations suggesting an apparent interaction: impairment of the UPS induces autophagy in vitro, and conditional knockout of autophagy in the mouse brain leads to neurodegeneration with ubiquitin-positive pathology(6-9). It is not known whether autophagy is strictly a parallel degradation system, or whether it is a compensatory degradation system when the UPS is impaired; furthermore, if there is a compensatory interaction between these systems, the molecular link is not known. Here we show that autophagy acts as a compensatory degradation system when the UPS is impaired in Drosophila melanogaster, and that histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase that interacts with polyubiquitinated proteins(10), is an essential mechanistic link in this compensatory interaction. We found that compensatory autophagy was induced in response to mutations affecting the proteasome and in response to UPS impairment in a fly model of the neurodegenerative disease spinobulbar muscular atrophy. Autophagy compensated for impaired UPS function in an HDAC6-dependent manner. Furthermore, expression of HDAC6 was sufficient to rescue degeneration associated with UPS dysfunction in vivo in an autophagy-dependent manner. This study suggests that impairment of autophagy ( for example, associated with ageing or genetic variation) might predispose to neurodegeneration. Morover, these findings suggest that it may be possible to intervene in neurodegeneration by augmenting HDAC6 to enhance autophagy. C1 Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20817 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Taylor, JP (reprint author), Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. EM jpt@mail.med.upenn.edu RI Schuldiner, Oren/K-1353-2012 OI Schuldiner, Oren/0000-0002-7350-9380 FU NINDS NIH HHS [R01 NS054022-02, R01 NS054022] NR 25 TC 650 Z9 665 U1 7 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 14 PY 2007 VL 447 IS 7146 BP 859 EP 863 DI 10.1038/nature05853 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 178FV UT WOS:000247207500045 PM 17568747 ER PT J AU Reboli, AC Rotstein, C Pappas, PG Chapman, SW Kett, DH Kumar, D Betts, R Wible, M Goldstein, BP Schranz, J Krause, DS Walsh, TJ Van Wijngaerden, E Bow, E Garber, G Laverdiere, M Libman, M Pelletier, R Sanche, S Cornely, O Kern, W Ruhnke, M Carosi, G Verweij, P Anaissie, E Bochan, M Carpenter, C Cicogna, C Cleary, J Finley, N Fetchick, R Friedman, B Graham, D Graybill, R Hsiao, C Jones, R Kerkering, T Kurtz, T McClain, D Nowakowski, J Ostrosky-Zeichner, L Perfect, J Pullman, J Quartin, A Reinhardt, J Segal, B Shahryar, S Shoham, S Sioson, P Sloan, L Solomkin, J Vazquez, J Zapata-Molina, N AF Reboli, Annette C. Rotstein, Coleman Pappas, Peter G. Chapman, Stanley W. Kett, Daniel H. Kumar, Deepali Betts, Robert Wible, Michele Goldstein, Beth P. Schranz, Jennifer Krause, David S. Walsh, Thomas J. Van Wijngaerden, E. Bow, E. Garber, G. Laverdiere, M. Libman, M. Pelletier, R. Sanche, S. Cornely, O. Kern, W. Ruhnke, M. Carosi, G. Verweij, P. Anaissie, E. Bochan, M. Carpenter, C. Cicogna, C. Cleary, J. Finley, N. Fetchick, R. Friedman, B. Graham, D. Graybill, R. Hsiao, C. Jones, R. Kerkering, T. Kurtz, T. McClain, D. Nowakowski, J. Ostrosky-Zeichner, L. Perfect, J. Pullman, J. Quartin, A. Reinhardt, J. Segal, B. Shahryar, S. Shoham, S. Sioson, P. Sloan, L. Solomkin, J. Vazquez, J. Zapata-Molina, N. CA Anidulafungin Study Grp TI Anidulafungin versus fluconazole for invasive candidiasis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-STREAM INFECTIONS; ANTIMICROBIAL SURVEILLANCE PROGRAM; AMPHOTERICIN-B; ANTIFUNGAL DRUGS; UNITED-STATES; CANDIDEMIA; TRIAL; EPIDEMIOLOGY; INFERIORITY; CASPOFUNGIN AB BACKGROUND: Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis. METHODS: Adults with invasive candidiasis were randomly assigned to receive either intravenous anidulafungin or intravenous fluconazole. All patients could receive oral fluconazole after 10 days of intravenous therapy. The primary efficacy analysis assessed the global response (clinical and microbiologic) at the end of intravenous therapy in patients who had a positive baseline culture. Efficacy was also assessed at other time points. RESULTS: Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a ``center effect''; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, -1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P=0.13). CONCLUSIONS: Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Infect Dis, Cooper Univ Hosp, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. McMaster Univ, Hamilton, ON, Canada. Univ Alabama, Birmingham, AL USA. Univ Mississippi, Jackson, MS 39216 USA. Univ Miami, Miller Sch Med, Miami, FL 33152 USA. Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. Univ Rochester, Rochester, NY USA. Vicuron Pharmaceut, King Of Prussia, PA USA. NCI, Bethesda, MD 20892 USA. RP Reboli, AC (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Infect Dis, Cooper Univ Hosp, Educ & Res Bldg,401 Haddon Ave,Rm 270, Camden, NJ 08103 USA. EM reboli-annette@cooperhealth.edu NR 31 TC 407 Z9 428 U1 1 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2007 VL 356 IS 24 BP 2472 EP 2482 DI 10.1056/NEJMoa066906 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 178DR UT WOS:000247201900007 PM 17568028 ER PT J AU Bloch, CA Korach, KS AF Bloch, Clifford A. Korach, Kenneth S. TI Prepubertal gynecomastia linked to lavender and tea tree oils - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Pediat Endocrine Associates, Greenwood Village, CO 80111 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Bloch, CA (reprint author), Pediat Endocrine Associates, Greenwood Village, CO 80111 USA. EM korach@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 14 PY 2007 VL 356 IS 24 BP 2543 EP 2544 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 178DR UT WOS:000247201900032 ER PT J AU Riz, I Akimov, SS Eaker, SS Baxter, KK Lee, HJ Marino-Ramirez, L Landsman, D Hawley, TS Hawley, RG AF Riz, I. Akimov, S. S. Eaker, S. S. Baxter, K. K. Lee, H. J. Marino-Ramirez, L. Landsman, D. Hawley, T. S. Hawley, R. G. TI TLX1/HOX11-induced hematopoietic differentiation blockade SO ONCOGENE LA English DT Article DE TLX1/HOX11 oncogene; erythropoiesis; conditional differentiation block; CBP; GATA-1; repressive chromatin domains ID TRANSCRIPTION FACTOR GATA-1; CREB-BINDING PROTEIN; T-CELL LEUKEMIA; THYMOCYTE DIFFERENTIATION; ERYTHROID-CELLS; HOX11 INTERACTS; HOMEOBOX GENES; CBP; ACETYLATION; ONCOPROTEIN AB Aberrant expression of the human homeobox-containing proto-oncogene TLX1/HOX11 inhibits hematopoietic differentiation programs in a number of murine model systems. Here, we report the establishment of a murine erythroid progenitor cell line, iEBHX1S-4, developmentally arrested by regulatable TLX1 expression. Extinction of TLX1 expression released the iEBHX1S-4 differentiation block, allowing erythropoietin-dependent acquisition of erythroid markers and hemoglobin synthesis. Coordinated activation of erythroid transcriptional networks integrated by the acetyltransferase co-activator CREB-binding protein (CBP) was suggested by bioinformatic analysis of the upstream regulatory regions of several conditionally induced iEBHX1S-4 gene sets. In accord with this notion, CBP-associated acetylation of GATA-1, an essential regulator of erythroid differentiation, increased concomitantly with TLX1 downregulation. Coimmunoprecipitation experiments and glutathione-S-transferase pull-down assays revealed that TLX1 directly binds to CBP, and confocal laser microscopy demonstrated that the two proteins partially colocalize at intranuclear sites in iEBHX1S-4 cells. Notably, the distribution of CBP in conditionally blocked iEBHX1S-4 cells partially overlapped with chromatin marked by a repressive histone methylation pattern, and downregulation of TLX1 coincided with exit of CBP from these heterochromatic regions. Thus, we propose that TLX1-mediated differentiation arrest may be achieved in part through a mechanism that involves redirection of CBP and/or its sequestration in repressive chromatin domains. C1 George Washington Univ, Dept Anat & Cell Biol, Med Ctr, Washington, DC 20037 USA. NanoDetect Technol, Knoxville, TN USA. George Washington Univ, Mol Med Program, Med Ctr, Washington, DC 20037 USA. George Washington Univ, Genom & Bioinformat Program, Med Ctr, Washington, DC 20037 USA. Natl Ctr Biotechnol Informat, Computat Biol Branch, Natl Lib Med, NIH, Bethesda, MD USA. George Washington Univ, Flow Cytometry Core Facil, Med Ctr, Washington, DC 20037 USA. RP Hawley, TS (reprint author), George Washington Univ, Dept Anat & Cell Biol, Med Ctr, 2300 I St NW, Washington, DC 20037 USA. EM rghawley@gwu.edu RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999]; NHLBI NIH HHS [R01 HL065519-01A1, R01 HL065519, R01 HL065519-02, R01 HL065519-03, R01 HL065519-04, R01 HL065519-05, R01 HL065519-06, R01 HL066305, R01 HL066305-01A1, R01 HL066305-02, R01 HL066305-03, R01 HL066305-04, R01 HL066305-05] NR 55 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 14 PY 2007 VL 26 IS 28 BP 4115 EP 4123 DI 10.1038/sj.onc.1210185 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 178XD UT WOS:000247252700007 PM 17213805 ER PT J AU Joshi, S Davies, H Sims, LP Levy, SE Dean, J AF Joshi, Saurabh Davies, Holly Sims, Lauren Porter Levy, Shawn E. Dean, Jurrien TI Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID MATERNAL-EFFECT GENE; GERM-CELL DIFFERENTIATION; EARLY EMBRYONIC-DEVELOPMENT; ZONA-PELLUCIDA GENES; FALSE DISCOVERY RATE; SERIAL ANALYSIS; MOUSE OOCYTES; PROMOTER ACTIVITY; CDNA MICROARRAY; DNA-BINDING AB Background: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ- cell specific, basic helix- loop- helix transcription factor, FIGLA ( Factor In the GermLine, Alpha) and demonstrated its involvement in two independent developmental processes: formation of the primordial follicle and coordinate expression of zona pellucida genes. Results: Taking advantage of Figla null mouse lines, we have used a combined approach of microarray and Serial Analysis of Gene Expression ( SAGE) to identify potential downstream target genes. Using high stringent cutoffs, we find that FIGLA functions as a key regulatory molecule in coordinating expression of the NALP family of genes, genes of known oocyte- specific expression and a set of functionally un- annotated genes. FIGLA also inhibits expression of male germ cell specific genes that might otherwise disrupt normal oogenesis. Conclusion: These data implicate FIGLA as a central regulator of oocyte- specific genes that play roles in folliculogenesis, fertilization and early development. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN 37232 USA. RP Joshi, S (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM saurabhj@mail.nih.gov; hdavies@ups.edu; lauren.p.sims@vanderbilt.edu; shawn.levy@vanderbilt.edu; jurrien@helix.nih.gov FU Intramural NIH HHS NR 79 TC 51 Z9 59 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD JUN 13 PY 2007 VL 7 AR 67 DI 10.1186/1471-213X-7-67 PG 13 WC Developmental Biology SC Developmental Biology GA 185ZP UT WOS:000247749200001 PM 17567914 ER PT J AU Denny, CC Emanuel, EJ Pearson, SD AF Denny, Colleen C. Emanuel, Ezekiel J. Pearson, Steven D. TI Why well-insured patients should demand value-based insurance benefits SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID METASTATIC COLORECTAL-CANCER; PLUS IRINOTECAN; CARE; INNOVATION; QUALITY; COSTS C1 NIH, Dept Bioeth, NIH Clin Ctr, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, NIH Clin Ctr, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@cc.nih.gov NR 23 TC 9 Z9 9 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 13 PY 2007 VL 297 IS 22 BP 2515 EP 2518 DI 10.1001/jama.297.22.2515 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 177TX UT WOS:000247176500026 PM 17565086 ER PT J AU Scott, BH Malone, BJ Semple, MN AF Scott, Brian H. Malone, Brian J. Semple, Malcolm N. TI Effect of behavioral context on representation of a spatial cue in core auditory cortex of awake macaques SO JOURNAL OF NEUROSCIENCE LA English DT Article DE interaural; phase; binaural; hearing; primate; psychophysics ID SINGLE-UNIT ACTIVITY; RECEPTIVE-FIELD PLASTICITY; SOUND-LOCALIZATION; RHESUS-MONKEY; INTERAURAL INTENSITY; NEURONS; FREQUENCY; LATERALIZATION; PHASE; DISCRIMINATION AB Primary auditory cortex plays a crucial role in spatially directed behavior, but little is known about the effect of behavioral state on the neural representation of spatial cues. Macaques were trained to discriminate binaural cues to sound localization, eventually allowing measurement of thresholds comparable to human hearing. During behavior and passive listening, single units in low-frequency auditory cortex showed robust and consistent tuning to interaural phase difference ( IPD). In most neurons, behavior exerted an effect on peak discharge rate ( 58% increased, 13% decreased), but this was not accompanied by a detectable shift in the best IPD of any cell. Neurometric analysis revealed a difference in discriminability between the behaving and passive condition in half of the sample ( 52%), but steepening of the neurometric function ( 29%) was only slightly more common than flattening ( 23%). This suggests that performance of a discrimination task does not necessarily confer an advantage in understanding the representation of the spatial cue in primary auditory cortex but nevertheless revealed some physiological effects. These results suggest that responses observed during passive listening provide a valid representation of neuronal response properties in core auditory cortex. C1 NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Scott, BH (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr,Room 1B80, Bethesda, MD 20892 USA. EM brianscott@mail.nih.gov RI Scott, Brian/G-7932-2012; OI Scott, Brian/0000-0003-3949-9737 FU NIDCD NIH HHS [DC05287-01]; NIMH NIH HHS [MH12293] NR 47 TC 37 Z9 37 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 13 PY 2007 VL 27 IS 24 BP 6489 EP 6499 DI 10.1523/JNEUROSCI.0016-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 178WB UT WOS:000247249700016 PM 17567810 ER PT J AU O'Brien, EP Dima, RI Brooks, B Thirumalai, D AF O'Brien, Edward P. Dima, Ruxandra I. Brooks, Bernard Thirumalai, D. TI Interactions between hydrophobic and ionic solutes in aqueous guanidinium chloride and urea solutions: Lessons for protein denaturation mechanism SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; POTENTIAL FUNCTIONS; AMINO ACIDS; WATER; HYDROCHLORIDE; STABILITY; FORCE; NMR; SOLUBILITY; HYDRATION AB In order to clarify the mechanism of denaturant-induced unfolding of proteins we have calculated the interactions between hydrophobic and ionic species in aqueous guanidinium chloride and urea solutions using molecular dynamics simulations. Hydrophobic association is not significantly changed in urea or guanidinium chloride solutions. The strength of interaction between ion pairs is greatly diminished by the guanidinium ion. Although the changes in electrostatic interactions in urea are small, examination of structures, using appropriate pair functions, of urea and water around the solutes show strong hydrogen bonding between urea's carbonyl oxygen and the positively charged solute. Our results strongly suggest protein denaturation occurs by the direct interaction model according to which the most commonly used denaturants unfold proteins by altering electrostatic interactions either by solvating the charged residues or by engaging in hydrogen bonds with the protein backbone. To further validate the direct interaction model we show that, in urea and guanidinium chloride solutions, unfolding of an unusually stable helix (H1) from mouse PrPC (residues 144-153) occurs by hydrogen bonding of denaturants to charged side chains and backbone carbonyl groups. C1 Univ Maryland, Inst Phys Sci & Technol, Dept Chem & Biochem, Biophys Program, College Pk, MD 20742 USA. NIH, NHLBI, Lab Computat Biol, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Dept Chem & Biochem, Biophys Program, College Pk, MD 20742 USA. EM thirum@glue.umd.edu RI O'Brien, Edward/C-3587-2015 NR 49 TC 187 Z9 188 U1 4 U2 40 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 13 PY 2007 VL 129 IS 23 BP 7346 EP 7353 DI 10.1021/ja069232+ PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 176GH UT WOS:000247072300043 PM 17503819 ER PT J AU Yin, H Hummer, G Rasaiah, JC AF Yin, Hao Hummer, Gerhard Rasaiah, Jayendran C. TI Metastable water clusters in the nonpolar cavities of the thermostable protein tetrabrachion SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HIGH-PRESSURE CRYSTALLOGRAPHY; MOLECULAR-DYNAMICS; FREE-ENERGY; STAPHYLOTHERMUS-MARINUS; HYDROPHOBIC ENCLOSURE; CYTOCHROME P450CAM; INTERNAL CAVITIES; CARBON NANOTUBES; DISORDERED WATER; LIGAND-BINDING AB Water expulsion from the protein core is a key step in protein folding. Nevertheless, unusually large water clusters confined into the nonpolar cavities have been observed in the X-ray crystal structures of tetrabrachion, a bacterial protein that is thermostable up to at least 403 K (130 degrees C). Here, we use molecular dynamics (MD) simulations to investigate the structure and thermodynamics of water filling the largest cavity of the right-handed coiled-coil stalk of tetrabrachion at 365 K (92 degrees C), the temperature of optimal bacterial growth, and at room temperature (298 K). Hydrogen-bonded water clusters of seven to nine water molecules are found to be thermodynamically stable in this cavity at both temperatures, confirming the X-ray studies. Stability, as measured by the transfer free energy of the optimal size cluster, decreases with increasing temperature. Water filling is thus driven by the energy of transfer and opposed by the transfer entropy, both depending only weakly on temperature. Our calculations suggest that cluster formation becomes unfavorable at similar to 384 K (110 degrees C), signaling the onset of drying just slightly above the temperature of optimal growth. "Drying" thus precedes protein denaturation. At room temperature, the second largest cavity in tetrabrachion accommodates a five water molecule cluster, as reported in the X-ray studies. However, the simulations show that at 365 K the cluster is unstable and breaks up. We suggest that the large hydrophobic cavities may act as binding sites for two proteases, possibly explaining the unusual thermostability of the resulting protease-stalk complexes (up to similar to 393 K, 120 degrees C). C1 Univ Maine, Dept Chem, Orono, ME 04469 USA. NIH, NIDDKD, Phys Chem Lab, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), Univ Maine, Dept Chem, Orono, ME 04469 USA. EM Gerhard.Hummer@NIH.gov; rasaiah@maine.edu RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 53 TC 51 Z9 51 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 13 PY 2007 VL 129 IS 23 BP 7369 EP 7377 DI 10.1021/ja070456h PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 176GH UT WOS:000247072300046 PM 17508748 ER PT J AU Dikiy, A Novoselov, SV Fomenko, DE Sengupta, A Carlson, BA Cerny, RL Ginalski, K Grishin, NV Hatfield, DL Gladyshev, VN AF Dikiy, Alexander Novoselov, Sergey V. Fomenko, Dmitri E. Sengupta, Aniruddha Carlson, Bradley A. Cerny, Ronald L. Ginalski, Krzysztof Grishin, Nick V. Hatfield, Dolph L. Gladyshev, Vadim N. TI SelT, SelW, SelH, and Rdx12: Genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family SO BIOCHEMISTRY LA English DT Article ID SELENOCYSTEINE TRANSFER-RNA; 14-3-3 PROTEINS; RAT MUSCLE; EXPRESSION; GLUTATHIONE; BINDING; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION; FOLD AB Selenium is an essential trace element in many life forms due to its occurrence as a selenocysteine (Sec) residue in selenoproteins. The majority of mammalian selenoproteins, however, have no known function. Herein, we performed extensive sequence similarity searches to define and characterize a new protein family, designated Rdx, that includes mammalian selenoproteins SelW, SelV, SelT and SelH, bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domains of life. An additional member of this family is a mammalian cysteine-containing protein, designated Rdx12, and its fish selenoprotein orthologue. Rdx proteins are proposed to possess a thioredoxin-like fold and a conserved CxxC or CxxU (U is Sec) motif, suggesting a redox function. We cloned and characterized three mammalian members of this family, which showed distinct expression patterns in mouse tissues and different localization patterns in cells transfected with the corresponding GFP fusion proteins. By analogy to thioredoxin, Rdx proteins can use catalytic cysteine (or Sec) to form transient mixed disulfides with substrate proteins. We employed this property to identify cellular targets of Rdx proteins using affinity columns containing mutant versions of these proteins. Rdx12 was found to interact with glutathione peroxidase 1. whereas 14-3-3 protein was identified as one of the targets of mammalian SelW, suggesting a mechanism for redox regulation of the 14-3-3 family of proteins. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Warsaw Univ, Interdisciplinary Ctr Math & Computat Modelling, PL-02106 Warsaw, Poland. NTNU, Dept Biotechnol, N-7491 Trondheim, Norway. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU Intramural NIH HHS; NCRR NIH HHS [RR015468]; NIGMS NIH HHS [GM061603] NR 35 TC 98 Z9 108 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 12 PY 2007 VL 46 IS 23 BP 6871 EP 6882 DI 10.1021/bi602462q PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 177GN UT WOS:000247141700019 PM 17503775 ER PT J AU Ruan, Q Liu, T Kolbanovskiy, A Liu, Y Ren, J Skorvaga, M Zou, Y Lader, J Malkani, B Amin, S Van Houten, B Geacintov, NE AF Ruan, Qian Liu, Tongming Kolbanovskiy, Alexander Liu, Yang Ren, Jian Skorvaga, Milan Zou, Yue Lader, Joshua Malkani, Brijesh Amin, Shantu Van Houten, Bennett Geacintov, Nicholas E. TI Sequence context- and temperature-dependent nucleotide excision repair of a benzo[a]pyrene diol epoxide-guanine DNA adduct catalyzed by thermophilic UvrABC proteins SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; DAMAGE RECOGNITION; CRYSTAL-STRUCTURE; BASE SEQUENCE; THERMUS-THERMOPHILUS; PREINCISION COMPLEX; (A)BC EXCINUCLEASE; INCISION REACTION; DUPLEX STABILITY; NUCLEASE SYSTEM AB The influence of DNA base sequence context on the removal of a bulky benzo[a]pyrene diol epoxide-guanine adduct, (+)-trans-B[a]P-N-2-dG (G*), by UvrABC nuclease from the thermophilic organism Bacillus caldotenax was investigated. The lesion was flanked by either T or C in otherwise identical complementary 43-mer duplexes (TG*T or CG*C, respectively). It was reported earlier that in the CG*C context, a dominant minor groove adduct structure was observed by NMR methods with all Watson-Crick base pairs intact, and the duplex exhibited a rigid bend. In contrast, in the TG*T context, a highly flexible bend was observed, base pairing at G*, and two 5'-base pairs flanking the adduct were impaired, and multiple solvent-accessible adduct conformations were observed. The TG*T-43-mer duplexes are incised with consistently greater efficiency by UvrABC proteins from B. caldotenax by a factor of 2.3 +/- 0.3. The rates of incisions increase with increasing temperature and are characterized by linear Arrhenius plots with activation energies of 27.0 +/- 1.5 and 23.4 +/- 1.0 kcal/mol for CG*C and TG*T duplexes, respectively. These values reflect the thermophilic characteristics of the UVrABC nuclease complex and the contributions of the different DNA substrates to the overall activation energies. These effects are consistent with base sequence context-dependent differences in structural disorder engendered by a loss of local base stacking interactions and Watson-Crick base pairing in the immediate vicinity of the lesions in the TG*T duplexes. The local weakening of base pairing interactions constitutes a recognition element of the UvrABC nucleotide excision repair apparatus. C1 NYU, Chem Dept, New York, NY 10003 USA. NIEHS, Lab Mol Genet, NIH, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Canc Res Inst, Dept Mol Genet, Bratislava 83391, Slovakia. Penn State Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. RP Geacintov, NE (reprint author), NYU, Chem Dept, 31 Washington Pl, New York, NY 10003 USA. EM ngl@nyu.edu RI kolbanovskiy, aleksandr/I-7278-2013; KOLBANOVSKIY, АЛЕКСАНДР/J-9368-2013 OI KOLBANOVSKIY, АЛЕКСАНДР/0000-0003-2038-0197 FU Intramural NIH HHS; NCI NIH HHS [CA 099194] NR 79 TC 28 Z9 28 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 12 PY 2007 VL 46 IS 23 BP 7006 EP 7015 DI 10.1021/bi700294K PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 177GN UT WOS:000247141700032 PM 17506530 ER PT J AU Ingelsson, E Larson, MG Vasan, RS O'Donnell, CJ Yin, X Hirschhorn, JN Newton-Cheh, C Drake, JA Musone, SL Heard-Costa, NL Benjamin, EJ Levy, D Atwood, LD Wang, TJ Kathiresan, S AF Ingelsson, Erik Larson, Martin G. Vasan, Ramachandran S. O'Donnell, Christopher J. Yin, Xiaoyan Hirschhorn, Joel N. Newton-Cheh, Christopher Drake, Jared A. Musone, Stacey L. Heard-Costa, Nancy L. Benjamin, Emelia J. Levy, Daniel Atwood, Larry D. Wang, Thomas J. Kathiresan, Sekar TI Heritability, linkage, and genetic associations of exercise treadmill test responses SO CIRCULATION LA English DT Article DE blood pressure; exercise; genetics; heart rate ID BLOOD-PRESSURE RESPONSE; ACUTE MYOCARDIAL-INFARCTION; HEART-RATE RECOVERY; HERITAGE FAMILY; INSULIN-RESISTANCE; RISK; POLYMORPHISMS; HYPERTENSION; DISEASE; WOMEN AB Background - The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. Methods and Results - We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43 - 44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing. Conclusions - Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise. C1 Framingham Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, 25 New Chardon St,Suite 301, Boston, MA 02114 USA. EM skathiresan@partners.org OI Heard-Costa, Nancy/0000-0001-9730-0306; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL04334, K23-HL074077-01, K23-HL083102-01, U01-HL-66582] NR 41 TC 15 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2007 VL 115 IS 23 BP 2917 EP 2924 DI 10.1161/CIRCULATIONAHA.106.683821 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 177KZ UT WOS:000247153300004 PM 17548724 ER PT J AU Ohrt, C Obare, P Nanakorn, A Adhiambo, C Awuondo, K O'Meara, WP Remich, S Martin, K Cook, E Chretien, JP Lucas, C Osoga, J McEvoy, P Owaga, ML Odera, JS Ogutu, B AF Ohrt, Colin Obare, Peter Nanakorn, Ampon Adhiambo, Christine Awuondo, Ken O'Meara, Wendy Prudhomme Remich, Shon Martin, Kurt Cook, Earnest Chretien, Jean-Paul Lucas, Carmen Osoga, Joseph McEvoy, Peter Owaga, Martin Lucas Odera, James Sande Ogutu, Bernhards TI Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya SO MALARIA JOURNAL LA English DT Article ID PLASMODIUM-FALCIPARUM; PARASITE DENSITY; HEALTH-CARE; MICROSCOPY; IDENTIFICATION; QUALITY; IMPACT; VIVAX; GHANA; FIELD AB Background: Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists. Case description: A twelve-day " long" and a four- day " short" training course consisting of supervised laboratory practicals, lectures, group discussions, demonstrations, and take home assignments were developed. Well characterized slides were developed and training materials iteratively improved. Objective pre- and post- course evaluations consisted of 30 slides ( 19 negative, 11 positive) with a density range of 50 - 660 parasites/ mu l, a written examination ( 65 questions), a photographic image examination ( 30 images of artifacts and species specific characteristics), and a parasite counting examination. Discussion and Evaluation: To date, 209 microscopists have participated from 11 countries. Seventy-seven experienced microscopists participated in the " long" courses, including 47 research microscopists. Sensitivity improved by a mean of 14% (CI 9 - 19%) from 77% baseline (CI 73 - 81 %), while specificity improved by a mean of 17% (CI 11 - 23%) from 76% (CI 70 - 82%) baseline. Twenty-three microscopists who had been selected for a four- day refresher course showed continued improvement with a mean final sensitivity of 95% (CI 91 - 98%) and specificity of 97% (CI 95 - 100%). Only 9% of those taking the pre- test in the " long" course achieved a 90% sensitivity and 95% specificity, which increased to 61% of those completing the " short" course. All measures of performance improved substantially across each of the five organization types and in each course offered. Conclusion: The data clearly illustrated that false positive and negative malaria smears are a serious problem, even with research microscopists. Training dramatically improved performance. Quality microscopy can be provided by the Centre of Excellence concept. This concept can be extended to other diagnostics of public health importance, and comprehensive disease control strategies. C1 Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. Kenya Govt Med Res Ctr, Clin Res Ctr, Malaria Diagnost Ctr Excellence, Kismu, Kenya. US Army Med Unit Kenya, Water Reed Project, Kismu, Kenya. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Naval Med Res Ctr Detachment, Lima, Peru. Armed Forces Inst Pathol, Washington, DC 20306 USA. Ctr Dis Control, Kisumu, Kenya. Kenya Govt Med Res Ctr, Kisumu, Kenya. RP Ohrt, C (reprint author), Walter Reed Army Inst Res, Robert Grant Ave, Silver Spring, MD 20910 USA. EM colin.ohrt@us.army.mil; pobare@wrp-ksm.org; ampon2486@yahoo.com; CAdhiambo@wrp-ksm.org; kawuondo@kilifi.kemri-wellcome.org; prudhomw@mail.nih.gov; shon.remich2@amedd.army.mil; kurt.martin@us.army.mil; ecook@wrp-ksm.org; Jean-Paul.Chretien@na.amedd.army.mil; clucas@nmrcd.med.navy.mil; josoga@wrp-ksm.org; mcevoy@afip.osd.mil; jsande@wrp-ksm.org; MOwaga@ke.cdc.gov; bogutu@wrp-ksm.org OI Chretien, Jean-Paul/0000-0001-8143-6823 NR 24 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD JUN 12 PY 2007 VL 6 AR 7 DI 10.1186/1475-2875-6-79 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 194ML UT WOS:000248348400001 ER PT J AU Kovacs, M Thirumurugan, K Knight, PJ Sellers, JR AF Kovacs, Mihaly Thirumurugan, Kavitha Knight, Peter J. Sellers, James R. TI Load-dependent mechanism of nonmuscle myosin 2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kinetics; load dependence; myosin; actomyosin; cytoskeleton ID SMOOTH-MUSCLE MYOSIN; HEAVY-MEROMYOSIN; 2 HEADS; ACTIN; BINDING; FILAMENTS; STRAIN; ADP; PROCESSIVITY; CONTRACTION AB Loads on molecular motors regulate and coordinate their function. In a study that directly measures properties of internally strained myosin 2 heads bound to actin, we find that human nonmuscle myosins 2A and 2B show marked load-dependent changes in kinetics of ADP release but not in nucleotide binding. We show that the ADP release rate constant is increased 4-fold by the assisting load on one head and decreased 5-fold (for 2A) or 12-fold (for 213) by the resisting load on the other. Thus these myosins, especially 2B, have marked mechanosensitivity of product release. By regulating the actin attachment of myosin heads, this provides a basis for energy-efficient tension maintenance without obstructing cellular contractility driven by other motors such as smooth muscle myosin. Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment. C1 NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA. Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. Univ Leeds, Inst Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. RP Kovacs, M (reprint author), NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA. EM kovacsm@elte.hu RI Kovacs, Mihaly/A-6841-2011; OI Thirumurugan, Kavitha/0000-0002-4673-4099 FU FIC NIH HHS [D43 TW 006230, 1R01 TW 007241-01, R01 TW006230, R01 TW007241]; Wellcome Trust NR 33 TC 100 Z9 100 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 12 PY 2007 VL 104 IS 24 BP 9994 EP 9999 DI 10.1073/pnas.0701181104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180KW UT WOS:000247363000016 PM 17548820 ER PT J AU Wu, W Wu, LG AF Wu, Wei Wu, Ling-Gang TI Rapid bulk endocytosis and its kinetics of fission pore closure at a central synapse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calyx of Held; capacitance measurement; membrane invagination; synaptic transmission ID FROG NEUROMUSCULAR-JUNCTION; MEMBRANE CAPACITANCE; TRANSMITTER RELEASE; SECRETORY VESICLE; NERVE-TERMINALS; FUSION PORE; EXOCYTOSIS; SINGLE; RETRIEVAL; CLATHRIN AB Upon exocytosis, fused vesicles must be retrieved for recycling. One route of retrieval is to generate endosome-like structures, from which small vesicles bud off. Endosome-like structures are widely thought to be generated slowly (approximate to 1 min) from the plasma membrane, a process called bulk endocytosis. Although the concept of bulk endocytosis seems established, the kinetic evidence showing the instant of the bulk membrane fission at synapses is still missing. The present work provides this missing piece of evidence at a calyx-type synapse. We used the capacitance measurement technique, which offers a high time resolution (approximate to 1 ms)to resolve the fission process. The instant of bulk membrane fission was reflected as a brief downward capacitance shift (DCS) of approximate to 20-500 fF (mean = 123 fF) with 10-90% decay time of approximate to 30-500 ms. At least 8.6-11.0% of exocytosed vesicles were retrieved by DCSs. During a DCS, the decrease in the fission pore conductance was detected, from which we found that the fission pore diameter decreased at approximate to 39 nm/s. This provided the measurement of the rate of fission during bulk endocytosis at synapses. The DCS frequency peaked (approximate to 0.021 Hz) in <10 s after stimulation and decayed with a half time <20 s, indicating that the time course of bulk endocytosis is much faster than previously estimated with low time-resolution techniques. Our results also suggest that bulk endocytosis was composed of two kinetically different steps: the DCS that reflected the fission process and the time between stimulation and the DCS, during which membrane invagination led to the fission pore formation. C1 NINDS, Synapt Transmiss Unit, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Synapt Transmiss Unit, 35 Convent Dr,Bldg 35,Room 2B-1012, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov FU Intramural NIH HHS NR 27 TC 43 Z9 44 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 12 PY 2007 VL 104 IS 24 BP 10234 EP 10239 DI 10.1073/pnas.0611512104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180KW UT WOS:000247363000057 PM 17551019 ER PT J AU Maraldi, C Volpato, S Penninx, BW Yaffe, K Simonsick, EM Strotmeyer, ES Cesari, M Kritchevsky, SB Perry, S Ayonayon, HN Pahor, M AF Maraldi, Cinzia Volpato, Stefano Penninx, Brenda W. Yaffe, Kristine Simonsick, Eleanor M. Strotmeyer, Elsa S. Cesari, Matteo Kritchevsky, Stephen B. Perry, Sara Ayonayon, Hilsa N. Pahor, Marco TI Diabetes mellitus, glycemic control, and incident depressive symptoms among 70-to 79-year-old persons SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; BODY-COMPOSITION; COGNITIVE IMPAIRMENT; COMORBID DEPRESSION; WOMENS HEALTH; OLDER-ADULTS; RISK-FACTOR; METAANALYSIS; ASSOCIATION; DISABILITY AB Background: Cross-sectional studies find an elevated prevalence of depression among subjects with diabetes mellitus ( DM). The causal mechanisms and temporal sequence of this association have not been clearly delineated. This study investigated the prospective relationship between DM and depressive symptoms. Methods: The Health, Aging, and Body Composition Study was a cohort study conducted in the metropolitan areas of Memphis, Tenn, and Pittsburgh, Pa. The analysis included 2522 community-dwelling subjects, aged 70 to 79 years, without baseline depressive symptoms. Incident depressed mood was defined as use of antidepressants at follow-up visits or presence of depressive symptoms ( score >= 10 on the 10-item Center for Epidemiological Studies Depression scale). Presence of incident depressed mood at 2 consecutive annual clinic visits defined the incidence of recurrent depressed mood. Diabetes mellitus status, glycosylated hemoglobin ( HbA1c) level, and DM-related comorbidities were assessed at baseline. Diabetes mellitus status was further characterized as absent, controlled ( HbA1c level < 7%), or uncontrolled ( HbA1c level >= 7%). Discrete time survival analysis was used to estimate depressive events risk. Results: During a mean follow-up of 5.9 years, participants with DM had a higher age-, sex-, race-, and site-adjusted incidence of depressed mood ( 23.5% vs 19.0%) ( P = .02) and recurrent depressed mood ( 8.8% vs 4.3%) ( P < .001) than those without DM. Diabetes mellitus was associated with a 30% increased risk of incident depressed mood ( odds ratio [ OR], 1.31; 95% confidence interval [ CI], 1.07-1.61), which was attenuated after adjustment for DM-related comorbidities ( OR, 1.20; CI, 0.97-1.48). A stronger relationship was observed between DM and recurrent depressed mood ( OR, 1.91; CI, 1.32-2.76), particularly among participants with poor glycemic control. Conclusion: Among well-functioning older adults, DM is associated with increased risk of depressive symptoms. C1 Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. Univ Florida, Inst Aging, Gainesville, FL USA. Malcom Randall Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Gainesville, FL USA. VU Univ Med Ctr, EMGO Inst, Amsterdam, Netherlands. VU Univ Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Maraldi, C (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy. EM mrlcnz@unife.it RI Cesari, Matteo/A-4649-2008; Strotmeyer, Elsa/F-3015-2014; VOLPATO, STEFANO/H-2977-2014 OI Strotmeyer, Elsa/0000-0002-4093-6036; Cesari, Matteo/0000-0002-0348-3664; VOLPATO, STEFANO/0000-0003-4335-6034 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL72972]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 54 TC 65 Z9 66 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 11 PY 2007 VL 167 IS 11 BP 1137 EP 1144 DI 10.1001/archinte.167.11.1137 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 177HE UT WOS:000247143400005 PM 17563021 ER PT J AU Landgren, O Turesson, I Gridley, G Caporaso, NE AF Landgren, Ola Turesson, Ingemar Gridley, Gloria Caporaso, Neil E. TI Risk of malignant disease among 1525 adult male US veterans with gaucher disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; GLUCOCEREBROSIDASE MUTATIONS; AFRICAN-AMERICAN; CANCER; GLUCOSYLCERAMIDE; PATHOGENESIS; COEXISTENCE AB Background: Some, but not all, reports suggest that patients with Gaucher disease are at increased risk of developing malignancies, particularly hematopoietic tumors. The aim of this study was to assess the pattern of Gaucher disease and subsequent malignancies among male veterans admitted to US Veterans Affairs hospitals. Methods: Among 832 294 African American and 3 668 983 white male veterans with at least 1 hospital admission in US Veterans Affairs hospitals and up to 27 years of follow-up, we identified a total of 1525 patients with Gaucher disease; 11.7% were African Americans. We used Poisson regression methods for cohort data to estimate relative risks ( RRs) and 95% confidence intervals ( CIs) after adjusting for attained age and calendar year, race, number of hospital visits, and latency. Results: When patients with Gaucher disease were compared with patients without Gaucher disease, the RR of any cancer was 0.91 ( 95% CI, 0.76-1.08 [ n = 137]). When we stratified our analyses by race, risks were similar for whites ( RR, 0.89; 95% CI, 0.74-1.07 [ n = 120]) and African Americans ( RR, 1.00; 95% CI, 0.61-1.64 [ n = 17]). Patients with Gaucher disease had an elevated risk for non-Hodgkin lymphoma ( RR, 2.54; 95% CI, 1.32-4.88 [ n = 9]), malignant melanoma ( RR, 3.07; 95% CI, 1.28-7.38 [ n = 5]), and pancreatic cancer ( RR, 2.37; 95% CI, 1.13-4.98 [ n = 7]). Among the remaining 19 cases involving defined solid tumors and 7 other hematologic malignancies, we found no statistical association with Gaucher disease. Conclusion: We found 2- to 3-fold risks of non-Hodgkin lymphoma, malignant melanoma, and pancreatic cancer in patients with Gaucher disease, but no significant association between Gaucher disease and cancer in general or with other specific malignancies such as multiple myeloma. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Lund Univ, Malmo Univ Hosp, Dept Med, Sect Hematol, Lund, Sweden. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Bldg EPS,Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU Intramural NIH HHS NR 59 TC 21 Z9 25 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 11 PY 2007 VL 167 IS 11 BP 1189 EP 1194 DI 10.1001/archinte.167.11.1189 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 177HE UT WOS:000247143400013 PM 17563029 ER PT J AU Cohen-Gihon, I Nussinov, R Sharan, R AF Cohen-Gihon, Inbar Nussinov, Ruth Sharan, Roded TI Comprehensive analysis of co-occurring domain sets in yeast proteins SO BMC GENOMICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORK; VHS DOMAIN; DATABASE; EVOLUTION; ORGANIZATION; SUPERFAMILY; ANNOTATION; SUPPLEMENT; SEQUENCES AB Background: Protein domains are fundamental evolutionary units of protein architecture, composing proteins in a modular manner. Combinations of two or more, possibly non- adjacent, domains are thought to play specific functional roles within proteins. Indeed, while the number of potential co- occurring domain sets ( CDSs) is very large, only a few of these occur in nature. Here we study the principles governing domain content of proteins, using yeast as a model species. Results: We design a novel representation of proteins and their constituent domains as a protein-domain network. An analysis of this network reveals 99 CDSs that occur in proteins more than expected by chance. The identified CDSs are shown to preferentially include ancient domains that are conserved from bacteria or archaea. Moreover, the protein sets spanned by these combinations were found to be highly functionally coherent, significantly match known protein complexes, and enriched with protein- protein interactions. These observations serve to validate the biological significance of the identified CDSs. Conclusion: Our work provides a comprehensive list of co- occurring domain sets in yeast, and sheds light on their function and evolution. C1 Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NCI, SAIC Frederick Inc, Nanobiol Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Sharan, R (reprint author), Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM inbarg@tau.ac.il; ruthn@ncifcrf.gov; roded@post.tau.ac.il FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 46 TC 12 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 11 PY 2007 VL 8 AR 161 DI 10.1186/1471-2164-8-161 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 191HP UT WOS:000248122600001 PM 17562021 ER PT J AU Coxon, B AF Coxon, Bruce TI A Karplus equation for (3)J(HCCN) in amino sugar derivatives SO CARBOHYDRATE RESEARCH LA English DT Article DE amino sugars; C-13 NMR chemical shifts; COSY; cryoprobe; H-1 NMR chemical shifts; HMBC; HSQC; HSQMBC; Karplus equation; molecular dynamics; N-15 NMR coupling constants ID PROTON COUPLING-CONSTANTS; NUCLEAR MAGNETIC-RESONANCE; NMR-SPECTROSCOPY; SUBSTITUENT ELECTRONEGATIVITIES; ANGULAR-DEPENDENCE; FOURIER-TRANSFORM; STEREOCHEMICAL DEPENDENCE; CONFORMATIONAL-ANALYSIS; BOAT CONFORMATIONS; TORSION ANGLE AB The H-1-N-15 coupling constants of a suite of organic-soluble amino sugar derivatives have been measured by one-dimensional and two-dimensional H-1/N-15 heteronuclear single quantum, multiple bond correlation (HSQMBC), and the values so obtained are compared with those measured by analysis of H-1 spectra of N-15-labeled amino sugar derivatives. A number of bicyclic amino sugar models have been studied, including methyl 2-(and 3-)amino-4,6-O-benzylidene-2- (and 3-)deoxy-alpha-D-hexopyranosides in chair or skew conformations, and methyl 2,6-anhydro-3-deoxy-3-phthalimido-alpha-D-mannopyranoside in a locked, almost classical boat conformation. The magnitudes of the vicinal H-1-N-15 coupling constants (3)j(HCCN) have been correlated with H-1/N-15 dihedral angles phi computed for the favored conformations by molecular dynamics with molecular mechanics energy minimization. Nonlinear regression of the coupling constants on the dihedral angles has yielded a Karplus equation: (3)J(HCCN) = 3.1 cos(2) phi-0.6 cos phi + 0.4. The coefficients of the terms in this equation have been compared with those reported for 15 other pairs of nuclei, and the coefficient of the important cos(2) phi term found to be numerically smallest for (3)J(HCCN). Published by Elsevier Ltd. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Coxon, B (reprint author), NICHHD, NIH, 31 Ctr Dr,MSC 2423, Bethesda, MD 20892 USA. EM coxonb@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 57 TC 9 Z9 9 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUN 11 PY 2007 VL 342 IS 8 BP 1044 EP 1054 DI 10.1016/j.carres.2007.02.023 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 165TX UT WOS:000246329800006 PM 17368582 ER PT J AU Johansson, C Wetzel, JD He, JP Mikacenic, C Dermody, TS Kelsall, BL AF Johansson, Cecilia Wetzel, J. Denise He, JianPing Mikacenic, Carmen Dermody, Terence S. Kelsall, Brian L. TI Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTOR-3; INNATE IMMUNE RECOGNITION; NATURAL-KILLER-CELLS; IFN-ALPHA-BETA; NF-KAPPA-B; PEYERS-PATCHES; IMMUNOGLOBULIN-A; VIRAL-INFECTION; DENDRITIC CELLS; VIRUS AB We defined the function of type I interferons (IFNs) in defense against reovirus strain type 1 Lang (T1L), which is a double-stranded RNA virus that infects Peyer's patches (PPs) after peroral inoculation of mice. T1L induced expression of mRNA for IFN-alpha, IFN-beta, and Mx-1 in PPs and caused localized intestinal infection that was cleared in 10 d. In contrast, T1L produced fatal systemic infection in IFN alpha R1 knockout (KO) mice with extensive cell loss in lymphoid tissues and necrosis of the intestinal mucosa. Studies of bone-marrow chimeric mice indicated an essential role for hematopoietic cells in IFN-dependent viral clearance. Dendritic cells (DCs), including conventional DCs (cDCs), were the major source of type I IFNs in PPs of reovirus-infected mice, whereas all cell types expressed the antiviral protein Mx-1. Neither NK cells nor signaling via Toll-like receptor 3 or MyD88 were essential for viral clearance. These data demonstrate a requirement for type I IFNs in the control of an intestinal viral infection and indicate that cDCs are a significant source of type I IFN production in vivo. Therefore, innate immunity in PPs is an essential component of host defense that limits systemic spread of pathogens that infect the intestinal mucosa. C1 NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. RP Dermody, TS (reprint author), NIAID, NIH, Lab Mol Immunol, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM terry.dermody@vanderbilt.edu; kelsall@nih.gov OI Johansson, Cecilia/0000-0002-6607-5000 FU NCI NIH HHS [CA68485, P30 CA068485]; NIAID NIH HHS [AI50080, R01 AI050080]; NIDDK NIH HHS [P30 DK020593, DK20593, P60 DK020593] NR 47 TC 38 Z9 39 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 11 PY 2007 VL 204 IS 6 BP 1349 EP 1358 DI 10.1084/jem.20061587 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 177MX UT WOS:000247158300015 PM 17502662 ER PT J AU Precopio, ML Betts, MR Parrino, J Price, DA Gostick, E Ambrozak, DR Asher, TE Douek, DC Harari, A Pantaleo, G Bailer, R Graham, BS Roederer, M Koup, RA AF Precopio, Melissa L. Betts, Michael R. Parrino, Janie Price, David A. Gostick, Emma Ambrozak, David R. Asher, Tedi E. Douek, Daniel C. Harari, Alexandre Pantaleo, Giuseppe Bailer, Robert Graham, Barney S. Roederer, Mario Koup, Richard A. TI Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID POLYCHROMATIC FLOW-CYTOMETRY; SMALLPOX VACCINATION; ANTIVIRAL IMMUNITY; PRIMARY INFECTION; ESCAPE VARIANTS; LYMPHOCYTES; VIREMIA; MEMORY; MVA; IMMUNOGENICITY AB Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8(+) T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus - specific CD8(+) T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon gamma, interleukin 2, macrophage inflammatory protein 1 beta, and tumor necrosis factor.. after antigenic stimulation. Responding CD8(+) T cells exhibited an unusual phenotype (CD45RO - CD27(intermediate)). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8(+) T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated. C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. NIAID, NIH, Viral Pathogenesis Lab, Bethesda, MD 20892 USA. NIAID, NIH, Human Immunol Sect, Bethesda, MD 20892 USA. NIAID, NIH, Immunol Core Lab, Bethesda, MD 20892 USA. NIAID, NIH, Vaccine Res Ctr, ImmunoTechnol Sect, Bethesda, MD 20892 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Oxford, Weatherall Inst Mol Med, Oxford 0X3 9DS, England. Univ Lausanne, Ctr Hosp Univ Vaudois, Dept Med, Div Immunol & Allergy,Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland. RP Koup, RA (reprint author), NIAID, NIH, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013; Pantaleo, Giuseppe/K-6163-2016; OI Price, David/0000-0001-9416-2737; Harari, Alexandre/0000-0002-1055-2090 FU Intramural NIH HHS; Medical Research Council [G0501963] NR 49 TC 295 Z9 298 U1 2 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 11 PY 2007 VL 204 IS 6 BP 1405 EP 1416 DI 10.1084/jem.20062363 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 177MX UT WOS:000247158300020 PM 17535971 ER PT J AU Sihag, RK Inagaki, M Yamaguchi, T Shea, TB Pant, HC AF Sihag, Ram K. Inagaki, Masaki Yamaguchi, Tomoya Shea, Thomas B. Pant, Harish C. TI Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE intermediate filaments; neurofilaments; vimentin; phosphorylation; protein kinases; protein assembly ID SLOW AXONAL-TRANSPORT; AMYOTROPHIC-LATERAL-SCLEROSIS; SITE-SPECIFIC PHOSPHORYLATION; WEIGHT NEUROFILAMENT PROTEIN; MOLECULAR-MASS SUBUNIT; RHO-ASSOCIATED KINASE; TERMINAL HEAD DOMAIN; MARIE-TOOTH-DISEASE; MONOCLONAL-ANTIBODIES DISTINGUISH; GANGLION-CELL NEURONS AB Phosphorylation of types III and IV intermediate filaments (IFs) is known to regulate their organization and function. Phosphorylation of the amino-terminal head domain sites on types III and IV IF proteins plays a key role in the assembly/disassembly of IF subunits into 10 nm filaments, and influences the phosphorylation of sites on the carboxyl-terminal tail domain. These phosphorylation events are largely under the control of second messenger-dependent protein kinases and provide the cells a mechanism to reorganize the IFs in response to the changes in second messenger levels. In mitotic cells, Cdk1, Rho kinase, PAKI and Aurora-B kinase are believed to regulate vimentin and glial fibrillary acidic protein phosphorylation in a spatio-temporal manner. In neurons, the carboxyl-terminal tail domains of the NF-M and NF-H subunits of heteropolymeric neurofilaments (NFs) are highly phosphorylated by proline-directed protein kinases. The phosphorylation of carboxyl-terminal tail domains of NFs has been suspected to play roles in forming cross-bridges between NFs and microtubules, slowing axonal transport and promoting their integration into cytoskeleton lattice and, in doing so, to control axonal caliber and stabilize the axon. The role of IF phosphorylation in disease pathobiology is discussed. (c) 2007 Elsevier Inc. All rights reserved. C1 NIH, Natl Inst Neurol Dis & Stroke, Neurochem Lab, Bethesda, MD 20892 USA. Aichi Canc Ctr, Res Inst, Biochem Lab, Nagoya, Aichi 464, Japan. Univ Massachusetts, Dept Biol Sci & Biochem, Lowell, MA 01854 USA. RP Sihag, RK (reprint author), NIH, Natl Inst Neurol Dis & Stroke, Neurochem Lab, Bldg 49 Rm 2A28, Bethesda, MD 20892 USA. EM RS1950@Verizon.net; panth@mail.nih.gov RI Inagaki, Masaki/B-9920-2016 FU Intramural NIH HHS [Z01 NS002725-21] NR 142 TC 136 Z9 139 U1 1 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2007 VL 313 IS 10 BP 2098 EP 2109 DI 10.1016/j.yexcr.2007.04.010 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 179ZC UT WOS:000247328300011 PM 17498690 ER PT J AU Stewart, CL Kozlov, S Fong, LG Young, SG AF Stewart, Colin L. Kozlov, Serquei Fong, Loren G. Young, Stephen G. TI Mouse models of the laminopathies SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE lamins; nucleus; laminopathies; progeria ID HUTCHINSON-GILFORD-PROGERIA; LAMIN A/C GENE; DREIFUSS MUSCULAR-DYSTROPHY; FAMILIAL PARTIAL LIPODYSTROPHY; CHARCOT-MARIE-TOOTH; A-TYPE LAMINS; NUCLEAR-ENVELOPE; PRELAMIN-A; DILATED CARDIOMYOPATHY; MANDIBULOACRAL DYSPLASIA AB The A and B type lamins are nuclear intermediate filament proteins that comprise the bulk of the nuclear lamina, a thin proteinaceous structure underlying the inner nuclear membrane. The A type lamins are encoded by the lamin A gene (LMNA). Mutations in this gene have been linked to at least nine diseases, including the progeroid diseases Hutchinson-Gilford progeria and atypical Werner's syndromes, striated muscle diseases including muscular dystrophies and dilated cardiomyopathies, lipodystrophies affecting adipose tissue deposition, diseases affecting skeletal development, and a peripheral neuropathy. To understand how different diseases arise from different mutations in the same gene, mouse lines carrying some of the same mutations found in the human diseases have been established. We, and others have generated mice with different mutations that result in progeria, muscular dystrophy, and dilated cardiomyopathy. To further our understanding of the functions of the lamins, we also created mice lacking lamin B1, as well as mice expressing only one of the A type lamins. These mouse lines are providing insights into the functions of the lamina and how changes to the lamina affect the mechanical integrity of the nucleus as well as signaling pathways that, when disrupted, may contribute to the disease. Published by Elsevier Inc. C1 NCI, Lab Canc & Dev Biol, Frederick, MD 21702 USA. Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Stewart, CL (reprint author), NCI, Lab Canc & Dev Biol, PO Box B, Frederick, MD 21702 USA. EM stewartc@ncifcrf.gov; sgyoung@mednet.ucla.edu FU Intramural NIH HHS [Z01 BC010377-07] NR 85 TC 59 Z9 61 U1 0 U2 2 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2007 VL 313 IS 10 BP 2144 EP 2156 DI 10.1016/j.yexcr.2007.03.026 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 179ZC UT WOS:000247328300015 PM 17493612 ER PT J AU Ballard-Barbash, R McTiernan, A AF Ballard-Barbash, Rachel McTiernan, Anne TI Is the whole larger than the sum of the parts? The promise of combining physical activity and diet to improve cancer outcomes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; TRIAL; SURVIVAL; PATTERN; WOMEN C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Ballard-Barbash, R (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 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 JUN 10 PY 2007 VL 25 IS 17 BP 2335 EP 2337 DI 10.1200/JCO.2007.10.7326 PG 3 WC Oncology SC Oncology GA 178SY UT WOS:000247241600001 PM 17557943 ER PT J AU Laine, C Horton, R DeAngelis, CD Drazen, JM Frizelle, FA Godlee, F Haug, C Hebert, PC Kotzin, S Marusic, A Sahni, P Schroeder, TV Sox, HC Van der Weyden, MB Verheugt, FWA AF Laine, Christine Horton, Richard DeAngelis, Catherine D. Drazen, Jeffrey M. Frizelle, Frank A. Godlee, Fiona Haug, Charlotte Hebert, Paul C. Kotzin, Sheldon Marusic, Ana Sahni, Peush Schroeder, Torben V. Sox, Harold C. Van der Weyden, Martin B. Verheugt, Freek W. A. TI Clinical trial registration: looking back and moving ahead SO LANCET LA English DT Editorial Material C1 Canadian Med Assoc, Ottawa, ON, Canada. Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 5 TC 36 Z9 39 U1 0 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 9 PY 2007 VL 369 IS 9577 BP 1909 EP 1911 DI 10.1016/S0140-6736(07)60894-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 177IQ UT WOS:000247147200008 PM 17560431 ER PT J AU Lewis, PA Greggio, E Beilina, A Jain, S Baker, A Cookson, MR AF Lewis, Patrick A. Greggio, Elisa Beilina, Alexandra Jain, Shushant Baker, Acacia Cookson, Mark R. TI The R1441C mutation of LRRK2 disrupts GTP hydrolysis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE LRRK2; Parkinson's disease; GTPase; kinase; dardarin ID DISEASE-ASSOCIATED MUTATIONS; FAMILIAL PARKINSONS-DISEASE; PROTEIN-KINASE ACTIVITY; NEURONAL TOXICITY; BINDING; GENE; DOMAIN; ROC AB Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause of Parkinson's disease (PD). LRRK2 is predicted to contain kinase and GTPase enzymatic domains, with recent evidence suggesting that the kinase activity of LRRK2 is central to the pathogenic process associated with this protein. The GTPase domain of LRRK2 plays an important role in the regulation of kinase activity. To investigate how the GTPase domain might be related to disease, we examined the GTP binding and hydrolysis properties of wild type and a mutant form of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable GTPase activity that is disrupted by a familial mutation associated with PD located within the GTPase domain, R1441C. Published by Elsevier Inc. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov RI Lewis , Patrick/C-3674-2009; Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Lewis, Patrick/0000-0003-4537-0489 FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000953-04] NR 14 TC 147 Z9 150 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 8 PY 2007 VL 357 IS 3 BP 668 EP 671 DI 10.1016/j.bbrc.2007.04.006 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 166MJ UT WOS:000246382700016 PM 17442267 ER PT J AU Matsumoto, T Hwang, PM AF Matsumoto, Takumi Hwang, Paul M. TI Resizing the genomic regulation of restenosis SO CIRCULATION RESEARCH LA English DT Editorial Material DE microRNA; vascular smooth muscle cells; neointima; cell cycle ID MICRORNA; ATHEROSCLEROSIS; DISEASE; COMPLEX; STENT C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Hwang, PM (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10-CRC,Rm 5-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS NR 21 TC 4 Z9 6 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 8 PY 2007 VL 100 IS 11 BP 1537 EP 1539 DI 10.1161/CIRCRESAHA.107.101103 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 176ID UT WOS:000247077300003 PM 17556665 ER PT J AU Garg, H Joshi, A Freed, EO Blumenthal, R AF Garg, Himanshu Joshi, Anjali Freed, Eric O. Blumenthal, Robert TI Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 T-CELLS; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; IN-VIVO; TYPE-1 ENVELOPE; INFLUENZA HEMAGGLUTININ; VIROLOGICAL SYNAPSE; PROTEASE INHIBITOR; CYTOPLASMIC TAIL AB The loss of CD4(+) T cells in HIV-1 infections is hypothesized to be caused by apoptosis of bystander cells mediated by cell surface-expressed HIV-1 Env glycoprotein. However, the mechanism by which Env mediates this process remains controversial. Specifically, the role of HIV-1 gp120 binding to CD4 and CXCR4 versus the fusion process mediated by gp41 remains unresolved. Env-induced apoptosis in bystander cells has been shown to be gp41-dependent and correlates with the redistribution of membrane lipids between Env-expressing cells and target cells (hemifusion). Using a rational mutagenesis approach aimed at targeting Env function via the gp41 subunit, we examined the role of HIV gp41 in bystander apoptosis. A mutation in the fusion domain of gp41 (V513E) resulted in a fusion-defective Env that failed to induce apoptosis. A mutation in the gp41 N-terminal helix (G547D) reduced cell fusion capacity and apoptosis; conversely, an Env mutant with a deletion of the gp41 cytoplasmic tail (Ct Del) enhanced both cell-to-cell fusion and apoptosis. Most significantly, an Env mutant containing a substitution in the loop region of gp41 (D589L) mediated transfer of lipids (hemifusion) to bystander cells but was defective in cell-to-cell and to a lesser degree virus-to-cell fusion. This mutant was still able to induce apoptosis in bystander cells. Hence, we have provided the first direct evidence that gp41-mediated hemifusion is both required and sufficient for induction of apoptosis in bystander cells. These results may help to explain the mechanism of HIV-1 Env-induced T cell depletion. C1 NCI, Membrane Struct & Funct Sect, Canc Res Ctr, Nanobiol Program,NIH, Frederick, MD 21702 USA. NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), NCI, Membrane Struct & Funct Sect, Canc Res Ctr, Nanobiol Program,NIH, Frederick, MD 21702 USA. EM blumen@helix.nih.gov FU Intramural NIH HHS NR 43 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 16899 EP 16906 DI 10.1074/jbc.M701701200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500022 PM 17416587 ER PT J AU Deval, J D'Abramo, CM Zhao, ZJ McCormick, S Coutsinos, D Hess, S Kvaratskhelia, M Gotte, M AF Deval, Jerome D'Abramo, Claudia M. Zhao, Zhuojun McCormick, Suzanne Coutsinos, Dimitrios Hess, Sonja Kvaratskhelia, Mamuka Gotte, Matthias TI High resolution footprinting of the hepatitis C virus polymerase NS5B in complex with RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DE-NOVO INITIATION; HIV-1 REVERSE-TRANSCRIPTASE; REPLICATION-PROTEIN-A; VIRAL-RNA; CRYSTAL-STRUCTURE; NONNUCLEOSIDE INHIBITORS; BINDING; SITE; DNA; MODULATION AB The nucleic acid binding channel of the hepatitis C virus RNA polymerase remains to be defined. Here we employed complementary footprinting techniques and show that the enzyme binds to a newly synthesized duplex of approximately seven to eight base pairs. Comparative analysis of surface topologies of free enzyme versus the nucleoprotein complex revealed certain lysines and arginines that are protected from chemical modification upon RNA binding. The protection pattern helps to define the trajectory of the nucleic acid substrate. Lys(81), Lys(98), Lys(100), Lys(106), Arg(158), Arg(386), and Arg(394) probably interact with the bound RNA. The selective protection of amino acids of the arginine-rich region in helix T points to RNA-induced conformational rearrangements. Together, these findings suggest that RNA-protein interaction through the entire substrate binding channel can modulate intradomain contacts at the C terminus. C1 McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Med, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Biochem, Montreal, PQ H3A 2B4, Canada. Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Gotte, M (reprint author), McGill Univ, Dept Microbiol & Immunol, Duff Med Bldg,3775 Univ St, Montreal, PQ H3A 2B4, Canada. EM matthias.gotte@mcgill.ca RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU NIAID NIH HHS [R01 AI062520] NR 37 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 16907 EP 16916 DI 10.1074/jbc.M701973200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500023 PM 17449464 ER PT J AU Matsumoto, K Yu, ST Jia, YZ Ahmed, MR Viswakarma, N Sarkar, J Kashireddy, PV Rao, MS Karpus, W Gonzalez, FJ Reddy, JK AF Matsumoto, Kojiro Yu, Songtao Jia, Yuzhi Ahmed, Mohamed R. Viswakarma, Navin Sarkar, Joy Kashireddy, Papreddy V. Rao, M. Sambasiva Karpus, William Gonzalez, Frank J. Reddy, Janardan K. TI Critical role for transcription coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein/TRAP220 in liver regeneration and PPAR alpha ligand-induced liver tumor development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE-LIVER; PARTIAL-HEPATECTOMY; NUCLEAR RECEPTORS; PROTEIN; EXPRESSION; MECHANISM; CAR; PBP; HEPATOTOXICITY; INTERACTS AB Disruption of the gene encoding for the transcription coactivator peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP/TRAP220/DRIP205/Med1) in the mouse results in embryonic lethality. Here, we have reported that targeted disruption of the Pbp/Pparbp gene in hepatocytes (Pbp(Delta Liv)) impairs liver regeneration with low survival after partial hepatectomy. Analysis of cell cycle progression suggests a defective exit from quiescence, reduced BrdUrd incorporation, and diminished entry into G(2)/M phase in Pbp(Delta Liv) hepatocytes after partial hepatectomy. Pbp(Delta Liv) hepatocytes failed to respond to hepatocyte growth factor/scatter factor, implying that hepatic PBP deficiency affects c-met signaling. Pbp gene disruption also abolishes primary mitogen-induced liver cell proliferative response. Striking abrogation of CCl4-induced hepatocellular proliferation and hepatotoxicity occurred in Pbp(Delta Liv) mice pretreated with phenobarbital due to lack of expression of xenobiotic metabolizing enzymes necessary for CCl4 activation. Pbp(Delta Liv) mice, chronically exposed to Wy-14,643, a PPAR alpha ligand, revealed a striking proliferative response and clonal expansion of a few Pbp(fl/fl) hepatocytes that escaped Cre-mediated gene deletion in Pbp(Delta Liv) livers, but no proliferative expansion of PBP null hepatocytes was observed. In these Pbp(Delta Liv) mice, none of the Wy-14,643-induced hepatic adenomas and hepatocellular carcinomas was derived from PBP Delta Liv hepatocytes; all liver tumors developing in Pbp(Delta Liv) mice maintained non-recombinant Pbp alleles and retained PBP expression. These studies provide direct evidence in support of a critical role of PBP/TRAP220 in liver regeneration, induction of hepatotoxicity, and hepatocarcinogenesis. C1 Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Canc Res Ctr, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Reddy, JK (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Pathol, 303 E Chicago Ave, Chicago, IL 60611 USA. EM jkreddy@northwestern.edu FU NCI NIH HHS [CA104578]; NIGMS NIH HHS [GM23750] NR 37 TC 32 Z9 35 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 17053 EP 17060 DI 10.1074/jbc.M701956200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500038 PM 17438330 ER PT J AU Ishima, R Torchia, DA Louis, JM AF Ishima, Rieko Torchia, Dennis A. Louis, John M. TI Mutational and structural studies aimed at characterizing the monomer of HIV-1 protease and its precursor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; POL POLYPROTEIN; STABILITY; KINETICS; MECHANISM; PEPTIDES; PROTEINS; INHIBITION; SUBSTRATE AB An experimental protocol for folding the mature human immunodeficiency virus-1 (HIV- 1) protease is presented that facilitates NMR studies at a low protein concentration of similar to 20 mu M. Under these conditions, NMRspectra show that the mature protease lacking its terminal beta-sheet residues 1-4 and 96-99 (PR5-95) exhibits a stable monomer fold spanning the region 10-90 that is similar to that of the single subunit of the wild-type dimer and the dimer bearing a D25N mutation (PRD25N). Urea- induced unfolding monitored both by changes in H-1- N-15 heteronuclear single quantum correlation spectra and by protein fluorescence indicates that although PR5-95 monomer displays a transition profile similar to that of the PRD25N dimer ( 50% unfolded (U-50) = similar to 1.9 M), extending the protease with 4 residues ( SFNF) of its N- terminally flanking sequence in the Gag-Pol precursor ((PRD25N)-P-SFNF) decreases the stability of the fold (U-50 = similar to 1.5 M). Assigned backbone chemical shifts were used to elucidate differences in the stability of the PRT26A (U50 = 2.5 M) and (PRD25N)-P-SFNF monomers and compared with PRD25N/T26A monomer. Discernible differences in the backbone chemical shifts were observed for N- terminal protease residues 3-6 of (PRD25N)-P-SFNF that may relate to the increase in the equilibrium dissociation constant ( Kd) and the very low catalytic activity of the protease prior to its autoprocessing at its N terminus from the Gag- Pol precursor. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. NIDCR, Mol Struct Biol Unit, NIH, Bethesda, MD 20892 USA. RP Louis, JM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm B2-29,LCP, Bethesda, MD 20892 USA. EM johnl@intra.niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 36 TC 39 Z9 39 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 17190 EP 17199 DI 10.1074/jbc.M701304200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500052 PM 17412697 ER PT J AU Dissanayake, SK Wade, M Johnson, CE O'Connell, MP Leotlela, PD French, AD Shah, KV Hewitt, KJ Rosenthal, DT Indig, FE Jiang, Y Nickoloff, BJ Taub, DD Trent, JM Moon, RT Bittner, M Weeraratna, AT AF Dissanayake, Samudra K. Wade, Michael Johnson, Carrie E. O'Connell, Michael P. Leotlela, Poloko D. French, Amanda D. Shah, Kavita V. Hewitt, Kyle J. Rosenthal, Devin T. Indig, Fred E. Jiang, Yuan Nickoloff, Brian J. Taub, Dennis D. Trent, Jeffrey M. Moon, Randall T. Bittner, Michael Weeraratna, Ashani T. TI The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; MALIGNANT-MELANOMA; MOLECULAR CLASSIFICATION; KISS-1 EXPRESSION; FRIZZLED HOMOLOGS; GENE-EXPRESSION; CARCINOMA-CELLS; DOWN-REGULATION; PROTEIN; INVASION AB We have shown that Wnt5A increases the motility of melanoma cells. To explore cellular pathways involving Wnt5A, we compared gain-of-function (WNT5A stable transfectants) versus loss-of-function (siRNA knockdown) of WNT5A by microarray analysis. Increasing WNT5A suppressed the expression of several genes, which were re-expressed after small interference RNA-mediated knockdown of WNT5A. Genes affected by WNT5A include KISS-1, a metastasis suppressor, and CD44, involved in tumor cell homing during metastasis. This could be validated at the protein level using both small interference RNA and recombinant Wnt5A (rWnt5A). Among the genes up-regulated by WNT5A was the gene vimentin, associated with an epithelial to mesenchymal transition (EMT), which involves decreases in E-cadherin, due to up-regulation of the transcriptional repressor, Snail. rWnt5A treatment increases Snail and vimentin expression, and decreases E-cadherin, even in the presence of dominant-negativeTCF4, suggesting that this activation is independent of Wnt/ss-catenin signaling. Because Wnt5A can signal via protein kinase C (PKC), the role of PKC in Wnt5A- mediated motility and EMT was also assessed using PKC inhibition and activation studies. Treating cells expressing low levels of Wnt5A with phorbol ester increased Snail expression inhibiting PKC in cells expressing high levels of Wnt5A C1 NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Howard Hughes Med Inst, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Inst Stem Cell & Regenerat Med, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Translat Genom Res Inst, Phoenix, AZ 85004 USA. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM weerarat@grc.nia.nih.gov RI Moon, Randall/B-1743-2014 OI Moon, Randall/0000-0002-9352-1408 FU Intramural NIH HHS [Z01 AG000442-04] NR 48 TC 196 Z9 208 U1 2 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 8 PY 2007 VL 282 IS 23 BP 17259 EP 17271 DI 10.1074/jbc.M700075200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174MN UT WOS:000246946500059 PM 17426020 ER PT J AU Arpiainen, S Lamsa, V Pelkonen, A Yim, SH Gonzalez, FJ Hakkola, J AF Arpiainen, Satu Lamsa, Virpi Pelkonen, Avi Yim, Sun Hee Gonzalez, Frank J. Hakkola, Jukka TI Aryl hydrocarbon receptor nuclear translocator and upstream stimulatory factor regulate Cytochrome P450 2a5 transcription through a common E-box site SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ARNT; homodimer; USF; CYP2A5; regulation ID MOUSE PRIMARY HEPATOCYTES; AH RECEPTOR; DNA-BINDING; GENE-EXPRESSION; FACTOR USF; COUMARIN 7-HYDROXYLASE; FUNCTIONAL DOMAINS; PROTEIN ARNT; CYP2A GENES; IDENTIFICATION AB The aryl hydrocarbon receptor nuclear translocator (ARNT) belongs to the basic-helix-loop-helix (bHLH) transcription factors and regulates several genes as heterodimers with other bHLH proteins. ARNT is also able to homodimerize, but no mammalian target genes for the homodimer have been shown. We identified a palindromic E-box element in the 5 regulatory region of the murine cytochrome P450 (Cyp) 2a5 gene that was found to be important for Cyp2a5 transcription in primary hepatocytes, and was found by chromatin immunoprecipitation assays to interact with ARNT. Electrophoretic mobility-shift assay experiments with in vitro translated ARNT showed binding without heterodimerization partner, indicating binding as a homodimer. Transfection studies in wild-type and ARNT-deficient Hepa-1 cells revealed that ARNT expression is necessary for full activity of the Cyp2a5 promoter. In the liver-specific Arnt-mill mouse line, the level of hepatic CYP2A5 mRNA was decreased significantly. Co-transfection studies with an ARNT expression vector lacking the transactivation. domain (TAD) demonstrated that the ARNT TAD is needed for Cyp2a5 activation, which suggests that ARNT transactivates Cyp2a5 as a homodimer. In primary hepatocytes, the mRNA levels of both CYP2A5 and ARNT splice variant 1 were increased during cultivation. Upstream stimulatory factors 1 and 2a were also able to bind to the same E-box as ARNT, indicating that there may be competition for DNA binding between these factors. Indeed, the upstream stimulatory factors activated the Cyp2a5 promoter through the E-box only in the presence of hepatocyte nuclear factor-4 alpha, while ARNT transactivation was independent of hepatocyte nuclear factor-4 alpha. In conclusion, these results indicate that ARNT controls Cyp2a5 transcription and thus, for the first time, suggest active involvement of the ARNT homodimer in mammalian gene regulation. (c) 2007 Elsevier Ltd. All rights reserved. C1 Oulu Univ, Dept Pharmacol & Toxicol, Oulu, Finland. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Hakkola, J (reprint author), Oulu Univ, Dept Pharmacol & Toxicol, Oulu, Finland. EM jukka.hakkola@oulu.fi NR 69 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 8 PY 2007 VL 369 IS 3 BP 640 EP 652 DI 10.1016/j.jmb.2007.03.075 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172NH UT WOS:000246810500005 PM 17466327 ER PT J AU Kim, YS Morgan, MJ Choksi, S Liu, ZG AF Kim, You-Sun Morgan, Michael J. Choksi, Swati Liu, Zheng-Gang TI TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death SO MOLECULAR CELL LA English DT Article ID NF-KAPPA-B; SMOOTH-MUSCLE-CELLS; REACTIVE OXYGEN; ENDOTHELIAL-CELLS; JNK ACTIVATION; SUPEROXIDE; APOPTOSIS; NECROSIS; ALPHA; GP91(PHOX) AB Tumor necrosis factor (TNF) is an important cytokine in immunity and inflammation and induces many cellular responses, including apoptosis and necrosis. TNF signaling enables the generation of superoxide in phagocytic and vascular cells through the activation of the NADPH oxidase Nox2/gp91. Here we show that TNF also activates the Nox1 NADPH oxidase in mouse fibroblasts when cells undergo necrosis. TNF treatment induces the formation of a signaling complex containing TRADD, RIP1, Nox1, and the small GTPase Rac1. TNF-treated RIP1-deficient fibroblasts fail to form such a complex, indicating that RIP1 is essential for Nox1 recruitment. Moreover, the prevention of TNF-induced superoxide generation with dominant-negative mutants of TRADD or Rac1, as well as knockdown of Nox1 using siRNA, inhibits necrosis. Thus our study suggests that activation of Nox1 through forming a complex with TNF signaling components plays a key role in TNF-induced necrotic cell death. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM liuzg@helix.nih.gov FU Intramural NIH HHS NR 35 TC 258 Z9 272 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 8 PY 2007 VL 26 IS 5 BP 675 EP 687 DI 10.1016/j.molcel.2007.04.021 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180PM UT WOS:000247378000007 PM 17560373 ER PT J AU Van Thienen, TG Horkay, F Braeckmans, K Stubbe, BG Demeester, J De Smedt, SC AF Van Thienen, T. G. Horkay, F. Braeckmans, K. Stubbe, B. G. Demeester, J. De Smedt, S. C. TI Influence of free chains on the swelling pressure of PEG-HEMA and dex-HEMA hydrogels SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE drug delivery; biodegradable hydrogels; swelling pressure; osmotic pressure ID POLY(ETHYLENE OXIDE) SOLUTIONS; DRUG-DELIVERY; CONTROLLED-RELEASE; GLYCOL) HYDROGELS; DEXTRAN; DEGRADATION; EQUILIBRIUM; BEHAVIOR; GELS; MICROSPHERES AB Insight in the osmotic behavior of degrading hydrogels is of great importance in the design of biodegradable hydrogels forbiornedical applications. This study compares the degradation behavior of PEG-HEMA (hydroxyethylmethacrylated polyethylene glycol) and dex-HEMA (hydroxyethylmethacrylated dextran) hydrogels. The degradation of PEG-HEMA gels takes several months to over a year, while that of dex-HEMA gels takes only days or weeks. The faster degradation kinetics of dex-HEMA networks can be attributed to stabilization of the keto-enol form by hydroxyl groups. Upon degradation of PEG-HEMA and dex-HEMA hydrogels, respectively, free PEG and free dextran chains are produced. We investigated the effect of unattached PEG and dextran chains on the swelling pressure of the degrading gels. It is found that low molecular weight free chains significantly increase the swelling pressure. However, the contribution of higher molecular weight free chains (M-w > 10kDa) is similar to that of the network chains. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Ghent, Dept Pharmaceut, Lab Gen Biochem & Phys Pharm, B-9000 Ghent, Belgium. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP De Smedt, SC (reprint author), Univ Ghent, Dept Pharmaceut, Lab Gen Biochem & Phys Pharm, Harelbekestr 72, B-9000 Ghent, Belgium. EM stefaan.desmedt@Ugent.be FU Intramural NIH HHS NR 42 TC 7 Z9 7 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JUN 7 PY 2007 VL 337 IS 1-2 BP 31 EP 39 DI 10.1016/j.ijpharm.2006.12.022 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180IH UT WOS:000247355800003 PM 17229536 ER PT J AU Wu, J Lee, A Lu, YH Lee, RJ AF Wu, Jun Lee, Alice Lu, Yanhui Lee, Robert J. TI Vascular targeting of doxorubicin using cationic liposomes SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE cationic liposomes; vascular targeting; doxorubicin; cancer ID STERICALLY STABILIZED LIPOSOMES; HUMAN TUMOR XENOGRAFT; MICROVASCULAR PERMEABILITY; STEALTH LIPOSOMES; MICE; EFFICACY; THERAPY; PHARMACOKINETICS; THERAPEUTICS; ACCUMULATION AB Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20 mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. The cationic liposomal DOX showed 10.8 and 9.1 times greater cytotoxicity than control PEGylated liposomal DOX in KB oral carcinoma and L1210 murine lymphocytic leukemia cells, and 7.7- and 6.8-fold greater cytotoxicity compared to control neutral non-PEGylated liposomal DOX, repectively, in these two cell lines. Although cationic liposomal DOX had higher tumor accumulation at 30 min after intravenous administration compared to control liposomes (p < 0.05), DOX uptake of these liposomes at 24 It post-injection was similar to that of PEGylated liposomal DOX (P > 0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L 12 10 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p < 0.01), neutral liposome control (P < 0.01), as well as PEGylated liposomes (p < 0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation. (c) 2007 Elsevier B.V. All rights reserved. C1 Ohio State Univ, Coll Pharm, Dept Pharmaceut, Columbus, OH 43210 USA. Ohio State Univ, NSF Nanoscale Sci & Engn Ctr Affordable Nanoengn, Columbus, OH 43210 USA. Ohio State Univ, NCI, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, 542 LM Parks Hall,500 W 12Th Ave, Columbus, OH 43210 USA. EM lee.1339@osu.edu NR 22 TC 60 Z9 63 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JUN 7 PY 2007 VL 337 IS 1-2 BP 329 EP 335 DI 10.1016/j.ijpharm.2007.01.003 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180IH UT WOS:000247355800038 PM 17275230 ER PT J AU Chanock, SJ Manolio, T Boehnke, M Boerwinkle, E Hunter, DJ Thomas, G Hirschhorn, JN Abecasis, G Altshuler, D Bailey-Wilson, JE Brooks, LD Cardon, LR Daly, M Donnelly, P Fraumeni, JF Freimer, NB Gerhard, DS Gunter, C Guttmacher, AE Guyer, MS Harris, EL Hoh, J Hoover, R Kong, CA Merikangas, KR Morton, CC Palmer, LJ Phimister, EG Rice, JP Roberts, J Rotimi, C Tucker, MA Vogan, KJ Wacholder, S Wijsman, EM Winn, DM Collins, FS AF Chanock, Stephen J. Manolio, Teri Boehnke, Michael Boerwinkle, Eric Hunter, David J. Thomas, Gilles Hirschhorn, Joel N. Abecasis, Goncalo Altshuler, David Bailey-Wilson, Joan E. Brooks, Lisa D. Cardon, Lon R. Daly, Mark Donnelly, Peter Fraumeni, Joseph F., Jr. Freimer, Nelson B. Gerhard, Daniela S. Gunter, Chris Guttmacher, Alan E. Guyer, Mark S. Harris, Emily L. Hoh, Josephine Hoover, Robert Kong, C. Augustine Merikangas, Kathleen R. Morton, Cynthia C. Palmer, Lyle J. Phimister, Elizabeth G. Rice, John P. Roberts, Jerry Rotimi, Charles Tucker, Margaret A. Vogan, Kyle J. Wacholder, Sholom Wijsman, Ellen M. Winn, Deborah M. Collins, Francis S. CA NCI-NHGRI Working Grp Rep TI Replicating genotype-phenotype associations SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON GENETIC-VARIANTS; FACTOR-H POLYMORPHISM; PARKINSON-DISEASE; MACULAR DEGENERATION; PROSTATE-CANCER; CROHNS-DISEASE; DYSBINDIN GENE; RISK LOCUS C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA. Harvard Univ, Sch Med, Childrens Hosp, Broad Inst MIT & Harvard,Cambridge Ctr 7, Boston, MA 02114 USA. Massachusetts Gen Hosp, Broad Inst MIT & Harvard, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Univ Oxford, Oxford OX1 3TG, England. Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA. NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA. Nature, New York, NY 10013 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. DeCode Genet, IS-101 Reykjavik, Iceland. NIMH, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Western Australian Inst Med Res, Nedlands, WA 6009, Australia. Univ Western Australia, Queen Elizabeth II Med Ctr, Nedlands, WA 6009, Australia. New England Journal Med, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Howard Univ, Genet Epidemiol Unit, Natl Human Genome Ctr, Washington, DC 20060 USA. Nature Genet, Cambridge, MA 02141 USA. Univ Washington, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NCI, Epidemiol & Genet Res Program, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov; manoliot@nhgri.nih.gov RI Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Palmer, Lyle/K-3196-2014; Tucker, Margaret/B-4297-2015; OI Altshuler, David/0000-0002-7250-4107; Palmer, Lyle/0000-0002-1628-3055; Bailey-Wilson, Joan/0000-0002-9153-2920; Wijsman, Ellen/0000-0002-2725-6669; Abecasis, Goncalo/0000-0003-1509-1825 NR 81 TC 907 Z9 930 U1 2 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUN 7 PY 2007 VL 447 IS 7145 BP 655 EP 660 DI 10.1038/447655a PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175RI UT WOS:000247030700034 ER PT J AU Rossi, DJ Bryder, D Seita, J Nussenzweig, A Hoeijmakers, J Weissman, IL AF Rossi, Derrick J. Bryder, David Seita, Jun Nussenzweig, Andre Hoeijmakers, Jan Weissman, Irving L. TI Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age SO NATURE LA English DT Article ID LIFE-SPAN; SERIAL TRANSPLANTATION; SELF-RENEWAL; MOUSE MODEL; MICE; TELOMERASE; CANCER; TRANSCRIPTION; DEFECTS; STRESS AB A diminished capacity to maintain tissue homeostasis is a central physiological characteristic of ageing. As stem cells regulate tissue homeostasis, depletion of stem cell reserves and/or diminished stem cell function have been postulated to contribute to ageing(1). It has further been suggested that accumulated DNA damage could be a principal mechanism underlying age-dependent stem cell decline(2). We have tested these hypotheses by examining haematopoietic stem cell reserves and function with age in mice deficient in several genomic maintenance pathways including nucleotide excision repair(3,4), telomere maintenance(5,6) and non-homologous end-joining(7,8). Here we show that although deficiencies in these pathways did not deplete stem cell reserves with age, stem cell functional capacity was severely affected under conditions of stress, leading to loss of reconstitution and proliferative potential, diminished self-renewal, increased apoptosis and, ultimately, functional exhaustion. Moreover, we provide evidence that endogenous DNA damage accumulates with age in wild-type stem cells. These data are consistent with DNA damage accrual being a physiological mechanism of stem cell ageing that may contribute to the diminished capacity of aged tissues to return to homeostasis after exposure to acute stress or injury. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol, NIH, Bethesda, MD 20892 USA. Erasmus MC, MGC CBG Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. RP Rossi, DJ (reprint author), Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. EM drossi@stanford.edu OI Seita, Jun/0000-0002-3008-3615 NR 35 TC 534 Z9 550 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 7 PY 2007 VL 447 IS 7145 BP 725 EP U15 DI 10.1038/nature05862 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175RI UT WOS:000247030700046 PM 17554309 ER PT J AU Kruhlak, M Crouch, EE Orlov, M Montano, C Gorski, SA Nussenzweig, A Misteli, T Phair, RD Casellas, R AF Kruhlak, Michael Crouch, Elizabeth E. Orlov, Marika Montano, Carolina Gorski, Stanislaw A. Nussenzweig, Andre Misteli, Tom Phair, Robert D. Casellas, Rafael TI The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaks SO NATURE LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-DAMAGE; CELLS; PHOSPHORYLATION; COMPONENTS; NUCLEOLUS; STRESS; GENOME; VIVO AB DNA lesions interfere with DNA and RNA polymerase activity. Cyclobutane pyrimidine dimers and photoproducts generated by ultraviolet irradiation cause stalling of RNA polymerase II, activation of transcription-coupled repair enzymes, and inhibition of RNA synthesis(1,2). During the S phase of the cell cycle, collision of replication forks with damaged DNA blocks ongoing DNA replication while also triggering a biochemical signal that suppresses the firing of distant origins of replication(3,4). Whether the transcription machinery is affected by the presence of DNA double-strand breaks remains a long-standing question. Here we monitor RNA polymerase I ( Pol I) activity in mouse cells exposed to genotoxic stress and show that induction of DNA breaks leads to a transient repression in Pol I transcription. Surprisingly, we find Pol I inhibition is not itself the direct result of DNA damage but is mediated by ATM kinase activity and the repair factor proteins NBS1 ( also known as NLRP2) and MDC1. Using live-cell imaging, laser micro-irradiation, and photobleaching technology we demonstrate that DNA lesions interfere with Pol I initiation complex assembly and lead to a premature displacement of elongating holoenzymes from ribosomal DNA. Our data reveal a novel ATM/NBS1/MDC1-dependent pathway that shuts down ribosomal gene transcription in response to chromosome breaks. C1 NIAMS, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Integrat Bioinformat, Los Altos, CA 94024 USA. RP Casellas, R (reprint author), NIAMS, NIH, Bethesda, MD 20892 USA. EM casellar@mail.nih.gov FU Intramural NIH HHS NR 22 TC 110 Z9 114 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 7 PY 2007 VL 447 IS 7145 BP 730 EP U16 DI 10.1038/nature05842 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175RI UT WOS:000247030700047 PM 17554310 ER PT J AU Reiman, EM Webster, JA Myers, AJ Hardy, J Dunckley, T Zismann, VL Joshipura, KD Pearson, JV Hu-Lince, D Huentelman, MJ Craig, DW Coon, KD Liang, WS Herbert, RH Beach, T Rohrer, KC Zhao, AS Leung, D Bryden, L Marlowe, L Kaleem, M Mastroeni, D Grover, A Heward, CB Ravid, R Rogers, J Hutton, ML Melquist, S Petersen, RC Alexander, GE Caselli, RJ Kukull, W Papassotiropoulos, A Stephan, DA AF Reiman, Eric M. Webster, Jennifer A. Myers, Amanda J. Hardy, John Dunckley, Travis Zismann, Victoria L. Joshipura, Keta D. Pearson, John V. Hu-Lince, Diane Huentelman, Matthew J. Craig, David W. Coon, Keith D. Liang, Winnie S. Herbert, RiLee H. Beach, Thomas Rohrer, Kristen C. Zhao, Alice S. Leung, Doris Bryden, Leslie Marlowe, Lauren Kaleem, Mona Mastroeni, Diego Grover, Andrew Heward, Christopher B. Ravid, Rivka Rogers, Joseph Hutton, Michael L. Melquist, Stacey Petersen, Ron C. Alexander, Gene E. Caselli, Richard J. Kukull, Walter Papassotiropoulos, Andreas Stephan, Dietrich A. TI GAB2 alleles modify Alzheimer's risk in APOE epsilon 4 carriers SO NEURON LA English DT Article ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E; HIPPOCAMPAL VOLUME; DISEASE; GENOME; GENE; ASSOCIATION; POPULATION; GENOTYPE; BRAIN AB The apolipoprotein E (APOE) epsilon 4 allele is the best established genetic risk factor for late-onset Alzheimer's disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In epsilon 4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB-associated binding protein 2 (GAB2) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81-14.69), which interacts with APOE epsilon 4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon 4 carriers and influences Alzheimer's neuropathology. C1 Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA. Banner Alzheimers Inst, Phoenix, AZ 85006 USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Inst Neurol, Reta Lila Weston Labs, Dept Mol Neurosci, London WC1N 3BG, England. St Josephs Hosp, Div Thorac Oncol Res, Phoenix, AZ 85013 USA. Sun Hlth Res Inst, Sun City, AZ 85351 USA. Kronos Sci Lab, Phoenix, AZ 85016 USA. Dutch Royal Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85281 USA. Mayo Clin, Dept Neurol, Scottsdale, AZ 85259 USA. Univ Basel, Biozentrum, Div Mol Psychol & Life Sci Training Facil, Basel, Switzerland. Univ Washington, Natl Alzheimers Coordinating Ctr, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Arizona Alzheimers Consortium, Phoenix, AZ 85006 USA. RP Reiman, EM (reprint author), Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA. EM eric.reiman@bannerhealth.com; dstephan@tgen.org RI Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pearson, John/F-2249-2011; Leung, Doris/R-5447-2016 OI Myers, Amanda/0000-0002-3100-9396; Pearson, John/0000-0003-0904-4598; Leung, Doris/0000-0002-2558-7798 FU Intramural NIH HHS; Medical Research Council [G0701075]; NHLBI NIH HHS [U01HL084744]; NIA NIH HHS [R01 AG23193, AG025688, K01 AG024079, K01 AG024079-01A2, K01 AG024079-02, K01AG024079, P30 AG010161, P30 AG012300, P30 AG013846, P30 AG01542, P30 AG017824, P30 AG019610, P30 AG10161, P30 AG13846, P30 AG19610, P30-AG12300, P50 AG 05681, P50 AG005128, P50 AG005134, P50 AG005136, P50 AG005142, P50 AG005144, P50 AG005146, P50 AG005681, P50 AG008671, P50 AG008702, P50 AG016570, P50 AG016574, P50 AG025688, P50 AG025711, P50 AG05128, P50 AG05134, P50 AG05136, P50 AG05142, P50 AG05144, P50 AG05146, P50 AG08671, P50 AG08702, P50 AG16570, P50 AG16574, P50 AG17824, P50 AG25711, R01 AG023193, R21 AG029576, R21 AG029576-01, U01 AG016976]; NIMH NIH HHS [P50 MH060451, R01 MH60451]; NINDS NIH HHS [P50 NS039764, R01 NS39764, U24 NS051872, U24NS051872] NR 32 TC 308 Z9 320 U1 5 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 7 PY 2007 VL 54 IS 5 BP 713 EP 720 DI 10.1016/j.neuron.2007.05.022 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 179ZQ UT WOS:000247329900006 PM 17553421 ER PT J AU Lipsky, PE AF Lipsky, Peter E. TI Why does rheumatoid arthritis involve the joints? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NR 5 TC 14 Z9 17 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2007 VL 356 IS 23 BP 2419 EP 2420 DI 10.1056/NEJMcibr070846 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 175QY UT WOS:000247029300015 PM 17554126 ER PT J AU Snyder, DJ Miller, FG Rosenstein, DL AF Snyder, Deborah J. Miller, Franklin G. Rosenstein, Donald L. TI Solicitation of deceased and living organ donors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Snyder, DJ (reprint author), NIMH, Bethesda, MD 20892 USA. EM snyderd@intra.nimh.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2007 VL 356 IS 23 BP 2427 EP 2427 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 175QY UT WOS:000247029300031 PM 17563924 ER PT J AU Knapp, S Abdo, M Ajayi, K Huhn, RA Emge, TJ Kim, EJ Hanover, JA AF Knapp, Spencer Abdo, Mohannad Ajayi, Kehinde Huhn, Richard A. Emge, Thomas J. Kim, Eun Ju Hanover, John A. TI Tautomeric modification of GlcNAc-thiazoline SO ORGANIC LETTERS LA English DT Article ID O-GLCNACASE; BETA-HEXOSAMINIDASE; N-ACETYLGLUCOSAMINE; TAY-SACHS; STRUCTURAL INSIGHTS; NAG-THIAZOLINE; INHIBITOR; PUGNAC; SUBSTRATE; GLUCOSAMINIDASE AB The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (X-n = D-3, F, N-3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered. C1 Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Knapp, S (reprint author), Rutgers State Univ, Dept Chem & Chem Biol, 610 Taylor Rd, Piscataway, NJ 08854 USA. EM spencer.knapp@rutgers.edu FU NIAID NIH HHS [AI055760] NR 34 TC 30 Z9 31 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUN 7 PY 2007 VL 9 IS 12 BP 2321 EP 2324 DI 10.1021/ol0706814 PG 4 WC Chemistry, Organic SC Chemistry GA 172ZF UT WOS:000246842600019 PM 17508759 ER PT J AU Pokorski, JK Jenkins, LMM Feng, HQ Durell, SR Bai, YW Appella, DH AF Pokorski, Jonathan K. Jenkins, Lisa M. Miller Feng, Hanqiao Durell, Stewart R. Bai, Yawen Appella, Daniel H. TI Introduction of a triazole amino acid into a peptoid oligomer induces turn formation in aqueous solution SO ORGANIC LETTERS LA English DT Article ID BETA-HAIRPIN STABILITY; AROMATIC SIDE-CHAINS; SECONDARY STRUCTURE; PEPTIDES; CYCLOADDITION; ANALOGS; ALKYNES; DESIGN; AZIDES AB Peptoids are a non-natural class of oligomers that are composed of repeating N-substituted glycine units and are capable of folding into helices that mimic peptide structure and function. In this letter, we report the concise synthesis of a 1,5-substituted triazole amino acid (Tzl) and its subsequent incorporation into a short peptoid. The Tzl amino acid was shown to induce turn formation in aqueous solution, thus expanding the structural repertoire available to peptoid chemists. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Biochem & Mol Biol Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Pokorski, JK (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov OI Pokorski, Jonathan/0000-0001-5869-6942 FU Intramural NIH HHS NR 22 TC 63 Z9 63 U1 1 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUN 7 PY 2007 VL 9 IS 12 BP 2381 EP 2383 DI 10.1021/ol070817y PG 3 WC Chemistry, Organic SC Chemistry GA 172ZF UT WOS:000246842600034 PM 17506576 ER PT J AU Molina, GA Watkins, SC Tsang, M AF Molina, Gabriela A. Watkins, Simon C. Tsang, Michael TI Generation of FGF reporter transgenic zebrafish and their utility in chemical screens SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; MIDBRAIN-HINDBRAIN BOUNDARY; IN-VIVO; FACTOR RECEPTOR; SMALL-MOLECULE; CELL-PROLIFERATION; INDUCED ANTAGONIST; KINASE INHIBITOR; KUPFFERS VESICLE; FACTORS ERM AB Background: Fibroblast Growth Factors (FGFs) represent a large family of secreted proteins that are required for proper development and physiological processes. Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and lethality. A key to understanding the precise role for these factors is to determine their spatial and temporal activity during embryogenesis. Results: Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3) is controlled by FGF signalling throughout development. The Dusp6 promoter was isolated from zebrafish and used to drive expression of destabilized green fluorescent protein (d2EGFP) in transgenic embryos (Tg(Dusp6:d2EGFP)). Expression of d2EGFP is initiated as early as 4 hours post-fertilization (hpf) within the future dorsal region of the embryo, where fgf3 and fgf8 are initially expressed. At later stages, d2EGFP is detected within structures that correlate with the expression of Fgf ligands and their receptors. This includes the mid-hindbrain boundary (MHB), pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's vesicle. The expression of d2EGFP is under the control of FGF signalling as treatment with FGF Receptor (FGFR) inhibitors results in the suppression of d2EGFP expression. In a pilot screen of commercially available small molecules we have evaluated the effectiveness of the transgenic lines to identify specific FGF inhibitors within the class of indolinones. These compounds were counter screened with the transgenic line Tg(FliI: EGFP)(yI), that serves as an indirect read-out for Vascular Endothelial Growth Factor (VEGF) signalling in order to determine the specificity between related receptor tyrosine kinases (RTKs). From these assays it is possible to determine the specificity of these indolinones towards specific RTK signalling pathways. This has enabled the identification of compounds that can block specifically the VEGFR or the FGFR signalling pathway. Conclusion: The generation of transgenic reporter zebrafish lines has allowed direct visualization of FGF signalling within the developing embryo. These FGF reporter transgenic lines provide a tool to screen for specific compounds that can distinguish between two conserved members of the RTK family. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Ctr Biol Imaging, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. NICHD, NIH, LMG, Bethesda, MD 20892 USA. RP Tsang, M (reprint author), Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. EM gam20@pitt.edu; swatkins@pitt.edu; tsang@mgb.pitt.edu RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 FU NCRR NIH HHS [1U54 RR02241-01] NR 73 TC 63 Z9 65 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD JUN 6 PY 2007 VL 7 AR 62 DI 10.1186/1471-213X-7-62 PG 14 WC Developmental Biology SC Developmental Biology GA 185ZK UT WOS:000247748700001 PM 17553162 ER PT J AU Fontaine, F Bolton, E Borodina, Y Bryant, SH AF Fontaine, Fabien Bolton, Evan Borodina, Yulia Bryant, Stephen H. TI Fast 3D shape screening of large chemical databases through alignment-recycling SO CHEMISTRY CENTRAL JOURNAL LA English DT Article ID MOLECULAR SIMILARITY; GAUSSIAN DESCRIPTION; IDENTIFICATION; PERFORMANCE; DESIGN AB Background: Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes. Results: Using a dataset of more than one million PubChem compounds of limited size (< 28 heavy atoms) and flexibility (< 6 rotatable bonds), we obtained a set of a few thousand diverse structures covering entirely the 3D shape space of the conformers of the dataset. Transformation matrices gathered from the overlays between these diverse structures and the 3D conformer dataset allowed us to drastically (100-fold) reduce the CPU time required for shape overlay. The alignment-recycling heuristic produces results consistent with de novo alignment calculation, with better than 80% hit list overlap on average. Conclusion: Overlay-based 3D methods are computationally demanding when searching large databases. Alignment-recycling reduces the CPU time to perform shape similarity searches by breaking the alignment problem into three steps: selection of diverse shapes to describe the database shape-space; overlay of the database conformers to the diverse shapes; and non-optimized overlay of query and database conformers using common reference shapes. The precomputation, required by the first two steps, is a significant cost of the method; however, once performed, querying is two orders of magnitude faster. Extensions and variations of this methodology, for example, to handle more flexible and larger small-molecules are discussed. C1 [Fontaine, Fabien; Bolton, Evan; Borodina, Yulia; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ffontaine@gmail.com; bolton@ncbi.nlm.nih.gov; borodina@ncbi.nlm.nih.gov; sbryant@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX The authors are thankful to Anthony Nicholls for constructive comments, Wolf-D. Ihlenfeldt who helped write CACTVS scripts, and OpenEye Scientific Software for intuitive insights and useful 3D tools. This research was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 26 TC 12 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-153X J9 CHEM CENT J JI Chem. Cent. J. PD JUN 6 PY 2007 VL 1 AR 12 DI 10.1186/1752-153X-1-12 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA 345WJ UT WOS:000259028000001 PM 17880744 ER PT J AU Hasler, G Fromm, S Alvarez, RP Luckenbaugh, DA Drevets, WC Grillon, C AF Hasler, Gregor Fromm, Stephen Alvarez, Ruben P. Luckenbaugh, David A. Drevets, Wayne C. Grillon, Christian TI Cerebral blood flow in immediate and sustained anxiety SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fear; anxiety; amygdala; hippocampus; context; cerebral blood flow ID MEDIAL PREFRONTAL CORTEX; FEAR-POTENTIATED STARTLE; CONTEXTUAL FEAR; ANIMAL-MODELS; HUMAN BRAIN; AMYGDALA; ACTIVATION; STRESS; RESPONSES; LESIONS AB The goal of this study was to compare cerebral blood flow (CBF) changes associated with phasic cued fear versus those associated with sustained contextual anxiety. Positron emission tomography images of CBF were acquired using [O-15] H(2)0 in 17 healthy human subjects as they anticipated unpleasant electric shocks that were administered predictably (signaled by a visual cue) or unpredictably (threatened by the context). Presentation of the cue in either threat condition was associated with increased CBF in the left amygdala. A cue that specifically predicted the shock was associated with CBF increases in the ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left insula, and bilateral putamen. The sustained threat context increased CBF in the right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This study showed distinct neuronal networks involved in cued fear and contextual anxiety underlying the importance of this distinction for studies on the pathophysiology of anxiety disorders. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Psychiat Univ Hosp, CH-8091 Zurich, Switzerland. RP Hasler, G (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, 15K N Dr,room 200,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Intramural NIH HHS [Z01 MH002798-06] NR 45 TC 81 Z9 81 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 6 PY 2007 VL 27 IS 23 BP 6313 EP 6319 DI 10.1523/JNEUROSCI.5369-06.2007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 175YG UT WOS:000247049300027 PM 17554005 ER PT J AU Marcus, PM Harris, A Offord, KP AF Marcus, Pamela M. Harris, Ann Offord, Kenneth P. TI Re: Extended lung cancer incidence follow-up in the Mayo lung project and overdiagnosis - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20895 USA. Mayo Clin, Survey Res Ctr, Div Canc Prevent, Biometry Res Grp, Rochester, MN 20895 USA. RP Marcus, PM (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, 6130 Execut Blvd,Ste 3131, Bethesda, MD 20895 USA. EM pm145q@nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 6 PY 2007 VL 99 IS 11 BP 899 EP 899 DI 10.1093/jnci/djk204 PG 1 WC Oncology SC Oncology GA 177ZK UT WOS:000247190800016 ER PT J AU Bihl, F Castelli, D Marincola, F Dodd, RY Brander, C AF Bihl, Florian Castelli, Damiano Marincola, Francesco Dodd, Roger Y. Brander, Christian TI Transfusion-transmitted infections SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID WEST-NILE-VIRUS; HEPATITIS-B-VIRUS; NUCLEIC-ACID TECHNOLOGY; PARVOVIRUS B19 TRANSMISSION; CREUTZFELDT-JAKOB-DISEASE; INACTINE PEN110 CHEMISTRY; PLASTIC CULTURE BOTTLES; SURFACE-ANTIGEN GENE; BLOOD-TRANSFUSION; PATHOGEN INACTIVATION AB Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens. C1 Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. Swiss Red Cross Blood Transfus Serv So Switzerlan, Lugano, Switzerland. NIH Clin Ctr, HLA Typing Lab, Bethesda, MD USA. Amer Red Cross, Holland Lab, Rockville, MD USA. RP Bihl, F (reprint author), Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM f.bihl@mac.com; damiano.castelli@eoc.ch; FMarincola@cc.nih.gov; Dodd@usa.redcross.org OI Brander, Christian/0000-0002-0548-5778 NR 145 TC 46 Z9 50 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 6 PY 2007 VL 5 AR 25 DI 10.1186/1479-5876-5-25 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 185CE UT WOS:000247688100001 PM 17553144 ER PT J AU Cohen, JI Hohman, P Preuss, JC Li, L Fischer, SH Fedorko, DP AF Cohen, Jeffrey I. Hohman, Patricia Preuss, Jeanne C. Li, Li Fischer, Steven H. Fedorko, Daniel P. TI Detection of vaccinia virus DNA, but not infectious virus, in the blood of smallpox vaccine recipients SO VACCINE LA English DT Article DE smallpox vaccine; vaccinia virus; poxvirus ID VIREMIA; ABSENCE AB The authors of a recent study [Savona MR, Dela Cruz WP, Jones MS, Thornton JA, Xia D, Hadfield TL, et al. Detection of vaccinia DNA in the blood following smallpox vaccination. JAMA 2006; 295:1898-1900] suggested that the duration of deferral for blood donations by smallpox vaccinees should be extended, based on detection of vaccinia virus DNA in five blood samples by polymerase chain reaction (PCR) and the potential for viremia. We found that 4 of 202 blood specimens (from 3 of 27 smallpox vaccinees) were positive for vaccinia virus DNA by PCR; none were positive for virus by culture. Throat swabs were negative by PCR and culture. Thus, while some blood specimens contained vaccinia virus DNA, infectious virus was not detected. Current guidelines for deferral of blood donation in vaccinees seem appropriate. Published by Elsevier Ltd. C1 NIH, NIAID, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000923-05] NR 12 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 6 PY 2007 VL 25 IS 23 BP 4571 EP 4574 DI 10.1016/j.vaccine.2007.03.044 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 177BV UT WOS:000247129500010 PM 17493714 ER PT J AU Lerner, A Bagic, A Boudreau, EA Hanakawa, T Pagan, F Mari, Z Bara-Jimenez, W Aksu, M Garraux, G Simmons, JM Sato, S Murphy, DL Hallett, M AF Lerner, A. Bagic, A. Boudreau, E. A. Hanakawa, T. Pagan, F. Mari, Z. Bara-Jimenez, W. Aksu, M. Garraux, G. Simmons, J. M. Sato, S. Murphy, D. L. Hallett, M. TI Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome SO NEUROLOGY LA English DT Article ID OLD-WORLD MONKEY; MOTOR CORTEX; FUNCTIONAL NEUROANATOMY; BASAL GANGLIA; CEREBELLUM; DISORDER; MRI; NUCLEI; INSULA; BRAIN AB Objective: To identify brain regions generating tics in patients with Tourette syndrome using sleep as a baseline. Methods: We used [O-15]H2O PET to study nine patients with Tourette syndrome and nine matched control subjects. For patients, conditions included tic release states and sleep stage 2; and for control subjects, rest states and sleep stage 2. Results: Our study showed robust activation of cerebellum, insula, thalamus, and putamen during tic release. Conclusion: The network of structures involved in tics includes the activated regions and motor cortex. The prominent involvement of cerebellum and insula suggest their involvement in tic initiation and execution. C1 NIMH, Mol Imaging Branch, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Lerner, A (reprint author), NIMH, Mol Imaging Branch, Neuropsychol Lab, NIH, 31 Ctr Dr MSC 2035,Bldg 31,Room B2-B34, Bethesda, MD 20892 USA. EM lernera@mail.nih.gov RI Garraux, Gaetan/G-9050-2011 FU Intramural NIH HHS NR 43 TC 43 Z9 45 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 5 PY 2007 VL 68 IS 23 BP 1979 EP 1987 DI 10.1212/01.wnl.0000264417.18604.12 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 174UY UT WOS:000246969500004 PM 17548547 ER PT J AU DiNapoli, JM Kotelkin, A Yang, L Elankumaran, S Murphy, BR Samal, SK Collins, PL Bukreyev, A AF DiNapoli, Joshua M. Kotelkin, Alexander Yang, Lijuan Elankumaran, Subbiah Murphy, Brian R. Samal, Siba K. Collins, Peter L. Bukreyev, Alexander TI Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE severe acute respiratory syndrome (SARS); respiratory tract; monkey ID ACUTE RESPIRATORY SYNDROME; CORONAVIRUS SPIKE PROTEIN; SARS CORONAVIRUS; NEUTRALIZING ANTIBODIES; PROTECTIVE EFFICACY; RHESUS-MONKEYS; AFRICAN-GREEN; MICE; IMMUNOGENICITY; IMMUNITY AB The international outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in 2002-2003 highlighted the need to develop pretested human vaccine vectors that can be used in a rapid response against newly emerging pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is highly attenuated in primates, as a topical respiratory vaccine vector with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to express the SARSCoV spike S glycoprotein, the viral neutralization and major protective antigen, from an added transcriptional unit. African green monkeys immunized through the respiratory tract with two doses of the vaccine developed a titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary response observed in animals that have been immunized with a different experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals immunized with NDV expressing S were challenged with a high dose of SARS-CoV, direct viral assay of lung tissues taken by necropsy at the peak of viral replication demonstrated a 236- or 1,102-fold (depending on the NDV vector construct) mean reduction in pulmonary SARS-CoV titer compared with control animals. NDV has the potential for further development as a pretested, highly attenuated, intranasal vector to be available for expedited vaccine development for humans, who generally lack preexisting immunity against NDV. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. RP Bukreyev, A (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr,Room 6505, Bethesda, MD 20892 USA. EM ab176v@nih.gov RI Subbiah, Elankumaran/E-9277-2010 OI Subbiah, Elankumaran/0000-0003-4135-9477 FU Intramural NIH HHS NR 45 TC 60 Z9 64 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 5 PY 2007 VL 104 IS 23 BP 9788 EP 9793 DI 10.1073/pnas.0703584104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176VX UT WOS:000247114100045 PM 17535926 ER PT J AU Muhs, A Hickman, DT Pihlgren, M Chuard, N Giriens, V Meerschman, C van der Auwera, I van Leuven, F Sugawara, M Weingertner, MC Bechinger, B Greferath, R Kolonko, N Nagel-Steger, L Riesner, D Brady, RO Pfeifer, A Nicolau, C AF Muhs, Andreas Hickman, David T. Pihlgren, Maria Chuard, Nathalie Giriens, Valerie Meerschman, Carine van der Auwera, Ingrid van Leuven, Fred Sugawara, Masae Weingertner, Marie-Catherine Bechinger, Burkhard Greferath, Ruth Kolonko, Nadine Nagel-Steger, Luitgard Riesner, Detlev Brady, Roscoe O. Pfeifer, Andrea Nicolau, Claude TI Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's disease; beta-amyloid; vaccine ID DISEASE MOUSE MODEL; SOLID-STATE NMR; A-BETA BURDEN; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; MEMORY DEFICITS; SECONDARY STRUCTURE; STRUCTURAL-CHANGES; GENE VACCINATION; BRAIN AB We investigated the therapeutic effects of two different versions of A beta(1-15 (16)) liposome-based vaccines. inoculation of APP-V717IxPS-1 (APPxPS-1) double-transgenic mice with tetrapalmitoylated amyloid 1-15 peptide (palmA beta 1-15), or with amyloid 1-16 peptide (PEG-A beta(1-16)) linked to a polyethyleneglycol spacer at each end, and embedded within a liposome membrane, elicited fast immune responses with identical binding epitopes. PaImA beta(1-15) liposomal vaccine elicited an immune response that restored the memory defect of the mice, whereas that of PEG-A beta(1-16) had no such effect. Immunoglobulins that were generated were predominantly of the IgG class with paimA beta(1-15), whereas those elicited by PEG-A beta(1-16) were primarily of the IgM class. The IgG subclasses of the antibodies generated by both vaccines were mostly IgG2b indicating noninflammatory Th2 isotype. CID and NMR revealed predominantly P-sheet conformation of palmA beta(1-15) and random coil of PEG-A beta(1-16). We conclude that the association with liposomes induced a variation of the immunogenic structures and thereby different immunogenicities. This finding supports the hypothesis that Alzheimer's disease is a "conformational" disease, implying that antibodies against amyloid sequences in the beta-sheet conformation are preferred as potential therapeutic agents. C1 NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. Univ Dusseldorf, Inst Biophys Chem, D-40225 Dusseldorf, Germany. Univ Strasbourg 1, Inst Sci & Ingn Supramol, F-67083 Strasbourg, France. Katholieke Univ Leuven, Expt Genet Grp, B-3000 Louvain, Belgium. reMYND nv, B-3000 Louvain, Belgium. Ecole Polytech Fed Lausanne, AC Immune, PSE B, CH-1015 Lausanne, Switzerland. RP Brady, RO (reprint author), NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. EM rb57v@nih.gov; claude.nicolau@acimrnune.com OI Nagel-Steger, Luitgard/0000-0001-5232-2149 NR 45 TC 80 Z9 82 U1 3 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 5 PY 2007 VL 104 IS 23 BP 9810 EP 9815 DI 10.1073/pnas.0703137104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176VX UT WOS:000247114100049 PM 17517595 ER PT J AU Gautam, R Carter, AC Katz, N Butler, IF Barnes, M Hasegawa, A Ratterree, M Silvestri, G Marx, PA Hirsch, VM Pandrea, I Apetrei, C AF Gautam, Rajeev Carter, Anders Chase Katz, Nathalia Butler, Isolde F. Barnes, Mary Hasegawa, Atsuhiko Ratterree, Marion Silvestri, Guido Marx, Preston A. Hirsch, Vanessa M. Pandrea, Ivona Apetrei, Cristian TI In vitro characterization of primary SIVsmm isolates belonging to different lineages. In vitro growth on rhesus macaque cells is not predictive for in vivo replication in rhesus macaques SO VIROLOGY LA English DT Article DE SIVsmm; rhesus macaque; in vitro replication; sooty mangabey; pathogenesis ID SIMIAN IMMUNODEFICIENCY VIRUS; INFECTED SOOTY MANGABEYS; RED-CAPPED MANGABEY; NATURAL INFECTION; VIRAL LOAD; CERCOCEBUS-ATYS; WEST-AFRICA; GENETIC-CHARACTERIZATION; DISEASE PROGRESSION; COTE-DIVOIRE AB We report in vitro characterization of 11 SIVsmm strains of six lineages co-circulating in naturally infected sooty mangabeys (SMs) from US Primate Centers and showed no major differences in the in vitro replication pattern between different SIVsmm lineages. Primary SIVsmm isolates utilized CCR5 and Bonzo co-receptors in vitro. SIVsmm growth in human T cell lines was isolate-, not lineage-specific, with poor replication on Molt4-Clone8, CEMss and PM I cells and better replication on MT2, SupT1 and CEMx174 cells. All primary SIVsmm isolates replicated on SM and human PBMCs. In vitro replication in macaques varied widely, with moderate to high replication in pig-tailed macaque PBMCs, enhanced by CD8(+) T cell depletion, and highly variable replication on rhesus macaque (Rh) PBMCs. Primary SIVsmm isolates replicated in Rh monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). In vivo, SIVsmm isolates replicated at high levels in all SIVsmm-infected Rh. The poor in vitro replication of primary SIVsmm isolates in Rh cells did not correlate with in vivo replication, emphasizing the value of in vivo studies. (C) 2007 Elsevier Inc. All rights reserved. C1 Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA. Tulane Natl Primate Res Ctr, Div Immunol, Covington, LA 70433 USA. Univ Penn, Clin Virol Lab, Philadelphia, PA 19107 USA. Tulane Univ, Dept Trop Med, Sch Publ Hlth, New Orleans, LA 70112 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Tulane Univ, Sch Med, Dept Pathol, New Orleans, LA 70112 USA. RP Apetrei, C (reprint author), Tulane Natl Primate Res Ctr, Div Microbiol, 18703 3 Rivers Rd, Covington, LA 70433 USA. EM capetrei@tulane.edu FU NCRR NIH HHS [P51 RR000164-440155, C06 RR12112, G20 RR013466, G20 RR016930, G20 RR018397, G20 RR019628, P20 RR020159, P20 RR020159-037539, P51 RR000164, P51 RR000164-430206, P51 RR000164-455211, RR013466, RR018397, RR019628, RR05169]; NIAID NIH HHS [R01 AI064066, R01 AI065325, R01 AI065325-01A1] NR 72 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2007 VL 362 IS 2 BP 257 EP 270 DI 10.1016/j.virol.2006.12.037 PG 14 WC Virology SC Virology GA 172GJ UT WOS:000246791800002 PM 17303205 ER PT J AU Rutigliano, JA Ruckwardt, TJ Martin, JE Graham, BS AF Rutigliano, John A. Ruckwardt, Tracy J. Martin, Julie E. Graham, Barney S. TI Relative dominance of epitope-specific CD8+T cell responses in an F1 hybrid mouse model of respiratory syncytial virus infection SO VIROLOGY LA English DT Article DE RSV; CD8+CTL; epitope; mice; immunodominance ID INFLUENZA-A VIRUS; EFFECTOR T-CELLS; LYMPHOCYTIC CHORIOMENINGITIS; HYBRID RESISTANCE; MICE; IMMUNODOMINANCE; EXPRESSION; CONTRACTION; PERSISTENCE; COMPETITION AB CD8+ cytotoxic T lymphocytes are key effectors of adaptive immunity for the control of virus infections. Epitope-specific responses are hierarchical and the rules for dominance are not well defined. Here we show that the H2-K-d-restricted RSV M2(82-90) (K(d)M2(82-90)) epitope dominates the H2-D-b-restricted RSV M187-195 ((DM)-M-b 187-195) epitope and influences epitope-specific effector function in the acute and memory phases of the immune response to primary RSV infection in H-2(b/d) hybrid mice. The hybrid mouse model provides a system to define rules of epitope hierarchy and better understand how antigen presentation and epitope competition affect the phenotype of effector and memory T cells. Published by Elsevier Inc. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU Intramural NIH HHS [Z01 AI005027-06] NR 31 TC 22 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2007 VL 362 IS 2 BP 314 EP 319 DI 10.1016/j.virol.2006.12.023 PG 6 WC Virology SC Virology GA 172GJ UT WOS:000246791800007 PM 17275872 ER PT J AU van Zeijl, L Ponsioen, B Giepmans, BNG Ariaens, A Postma, FR Varnai, P Balla, T Divecha, N Jalink, K Moolenaar, WH AF van Zeijl, Leonie Ponsioen, Bas Giepmans, Ben N. G. Ariaens, Aafke Postma, Friso R. Varnai, Peter Balla, Tamas Divecha, Nullin Jalink, Kees Moolenaar, Wouter H. TI Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-CELL COMMUNICATION; INTERCELLULAR COMMUNICATION; PROTEIN CONNEXIN-43; PHOSPHOLIPASE-C; LIVING CELLS; ION CHANNELS; WOUND REPAIR; PHOSPHORYLATION; ACTIVATION; RECEPTORS AB Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5] P-2) from the plasma membrane. Knockdown of phospholipase C beta 3 (PLC beta 3) inhibits PtdIns(4,5) P2 hydrolysis and keeps Cx43 channels open after receptor activation. Using a translocatable 5-phosphatase, we show that PtdIns(4,5) P2 depletion is sufficient to close Cx43 channels. When PtdIns(4,5) P2 is overproduced by PtdIns(4)P 5-kinase, Cx43 channel closure is impaired. We. nd that the Cx43 binding partner zona occludens 1 (ZO-1) interacts with PLC beta 3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5) P-2-hydrolyzing receptors to inhibit cell-cell communication, but not for receptor PLC coupling. Our results show that PtdIns(4,5) P-2 is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLC beta 3 and Cx43 into a signaling complex to allow regulation of cell-cell communication by localized changes in PtdIns(4,5) P2. C1 Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands. Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Moolenaar, WH (reprint author), Netherlands Canc Inst, Div Cellular Biochem, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM k.jalink@nki.nl; w.moolenaar@nki.nl RI Giepmans, Ben/R-4564-2016; OI Giepmans, Ben/0000-0001-5105-5915; Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS NR 62 TC 60 Z9 62 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 4 PY 2007 VL 177 IS 5 BP 881 EP 891 DI 10.1083/jcb.200610144 PG 11 WC Cell Biology SC Cell Biology GA 176GK UT WOS:000247072700013 PM 17535964 ER PT J AU Dyer, KD Schellens, IMM Bonville, CA Martin, BV Domachowske, JB Rosenberg, HF AF Dyer, Kimberly D. Schellens, Ingrid M. M. Bonville, Cynthia A. Martin, Brittany V. Domachowske, Joseph B. Rosenberg, Helene F. TI Efficient replication of pneumonia virus of mice (PVM) in a mouse macrophage cell line SO VIROLOGY JOURNAL LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; INFECTION IN-VIVO; PNEUMOVIRUS INFECTION; ALVEOLAR MACROPHAGES; INFLAMMATORY PROTEIN-1-ALPHA; RAT COLONIES; RESPONSES; BRONCHIOLITIS; PATHOGENESIS; MODEL AB Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia. However, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to PVM infection. We have evaluated several rodent and primate cell lines for susceptibility to PVM infection, and detected highest virus titers from infection of the mouse monocyte-macrophage RAW 264.7 cell line. Additionally, virus replication in RAW 264.7 cells induces the synthesis and secretion of proinflammatory cytokines relevant to respiratory virus disease, including tumor necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), macrophage inflammatory proteins I alpha and I beta (MIP-I alpha and MIP-I beta) and the functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP-2). Identification and characterization of a rodent cell line that supports the replication of PVM and induces the synthesis of disease-related proinflammatory mediators will facilitate studies of molecular mechanisms of viral pathogenesis that will complement and expand on findings from mouse model systems. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA. Univ Utrecht, Med Ctr, Dept Immunol, NL-3508 TC Utrecht, Netherlands. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80206 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kdyer@niaid.nih.gov; I.Schellens@umcutrecht.nl; bonvillc@upstate.edu; Brittany.Martin@UCHSC.edu; domachoj@upstate.edu; hrosenberg@niaid.nih.gov NR 29 TC 13 Z9 13 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD JUN 4 PY 2007 VL 4 AR 48 DI 10.1186/1743-422X-4-48 PG 4 WC Virology SC Virology GA 182SA UT WOS:000247523100002 PM 17547763 ER PT J AU Kuzmiak, CM Pisano, ED Chung, Y Britt, GG Burns, B Cole, E AF Kuzmiak, Cherie M. Pisano, Etta D. Chung, Yeonseung Britt, Gerald G. Burns, Barry Cole, Elodia TI Factors affecting decreasing radiation dose for mammography in North Carolina after 2002: An analysis of food and drug administration annual surveys SO ACADEMIC RADIOLOGY LA English DT Article DE mammography; radiation dose; survey data AB Rationale and Objectives. We sought to determine which factors affected the decrease in average glandular dose recorded at the annual U.S. Food and Drug Administration Mammography Quality Standards Act inspections of mammography equipment in North Carolina from 2002 through 2005. Materials and Methods. Average glandular dose, half-value layer, kVp, equipment age, processing speed, and system speed for every mammography unit in the state were collected by Food and Drug Administration-trained state inspectors. A mixed-effect model was used to evaluate the changes of glandular dose over time and to identify the factors associated with these changes. Results. There was a statistically significant decrease in average glandular dose in North Carolina since 2002. Factors that were statistically significantly associated with this effect were changes in kVp, equipment age, processing speed, and system speed. Conclusion. Average glandular dose for mammography has decreased in North Carolina after 2002. This change is probably at least partially due to the cumulative effect of direct intervention by mammography consultants and statewide educational seminars on mammography quality control. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Radiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Biomed Res Imaging Ctr, Chapel Hill, NC 27599 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina Div Radiat Protect, N Carolina Radiat Protect Sect, Raleigh, NC USA. N Carolina Div Publ Hlth, Raleigh, NC USA. RP Kuzmiak, CM (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Radiol, CB 5120 Manning Dr,Room 513, Chapel Hill, NC 27599 USA. EM cherie_kuzmiak@med.unc.edu RI Chung, Yeonseung/C-1844-2011; OI Cole, Elodia/0000-0002-2301-7468 NR 11 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2007 VL 14 IS 6 BP 685 EP 691 DI 10.1016/j.acra.2007.02.012 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173GK UT WOS:000246861300007 PM 17502258 ER PT J AU Phan, J Tropea, JE Waugh, DS AF Phan, Jason Tropea, Joseph E. Waugh, David S. TI Structure-assisted discovery of Variola major H1 phosphatase inhibitors SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; YERSINIA-PESTIS; IN-VITRO; INSIGHTS; BINDING; YOPH; KINASES; PHOSPHORYLATION AB Variola major virus, the causative agent of smallpox, encodes the dual-specificity H1 phosphatase. Because this enzyme is essential for the production of mature virus particles, it is an attractive molecular target for the development of therapeutic countermeasures for this potential agent of bioterrorism. As a first step in this direction, the crystal structure of H1 phosphatase has been determined at a resolution of 1.8 angstrom. In silico screening methods have led to the identification of several small molecules that inhibit Variola HI phosphatase with IC50 values in the low micromolar range. These molecules provide novel leads for future drug development. C1 NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Canc Res Ctr, POB B, Frederick, MD USA. EM waughd@ncifcrf.gov NR 48 TC 14 Z9 14 U1 0 U2 0 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 JUN PY 2007 VL 63 BP 698 EP 704 DI 10.1107/S0907444907014904 PN 6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 189SQ UT WOS:000248009200005 PM 17505108 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Calcium and neurodegeneration SO AGING CELL LA English DT Review DE Alzheimer's disease; amyloid; apoptosis; endoplasmic reticulum; N-methyl-D-aspartate; Parkinson's disease; presenilin ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID BETA-PEPTIDE; PROTECTS HIPPOCAMPAL-NEURONS; LIPID-PEROXIDATION PRODUCT; SELECTIVE MOTONEURON VULNERABILITY; MANGANESE SUPEROXIDE-DISMUTASE; ENDOPLASMIC-RETICULUM STRESS; PRESYNAPTIC NERVE-TERMINALS; IMPAIRS GLUTAMATE TRANSPORT; FIBROBLAST GROWTH-FACTOR AB When properly controlled, Ca2+ fluxes across the plasma membrane and between intracellular compartments play critical roles in fundamental functions of neurons, including the regulation of neurite outgrowth and synaptogenesis, synaptic transmission and plasticity, and cell survival. During aging, and particularly in neurodegenerative disorders, cellular Ca2+-regulating systems are compromised resulting in synaptic dysfunction, impaired plasticity and neuronal degeneration. Oxidative stress, perturbed energy metabolism and aggregation of disease-related proteins (amyloid beta-peptide, alpha-synuclein, huntingtin, etc.) adversely affect Ca2+ homeostasis by mechanisms that have been elucidated recently. Alterations of Ca2+-regulating proteins in the plasma membrane (ligand- and voltage-gated Ca2+ channels, ion-motive ATPases, and glucose and glutamate transporters), endoplasmic reticulum (presenilin-1, Herp, and ryanodine and inositol triphosphate receptors), and mitoichondria (electron transport chain proteins, Bcl-2 family members, and uncoupling proteins) are implicated in age-related neuronal dysfunction and disease. The adverse effects of aging on neuronal Ca2+ regulation are subject to modification by genetic (mutations in presenilins, alpha-synuclein, huntingtin, or Cu/Zn-superoxide dismutase; apolipoprotein E isotype, etc.) and environmental (dietary energy intake, exercise, exposure to toxins, etc.) factors that may cause or affect the risk of neuroclegenerative disease. A better understanding of the cellular and molecular mechanisms that promote or prevent disturbances in cellular Ca2+ homeostasis during aging may lead to novel approaches for therapeutic intervention in neurological disorders such as Alzheimer's and Parkinson's diseases and stroke. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 197 TC 365 Z9 373 U1 8 U2 49 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD JUN PY 2007 VL 6 IS 3 BP 337 EP 350 DI 10.1111/j.1474-9726.2007.00275.x PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 179UH UT WOS:000247315100010 PM 17328689 ER PT J AU Antonelli-Incalzi, R Pedone, C Cesari, M Di Iorio, A Bandinelli, S Ferrucci, L AF Antonelli-Incalzi, Raffaele Pedone, Claudio Cesari, Matteo Di Iorio, Angelo Bandinelli, Stefania Ferrucci, Luigi TI Relationship between the occiput-wall distance and physical performance in the elderly: a cross sectional study SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aged; kyphosis; physical performance ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; REPLACEMENT THERAPY; BODY-COMPOSITION; OLDER PERSONS; WOMEN; KYPHOSIS; AGE; STRENGTH; POSTURE AB Background and aims: The occiput-wall distance (OWD), a measure of kyphosis, has been associated with postural instability, osteoporosis, disability and depression. The association between OWD and measures of physical performance was evaluated. Methods: Data from the Invecchiare in Chianti (InCHIANTI) study on home-dwelling people were used. People younger than 65 years and with overt disability at baseline assessment were excluded. The sample population was divided into three groups according to the OWD distribution (1st quartile: short OWD; 2nd and 3rd quartiles: medium OWD; 4th quartile: long OWD). Performance scores were expressed as the percentage of the best performance in this population. Results: 783 persons (55% women) were studied. The mean age for men was 73.8 (SD 6.34) and 75.0 (SD 6.85) for women. In men, a longer OWD was associated with reduced balance and walking speed, but not with impaired performance at the chair standing test. Overall, the association between increased OWD and reduced physical function was weak. In women, OWD was associated with a reduced walking speed, expressed as a percentage of the best performance (mean [SD]. 77% [12], 72% [14], 66% [15] in short, medium and long OWD groups, respectively), and impaired balance (mean [SD]: 97% [11], 95% [13], 90% [21] for short, medium and long OWD groups, respectively). Conclusions: Our findings suggest that OWD is an easily measurable marker of poor physical function in women. Further research should verify whether OWD predicts incident disability. C1 Dept Geriatr, Rome 00128, Italy. Univ Florida, Inst Aging, Gainesville, FL USA. Univ G dAnnunzio, Chieti, Italy. INRCA, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. Natl Inst Aging, Intramural Res Program, Baltimore, MD USA. RP Antonelli-Incalzi, R (reprint author), Dept Geriatr, Univ Campus Biomed,Via Compositori 131, Rome 00128, Italy. EM r.antonelli@unicampus.it RI Cesari, Matteo/A-4649-2008; Pedone, Claudio/F-9488-2010; Antonelli Incalzi, Raffaele/G-3978-2012; OI Cesari, Matteo/0000-0002-0348-3664; Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Pedone, Claudio/0000-0003-1847-9032 FU Intramural NIH HHS [Z99 AG999999] NR 26 TC 13 Z9 14 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD JUN PY 2007 VL 19 IS 3 BP 207 EP 212 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 215OY UT WOS:000249820100007 PM 17607088 ER PT J AU Horiguchi, N Ishac, EJN Gao, B AF Horiguchi, Norio Ishac, Edward J. N. Gao, Bin TI Liver regeneration is suppressed in alcoholic cirrhosis: correlation with decreased STAT3 activation SO ALCOHOL LA English DT Article DE alcohol; STAT3; liver regeneration; cirrhosis; HCV; cell proliferation ID HEPATOCYTE PROLIFERATIVE ACTIVITY; CYCLIN-DEPENDENT KINASE; LONG-TERM ETHANOL; HEPATITIS-C; PARTIAL-HEPATECTOMY; CULTURED-HEPATOCYTES; PROGENITOR CELLS; IN-VITRO; T-CELL; DISEASE AB Liver regeneration is suppressed in alcoholic patients; however, the underlying mechanisms are not fully understood. We examined liver regeneration and signal transducer and activator of transcription 3 (STAT3) activation (an important signal for liver regeneration) in cirrhotic livers from alcoholics, hepatitis C virus (HCV) infection, and alcoholic plus HCV infection. Liver regeneration and STAT3 activation were determined by immunohistochemistry analysis of Ki67 and STAT3 phosphorylation, respectively, in 20 alcoholic cirrhosis, 13 HCV cirrhosis, 13 alcoholic + HCV cirrhosis. Alcoholic or alcoholic plus HCV cirrhotic livers had significantly lower Ki67(+) and phospho-STAT3(+) (pSTAT3(+)) hepatocytes and bile duct cells than HCV cirrhotic livers. The pSTAT3 positive staining did not correlate with liver injury (elevation of serum levels of aspartate transaminase [AST] and alkaline phosphatase [ALP]) but correlated positively with cell proliferation (Ki67 positive staining). In conclusion: liver regeneration is suppressed in alcoholic cirrhotic livers, which may be partly due to decreased STAT3 activation. (C) 2007 Elsevier Inc. All rights reserved. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU Intramural NIH HHS [Z01 AA000369-06]; NIDDK NIH HHS [N01-DK-9-2310] NR 43 TC 17 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2007 VL 41 IS 4 BP 271 EP 280 DI 10.1016/j.alcohol.2007.04.008 PG 10 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 194TZ UT WOS:000248368000004 PM 17630087 ER PT J AU Chen, SA Suomi, SJ Heilig, MA Barr, CS AF Chen, S. A. Suomi, S. J. Heilig, M. A. Barr, C. S. TI Effects of naltrexone on ethanol self-administration in rhesus macaques: Role of sex and early-life stress SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIH, Anim Ctr, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600055 ER PT J AU Horiguchi, N Wang, L Park, O Gao, B AF Horiguchi, Norio Wang, Lei Park, Ogyi Gao, Bin TI Anti-steatotic effect of stat3 in alcoholic fatty liver disease via suppression of SREBP-1 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, Sect Liver Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 33A EP 33A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600098 ER PT J AU Ramchandani, VA Kumar, SR Saxena, NA Spero, DE Momenan, R Hommer, D AF Ramchandani, V. A. Kumar, S. R. Saxena, N. A. Spero, D. E. Momenan, R. Hommer, D. TI Influence of age and sex on alcohol elimination rates and subjective effects of alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 51A EP 51A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600170 ER PT J AU Gupte, M Dvoskin, RL Mcgee, M Schwandt, ML Lindell, SG Sun, H Goldman, D Higley, JD Heilig, M Barr, CS AF Gupte, M. Dvoskin, R. L. McGee, M. Schwandt, M. L. Lindell, S. G. Sun, H. Goldman, D. Higley, J. D. Heilig, M. Barr, C. S. TI CRH promoter variation is associated with oral alcohol selfadministration as a function of early stress exposures in male rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 73A EP 73A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600260 ER PT J AU Bjork, K Hansson, AC Heilig, M Sommer, WH AF Bjork, K. Hansson, A. C. Heilig, M. Sommer, W. H. TI Beta-arrestin 2 regulation by ethanol in post-dependent rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 77A EP 77A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600276 ER PT J AU Rhoads, DE Wang, J Chung, CS AF Rhoads, D. E. Wang, J. Chung, C.-S. TI Altered pattern of isoform expression for Na,K-ATPase during chronic alcohol consumption by pre-adolescent rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 Monmouth Univ, Dept Biol, W Long Branch, NJ USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 77A EP 77A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600277 ER PT J AU Lee, YM Kim, BJ Song, BJ AF Lee, Y. M. Kim, B. J. Song, B. J. TI Mitochondria-dependent apoptosis of human colon cancer cells by ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, Lab Memb Biochem Biophys, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 96A EP 96A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600351 ER PT J AU Schwandt, ML Suomi, SJ Higley, JD Heilig, M Barr, CS AF Schwandt, M. L. Suomi, S. J. Higley, J. D. Heilig, M. Barr, C. S. TI Change in response to the effects of ethanol between two sequential equivalent doses of ethanol in naive rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIH, Anim Ctr, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 150A EP 150A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959600565 ER PT J AU Neznanova, O Sommer, W Rimondini, R Hyytia, P Heilig, M AF Neznanova, O. Sommer, W. Rimondini, R. Hyytia, P. Heilig, M. TI Signal transiduction in alcohol-preferring AA and alcohol-avoiding ANA rat lines SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 193A EP 193A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601123 ER PT J AU Zhang, L Dong, LX Lovinger, DM AF Zhang, L. Dong, L. X. Lovinger, D. M. TI Evaluation of ethanol potentiation of human 5-HT3A receptors expressed in HEK293 cells using fast agonist perfusion SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 204A EP 204A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601166 ER PT J AU Koo, BN Xiong, W Zhang, L AF Koo, Bon-Nyeo Xiong, Wei Zhang, Li TI Low dose Delta 9-tetrahydrocannabinol and ethanol synergistically potentiate the function of human glycine alpha 1 receptors express SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Rockville, MD 20852 USA. RI Xiong, Wei/F-8251-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 205A EP 205A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601169 ER PT J AU Park, O Horiguchi, N Pan, HN Sun, R Jeong, WI Gao, B AF Park, Ogyi Horiguchi, Norio Pan, Hong-na Sun, Rui Jeong, Won-Il Gao, Bin TI Chronic ethanol consumption inhibits hepatic ink cell activity by attenuation of activating signal and accelerates MCMV-induced hepatitis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, Sect Liver Biol, LPS, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 217A EP 217A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601216 ER PT J AU Costa, RM AF Costa, R. M. TI Plasticity in dorsal striatum during action learning SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 254A EP 254A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601366 ER PT J AU Song, BJ Moon, KH AF Song, B. J. Moon, K. H. TI Identification of oxidatviely-modified proteins in alcohol-exposed animals SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, LMBB, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 256A EP 256A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601374 ER PT J AU Bryant, KJ AF Bryant, Kendall J. TI Strengthening biomedical research on alcohol and aids SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 263A EP 263A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601399 ER PT J AU Hommer, DW Momenan, R Gilman, J AF Hommer, D. W. Momenan, R. Gilman, J. TI Gender and brain shrinkage in alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 CRC, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 265A EP 265A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601408 ER PT J AU Kunos, G Jeong, WI Osei-Hyiaman, D Harvey-White, J Gao, B AF Kunos, George Jeong, Won-Il Osei-Hyiaman, Douglas Harvey-White, Judith Gao, Bin TI Role of endocannabinoids and CB1 receptors in alcoholic fatty liver SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 30th Annual Meeting of the Research-Society-on-Alcoholism CY JUL 07-11, 2007 CL Chicago, IL SP Res Soc Alcoholism C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2007 VL 31 IS 6 SU S BP 310A EP 310A PG 1 WC Substance Abuse SC Substance Abuse GA 174RD UT WOS:000246959601587 ER PT J AU Sanders, GD Al-Khatib, SM Berliner, E Bigger, JT Buxton, AE Califf, RM Carlson, M Curtis, AB Curtis, JP Domanski, M Fain, E Gersh, BJ Gold, MR Goldberger, J Haghighi-Mood, A Hammill, SC Harder, J Healey, J Hlatky, MA Hohnloser, SH Lee, KL Mark, DB Mitchell, B Phurrough, S Prystowsky, E Smith, JM Stockbridge, N Temple, R AF Sanders, Gillian D. Al-Khatib, Sana M. Berliner, Elise Bigger, J. Thomas Buxton, Alfred E. Califf, Robert M. Carlson, Mark Curtis, Anne B. Curtis, Jeptha P. Domanski, Michael Fain, Eric Gersh, Bernard J. Gold, Michael R. Goldberger, Jeffrey Haghighi-Mood, Ali Hammill, Stephen C. Harder, Joel Healey, Jeffrey Hlatky, Mark A. Hohnloser, Stefan H. Lee, Kerry L. Mark, Daniel B. Mitchell, Brent Phurrough, Steve Prystowsky, Eric Smith, Joseph M. Stockbridge, Norman Temple, Robert TI Preventing tomorrow's sudden cardiac death today: Part 11: Translating sudden cardiac death risk assessment strategies into practice and policy SO AMERICAN HEART JOURNAL LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LEFT-VENTRICULAR DYSFUNCTION; COST-EFFECTIVENESS; MYOCARDIAL-INFARCTION; PROPHYLACTIC USE; HEART-FAILURE; RESYNCHRONIZATION THERAPY; DEVICE ADVISORIES; AMIODARONE; CARDIOMYOPATHY AB Although current evidence supporting a more precise strategy for identifying patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for translating existing and future evidence into clinical practice and policy are needed today. A great many unanswered questions exist. Examples include the following: At what level of risk for SCD should we pursue further testing or therapy? How should clinical strategies ethically and economically balance alternative outcomes? How can we best translate optimal strategies into clinical practice so as to prevent tomorrow's SCDs? On July 20 and 2 1, 2006, a group of individuals with expertise in clinical cardiovascular medicine, biostatistics, economics, and health policy was joined by government (Food and Drug Administration; Centers for Medicare and Medicaid Services; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality), professional societies (Heart Rhythm Society), and industry to discuss strategies for risk assessment and prevention of SCD. The meeting was organized by the Duke Center for the Prevention of Sudden Cardiac Death and the Duke Clinical Research Institute. This article, the second of 2 documents, summarizes the policy discussions of that meeting, discusses an analytic framework for evaluating the risks and benefits associated with SCD prevention and risk stratification, and addresses the translation of SCD risk assessment strategies into practice and policy. C1 Duke Med Ctr, Duke Clin Res Inst, Durham, NC USA. Agcy Hlth Res & Qual, Rockville, MD USA. Columbia Univ, New York, NY USA. Rhode Isl Hosp, Providence, RI USA. St Jude Med, Sunnyvale, CA USA. Univ S Florida, Tampa, FL USA. Yale Univ, Sch Med, New Haven, CT USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mayo Clin, New Rochelle, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Cambridge Heart Inc, Bedford, MA USA. Heart Rhythm Soc, Washington, DC USA. McMaster Univ, Gen Hosp, Hamilton, ON, Canada. Sch Med, Stanford, CA USA. Univ Frankfurt, D-6000 Frankfurt, Germany. Libin Cardiovasc Inst Alberta, Albany, CA USA. Ctr Med, Medicoid Serv, Baltimore, MD USA. St Vincents Hosp, Indianapolis, IN USA. Boston Sci Inc, St Paul, MN USA. US FDA, Silver Spring, MD USA. RP Sanders, GD (reprint author), Duke Univ, Duke Clin Res Inst, PO Box 17969, Durham, NC 27715 USA. EM gillion.sanders@duke.edu NR 32 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2007 VL 153 IS 6 BP 951 EP 959 DI 10.1016/j.ahj.2007.03.002 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 182YT UT WOS:000247540600009 PM 17540195 ER PT J AU Thakore, AH Guo, CY Larson, MG Corey, D Wang, TJ Vasan, RS D'Agostino, RB Lipinska, I Keaney, JF Benjamin, EJ O'Donnell, CJ AF Thakore, Avni H. Guo, Chao-Yu Larson, Martin G. Corey, Diane Wang, Thomas J. Vasan, Ramachandran S. D'Agostino, Ralph B., Sr. Lipinska, Izabella Keaney, John F., Jr. Benjamin, Emelia J. O'Donnell, Christopher J. TI Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham heart study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; PUBLIC-HEALTH PRACTICE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK; ARTERY; ATHEROSCLEROSIS; STROKE; INTERLEUKIN-6; OBESITY AB Inflammatory markers, particularly C-reactive protein. (CRP), predict incident cardiovascular disease and are associated with the presence of subclinical atherosclerosis. The relations between multiple inflammatory markers and direct measures of atherosclerosis are less well established. Participants in the Offspring Cohort of the Framingham Heart Study (n = 2,885, 53% women, mean age 59 years) received routine assessments of common carotid artery intima-media thickness (CCA-IMT), internal carotid artery intima-media thickness (ICA-IMT), and the presence or absence of >= 25% carotid stenosis by ultrasonography. Circulating inflammatory markers assessed from an examination 4 years later included CRP, interleukin-6 (IL-6), intercellular adhesion molecule-1, monocyte chemoattractant protein-1, P-selectin, and CD40 ligand. Assessed as a group, inflammatory markers were significantly associated with ICA-IMT (p = 0.01), marginally with carotid stenosis (p = 0.08), but not with CCA-IMT. Individually, with an increase from the 25th to 75th percentile in IL-6, there were significant increases in ICA-IMT and carotid stenosis (for ICA-IMT, estimated fold increase 1.04, 95% confidence interval 1.03 to 1.06, p = 0.0004; for carotid stenosis, odds ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.007) after adjustment for age, gender, and established risk factors for atherosclerosis. There was a similar significant multivariate-adjusted association of CRP with ICA-IMT but not with carotid stenosis. Smoking appeared to modify the associations of ICA-IMT with CRP (p = 0.009) and with IL-6 (p = 0.006); the association was more pronounced in current (vs former or never) smokers. In conclusion, there were modest associations of inflammatory markers, particularly IL-6, with carotid atherosclerosis. This association appears more pronounced in current smokers than in former smokers and nonsmokers. (c) 2007 Elsevier Inc. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM emelia@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 [HL70139, 1 R01 HL076784, HL04334, HL074077, HL60886, HL64753, N01-HC-25195]; NIDDK NIH HHS [DK55656] NR 25 TC 79 Z9 82 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2007 VL 99 IS 11 BP 1598 EP 1602 DI 10.1016/j.amjcard.2007.01.036 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YV UT WOS:000247121700023 PM 17531588 ER PT J AU Balk, EM Horsley, TA Newberry, SJ Lichtenstein, AH Yetley, EA Schachter, HM Moher, D MacLean, CH Lau, J AF Balk, Ethan M. Horsley, Tanya A. Newberry, Sydne J. Lichtenstein, Alice H. Yetley, Elizabeth A. Schachter, Howard M. Moher, David MacLean, Catherine H. Lau, Joseph TI A collaborative effort to apply the evidence-based review process to the field of nutrition: challenges, benefits, and lessons learned SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; N-3 FATTY-ACIDS; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; CONSORT STATEMENT; SYSTEMATIC REVIEWS; CLINICAL-TRIALS; QUALITY; OMEGA-3-FATTY-ACIDS; METAANALYSIS AB Evidence-based systematic reviews evaluating dietary intake and nutritional interventions are becoming common but are relatively few compared with other applications. Concerns remain that systematic reviews of nutrition topics pose several unique challenges. We present a successful collaboration to systematically review the health effects of a common nutrient, n-3 (or omega-3) fatty acids, across a wide range of clinical conditions. More generally, we discuss the challenges faced and the lessons learned during the review, the benefits of systematic review of nutritional topics, and recommendations for conducting and reviewing nutrition-related studies. Through a structured but flexible process, 3 Evidence-based Practice Centers in the Agency for Healthcare Research and Quality program produced I I reports on a wide range of n-3 fatty acid-related topics. An important resource has been created, through which nutrition and dietetics researchers, clinical dietitians and nutritionists, clinicians, and the general public can understand the state of the science. The process identified challenges and problems in evaluating the health effects of n-3 fatty acid consumption, highlighted challenges to reviewing the human nutrition literature, and yielded recommendations for future research. The goals of these systematic reviews, the processes that were used, the benefits and limitations of the collaboration, and the conclusions of the reviews, including recommendations for future research, are summarized here. C1 Tufts Univ, New England Med Ctr Evidence Based Practice Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. Univ Ottawa, Evidence Based Practice Ctr, Ottawa, ON, Canada. Childrens Hosp Eastern Ontario, Res Inst, Chalmers Res Grp, Ottawa, ON K1H 8L1, Canada. Childrens Hosp Eastern Ontario, Res Inst, Dept Pediat, Ottawa, ON K1H 8L1, Canada. RAND Hlth, So California RAND Evidence Based Ctr, Santa Monica, CA 90407 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Univ Ottawa, Fac Med, Ottawa, ON, Canada. RP Balk, EM (reprint author), Tufts Univ, New England Med Ctr Evidence Based Practice Ctr, Inst Clin Res & Hlth Policy Studies, NEMC 63,750 Washington St, Boston, MA 02111 USA. EM ebalk@tufts-nemc.org OI Horsley, Tanya/0000-0002-1256-9582; Moher , David /0000-0003-2434-4206 FU PHS HHS [290-02-0021, 290-02-0023, 290-02-003] NR 39 TC 25 Z9 25 U1 3 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2007 VL 85 IS 6 BP 1448 EP 1456 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 178BN UT WOS:000247196300004 PM 17556679 ER PT J AU Infante-Rivard, C Vermunt, JK Weinberg, CR AF Infante-Rivard, Claire Vermunt, Jeroen K. Weinberg, Clarice R. TI Excess transmission of the NAD(P)H: Quinone oxidoreductase 1 (NQO1) C609T polymorphism in families of children with acute lymphoblastic leukemia SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE association; child; infant; leukemia; linkage (genetics); models; genetic; NAD(P)H dehydrogenase (quinone); polymorphism; genetic ID CASE-PARENT TRIADS; CHILDHOOD LEUKEMIA; NAD(P)H-QUINONE OXIDOREDUCTASE; CHROMOSOME TRANSLOCATIONS; GENETIC POLYMORPHISMS; INCREASED RISK; GENOTYPE; EXPOSURE; DISEASE; ALLELE AB Topoisomerase II is a DNA-processing enzyme, and secondary acute myeloid leukemia has been associated with exposure to drugs that inhibit its action. Hence, prenatal exposure to chemicals that inhibit topoisomerase II could plausibly contribute to the incidence of childhood leukemia. The NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme is involved in the metabolism of topoisomerase II-inhibiting chemicals. A functional polymorphism (C609T) associated with reduced activity has been identified on the NQO1 gene. To assess its role in the etiology of childhood acute lymphoblastic leukemia, the authors studied transmission of the variant T allele in the families (parents and grandparents) of 657 affected children in Quebec, Canada (1980-2000). Log-linear models that stratified on parental or grandparental mating types were used. Prenatal exposure to potential topoisomerase II inhibitors such as benzene and maternal smoking was studied, as well as interactions between the variant and these exposures. The variant allele was transmitted to cases more frequently than expected (for one or two copies of the allele vs. none, relative risk = 1.39, 95% confidence interval: 1.07, 1.79). There was no evidence of a maternally mediated genetic effect on risk, based on a log-linear assessment of genetic symmetry between mothers and fathers, nor was there evidence of interaction between the studied maternal exposures and the child or maternal variant. C1 McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A3, Canada. Tilburg Univ, Fac Social & Behav Sci, Dept Methodol & Stat, NL-5000 LE Tilburg, Netherlands. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Infante-Rivard, C (reprint author), McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, 1110 Pine Ave W, Montreal, PQ H3A 1A3, Canada. EM claire.infante-rivard@mcgill.ca RI vermunt, jeroen/K-3680-2012 OI vermunt, jeroen/0000-0001-9053-9330 FU Intramural NIH HHS [Z01 ES045005-11] NR 40 TC 23 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 BP 1248 EP 1254 DI 10.1093/aje/kwm022 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175HU UT WOS:000247005500005 PM 17332311 ER PT J AU Splansky, GL Corey, D Yang, Q Atwood, LD Cupples, LA Benjamin, EJ D'Agostino, RB Fox, CS Larson, MG Murabito, JM O'Donnell, CJ Vasan, RS Wolf, PA Levy, D AF Splansky, Greta Lee Corey, Diane Yang, Qiong Atwood, Larry D. Cupples, L. Adrienne Benjamin, Emelia J. D'Agostino, Ralph B., Sr. Fox, Caroline S. Larson, Martin G. Murabito, Joanne M. O'Donnell, Christopher J. Vasan, Ramachandran S. Wolf, Philip A. Levy, Daniel TI The third generation cohort of the national heart, lung, and blood institute's Framingham Heart Study: Design, recruitment, and initial examination SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE atherosclerosis; cardiovascular diseases; cohort studies; epiderniologic research design; patient selection; physical examination; risk factors AB For nearly 60 years, the Framingham Heart Study has examined the natural history, risk factors, and prognosis of cardiovascular, lung, and other diseases. Recruitment of the Original Cohort began in 1948. Twenty-three years later, 3,548 children of the Original Cohort, along with 1,576 of their spouses, enrolled in the Offspring Cohort. Beginning in 2002, 4,095 adults having at least one parent in the Offspring Cohort enrolled in the Third Generation Cohort, along with 103 parents of Third Generation Cohort participants who were not previously enrolled in the Offspring Cohort. The objective of new recruitment was to complement phenotypic and genotypic information obtained from prior generations, with priority assigned to larger families. From a pool of 6,553 eligible individuals, 1,912 men and 2,183 women consented and attended the first examination (mean age: 40 (standard deviation: 9) years; range: 19-72 years). The examination included clinical and laboratory assessments of vascular risk factors and imaging for subclinical atherosclerosis, as well as assessment of cardiac structure and function. The comparison of Third Generation Cohort data with measures previously collected from the first two generations will facilitate investigations of genetic and environmental risk factors for subclinical and overt diseases, with a focus on cardiovascular and lung disorders. C1 Boston Univ, Sch Med, NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Framigham Heart Study, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Cardiol & Prevent Med Sect, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02215 USA. RP Splansky, GL (reprint author), Boston Univ, Sch Med, NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM gretalee@bu.edu RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, R01 HL 70100] NR 4 TC 289 Z9 293 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 BP 1328 EP 1335 DI 10.1093/aje/kwm021 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175HU UT WOS:000247005500015 PM 17372189 ER PT J AU Basso, O Wilcox, AJ Weinberg, CR Lie, RT AF Basso, O. Wilcox, A. J. Weinberg, C. R. Lie, R. T. TI Xenobiotic-metabolizing genes and birth weight. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, NIH, HHS, Res Triangle Pk, NC 27707 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S29 EP S29 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500115 ER PT J AU Berndt, SI Carter, HB Schoenberg, MP Newschaffer, CJ AF Berndt, S. I. Carter, H. B. Schoenberg, M. P. Newschaffer, C. J. TI Disparities in survival between black and white patients with renal cell cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S7 EP S7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500026 ER PT J AU Boyles, AL Wilcox, AJ Meyer, K Fredriksen, A Ueland, PM Drevon, CA Solvoll, K Lie, RT AF Boyles, A. L. Wilcox, A. J. Meyer, K. Fredriksen, A. Ueland, P. M. Drevon, C. A. Solvoll, K. Lie, R. T. TI Folate metabolism genes and the risk of orofacial clefts. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, NIH, Durham, NC 27709 USA. Univ Bergen, Bergen, Norway. Univ Oslo, Oslo, Norway. RI Ueland, Per/C-7340-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S118 EP S118 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500470 ER PT J AU DeRoo, LA Wilcox, AJ Lie, RT AF DeRoo, L. A. Wilcox, A. J. Lie, R. T. TI Maternal alcohol consumption and the risk of oral clefts in Norway. A population-based case-control study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Bergen, N-5020 Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S1 EP S1 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500005 ER PT J AU Doria-Rose, VP Marcus, PM AF Doria-Rose, V. P. Marcus, P. M. TI Sensitivity and specificity of death certificates in assigning lung cancer as the cause of death in the Mayo Lung Project. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S32 EP S32 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500129 ER PT J AU Doria-Rose, VP Marcus, PM Church, TR Mongin, S Prorok, PC AF Doria-Rose, V. P. Marcus, P. M. Church, T. R. Mongin, S. Prorok, P. C. TI The evaluation of self-selection bias in observational studies of cancer screening using data from randomized controlled trials. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500130 ER PT J AU Gierach, G Lacey, J Schatzkin, A Leitzmann, M Mouw, T Brinton, L AF Gierach, G. Lacey, J., Jr. Schatzkin, A. Leitzmann, M. Mouw, T. Brinton, L. TI Non-steroidal anti-inflammatory drugs (NSAIDS) and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Rockville, MD 20892 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S58 EP S58 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500233 ER PT J AU Goldstein, RB Grant, BF AF Goldstein, R. B. Grant, B. F. TI Antisocial behavioral syndromes and DSM-IV drug use disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S70 EP S70 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500278 ER PT J AU Huang, AT Kogevinas, M Silverman, D Malats, N Rothman, N Real, F Tardon, A Serra, C Garcia-Closas, R Carrato, A Dosemeci, M Cantor, K AF Huang, A-T Kogevinas, M. Silverman, D. Malats, N. Rothman, N. Real, F. Tardon, A. Serra, C. Garcia-Closas, R. Carrato, A. Dosemeci, M. Cantor, K. TI Bladder cancer and reproductive factors among women in Spain. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. RI Serra, C/E-6879-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S147 EP S147 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500589 ER PT J AU Jukic, A Weinberg, C Hornsby, P McConnaughey, D Wilcox, A Baird, D AF Jukic, A. Weinberg, C. Hornsby, P. McConnaughey, D. Wilcox, A. Baird, D. TI Accuracy of menstrual cycle length reporting. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, NIH, Durham, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S22 EP S22 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500089 ER PT J AU Kalaydjian, A Dierker, L Merikangas, K AF Kalaydjian, A. Dierker, L. Merikangas, K. TI Effects of mood and anxiety disorders on progression of smoking and nicotine dependence in a nationally representative sample of US adults. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S70 EP S70 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500279 ER PT J AU Keim, SA Klebanoff, MA AF Keim, S. A. Klebanoff, M. A. TI Preterm and small-for-gestational age at birth and risk of depression, depression during pregnancy and postpartum in adulthood. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, Div Epidemiol, Bethesda, MD 20852 USA. RI Keim, Sarah/F-8929-2013 OI Keim, Sarah/0000-0003-3490-3649 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S51 EP S51 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500202 ER PT J AU Lam, TV Pawlish, K Cross, H AF Lam, T. V. Pawlish, K. Cross, H. TI Epstein-Barr virus serology and gastric cancer incidence and survival. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiol Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S7 EP S7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500027 ER PT J AU Louis, GMB Cooney, MA AF Louis, G. M. Buck Cooney, M. A. TI Endocrine disrupting chemicals and endometriosis. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, Epidemiol Branch, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S41 EP S41 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500165 ER PT J AU Mahajan, R Blair, A Coble, J Lynch, CF Hoppin, JA Sandler, DP Alavanja, MCR AF Mahajan, R. Blair, A. Coble, J. Lynch, C. F. Hoppin, J. A. Sandler, D. P. Alavanja, M. C. R. TI Carbaryl exposure and incident cancer in the agricultural health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, DHHS, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch,NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S99 EP S99 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500396 ER PT J AU Miller, BA Chu, KC Ries, LAG Hankey, BF Edwards, BK AF Miller, B. A. Chu, K. C. Ries, L. A. G. Hankey, B. F. Edwards, B. K. TI Cancer incidence patterns among specific Asian and Pacific Islander populations in the US. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S6 EP S6 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500022 ER PT J AU Montgomery, MP Hoppin, JA Umbach, DM Alavanja, MCR Blair, A Sandler, DP Kamel, F AF Montgomery, M. P. Hoppin, J. A. Umbach, D. M. Alavanja, M. C. R. Blair, A. Sandler, D. P. Kamel, F. TI Pesticide use and incident, self-reported retinal degeneration in the agricultural health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiol Res C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S132 EP S132 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500529 ER PT J AU Mumford, SL Schisterman, EF Vexler, A AF Mumford, S. L. Schisterman, E. F. Vexler, Albert TI An optimal cost-efficient design that accounts for measurement error: Pooled-unpooled design. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, DESPR, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S36 EP S36 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500145 ER PT J AU Nguyen, RHN Wilcox, AJ Skjaerven, R Baird, DD AF Nguyen, R. H. N. Wilcox, A. J. Skjaerven, R. Baird, D. D. TI Men's body mass index and infertility. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S25 EP S25 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500101 ER PT J AU Perkins, NJ Schisterman, EF Vexler, A AF Perkins, N. J. Schisterman, E. F. Vexler, A. TI Area under the roc curve for the best linear combination of two biomarkers with limits of detection. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, NIH, DESPR, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500265 ER PT J AU Rubio, M Saenz, R AF Rubio, M. Saenz, R. TI Disability among elderly Mexicans in the United States: The case of the 0.25 generation and beyond. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIMH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S86 EP S86 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500343 ER PT J AU Ruopp, MD Perkins, NJ Whitcomb, BW Schisterman, EF AF Ruopp, M. D. Perkins, N. J. Whitcomb, B. W. Schisterman, E. F. TI Youden index and optimal cut-point estimated from observations subject to a lower limit of detection. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, NIH, DESPR, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500266 ER PT J AU Samanic, CM Stewart, PA De Roos, AJ Rajaraman, P Inskip, PD AF Samanic, C. M. Stewart, P. A. De Roos, A. J. Rajaraman, P. Inskip, P. D. TI Occupational exposure to pesticides and risk of adult brain tumors. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S102 EP S102 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500407 ER PT J AU Shariff-Marco, S Breen, N Klabunde, C Stinchcomb, D AF Shariff-Marco, S. Breen, N. Klabunde, C. Stinchcomb, D. TI How contextual factors influence disparities in colorectal cancer screening. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S31 EP S31 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500123 ER PT J AU Sherman, ME AF Sherman, M. E. TI Application of tissue microarrays in molecular epidemiologic research: Getting to the core of the matter. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S47 EP S47 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500186 ER PT J AU Smith, SM Goldstein, RB Grant, BF AF Smith, S. M. Goldstein, R. B. Grant, B. F. TI Racial and ethnic differences in stigma towards people with alcohol use disorders. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S81 EP S81 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500324 ER PT J AU Ward, MH Nuckols, JR Riggs, P Maxwell, S AF Ward, M. H. Nuckols, J. R. Riggs, P. Maxwell, S. TI Using geographic information systems (GIS) for exposure assessment in environmental epidemiology studies of cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. RI Mavoa, Suzanne/B-5372-2010 NR 0 TC 0 Z9 1 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S137 EP S137 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500549 ER PT J AU Weinstein, SJ Albanes, D Selhub, J Stolzenberg-Solomon, R AF Weinstein, S. J. Albanes, D. Selhub, J. Stolzenberg-Solomon, R. TI Serum one-carbon metabolism factors and risk of colorectal cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NCI, NIH, DHHS, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S132 EP S132 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500528 ER PT J AU Whitcomb, BW Schisterman, EF Klebanoff, MA Luo, X Chegini, N AF Whitcomb, B. W. Schisterman, E. F. Klebanoff, M. A. Luo, X. Chegini, N. TI Circulating granulocyte colony stimulating factor and preterm birth. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NICHD, NIH, DESPR, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S24 EP S24 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500096 ER PT J AU Wilcox, A Skjaerven, R Lie, RT AF Wilcox, A. Skjaerven, R. Lie, R. Terje TI The heritability of preterm delivery: Maternal and fetal contributions. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 NIEHS, NIH, Durham, NC 27709 USA. Univ Bergen, Bergen, Norway. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S21 EP S21 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500085 ER PT J AU Zablotska, L AF Zablotska, L. CA Chornobyl Thyroid Dis Study Grp TI A cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident: Dose-response analysis of thyroid follicular adenomas detected during first screening in Ukraine (1998-2000). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 Columbia Univ, New York, NY 10032 USA. NCI, Chronobyl Res Unit, Bethesda, MD 20852 USA. Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S3 EP S3 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500011 ER PT J AU Penninx, BWJH Beekman, ATF Bandinelli, S Corsi, AM Bremmer, M Hoogendijk, WJ Guralnik, JM Ferrucci, L AF Penninx, Brenda W. J. H. Beekman, Aartjan T. F. Bandinelli, Stephania Corsi, Anna Maria Bremmer, Marijke Hoogendijk, Witte J. Guralnik, Jack M. Ferrucci, Luigi TI Late-life depressive symptoms are associated with both hyperactivity and hypoactivity of the hypothalamo-pituitary-adrenal axis SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depressive symptoms; cortisol; hypothalamo-pituitary-adrenal axis; frailty; older persons ID 24-HOUR URINARY CORTISOL; EXCRETION; DISEASE; STRESS; EPIDEMIOLOGY; VALIDITY; SYSTEM AB Objective: Although depression has been associated with hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis, recent studies among depressed elderly have found decreased cortisol levels, which may be due to underlying physical frailty associated with HPA-axis hypoactivity. The authors examined the relationship between urinary cortisol level and late-life depressive symptoms. The authors also explored whether hypo- and hypercortisolemic depressive symptoms are qualitatively different. Methods: Data are from 881 community-dwelling participants, average age 74.2 years, of the Aging in the Chianti Area Study. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) scale and cortisol levels were determined in 24-hour urine samples. Results: Mean urinary cortisol level was 98.9 mu g/24 hours ( SD = 47.8), and 31% of the sample had significant depressive symptoms (CES-D >= 16). There was no linear association between urinary cortisol level and depressive symptoms; however, there was a nonlinear association between urinary cortisol level and depressive symptoms. Older persons in the lowest and highest urinary cortisol deciles were 2.2 and 1.9 times more likely to have significant depressive symptoms than older persons in all other deciles. Depressed persons with low cortisol presented more physical frailty than depressed persons with high cortisol. Conclusion: Late-life depressive symptoms are associated with both hyperactivity and hypoactivity of the HPA axis, which suggests distinct mechanisms for these associations. C1 VU Univ Med Ctr, Dept Psychiat, Amsterdam, Netherlands. VU Univ Med Ctr, EMGO Inst, Amsterdam, Netherlands. Tuscany Reg Hlth Agcy, Florence, Italy. ASF, Geriatr Rehabil Unit, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Penninx, BWJH (reprint author), VU Univ Med Ctr GGZ Buitenamstel, Inst Res Extramural Med, Dept Psychiat, Oldenaller 1, NL-1081 HJ Amsterdam, Netherlands. EM b.penninx@vumc.nl FU Intramural NIH HHS [Z99 AG999999]; NHLBI NIH HHS [1 R01 HL972972]; NIMHD NIH HHS [R01 MD009164] NR 25 TC 70 Z9 70 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2007 VL 15 IS 6 BP 522 EP 529 DI 10.1097/JGP.0b013e318033ed80 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 174ND UT WOS:000246948100009 PM 17545451 ER PT J AU Tanno, T Bhanu, NV Oneal, PA Goh, SH Staker, P Lee, YT Childs, R Leitman, SF Luban, NL Miller, JL AF Tanno, T. Bhanu, N. V. Oneal, P. A. Goh, S. H. Staker, P. Lee, Y. T. Childs, R. Leitman, S. F. Luban, N. L. Miller, J. L. TI Growth differentiation factor 15 is produced at high levels in patients with beta thalassemia and inhibits hepcidin expression in primary hepatocyte. SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NIDDK, Mol Med Branch, Bethesda, MD USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 507 EP 507 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600034 ER PT J AU Missirlis, F Rouault, T AF Missirlis, F. Rouault, T. TI Drosophila as a model system to study iron metabolism SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico. NR 3 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 510 EP 511 PG 2 WC Hematology SC Hematology GA 172ID UT WOS:000246796600045 ER PT J AU Ghosh, MC Cooperman, S Zhang, D Tong, WH Ollivierre-Wilson, H Meyron-Holtz, E Mitchell, J Rouault, TA AF Ghosh, M. C. Cooperman, S. Zhang, D. Tong, W. H. Ollivierre-Wilson, H. Meyron-Holtz, E. Mitchell, J. Rouault, T. A. TI Roles of iron regulatory proteins 1 and 2 in mammalian iron metabolism SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Techion, Haifa, Israel. RI Meyron-Holtz, Esther/B-5991-2013; Zhang, Deliang/F-7848-2013 NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 511 EP 512 PG 2 WC Hematology SC Hematology GA 172ID UT WOS:000246796600049 ER PT J AU Philpott, CC Shi, H AF Philpott, C. C. Shi, H. TI Identification of genes facilitating iron storage in ferritin SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 511 EP 511 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600046 ER PT J AU Philpott, CC Mukhopadhyay, B AF Philpott, C. C. Mukhopadhyay, B. TI Identification of Uga3 as an iron-regulated transcription factor controlling the activity of the GABA shunt in Saccharomyces cerevisiae SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NIDDK, Live Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 516 EP 516 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600061 ER PT J AU Tong, WH Li, K Uhrigshardt, H Rouault, TA AF Tong, W.-H. Li, K. Uhrigshardt, H. Rouault, T. A. TI The role of mitochondrial and cytosolic iron-sulfur cluster biogenesis in maintainence of mammalian iron homeostasis SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 NICHHD, 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 521 EP 521 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600078 ER PT J AU McLaren, GD McLaren, CE Adams, PC Barton, JC Reboussin, DM Gordeuk, VR Acton, RT Harris, EL Speechley, M Sholinsky, P Dawkins, FW Snively, BM Vogt, T Eckfeldt, JH AF McLaren, G. D. McLaren, C. E. Adams, P. C. Barton, J. C. Reboussin, D. M. Gordeuk, V. R. Acton, R. T. Harris, E. L. Speechley, M. Sholinsky, P. Dawkins, F. W. Snively, B. M. Vogt, T. Eckfeldt, J. H. CA Hemochromatosis Iron Overload TI Symptoms, signs, and clinical conditions in hfe C282Y homozygotes identified by screening in primary care SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Dept Vet Affairs Long Beach Healthcare Syst, Hematol Oncol Sect, Long Beach, CA 27109 USA. Univ Calif Irvine, Irvine, CA 20059 USA. London Hlth Sci Ctr, London, England. So Iron Disorders Ctr, Birmingham, AL USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Howard Univ, Washington, DC 20892 USA. Univ Alabama, Birmingham, AL USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Western Ontario, London, ON, Canada. NHLBI, NIH, DHHS, Bethesda, MD USA. Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. Univ Minnesota, Minneapolis, MN 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 553 EP 553 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600181 ER PT J AU McLaren, CE Harris, EL Reboussin, DM Gordeuk, V Barton, JC Acton, RT McLaren, GD Vogt, TM AF McLaren, C. E. Harris, E. L. Reboussin, D. M. Gordeuk, Vr. Barton, J. C. Acton, R. T. McLaren, G. D. Vogt, T. M. CA HEIRS Investigators TI Serum ferritin and transferrin saturation in asians and pacific islanders living in the US and Canada: The hemochromatosis and iron overload screening (heirs) study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Univ Calif Irvine, Irvine, CA USA. Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Howard Univ, Washington, DC 20059 USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Univ Minnesota, Med Ctr, Minneapolis, MN USA. Centenary Hlth Ctr, Toronto, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. NHGRI, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 574 EP 574 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600250 ER PT J AU Leveen, P Kotarsky, H Karikoski, R Zhang, D Fellman, V AF Leveen, Per Kotarsky, Heike Karikoski, Riitta Zhang, Deliang Fellman, Vineta TI GRACILE Syndrome complex III deficiency with iron overload SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Lund Univ, Dept Pediat, Lund, Sweden. Univ Helsinki, Hosp Lab Diagnost, Cent Pathol Lab, Helsinki, Finland. NIH, Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Helsinki, Dept Pediat, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 576 EP 576 PG 1 WC Hematology SC Hematology GA 172ID UT WOS:000246796600257 ER PT J AU McLaren, GD Gordeuk, VR Reboussin, DM Barton, JC Acton, RT McLaren, CE Harris, EL Reiss, JA Adams, PC Speechley, M Phatak, PD Sholinsky, P Eckfeldt, JH Passmore, L Dawkins, FW AF McLaren, G. D. Gordeuk, V. R. Reboussin, D. M. Barton, J. C. Acton, R. T. McLaren, C. E. Harris, E. L. Reiss, J. A. Adams, P. C. Speechley, M. Phatak, P. D. Sholinsky, P. Eckfeldt, J. H. Passmore, Leah Dawkins, F. W. CA HEIRS Study Res Investigators TI Serum ferritin concentration and body iron stores among 101,168 primary care participants SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 Long Beach Healthcare Syst, Dept Vet Affairs, Long Beach, CA 92717 USA. Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 20059 USA. Howard Univ, Ctr Sickle Cell Dis, Dept Med, Washington, DC 27109 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA. So Iron Disorders Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Genet & Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Int Hlth, Birmingham, AL USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Kaiser Permanente, Dept Genet, Portland, OR USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON 14621, Canada. Rochester Gen Hosp, Rochester, NY 20892 USA. NHLBI, NIH, DHHS, Epidemiol Branch, Bethesda, MD 55455 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2007 VL 82 IS 6 BP 594 EP 595 PG 2 WC Hematology SC Hematology GA 172ID UT WOS:000246796600316 ER PT J AU Tian, C Hinds, DA Shigeta, R Adler, SG Lee, A Pahl, MV Silva, G Belmont, JW Hanson, RL Knowler, WC Gregersen, PK Ballinger, DG Seldin, MF AF Tian, Chao Hinds, David A. Shigeta, Russell Adler, Sharon G. Lee, Annette Pahl, Madeleine V. Silva, Gabriel Belmont, John W. Hanson, Robert L. Knowler, William C. Gregersen, Peter K. Ballinger, Dennis G. Seldin, Michael F. TI A genomewide single-nucleotide-polymorphism panel for Mexican American admixture mapping SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; LINKAGE DISEQUILIBRIUM; ADMIXED POPULATIONS; AFRICAN-AMERICAN; RHEUMATOID-ARTHRITIS; DISEASE; ANCESTRY; MARKERS; MAP AB For admixture mapping studies in Mexican Americans (MAM), we define a genomewide single-nucleotide-polymorphism (SNP) panel that can distinguish between chromosomal segments of Amerindian (AMI) or European (EUR) ancestry. These studies used genotypes for > 400,000 SNPs, defined in EUR and both Pima and Mayan AMI, to define a set of ancestry-informative markers (AIMs). The use of two AMI populations was necessary to remove a subset of SNPs that distinguished genotypes of only one AMI subgroup from EUR genotypes. The AIMs set contained 8,144 SNPs separated by a minimum of 50 kb with only three intermarker intervals > 1 Mb and had EUR/AMI values F-ST > 0.30 (mean F-ST = 0.48) and Mayan/Pima values F-ST < 0.05 (mean Fst < 0.01). Analysis of a subset of these SNP AIMs suggested that this panel may also distinguish ancestry between EUR and other disparate AMI groups, including Quechuan from South America. We show, using realistic simulation parameters that are based on our analyses of MAM genotyping results, that this panel of SNP AIMs provides good power for detecting disease-associated chromosomal segments for genes with modest ethnicity risk ratios. A reduced set of 5,287 SNP AIMs captured almost the same admixture mapping information, but smaller SNP sets showed substantial drop-off in admixture mapping information and power. The results will enable studies of type 2 diabetes, rheumatoid arthritis, and other diseases among which epidemiological studies suggest differences in the distribution of ancestry-associated susceptibility. C1 Univ Calif Davis, Dept Biochem, Rowe Program Human Genet, Davis, CA 95616 USA. Univ Calif Davis, Dept Med, Rowe Program Human Genet, Davis, CA 95616 USA. Perlegen Sci, Mountain View, CA USA. Calif State Univ Los Angeles, David Geffen Sch Med, Los Angeles Biomed Res Inst Harbor, Div Nephrol & Hypertens, Torrance, CA 90032 USA. Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, N Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA. Univ Calif Irvine, Ctr Med, Div Nephrol & Hypertens, Orange, CA 92668 USA. Obras Sociales Hermano Pedro, Antigua, Guatemala. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NIDDKD, NIH, Phoenix, AZ 85016 USA. RP Seldin, MF (reprint author), Univ Calif Davis, Dept Biochem, Rowe Program Human Genet, Room 4453,Tupper Hall,1 Shields Ave, Davis, CA 95616 USA. EM mfseldin@ucdavis.edu RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Belmont, John/0000-0001-7409-3578 FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK071185, U01 DK057249, U01 DK57249] NR 38 TC 91 Z9 92 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2007 VL 80 IS 6 BP 1014 EP 1023 DI 10.1086/513522 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 168WD UT WOS:000246553800002 PM 17557415 ER PT J AU Price, AL Patterson, N Yu, F Cox, DR Waliszewska, A McDonald, GJ Tandon, A Schirmer, C Neubauer, J Bedoya, G Duque, C Villegas, A Bortolini, MC Salzano, FM Gallo, C Mazzotti, G Tello-Ruiz, M Riba, L Aguilar-Salinas, CA Canizales-Quinteros, S Menjivar, M Klitz, W Henderson, B Haiman, CA Winkler, C Tusie-Luna, T Ruiz-Linares, A Reich, D AF Price, Alkes L. Patterson, Nick Yu, Fuli Cox, David R. Waliszewska, Alicja McDonald, Gavin J. Tandon, Arti Schirmer, Christine Neubauer, Julie Bedoya, Gabriel Duque, Constanza Villegas, Alberto Bortolini, Maria Catira Salzano, Francisco M. Gallo, Carla Mazzotti, Guido Tello-Ruiz, Marcela Riba, Laura Aguilar-Salinas, Carlos A. Canizales-Quinteros, Samuel Menjivar, Marta Klitz, William Henderson, Brian Haiman, Christopher A. Winkler, Cheryl Tusie-Luna, Teresa Ruiz-Linares, Andres Reich, David TI A genomewide admixture map for Latino populations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AFRICAN-AMERICAN; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; MEXICAN-AMERICAN; PROSTATE-CANCER; ANCESTRY; MARKERS; RISK; PATTERNS; LOCUS AB Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. MIT, Broad Inst, Med & Populat Genet Grp, Cambridge, MA 02139 USA. Perlegen Sci, Mountain View, CA USA. Univ Antioquia, Genet Mol Lab, Medellin, Colombia. Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil. Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Labs Invest & Desarrollo, Lima, Peru. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Univ Nacl Autonoma Mexico, Unit Mol Biol & Genom Med, Inst Invest Biomed, Mexico City 04510, DF, Mexico. Univ Nacl Autonoma Mexico, Dept Biol, Fac Quim, Mexico City 04510, DF, Mexico. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City, DF, Mexico. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Inst Publ Hlth, Oakland, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21701 USA. UCL, Dept Biol, Galton Lab, London, England. RP Reich, D (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM reich@genetics.med.harvard.edu RI Salzano, Francisco/L-7916-2015; OI Gallo, Carla/0000-0001-8348-0473 FU Intramural NIH HHS; NCI NIH HHS [N01 CO12400, N01CO12400]; NCRR NIH HHS [U54 RR020278, U54 RR020278-01]; NIDDK NIH HHS [DK073818, F32 DK076277, R21 DK073818]; NINDS NIH HHS [NS043538, R01 NS043538] NR 39 TC 166 Z9 170 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2007 VL 80 IS 6 BP 1024 EP 1036 DI 10.1086/518313 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 168WD UT WOS:000246553800003 PM 17503322 ER PT J AU Balaci, L Spada, MC Olla, N Sole, G Loddo, L Anedda, F Naitza, S Zuncheddu, MA Maschio, A Altea, D Uda, M Pilia, S Sanna, S Masala, M Crisponi, L Fattori, M Devoto, M Doratiotto, S Rassu, S Mereu, S Giua, E Cadeddu, NG Atzeni, R Pelosi, U Corrias, A Perra, R Torrazza, PL Pirina, P Ginesu, F Marcias, S Schintu, MG Del Giacco, GS Manconi, PE Malerba, G Bisognin, A Trabetti, E Boner, A Pescollderungg, L Pignatti, PF Schlessinger, D Cao, A Pilia, G AF Balaci, Lenuta Spada, Maria Cristina Olla, Nazario Sole, Gabriella Loddo, Laura Anedda, Francesca Naitza, Silvia Zuncheddu, Maria Antonietta Maschio, Andrea Altea, Daniele Uda, Manuela Pilia, Sabrina Sanna, Serena Masala, Marco Crisponi, Laura Fattori, Matilde Devoto, Marcella Doratiotto, Silvia Rassu, Stefania Mereu, Simonetta Giua, Enrico Cadeddu, Natalina Graziella Atzeni, Roberto Pelosi, Umberto Corrias, Adriano Perra, Roberto Torrazza, Pier Luigi Pirina, Pietro Ginesu, Francesco Marcias, Silvano Schintu, Maria Grazia Del Giacco, Gennaro Sergio Manconi, Paolo Emilio Malerba, Giovanni Bisognin, Andrea Trabetti, Elisabetta Boner, Attilio Pescollderungg, Lydia Pignatti, Pier Franco Schlessinger, David Cao, Antonio Pilia, Giuseppe TI IRAK-M is involved in the pathogenesis of early-onset persistent asthma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TOLL-LIKE RECEPTORS; SARDINIAN POPULATION; NEGATIVE REGULATOR; LINKAGE ANALYSIS; IMMUNE-RESPONSE; DISEASE; ACTIVATION; HAPLOTYPES; PHENOTYPES; ASSOCIATION AB Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and 1100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/ disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF-kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma. C1 CNR, Ist Neurogenet & Neurofarmacol, Div Pneumol 2, Osped Binaghi, I-09042 Monserrato, CA, Italy. Univ Cagliari, Dipartimento Sci & Tecnol Biomed, Sez Patol Sperimentale, Div Pneumol 2,Osped Binaghi, Cagliari, Italy. Univ Cagliari, Dipartimento Sci Biomed & Biotecnol, Div Pneumol 2, Osped Binaghi, Cagliari, Italy. Univ Cagliari, Dipartimento Sci Pediat Allergol Pediat, Clin Pediat 1, Div Pneumol 2,Osped Binaghi, Cagliari, Italy. Osped Macciotta, Dipartimento Chirurg Materno Infantile Sci & Imma, Sez Pediat, Cagliari, Italy. Policlin Univ Cagliari, Ist Naz Riposo & Cura Anziani, Cagliari, Italy. Policlin Univ Cagliari, Allergol & Immunol Clin, Cagliari, Italy. Presidio Pneumotisiol, Oristano, Italy. Clin Pneumotisiol, Sassari, Italy. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. Osped Cesare Zonchello, Unita Operat Allergol, Nuoro, Italy. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, Rome, Italy. Univ Verona, Dipartimento Materno Infantile & Biol Genet, Sez Biol & Genet, I-37100 Verona, Italy. Univ Verona, Pediat Clin, I-37100 Verona, Italy. Osped Bolzano, Dipartimento Pediat, Bolzano, Italy. NIA, Genet Lab, Baltimore, MD 21224 USA. RP Cao, A (reprint author), CNR, Ist Neurogenet & Neurofarmacol, Div Pneumol 2, Osped Binaghi, Cittadella Univ Cagliari, I-09042 Monserrato, CA, Italy. EM acao@mcweb.unica.it RI Sole, Gabriella /I-4820-2013; Naitza, Silvia/D-5620-2017; OI Sole, Gabriella /0000-0001-5292-5038; Del Giacco, G. Sergio/0000-0001-9169-9440; sanna, serena/0000-0002-3768-1749; Malerba, Giovanni/0000-0001-8705-8560 FU Intramural NIH HHS; Telethon [E.0867] NR 42 TC 87 Z9 91 U1 0 U2 8 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 JUN PY 2007 VL 80 IS 6 BP 1103 EP 1114 DI 10.1016/518259 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 168WD UT WOS:000246553800009 PM 17503328 ER PT J AU Parle-McDermott, A Pangilinan, F Mills, JL Kirke, PN Gibney, ER Troendle, J O'Leary, VB Molloy, AM Conley, M Scott, JM Brody, LC AF Parle-McDermott, Anne Pangilinan, Faith Mills, James L. Kirke, Peadar N. Gibney, Eileen R. Troendle, James O'Leary, Valerie B. Molloy, Anne M. Conley, Mary Scott, John M. Brody, Lawrence C. TI The 19-bp deletion polymorphism in intron-1 of dihydrofolate reductase (DHFR) may decrease rather than increase risk for spina bifida in the Irish population SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neural tube defects; spina bifida; dihydrofolate reductase (DHFR); maternal risk; folate polymorphisms; deletion; gene expression; mRNA ID NEURAL-TUBE DEFECTS; METHIONINE SYNTHASE; GENE; EXPRESSION; PREVENTION; REGION; ORGANIZATION; VITAMIN; ENZYME; FOLATE AB Periconceptional maternal folic acid supplementation can prevent tip to 70% of pregnancies affected with neural tube defects (NTDs), including spina bifida. This has focused attention on folate-related genes such as dihydrofolate reductase (DHFR) in a bid to identify the genetic factors that influence NTD risk through either the fetal or maternal genotype. We considered a novel intronic 19-bp deletion polymorphism and two polymorphisms within the 3' untranslated region (721A > T and 829C > T) of the DHFR gene as candidates for NTD risk. We studied NTD cases (n = 283), mothers of cases (n = 280), fathers of cases (n = 279), and controls (n = 256). We did not find the DHFR 829C > T polymorphism to be variable within the Irish population. The 19-bp intron deletion and the 721A > T polymorphisms were found to be in linkage disequilibrium. In contrast to a previous study, the 19-bp intron deletion allele did show a significant protective effect in mothers of NTD cases when present in one (relative risk 0.59 [95%CI: 0.39-0-89], P= 0.01) or two copies (relative risk 0.52 [95%CI: 0.32-0.86], P=0.01). Analysis of mRNA levels revealed a small increase in expression (similar to 1.5-fold) associated with the 19-bp intron deletion polymorphism, but this was not significant. In conclusion, the DHFR intron 19-bp deletion allele may be a protective NTD genetic factor by increasing DHFR mRNA levels in pregnant women. (C) 2007 Wiley-Liss, Inc, C1 Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland. NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA. NICHHD, US Dept HHS, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland. RP Parle-McDermott, A (reprint author), Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland. EM anne.parle-mcdermott@dcu.ic OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 FU Intramural NIH HHS NR 30 TC 41 Z9 45 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN 1 PY 2007 VL 143A IS 11 BP 1174 EP 1180 DI 10.1002/ajmg.a.31725 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 174PV UT WOS:000246955700007 PM 17486595 ER PT J AU Espinoza, J Kusanovic, JP Kim, CJ Kim, YM Kim, JS Hassan, SS Gotsch, F Goncalves, LF Erez, O Friel, L Soto, E Romero, R AF Espinoza, Jimmy Kusanovic, Juan Pedro Kim, Chong Jai Kim, Yeon Mee Kim, Jung-Sun Hassan, Sonia S. Gotsch, Francesca Goncalves, Luis F. Erez, Offer Friel, Lara Soto, Eleazar Romero, Roberto TI An episode of preterm labor is a risk factor for the birth of a small-for-gestational-age neonate SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists CY OCT 18-21, 2006 CL Las Vegas, NV SP Cent Assoc Obstetricians & Gynecol AB An episode of increased uterine contractility that requires hospitalization because of suspected preterm labor is a risk factor for the birth of a small-for-gestational-age neonate, even if the delivery occurred at term. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Espinoza, J (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HD002400-16] NR 0 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2007 VL 196 IS 6 BP 574 EP 575 AR 574.e1 DI 10.1016/j.ajog.2007.03.023 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 177EY UT WOS:000247137600031 PM 17547901 ER PT J AU Wong, TY Klein, R Islam, FMA Cotch, MF Couper, DJ Klein, BEK Hubbard, LD Sharrett, AR AF Wong, Tien Y. Klein, Ronald Islam, F. M. Amirul Cotch, Mary Frances Couper, David J. Klein, Barbara E. K. Hubbard, Larry D. Sharrett, A. Richey TI Three-year incidence and cumulative prevalence of retinopathy: The atherosclerosis risk in communities study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINAL MICROVASCULAR ABNORMALITIES; CORONARY-HEART-DISEASE; HYPERTENSIVE RETINOPATHY; CARDIOVASCULAR HEALTH; OLDER PERSONS; MORTALITY; POPULATION; STROKE; HOORN; ASSOCIATIONS AB Purpose: To describe the three-year incidence and cumulative prevalence of retinopathy and its risk factors. Design: Population,based, prospective cohort study in four US communities. Methods: In the Atherosclerosis Risk in Communities (ARIC) Study, 981 participants had retinal photography of one randomly selected eye at the third examination (1993 to 1995) and three years later at the fourth examination (1996). Photographs were graded on both occasions for retinopathy signs (for example, microaneurysm, retinal hemorrhage, and/or cotton wool spots). Incidence was defined as participants without retinopathy at the third examination who developed retinopathy at the fourth examination, and cumulative prevalence was defined to include incident retinopathy as well as participants who had retinopathy at both the third and fourth examinations. Results: The three-year incidence and cumulative prevalence of any retinopathy in the whole cohort was 3.8% and 7.7%, respectively. In multivariable analysis, incident retinopathy was related to higher mean arterial blood pressure (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0 to 2.3, per standard deviation increase in risk factor levels), fasting serum glucose (OR 1.6, 95% CI 1.3 to 2.1), serum total cholesterol (OR 1.4, 95% CI 1.0, 2.0), and plasma fibrinogen (OR 1.4, 95% CI 1.1 to 1.9). Among persons without diabetes, the three,year incidence and cumulative prevalence of nondiabetic retinopathy was 2.9% and 4.3%, respectively. Incident nondiabetic retinopathy was related to higher mean arterial blood pressure (OR 1.4, 95% CI 0.9 to 2.3) and fasting serum glucose (OR 1.5, 95% CI 1.0 to 2.3). Among persons with diabetes, the three-year incidence and cumulative prevalence of diabetic retinopathy was 10.1% and 27.2%, respectively. Conclusions: Retinopathy signs occur frequently in middle aged people, even in those without diabetes. Hypertension and hyperglycemia are risk factors for incident retinopathy. C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. Natl Univ Singapore, Eye Res Inst, Singapore 117548, Singapore. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z01 EY000426-04, Z01 EY000426-05, Z99 EY999999, ZIA EY000426-06, ZIA EY000426-07, ZIA EY000426-08]; NEI NIH HHS [R03 EY013939, R03 EY013939-01, R03 EY013939-02]; NHLBI NIH HHS [N01-HC-55018, N01-HC-35125, N01-HC-35126, N01-HC-55015, N01-HC-55016, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022] NR 32 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2007 VL 143 IS 6 BP 970 EP 976 DI 10.1016/j.ajo.2007.02.020 PG 7 WC Ophthalmology SC Ophthalmology GA 177QG UT WOS:000247167000008 PM 17399675 ER PT J AU Lissat, A Vraetz, T Tsokos, M Klein, R Braun, M Koutelia, N Fisch, P Romero, ME Long, L Noellke, P Mackall, CL Niemeyer, CM Kontny, U AF Lissat, Andrej Vraetz, Thomas Tsokos, Maria Klein, Ruth Braun, Matthias Koutelia, Nino Fisch, Paul Romero, Maria E. Long, Lauren Noellke, Peter Mackall, Crystal L. Niemeyer, Charlotte M. Kontny, Udo TI Interferon-gamma sensitizes resistant Ewing's sarcoma cells to tumor necrosis factor apoptosis-inducing ligand-induced apoptosis by up-regulation of caspase-8 without altering chemosensitivity SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRAIL-INDUCED APOPTOSIS; DRUG-INDUCED APOPTOSIS; NEUROECTODERMAL TUMORS; PROTEIN EXPRESSION; HUMAN HEPATOCYTES; FAMILY TUMORS; RECEPTOR; DEATH; GENE; NEUROBLASTOMA AB Ewing's sarcoma cells are highly susceptible to apoptosis via tumor necrosis factor apoptosis-inducing ligand (TRAIL). Resistance to TRAM has been linked to deficient expression of caspase-8 in vitro. Here, we report on the status of caspase-8 expression in tumors from patients with Ewing's sarcoma, the effect of interferon-gamma on caspase-8 expression and apoptosis, and the role of caspase-8 for TRAIL- and chemotherapy-mediated apoptosis in Ewing's sarcoma. Using immunohistochemistry, we show that low expression of caspase-8 is seen in about 24% of tumors. interferon-gamma induces expression of caspase-8 at concentrations achievable in humans and sensitizes cells to TRAM. Transfection of wild type but not mutant caspase-8 into caspase-8-deficient Ewing's sarcoma cells restored sensitivity to TRAIL, indicating that up-regulation of caspase-8 is sufficient to restore TRAM sensitivity. In contrast, no role for caspase-8 in chemotherapy-induced apoptosis was identified, because 1) transfection of caspase-8 or treatment with interferon-gamma did not alter the sensitivity of caspase-8-deficient cells to chemotherapeutics, 2) application of chemotherapy did not select for caspase-8-negative tumor cells in vivo, and 3) the caspase-8 status of tumors did not influence survival after chemotherapy-based protocols. In conclusion, our data provide a rationale for the inclusion of interferon-gamma in upcoming clinical trials with TRAIL. C1 Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany. Univ Freiburg, Inst Pathol, D-7800 Freiburg, Germany. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kontny, U (reprint author), Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Mathildenstr 1, D-79106 Freiburg, Germany. EM udo.kontny@uniklinik-freiburg.de FU Intramural NIH HHS NR 61 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2007 VL 170 IS 6 BP 1917 EP 1930 DI 10.2353/ajpath.2007.060993 PG 14 WC Pathology SC Pathology GA 174PR UT WOS:000246955300012 PM 17525260 ER PT J AU Na, KY Kim, GH Joo, KW Lee, JW Jang, HR Oh, YK Jeon, US Chae, SW Knepper, MA Han, JS AF Na, Ki Young Kim, Gheun-Ho Joo, Kwon Wook Lee, Jay Wook Jang, Hye Ryoun Oh, Yun Kyu Jeon, Un Sil Chae, Seoung-Wan Knepper, Mark A. Han, Jin Suk TI Chronic furosemide or hydrochlorothiazide administration increases H(+)-ATPase B1 subunit abundance in rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE distal acidification; amiloride; polyclonal anti-H(+)-ATPase B1 subunit antibody; pendrin; intercalated cells ID RENAL INTERCALATED CELLS; MOUSE KIDNEY; URINARY ACIDIFICATION; COLLECTING DUCT; PENDRIN; TRANSPORT; EXPRESSION; DIURETICS; B1-SUBUNIT; SECRETION AB Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H(+)-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H(+)-ATPase and whether electrogenic Na(+) reabsorption is involved in this process. A 7-day infusion of furosemide or hydrochlorothiazide (HCTZ) lowered urine pH significantly. However, this effect of furosemide-induced distal acidification was not changed with amiloride-blocking electrogenic Na(+) reabsorption. On immunoblotting, a polyclonal antibody against the H(+)-ATPase B1 subunit recognized a specific similar to 56-kDa band in membrane fractions from the kidney. The protein abundance of H(+)-ATPase was significantly increased by furosemide and HCTZ infusion in both the cortex and outer medulla. Furosemide plus amiloride administration also increased the H(+)-ATPase protein abundance significantly. However, no definite subcellular redistribution of H(+)-ATPase was observed by furosemide +/- amiloride infusion with immunohistochemistry. Chronic furosemide +/- amiloride administration induced a translocation of pendrin to the apical membrane, while total protein abundance was not increased. The mRNA expression of H(+)-ATPase was not altered by furosemide +/- amiloride infusion. We conclude that chronic administration of diuretics enhances distal acidification by increasing the abundance of H(+)-ATPase irrespective of electrogenic Na(+) reabsorption. This upregulation of H(+)-ATPase in the intercalated cells may be the result of tubular hypertrophy by diuretics. C1 Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea. Hanyang Univ, Coll Med, Dept Internal Med, Seoul 133791, South Korea. Sungkyunkwan Univ, Kangbuk Samsung Hosp, Sch Med, Dept Pathol, Seoul, South Korea. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28,Yougon Dong, Seoul 110744, South Korea. EM jshan@snu.ac.kr RI Oh, Yun Kyu/J-5542-2012; Han, Jin-Suk/J-5711-2012; Na, Ki Young/J-5456-2012; Joo, Kwon Wook/J-5675-2012; OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 28 TC 13 Z9 13 U1 0 U2 4 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 JUN PY 2007 VL 292 IS 6 BP F1701 EP F1709 DI 10.1152/ajprenal.00270.2006 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 188TK UT WOS:000247942000005 PM 17311909 ER PT J AU Compton, W AF Compton, Wilson TI Understanding the social epidemiology of drug abuse and HIV/AIDS SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 NIDA, Div Epidemiol Prevent & Serv Res, NIH, Div Epidemiol, Bethesda, MD 20892 USA. RP Compton, W (reprint author), NIDA, Div Epidemiol Prevent & Serv Res, NIH, Div Epidemiol, 6001 Execut Blvd,Room 5153, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 DA999999] NR 12 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2007 VL 32 IS 6 SU S BP S139 EP S140 DI 10.1016/j.amepre.2007.02.008 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 178IK UT WOS:000247214200001 PM 21776184 ER PT J AU Conway, KP Swendsen, JD Dierker, L Canino, G Merikangas, KR AF Conway, Kevin P. Swendsen, Joel D. Dierker, Lisa Canino, Glorisa Merikangas, Kathleen R. TI Psychiatric comorbidity and acculturation stress among Puerto Rican substance abusers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INTERNATIONAL DIAGNOSTIC INTERVIEW; NATIONAL EPIDEMIOLOGIC SURVEY; NON-HISPANIC WHITES; MEXICAN-AMERICANS; LIFETIME PREVALENCE; UNITED-STATES; MENTAL-DISORDERS; RISK-FACTORS; RELIABILITY; ALCOHOL AB Background: Although acculturation to the United States has been associated with an increase in substance, mood, and anxiety disorders in Latino populations, few studies have examined this concept relative to comorbidity among these syndromes. Methods: This study compares the prevalence and patterns of psychiatric comorbidity among Puerto Ricans with substance use disorders living in San Juan (Puerto Rico) to those who have migrated to New Haven (Connecticut) and examines the association between acculturation-related stress and the prevalence and patterns of psychiatric comorbidity among those who have migrated to New Haven. Results: Lifetime levels of nearly all comorbid psychiatric disorders among respondents with substance use disorders were generally similar across sites. However, the risk of any co-occurring psychiatric disorder was higher among substance use disorder cases in New Haven who reported high levels of total acculturation stress and family-specific acculturation stress. These findings were generally accounted for by associations between affective disorders and high scores on these indicators of acculturation stress. Conclusions: The overall prevalence and patterns of psychiatric comorbidity are remarkably similar among Puerto Rican substance abusers whether they live in San Juan or have migrated to New Haven, thereby demonstrating robustness to differences in geographic location. Nevertheless, the degree of acculturation-related family stress is positively associated with co-occurring substance and psychiatric disorders, particularly affective disorders. Intervention in family strain related to the acculturation process may diminish the development of comorbid mental disorders and assist in implementing successful treatment of substance abuse. C1 NIDA, Div Clin Neurosci & Behav Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Bordeaux 2, Dept Psychol, F-33076 Bordeaux, France. Wesleyan Univ, Dept Psychol, Middletown, CT USA. Behav Sci Res Inst, San Juan, PR USA. NIMH, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kconway@nida.nih.gov OI Conway, Kevin/0000-0002-7638-339X FU NIDA NIH HHS [R01 DA009055, R01 DA009055-05, R01DA09055] NR 49 TC 8 Z9 8 U1 5 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2007 VL 32 IS 6 SU S BP S219 EP S225 DI 10.1016/j.amepre.2007.02.033 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 178IK UT WOS:000247214200012 PM 17543714 ER PT J AU Thomas, YF AF Thomas, Yonette F. TI The social epidemiology of drug abuse SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID SOCIOECONOMIC-STATUS; SUBSTANCE USE; RISK-FACTORS; FAMILIAL TRANSMISSION; MALE TWINS; NEIGHBORHOOD; HEALTH; COCAINE; MULTILEVEL; MARIJUANA C1 NIH, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Thomas, YF (reprint author), NIH, Epidemiol Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd,Rm 5146,Suite 5153,MSC 9589, Bethesda, MD 20892 USA. EM yonette.thomas@nih.hhs.gov NR 54 TC 5 Z9 5 U1 5 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2007 VL 32 IS 6 SU S BP S141 EP S146 DI 10.1016/j.amepre.2007.03.007 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 178IK UT WOS:000247214200002 ER PT J AU Paukner, A Ferrari, P Visalberghi, E Fogassi, L Ruggiero, A Suomi, S AF Paukner, A. Ferrari, P. Visalberghi, E. Fogassi, L. Ruggiero, A. Suomi, S. TI The effects of facial and manual gestures on the behavior of neonatal rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Anim Ctr, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. CNR, Ist Sci Tech Cognizione, Rome, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 5 BP 32 EP 32 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700006 ER PT J AU Higley, JD Davis, E Woodward, RA Suomi, SJ AF Higley, J. D. Davis, E. Woodward, R. A. Suomi, S. J. TI Self-injurious behavior in rhesus macaques: Early history and present factors and the role of the serotonin system SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LCTS, Sect Study Primate Models Psychopathol, Poolesville, MD 20837 USA. Brigham Young Univ, Dept Psychol, Provo, UT 84602 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 21 BP 39 EP 40 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700022 ER PT J AU Ionica, CS Berman, C Li, J AF Ionica, C. S. Berman, C. Li, J. TI Post-conflict interactions with bystanders in Tibetan macaques (Macaca thibetana huangshanensis) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Comparat Ethol Lab, Dickerson, MD 20842 USA. SUNY Buffalo, Dept Anthropol, Buffalo, NY 14260 USA. SUNY Buffalo, Progrma Evolut Ecol & Behav, Buffalo, NY 14261 USA. Anhui Univ, Sch Life Sci, Hefei 230039, Peoples R China. RI Ionica, Consuel/A-5186-2009 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 27 BP 42 EP 43 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700028 ER PT J AU Wagner, PO AF Wagner, P. O'Neill TI Goals achieved with captive rhesus monkeys (Macaca mulatta) when utilizing innovative bottle challenge SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, DHHS PHS, NIH Anim Ctr,Lab Comparat Ethol, Poolesville, MD 20837 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 41 BP 49 EP 50 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700042 ER PT J AU Sheldon, EL Wolf, RF Novak, MFSX White, GL AF Sheldon, E. L. Wolf, R. F. Novak, M. F. S. X. White, G. L. TI Assessment of changes and additions to an enrichment program in captive colony of SPF baboons (Papio anubis) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pathol & Comparat Med, Oklahoma City, OK USA. NIH, NICHD, Comparat Ethol 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 51 BP 54 EP 55 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700052 ER PT J AU Robbins, KL Grays, PB Gerald, MS Laudenslager, ML Suomi, SJ AF Robbins, K. L. Grays, P. B. Gerald, M. S. Laudenslager, M. L. Suomi, S. J. TI Development of oxytocin in young female rhesus monkeys on Cayo Santiago SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIHAC, NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. Univ Nevada, Reno, NV 89557 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 59 BP 58 EP 58 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700060 ER PT J AU Schwandt, ML Newman, TK Suomi, SJ Higley, JD Heilig, M Barr, CS AF Schwandt, M. L. Newman, T. K. Suomi, S. J. Higley, J. D. Heilig, M. Barr, C. S. TI Monoamine oxidase A (MAOA) gene promoter variation interacts with early rearing condition to influence the behavioral response to social separation in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAAA, Lab Clin & Translat Studies, Poolesville, MD 20837 USA. Univ Cape Town, ZA-7700 Rondebosch, South Africa. NIH, NICHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Psychol, Provo, UT 84602 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 63 BP 60 EP 61 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700064 ER PT J AU Thomas, SJ Schwandt, ML Lindell, SG Suomi, SJ Barr, CS Higley, JD AF Thomas, S. J. Schwandt, M. L. Lindell, S. G. Suomi, S. J. Barr, C. S. Higley, J. D. TI Heritability of dominance rank in laboratory-housed juvenile nonhuman primates SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Brigham Young Univ, Dept Psychol, Provo, UT 84057 USA. NIH, NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NIH, NICHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 66 BP 62 EP 62 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700067 ER PT J AU Miller, ML Darcey, L Ruggiero, AM Schwandt, ML Barr, CS Suomi, SJ Novak, MFSX AF Miller, M. L. Darcey, L. Ruggiero, A. M. Schwandt, M. L. Barr, C. S. Suomi, S. J. Novak, M. F. S. X. TI Mother-only rearing in nuclear family caging produces species-typical behavioral development in rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NICHD, Res Animal Management Branch, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 68 BP 63 EP 63 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700069 ER PT J AU Ruggiero, AM Novak, MFSX Woodward, RA Suomi, SJ AF Ruggiero, A. M. Novak, M. F. S. X. Woodward, R. A. Suomi, S. J. TI Introduction of mother-infant pairs after delivery via cesarean section in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NICHD, Res Animal Management Branch, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 69 BP 63 EP 64 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700070 ER PT J AU Snyder, ML Lusk, A Miller, ML Darcey, L Ruggiero, AM Schwandt, ML Barr, CS Suomi, SJ Novak, MFSX AF Snyder, M. L. Lusk, A. Miller, M. L. Darcey, L. Ruggiero, A. M. Schwandt, M. L. Barr, C. S. Suomi, S. J. Novak, M. F. S. X. TI Handling and cognitive testing in infant rhesus monkeys (Macaca mulatta) alters their behavioral development SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. George Mason Univ, Fairfax, VA 22030 USA. NIH, NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 70 BP 64 EP 64 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700071 ER PT J AU Willard, SL Shively, CA AF Willard, S. L. Shively, C. A. TI Effects of social status on differences in mothering style in Macaca fascicularis SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Animal Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. George Mason Univ, Fairfax, VA 22030 USA. NIH, NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 71 BP 64 EP 65 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700072 ER PT J AU Halcrow, SR Schwandt, ML Suomi, SJ Barr, CS AF Halcrow, S. R. Schwandt, M. L. Suomi, S. J. Barr, C. S. TI Behavioral differences observed in mother and infant rhesus macaques (Macaca mulatta) during pre-separation and following reunion as a function of separation conditions SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD 20837 USA. NIH, NICHD, Comparat Ethol Lab, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 72 BP 65 EP 65 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700073 ER PT J AU Chisholm, K Schwandt, M Higley, JD Suomi, SJ Heilig, M Barr, CS AF Chisholm, K. Schwandt, M. Higley, J. D. Suomi, S. J. Heilig, M. Barr, C. S. TI Age and rearing condition influence behavioral responses to social intrusion in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAAA, Lab Clin & Translat Studies, Primate Unit, Poolesville, MD USA. NIH, NICHD, Comparat Ethol Lab, Poolesville, MD USA. Brigham Young Univ, Dept Psychol, Provo, UT 84602 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 79 BP 68 EP 69 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700080 ER PT J AU Dettmer, AM Ruggiero, AM Davenport, MD Novak, MA Meyer, JS Suomi, SJ AF Dettmer, A. M. Ruggiero, A. M. Davenport, M. D. Novak, M. A. Meyer, J. S. Suomi, S. J. TI Early rearing experience and hypothalamic pituitary adrenal (HPA) activity in infant rhesus monkeys (Macaca mulatta) after a separation challenge SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. NIH, NICHD, Comparat Ethol Lab, Poolesville, MD USA. Harvard Med Sch, New England Primate Res Ctr, Div Behav Biol, Southborough, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 78 BP 68 EP 68 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700079 ER PT J AU Novak, MFSX Miller, ML Sackett, GP Suomi, SJ AF Novak, M. F. S. X. Miller, M. L. Sackett, G. P. Suomi, S. J. TI Acute fetal reactions to maternal psychosocial experience SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. Washington Natl Primate Res Ctr, Seattle, WA 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 104 BP 81 EP 81 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700105 ER PT J AU Unbehagen, SJ Kertes, D Schwandt, M Suomi, SJ AF Unbehagen, S. J. Kertes, D. Schwandt, M. Suomi, S. J. TI Housing influences on serotonin metabolite levels in infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 129 BP 93 EP 94 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700130 ER PT J AU Kenhel, WM Quinn, AL Bell, RC Aronoff, EC Bernhards, DE Silva, AC Newman, JD AF Kenhel, W. M. Quinn, A. L. Bell, R. C. Aronoff, E. C. Bernhards, D. E. Silva, A. C. Newman, J. D. TI A new brain atlas of the common marmoset and its application to infant brain development SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 133 BP 95 EP 96 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700134 ER PT J AU Huntsberry, ME Roma, PG Christensen, CJ Ruggiero, AM Suomi, SJ AF Huntsberry, M. E. Roma, P. G. Christensen, C. J. Ruggiero, A. M. Suomi, S. J. TI Token exchange and the selective-value effect in capuchin monkeys (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Natl Inst Hlth Anim Hlth Ctr, Poolesville, MD USA. American Univ, Washington, DC 20016 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 141 BP 99 EP 100 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700142 ER PT J AU Herman, KN Nelson, EE Noble, PL Wojteczko, K Winslow, JT Pine, D Suomi, SJ Fox, NA AF Herman, K. N. Nelson, E. E. Noble, P. L. Wojteczko, K. Winslow, J. T. Pine, D. Suomi, S. J. Fox, N. A. TI Effects of rearing on aspartame consumption in male rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Comparat Ethol Lab, Poolesville, MD 20842 USA. Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA. NIMH, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 151 BP 104 EP 104 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700152 ER PT J AU Glover, EJ Willard, SL Dauenport, AT Thompson, J Friedman, DP Higley, JD DePetrillo, PB Singley, E Shively, CA AF Glover, E. J. Willard, S. L. Dauenport, A. T. Thompson, J. Friedman, D. P. Higley, J. D. DePetrillo, P. B. Singley, E. Shively, C. A. TI 5-HT1A receptor binding is increased in the hippocampus of depressed cynomolgus macaques (Macaca fascicularis) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Neurosci Program, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIAAA, Clin Studies 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 153 BP 105 EP 106 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700154 ER PT J AU Depeine, CD Bernhards, DE Newman, JD AF Depeine, C. D. Bernhards, D. E. Newman, J. D. TI Consistency of vocal behavior during brief separations in common marmosets SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 BP 107 EP 107 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700157 ER PT J AU Davis, EB Chisholm, KL Higley, JD Barr, CS Woodward, RA Schech, JM Suomi, SJ AF Davis, E. B. Chisholm, K. L. Higley, J. D. Barr, C. S. Woodward, R. A. Schech, J. M. Suomi, S. J. TI Rates of externally-directed aggression during intruder challenge testing does not differ between self-biting and non-biting rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, NICHD, Anim Ctr, Res Anim Management Branch, Poolesville, MD 20837 USA. NIH, NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD USA. Brigham Young Univ, Provo, UT 84602 USA. NIH, NICHD, Comparat Ethol Lab, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 161 BP 109 EP 110 PG 2 WC Zoology SC Zoology GA 176OB UT WOS:000247093700162 ER PT J AU Weed, JL O'Neill-Wagner, PL AF Weed, J. L. O'Neill-Wagner, P. L. TI Behavior research facilitates comprehensive captive animal care: The birth of behavioral management SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, DHHS, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. NIH, Anim Ctr, Comparat Ethol Lab, Poolesville, MD USA. NICHD, DHHS, PHS, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUN PY 2007 VL 69 SU 1 MA 176 BP 117 EP 117 PG 1 WC Zoology SC Zoology GA 176OB UT WOS:000247093700177 ER PT J AU Brogly, SB Watts, DH Ylitalo, N Franco, EL Seage, GR Oleske, J Eagle, M Van Dyke, R AF Brogly, Susan B. Watts, D. Heather Ylitalo, Nathalie Franco, Eduardo L. Seage, George R., III Oleske, James Eagle, Michelle Van Dyke, Russell TI Reproductive health of adolescent girls perinatally infected with HIV SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; RISK-FACTORS; WOMEN; PREVALENCE; PREDICTORS; PREGNANCY AB Objectives. We sought to describe the reproductive health of adolescent girls perinatally infected with HIM. Methods. We estimated the incidence of first pregnancy, genital infections, and abnormal cervical cytology for 638 girls aged 13 years and older in the Pediatric AIDS Clinical Trials Group protocol 219C. Results. Thirty-eight girls became pregnant, for a first pregnancy rate of 18.8/ 1000 person-years; 7 of these girls had additional pregnancies (95% confidence interval [CI] = 13.3, 25.7). Thirty-two pregnancies resulted in live births. All girls received antiretroviral therapy during pregnancy. One infant was HIV infected, 29 were uninfected, and 2 had unknown infection status, for a rate of mother-to-child transmission of HIV in infants with known infection status of 3.3% (95% CI=0.1, 18.6). Condylomata and trichomoniasis were the most frequent genital infections. Forty-eight (47.5%) of 101 girls with Papanicolaou test examinations had abnormal cervical cytology, including atypical cells of undetermined significance (n=18), low-grade squamous intraepithelial lesions (SIL; n=27), and highc rade SIL (n = 3). Many abnormalities persisted despite intervention. Conclusions. Pregnancy rates were lower and cervical abnormalities were higher than among non-HIV-infected adolescents. These findings underscore the importance of Papanicolaou tests and promotion of safer sexual practices in this population. C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3A 2T5, Canada. Univ Med & Dent New Jersey, Dept Pediat, Newark, NJ 07103 USA. Univ Florida, Div Pediat Infect Dis & Immunol, Gainesville, FL USA. Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA. RP Brogly, SB (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 661 Huntington Ave, Boston, MA 02115 USA. EM sbrogly@sdac.harvard.ealu OI Franco, Eduardo/0000-0002-4409-8084 FU NIAID NIH HHS [U01 AI041089, U01 AI041110, U01 AI41089, 5 U01 AI41110] NR 16 TC 59 Z9 60 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2007 VL 97 IS 6 BP 1047 EP 1052 DI 10.2105/AJPH.2005.071910 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 173IR UT WOS:000246867200017 PM 17463385 ER PT J AU Ren, P Rosas, IO MacDonald, SD Wu, HP Billings, EM Gochuico, BR AF Ren, Ping Rosas, Ivan O. MacDonald, Sandra D. Wu, Hai-Ping Billings, Eric M. Gochuico, Bernadette R. TI Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE monocytes/macrophages; transcription factors; TFII-H; lung ID HERMANSKY-PUDLAK-SYNDROME; HUNTINGTONS-DISEASE; COCKAYNE-SYNDROME; DNA-REPAIR; GENE; EXPRESSION; REVEALS; ROLES; MODEL; TFIIH AB Rationale: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins. Objectives: To identify potential molecular mechanisms of IPF. Methods: To examine large-scale gene expression, messenger RNA isolated from alveolar macrophages and peripheral blood mononuclear cells from subjects with IPF and normal volunteers was hybridized to cDNA filters. Measurements and Main Results: We showed that in IPF there is global down-regulation of gene expression in alveolar macrophages but not in blood monocytes. Nuclear run-on and pulse-chase studies showed that alveolar macrophages had significantly reduced transcription (p < 0.01). No significant difference in RNA degradation was found between subjects with IPF and normal volunteers. Western blot analyses revealed that concentrations of transcription factor II-H, a general transcription factor, were significantly lower in alveolar macrophages from subjects with IPF than in those from normal volunteers (p = 0.012). Conclusions: Impaired transcription in IPF is associated with decreased concentrations of transcription factor II-H in alveolar macrophages and may alter the intraalveolar milieu in IPF. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA. RP Gochuico, BR (reprint author), 10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. EM gochuicb@mail.nih.gov FU Intramural NIH HHS NR 23 TC 12 Z9 13 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 JUN 1 PY 2007 VL 175 IS 11 BP 1151 EP 1157 DI 10.1164/rccm.200607-958OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 173VN UT WOS:000246900700009 PM 17332483 ER PT J AU Kirk, AD Baldwin, WM Cascalho, MI Chong, AS Sykes, M West, LJ AF Kirk, A. D. Baldwin, W. M. Cascalho, M. I. Chong, A. S. Sykes, M. West, L. J. TI American Society of Transplantation Symposium on B cells in Transplantation: Harnessing humoral immunity from rodent models to clinical practice SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE antibody; immunosuppression; tolerance; transplantation ID RENAL-ALLOGRAFT REJECTION; NONLETHAL PREPARATIVE REGIMEN; INFANT HEART-TRANSPLANTATION; ANTIBODY-PRODUCING CELLS; MIXED CHIMERISM; ALPHA-1,3-GALACTOSYLTRANSFERASE-DEFICIENT MICE; GAL-ALPHA-1,3GAL EPITOPES; LYMPHOID NEOGENESIS; ORGAN ALLOGRAFTS; T-CELL AB There is growing awareness that B cells and alloantibodies are important mediators of both acute and chronic allograft injury. Unfortunately, few therapies are clinically available to mitigate the function of B cells or the effects of established alloantibody. As a result, many sensitized people await transplantation without a suitable donor, and several rejection syndromes are emerging that appear to involve B cells either as antibody producers or as antigen-presenting cells. In recognition of this unmet need in transplantation, the American Society of Transplantation organized a Symposium on B cells in Organ Transplantation to foster interest in this topic amongst basic researchers attending the annual meeting of the American Association of Immunologists. This manuscript will give an overview of the presentations from this symposium including the current risks of allosensitization, adaptive accommodation, approaches toward B-cell tolerance for allo- and xenoantigens and clinical application of these concepts in ABO incompatible neonatal cardiac transplantation. C1 NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Mayo Clin Coll Med, Dept Immunol, Rochester, MN USA. Mayo Clin Coll Med, Dept Surg, Rochester, MN USA. Mayo Clin Coll Med, Dept Pediat, Rochester, MN USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Boston, MA USA. Univ Alberta, Dept Pediat, Edmonton, AB, Canada. Univ Alberta, Dept Surg, Edmonton, AB, Canada. Univ Alberta, Dept Immunol, Edmonton, AB, Canada. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM AllanK@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012; OI Cascalho, Marilia/0000-0002-2695-3921 FU Intramural NIH HHS; NHLBI NIH HHS [HL79067, P01 HL18646, P01 HL70295, P01-HL079067, P01-HL56091]; NIAID NIH HHS [AI 052464, AI43631, AI53733, R01 AI42387] NR 40 TC 7 Z9 7 U1 0 U2 1 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 JUN PY 2007 VL 7 IS 6 BP 1464 EP 1470 DI 10.1111/j.1600-6143.2007.01815.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 169EY UT WOS:000246576700007 PM 17511676 ER PT J AU Amaral, MEJ Owens, KE Elliott, JS Fickey, C Schaffer, AA Agarwala, R Womack, JE AF Amaral, M. E. J. Owens, K. E. Elliott, J. S. Fickey, C. Schaeffer, A. A. Agarwala, R. Womack, J. E. TI Construction of a river buffalo (Bubalus bubalis) whole-genome radiation hybrid panel and preliminary RH mapping of chromosomes 3 and 10 SO ANIMAL GENETICS LA English DT Article DE gene mapping; radiation hybrid panel; river buffalo; whole genome ID HUMAN COMPARATIVE MAP; ASSIGNMENT; EVOLUTION; LOCI AB The buffalo (Bubalus bubalis) is a source of milk and meat, and also serves as a draft animal. In this study, a 5000-rad whole-genome radiation hybrid (RH) panel for river buffalo was constructed and used to build preliminary RH maps for BBU3 and BBU10 chromosomes. The preliminary maps contain 66 markers, including coding genes, cattle expressed sequence tags (ESTs) and microsatellite loci. The RH maps presented here are the starting point for mapping additional loci that will allow detailed comparative maps between buffalo, cattle and other species whose genomes may be mapped in the future. A large quantity of DNA has been prepared from the cell lines forming the river buffalo RH panel and will be made publicly available to the international community both for the study of chromosome evolution and for the improvement of traits important to the role of buffalo in animal agriculture. C1 Sao Paulo State Univ, Dept Biol, IBILCE, UNESP, BR-15054000 Sao Jose Rio Presto, SP, Brazil. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20984 USA. RP Amaral, MEJ (reprint author), Sao Paulo State Univ, Dept Biol, IBILCE, UNESP, BR-15054000 Sao Jose Rio Presto, SP, Brazil. EM eamaral@ibilce.unesp.br RI Schaffer, Alejandro/F-2902-2012; Amaral, Elisabete/K-9246-2013 FU Intramural NIH HHS NR 12 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD JUN PY 2007 VL 38 IS 3 BP 311 EP 314 DI 10.1111/j.1365-2052.2007.01587.x PG 4 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 176UD UT WOS:000247109500019 PM 17403053 ER PT J AU Chodick, G Shalev, V Goren, I Inskip, PD AF Chodick, Gabriel Shalev, Varda Goren, Iris Inskip, Peter D. TI Seasonality in birth weight in Israel: New evidence suggests several global patterns and different etiologies SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE macrosomia; sunlight; latitude; seasonality; birth weight ID FETAL MACROSOMIA; OUTDOOR TEMPERATURE; GROWTH; MELATONIN; CANCER; RISK; CHILDHOOD; SIZE; POPULATION; SECRETION AB Purpose: To investigate the effect of season on birth weight and whether it is expressed also in fluctuations of proportions of extreme birth weights. Methods: Information about 225,545 singletons born during 1998 to 2004 was obtained from a large health maintenance organization in Israel. We conducted a linear regression analysis of the weight with month and year of birth, sex, maternal age, diabetes, and several meteorological factors as independent variables, which were also incorporated into multivariate logistic regression models to examine the effect of season of birth on the frequency of low birth weight (LBW, < 2500 g) or macrosomia ( > 4000 g). Results: A significant (P <.001) seasonal pattern in birth weights was observed, with a peak in July and a trough in January. Babies born in summer had an OR of 1.12 (95% CI; 1.07 to 1.18) for macrosomia compared with those born in the winter. No such pattern was found for LBW. Conclusions: While in regions of mid-latitude, summer is associated with relatively lower birth weight, possibly because of exposure to cold temperature during early or mid-pregnancy, our data suggest that in Israel, the peak birth weight is in summer, possibly because of increased exposure to sunlight in the last weeks of the pregnancy. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Maccabi Healthcare Serv, Dept Med Informat, Tel Aviv, Israel. RP Chodick, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7238,Execut Plaza S,Room 704, Bethesda, MD 20892 USA. EM Chodickg@mail.nih.gov NR 51 TC 24 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUN PY 2007 VL 17 IS 6 BP 440 EP 446 DI 10.1016/j.annepidem.2006.10.013 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178YU UT WOS:000247257100006 PM 17300954 ER PT J AU Meijer, IA Dion, P Laurent, S Dupre, N Brais, B Levert, A Puymirat, J Rioux, MF Sylvain, M Zhu, PP Soderblom, C Stadler, J Blackstone, C Rouleau, GA AF Meijer, Inge A. Dion, Patrick Laurent, Sandra Dupre, Nicolas Brais, Bernard Levert, Annie Puymirat, Jacques Rioux, Marie France Sylvain, Michel Zhu, Peng-Peng Soderblom, Cynthia Stadler, Julia Blackstone, Craig Rouleau, Guy A. TI Characterization of a novel SPG3A deletion in a French-Canadian family SO ANNALS OF NEUROLOGY LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; EARLY-ONSET; ATLASTIN; MUTATION; GENE; NEUROPATHY; FREQUENT; MAPS AB Hereditary spastic paraplegias (HSPs) are characterized by progressive lower limb spasticity and weakness. Mutations in the SPG3A gene, which encodes the large guanosine triphosphatase atlastin, are the second most Common cause of autosomal dominant hereditary spastic paraplegia. In a large SPG3A screen of 70 hereditary spastic paraplegia subjects, a novel in-frame deletion, p.del436N, was identified. Characterization of this deletion showed that it affects neither the guanosine triphosphatase activity of atlastin nor interactions between atlastin and spastin. Interestingly, immunoblot analysis of lymphoblasts from affected patients demonstrated a significant reduction in atlastin protein levels, supporting a loss-of-function disease mechanism. C1 Univ Montreal, Ctr Study Brain Dis, CHU Montreal, Res Ctr,Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. Univ Laval, Fac Med, Dept Neurol Sci, Ctr Hosp Affilie Univ Quebec Enfant Jesus, Quebec City, PQ G1K 7P4, Canada. CHU Quebec, Quebec City, PQ, Canada. CHU Sherbrooke, Serv Neurol, Sherbrooke, PQ J1H 5N4, Canada. CHU Quebec, Serv Neurol Pediat, Quebec City, PQ, Canada. NINDS, Cellular Neurol Unit, NIH, Bethesda, MD USA. RP Rouleau, GA (reprint author), Seve Pavillon,Room Y-3633,1560,Sherbrooke St E, Montreal, PQ H2L 4M1, Canada. EM guy.rouleau@umontreal.ca FU Intramural NIH HHS NR 20 TC 15 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2007 VL 61 IS 6 BP 599 EP 603 DI 10.1002/ana.21114 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 189XI UT WOS:000248021500013 PM 17427918 ER PT J AU Bilchik, AJ Compton, C AF Bilchik, Anton J. Compton, Carolyn TI Close collaboration between surgeon and pathologist is essential for accurate staging of early colon cancer SO ANNALS OF SURGERY LA English DT Editorial Material ID COLORECTAL-CANCER; LYMPH-NODES; BREAST-CANCER; MICROMETASTASES; TRIAL; SURVIVAL; NUMBER; METASTASES; CARCINOMA; RESECTION C1 St Johns Hlth Ctr, John Wayne Canc Inst, Dept Gastrointestinal Oncol, Santa Monica, CA USA. NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Bilchik, AJ (reprint author), 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. EM bilchika@jwci.org NR 25 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 2007 VL 245 IS 6 BP 864 EP 866 DI 10.1097/SLA.0b013e31805d07e3 PG 3 WC Surgery SC Surgery GA 173KW UT WOS:000246873000005 PM 17522510 ER PT J AU Tran, SD Kodama, S Lodde, BM Szalayova, I Key, S Khalili, S Faustman, DL Mezey, E AF Tran, Simon D. Kodama, Shohta Lodde, Beatrijs M. Szalayova, Ildiko Key, Sharon Khalili, Saeed Faustman, Denise L. Mezey, Eva TI Reversal of Sjogren's-like syndrome in non-obese diabetic mice SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID COMPLEX CLASS-I; BONE-MARROW; NOD MICE; EXPRESSION; CELLS; AUTOIMMUNITY; VIVO AB Background: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and Sjogren's- like syndrome. Objective: To test whether a treatment that reverses end-stage diabetes in the NOD mouse would affect their Sjogren's- like syndrome. Methods: NOD mice have a proteasome defect. Improperly selected naive T cells escape, but can be killed by reintroducing major histocompatibility complex class I self- peptides on matched normal splenocytes. The proteasome defect also impairs nuclear factor kB, a transcription factor in pathogenic memory T cells, increasing their susceptibility to tumour necrosis factor- induced apoptosis stimulated through complete Freund's adjuvant (CFA). The impact of this two-limb therapy (injections of matched normal splenocytes and CFA) on the autoimmune salivary gland disease of the NOD mice was studied. Results: All NOD mice receiving the above treatment had a complete recovery of salivary flow and were protected from diabetes. Restoration of salivary flow could be the result of a combination of rescue and regeneration of the gland, as confirmed by immunohistochemical analysis. All untreated NOD mice showed a continuous decline in salivary flow, followed by hyperglycaemia and death. Conclusion: This study establishes that a brief intervention in NOD mice with Sjogren's- like syndrome can reverse salivary gland dysfunction. C1 McGill Univ, Montreal, PQ H3A 2B2, Canada. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NIH, NIDCR, CSDB, Bethesda, MD 20892 USA. RP Tran, SD (reprint author), McGill Univ, 3640 Univ St,M-43, Montreal, PQ H3A 2B2, Canada. EM simon.tran@mcgill.ca; mezeye@mail.nih.gov FU Intramural NIH HHS NR 16 TC 19 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 JUN PY 2007 VL 66 IS 6 BP 812 EP 814 DI 10.1136/ard.2006.064030 PG 3 WC Rheumatology SC Rheumatology GA 169LW UT WOS:000246594700017 PM 17179174 ER PT J AU Li, HQ Price, DK Figg, WD AF Li, Haiqing Price, Douglas K. Figg, William D. TI ADH1, an N-cadherin inhibitor, evaluated in preclinical models of angiogenesis and androgen-independent prostate cancer SO ANTI-CANCER DRUGS LA English DT Article DE ADH1; angiogenesis; N-cadherin; prostate cancer ID ALPHA-CATENIN EXPRESSION; CELL-CELL ADHESION; THALIDOMIDE ANALOGS; COMPLEX; PROGRESSION; INVASION; MIGRATION; SURVIVAL; PEPTIDE; DOMAIN AB The conversion from E-cadherin to N-cadherin has been observed in several human cancer types, including prostate cancer, with more homogenous expression of N-cadherin detected in high-grade prostate tumors. N-cadherin, in vitro, has been shown to promote cell mobility, migration and invasion of several cancer cell lines, indicating the possibility of N-cadherin as a molecular target of cancer therapy. Herein, we examined the potential of an N-cadherin inhibitor, ADH1, in reducing tumor angiogenesis ex vivo and delaying tumor progression in vivo. Our data demonstrate that ADH1, at the dosages evaluated, does not display either antiangiogenic activity in a rat aortic ring assay or antitumor potential in a PC3 subcutaneous xenograft tumor model. We detecteded cytotoxic activity in human umbilical vein endothelial cells, PC3, and Tsu-Pr1 cells, when ADH1 exposure was evaluated at 500 mu mol/l or above. C1 NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 32 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUN PY 2007 VL 18 IS 5 BP 563 EP 568 DI 10.1097/CAD.0b013e328020043e PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 159DD UT WOS:000245844700006 PM 17414625 ER PT J AU Meletiadis, J Stergiopoulou, T O'Shaughnessy, EM Peter, J Walsh, TJ AF Meletiadis, Joseph Stergiopoulou, Theodouli O'Shaughnessy, Elizabeth M. Peter, Joanne Walsh, Thomas J. TI Concentration-dependent synergy and antagonism within a triple antifungal drug combination against Aspergillus species: Analysis by a new response surface model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; LIPOSOMAL AMPHOTERICIN-B; GUINEA-PIG MODEL; IN-VITRO; CASPOFUNGIN; VORICONAZOLE; EFFICACY; THERAPY; PHARMACOKINETICS; ITRACONAZOLE AB Triple antifungal combinations are used against refractory invasive aspergillosis without an adequate understanding of their pharmacodynamic interactions. We initially studied the in vitro triple combination of voriconazole, amphotericin B, and caspofungin against Aspergillus fiumigatus, A. flavus, and A. terreus by a spectrophotometric microdilution broth method after 48 h of incubation. We then analyzed these results with a recently described nonlinear mixture response surface E-max-based model modified to assess pharmacodynamic interactions at various growth levels. The new model allows flexibility in all four parameters of the E-max model and is able to describe complex pharmacodynamic interactions. Concentration-dependent pharmacodynamic interactions were found within the triple antifungal combination. At the 50% growth level, synergy (median interaction indices of 0.43 to 0.82) was observed at low concentrations of voriconazole (<0.03 mg/liter) and amphotericin B (<= 0.20 mg/liter) and at intermediate concentrations of caspofungin (0.95 to 14.88 mg/ liter), whereas antagonism (median interaction indices of 1.17 to 1.80) was found at higher concentrations of voriconazole and amphotericin B. Ternary plot and interaction surface analysis further revealed the complexity of these concentration-dependent interactions. With increasing concentrations of amphotericin B, the synergistic interactions of voriconazole-caspofungin double combination decreased while the antagonistic interactions increased. A similar effect was observed when voriconazole was added to the double combination of amphotericin B and caspofungin. In conclusion, the new nonlinear mixture-amount response surface modeling of the triple antifungal combination demonstrated a net antagonism or synergy against Aspergillus species depending upon drug concentrations and species. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Clin Canc Res,NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Clin Canc Res,NIH, 10 Ctr Dr,Bldg 10,Rm 1-5888, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 43 TC 27 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2007 VL 51 IS 6 BP 2053 EP 2064 DI 10.1128/AAC.00873-06 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 175CY UT WOS:000246991400025 PM 17387150 ER PT J AU Amano, M Koh, Y Das, D Li, JF Leschenko, S Wang, YF Boross, PI Weber, IT Ghosh, AK Mitsuya, H AF Amano, Masayuki Koh, Yasuhiro Das, Debananda Li, Jianfeng Leschenko, Sofiya Wang, Yuan-Fang Boross, Peter I. Weber, Irene T. Ghosh, Arun K. Mitsuya, Hiroaki TI A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STRUCTURE-BASED DESIGN; HIV-1 PROTEASE; DRUG-RESISTANCE; TYPE-1 VARIANTS; THERAPY; P-2-LIGANDS; MECHANISMS; DISCOVERY; INFECTION; SELECTION AB We designed, synthesized, and identified GRL-98065, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing the structure-based designed privileged cyclic ether-derived nonpeptide P2 ligand, 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF), and a sulfonamide isostere, which is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0002 to 0.0005 mu M) with minimal cytotoxicity (50% cytotoxicity, 35.7 mu M in CD4(+) MT-2 cells). GRL-98065 blocked the infectivity and replication of each of the HIV-1(NL4-3) variants exposed to and selected by up to a 5 mu M concentration of saquinavir, indinavir, nelfinavir, or ritonavir and a 1 mu M concentration of lopinavir or atazanavir (EC50, 0.0015 to 0.0075 mu M), although it was less active against HIV-1(NL4-3) selected by amprenavir (EC50, 0.032 mu M). GRL-98065 was also potent against multiple-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents, HIV-1 isolates of various subtypes, and HIV-2 isolates examined. Structural analyses revealed that the close contact of GRL-98065 with the main chain of the protease active-site amino acids (Asp29 and Asp30) is important for its potency and wide-spectrum activity against multiple-PI-resistant HIV-1 variants. The present data demonstrate that the privileged nonpeptide P2 ligand, bis-THF, is critical for the binding of GRL-98065 to the HIV protease substrate binding site and that this scaffold can confer highly potent antiviral activity against a wide spectrum of HIV isolates. C1 Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hm21q@nih.gov RI Li, Jianfeng/F-5057-2014; Amano, Masayuki/N-7407-2016 OI Li, Jianfeng/0000-0002-8838-3872; Amano, Masayuki/0000-0003-0516-9502 FU Intramural NIH HHS; NIGMS NIH HHS [GM53386, GM62920, R01 GM053386, R01 GM062920, R01 GM062920-06, R01 GM062920-08, R37 GM053386, U01 GM062920] NR 33 TC 45 Z9 47 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2007 VL 51 IS 6 BP 2143 EP 2155 DI 10.1128/AAC.01413-06 PG 13 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 175CY UT WOS:000246991400038 PM 17371811 ER PT J AU Zorrilla, CD Van Dyke, R Bardeguez, A Acosta, EP Smith, B Hughes, MD Huang, S Watts, DH Heckman, B Jimenez, E McSherry, G Mofenson, L AF Zorrilla, Carmen D. Van Dyke, Russell Bardeguez, Arlene Acosta, Edward P. Smith, Betsy Hughes, Michael D. Huang, Sharon Watts, D. Heather Heckman, Barbara Jimenez, Eleanor McSherry, George Mofenson, Lynne CA Pediat AIDS Clin Trials Grp 386 Pr TI Clinical response and tolerability to and safety of saquinavir with low-dose ritonavir in human immunodeficiency virus type 1-infected mothers and their infants SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article AB Saquinavir boosted with low-dose ritonavir given with zidovudine and lamivudine was well tolerated by pregnant women and their infants. All mothers had <400 human immunodeficiency virus type I RNA copies/ml at delivery. Two had elevated liver transaminases and amylase. Seven infant adverse events were possibly treatment related (anemia, neutropenia, and hyperbilirubinemia). C1 Univ Puerto Rico, Sch Med, Dept Obstet Gynecol, San Juan, PR 00936 USA. Tulane Univ, Sch Med, New Orleans, LA 70118 USA. Univ Med & Dent New Jersey, Newark, NJ USA. Univ Alabama, Birmingham, AL 35233 USA. NIAID, Div AIDS, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NICHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. San Juan City Hosp, San Juan, PR USA. RP Zorrilla, CD (reprint author), Univ Puerto Rico, Sch Med, Dept Obstet Gynecol, POB 365067, San Juan, PR 00936 USA. EM czorrilla@rcm.upr.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 8 TC 14 Z9 14 U1 0 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 JUN PY 2007 VL 51 IS 6 BP 2208 EP 2210 DI 10.1128/AAC.00871-06 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 175CY UT WOS:000246991400050 PM 17420209 ER PT J AU Elford, H Lee, R Turchan, J Gallicchio, V Ussery, M Hiscott, J Nath, A AF Elford, Howard Lee, Ron Turchan, Jadwiga Gallicchio, Vincent Ussery, Michael Hiscott, John Nath, Avindra TI The virtues of unique ribonucleotide reductase inhibitors didox and trimidox for retrovirus therapy SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 McGill Univ, Montreal, PQ H3A 2T5, Canada. Johns Hopkins Univ, Baltimore, MD 21218 USA. Clemson Univ, Clemson, SC 29631 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 93 BP A65 EP A66 DI 10.1016/j.antiviral.2007.01.101 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600094 ER PT J AU Margolis, L AF Margolis, Leonid TI HIV interactions with other viruses determine pathogenesis in human lymphoid tissues SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 7 BP A29 EP A30 DI 10.1016/j.antiviral.2007.01.015 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600008 ER PT J AU Matsumura, T Kato, T Hu, ZH Juteau, JM Vaillant, A Liang, J AF Matsumura, Takuya Kato, Takanobu Hu, Zonghi Juteau, Jean-Marc Vaillant, Andrew Liang, Jake TI A novel class of amphipathic DNA polymers inhibits hepatitis C virus infection by blocking viral entry SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 NIDDK, NIH, Liver Dis Branch, Bethesda, MD USA. REPLICor Inc, Laval, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 81 BP A60 EP A60 DI 10.1016/j.antiviral.2007.01.089 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600082 ER PT J AU Schleiss, M Lacayo, J Belkaid, Y McGregor, A Stroup, G Rayner, J Alterson, K Chulay, J Smith, J AF Schleiss, Mark Lacayo, Juan Belkaid, Yasmine McGregor, Alistair Stroup, Greg Rayner, Jon Alterson, Kim Chulay, Jeff Smith, Jonathan TI Vaccination as an antiviral strategy for control of cytomegalovirus (CMV) disease: A vectored vaccine approach targeting the UL83 (pp65) homolog protects against congenital CMV disease in the guinea pig model SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Dept Pediat, Minneapolis, MN USA. NIAID, Mucosal Immun Unit, NIH, Bethesda, MD 20892 USA. Meridian Biosci, Cincinnati, OH USA. AlphaVax, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 36 BP A42 EP A42 DI 10.1016/j.antiviral.2007.01.044 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600037 ER PT J AU Vermeire, K Lisco, A Grivel, JC Blank, P Schram, V Duffy, N Scarbrough, E Dey, K Bell, T Margolis, L Schols, D AF Vermeire, Kurt Lisco, Andrea Grivel, Jean-Charles Blank, Paul Schram, Vincent Duffy, Noah Scarbrough, Emily Dey, Kaka Bell, Thomas Margolis, Leonid Schols, Dominique TI Design and cellular kinetics of dansyl-labeled CADA derivatives with specific anti-HIV and CD4 receptor down-modulating properties SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 20th International Conference on Antiviral Research CY APR 29-MAY 03, 2007 CL Palm Spring, CA SP Int Soc Antiviral Res C1 Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst Med Res, Louvain, Belgium. NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. Univ Nevada, Dept Chem, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2007 VL 74 IS 3 SI SI MA 101 BP A68 EP A69 DI 10.1016/j.antiviral.2007.01.109 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 161VD UT WOS:000246043600102 ER PT J AU Beare, PA Howe, D Cockrell, DC Heinzen, RA AF Beare, Paul A. Howe, Dale Cockrell, Diane C. Heinzen, Robert A. TI Efficient method of cloning the obligate intracellular bacterium Coxiella burnetii SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; RICKETTSIA-PROWAZEKII; Q-FEVER; PHASE-II; TRANSPOSON MUTAGENESIS; TRANSFORMATION; VARIANTS; RESISTANCE; CELLS; MODEL AB Coxiella burnetii is an obligate intracellular bacterium that replicates in a large lysosome-like parasitophorous vacuole (PV). Current methods of cloning C. burnetii are laborious and technically demanding. We have developed an alternative cloning method that involves excision of individual C. burnetii-laden PVs from infected cell monolayers by micromanipulation. To demonstrate the cloning utility and efficiency of this procedure, we coinfected Vero cells with isogenic variants of the Nine Mile strain of C. burnetii. Coinhabited PVs harboring Nine Mile phase 11 (NMII) and Nine Mile phase I (NMI) or Nine Mile crazy (NMC) were demonstrated by immunofluorescence. PVs were then randomly excised from cells coinfected with NMI and NMC by micromanipulation, and PVs harboring both strains were identified by PCR. Fresh Vero cells were subsequently infected with organisms from coinhabited PVs, and the PV excision and PCR screening process was repeated. Without exception, PVs obtained from second-round excisions contained clonal populations of either NMII or NMC, demonstrating that micromanipulation is an efficient and reproducible procedure for obtaining C. burnedi clones. C1 NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 38 TC 11 Z9 11 U1 0 U2 3 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 JUN PY 2007 VL 73 IS 12 BP 4048 EP 4054 DI 10.1128/AEM.00411-07 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 180VK UT WOS:000247394200032 PM 17468273 ER PT J AU Kalen, JD Hirsch, JI Kurdziel, KA Eckelman, WC Kiesewetter, DO AF Kalen, Joseph D. Hirsch, Jerry I. Kurdziel, Karen A. Eckelman, William C. Kiesewetter, Dale O. TI Automated synthesis of F-18 analogue of paclitaxel (PAC): [F-18]Paclitaxel (FPAC) SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE [F-18]Paclitaxel; multidrug resistance; PET; automated synthesis system; fluorine-18 ID P-GLYCOPROTEIN; MULTIDRUG TRANSPORTER; IN-VIVO; ACCUMULATION; MODULATION; PUMP AB A positron-emitting paclitaxel (PAC) derivative could allow in vivo measurement of multidrug resistance in tumors and, therefore, predict a potential chemotherapeutic benefit to patients. [F-18]Paclitaxel was produced using a 2-reaction vessel automated synthesizer followed by HPLC purification. Optimized reaction conditions resulted in radiochemical yields of 21.2 +/- 9.6% at end of bombardment, radiochemical purity > 99%, and specific activity of 159 +/- 43 GBq/mu mol. [F-18]Paclitaxel activities of 1.33 +/- 0.729 GBq (n =7) obtained in sterile, pyrogen-free solution for IV administration. (C) 2006 Elsevier Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Mol Imaging Ctr, Dept Radiol, Richmond, VA USA. Mol Tracer LLC, Bethesda, MD USA. NIBIB, NIH, Positron Emiss Tomog Radiochem Grp, Bethesda, MD USA. RP Kalen, JD (reprint author), Virginia Commonwealth Univ, Mol Imaging Ctr, Dept Radiol, Richmond, VA USA. EM jdkalen@vcu.edu OI Kalen, Joseph/0000-0002-7163-4604 FU NCI NIH HHS [R21 CA098334-01A1, R21 CA098334, R21CA098334] NR 16 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JUN PY 2007 VL 65 IS 6 BP 696 EP 700 DI 10.1016/j.apradiso.2006.10.015 PG 5 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 168QS UT WOS:000246539700011 PM 17161952 ER PT J AU Ye, XB Fu, H Guidotti, T AF Ye, Xibiao Fu, Hua Guidotti, Tee TI Environmental exposure and children's health in China SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Review DE chemical exposure; children; exposure assessment ID POLYBROMINATED DIPHENYL ETHERS; PERSISTENT ORGANIC POLLUTANTS; INDOOR AIR-POLLUTION; ORGANOPHOSPHATE PESTICIDE EXPOSURE; WASTE RECYCLING SITE; NEURAL-TUBE DEFECTS; HUMAN BREAST-MILK; ELECTRONIC-WASTE; SOUTH CHINA; PERFLUORINATED COMPOUNDS AB Concerns regarding adverse health effects of exposure to environmental pollutants among children are increasing. This subject area is particularly important in China because of environmental pollution problems associated with rapid development and a large population. The authors provide what is, to their knowledge, the first review in China of English- and Chinese-language literature regarding the current status of environmental exposures to children in China and the impact of these exposures on the health of children. Children in China are exposed to diverse environmental pollutants, including traditional pollutants such as lead and mercury and emerging pollutants such as phthalates and perfluorinated compounds. Incidence and prevalence of certain childhood diseases have increased in last decades. In China, a limited number of data on environmental exposure and children's health are available, and further high-quality studies are needed. C1 [Ye, Xibiao] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Ye, Xibiao; Fu, Hua] Fudan Univ, Sch Publ Hlth, Dept Prevent Med, Shanghai, Peoples R China. [Guidotti, Tee] George Washington Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Washington, DC USA. RP Ye, XB (reprint author), NIEHS, Epidemiol Branch, NIH, 11 TW Alexander Dr,MD A305, Res Triangle Pk, NC 27709 USA. EM yex2@niehs.nih.gov NR 190 TC 19 Z9 20 U1 6 U2 31 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1933-8244 EI 2154-4700 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PD SUM PY 2007 VL 62 IS 2 BP 61 EP 73 DI 10.3200/AEOH.62.2.61-73 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 272XL UT WOS:000253894900003 PM 18316263 ER PT J AU Keefe, RSE Bilder, RM Davis, SM Harvey, PD Palmer, BW Gold, JM Meltzer, HY Green, MF Capuano, G Stroup, TS McEvoy, JP Swartz, MS Roscnheck, RA Perkins, DO Davis, CE Hsiao, JK Lieberman, JA AF Keefe, Richard S. E. Bilder, Robert M. Davis, Sonia M. Harvey, Philip D. Palmer, Barton W. Gold, James M. Meltzer, Herbert Y. Green, Michael F. Capuano, George Stroup, T. Scott McEvoy, Joseph P. Swartz, Marvin S. Roscnheck, Robert A. Perkins, Diana O. Davis, Clarence E. Hsiao, John K. Lieberman, Jcffrey A. CA CATIE Investigators Neurocognitive TI Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat ID INTERVENTION EFFECTIVENESS CATIE; FIRST-EPISODE SCHIZOPHRENIA; COGNITIVE FUNCTION; NEUROPSYCHOLOGICAL CHANGE; SCHIZOAFFECTIVE DISORDER; DOUBLE-BLIND; TEST-PERFORMANCE; WORKING-MEMORY; 2ND-GENERATION ANTIPSYCHOTICS; CONVENTIONAL ANTIPSYCHOTICS AB Context: Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome. The relative effect of the second-generation (atypical) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined. change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Objective: To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic, perphenazine. Design: Randomized, double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine, perphenazine, quetiapine fumarate, or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration. Setting: Fifty-seven sites participated, including academic sites and treatment mental health facilities representative of the community. Patients: From a cohort of 1460 patients in t he treatment study, 817 completed neurocognitive testing immediately prior to randomization and then after 2 months of treatment. Main Outcome Measures: The primary outcome was change in a neurocognitive composite score after 2 months of treatment. Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains. Results: At 2 months, treatment resulted in small neurocognitive improvements of z=0.13 for olanzapine (P <.002),0.25 for perphenazine (P <.001), 0.18 for quetiapine (P <.001), 0.26 for risperidone (P <.001), and 0.12 for ziprasidone (P <.06), with no significant differences between groups. Results at 6 months were similar. After 18 months of treatment, neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups. Neurocognitive improvement predicted longer time to treatment discontinuation, independently from symptom improvement, in patients treated with quetiapine or ziprasidone. Conclusions: After 2 months of antipsychotic treatment, all groups had a small but significant improvement in neurocognition. There were no differences between any pair, of agents, including the typical drug perphenazine. These results differ from the majority of previous studies, and the possible reasons are discussed. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Behav Sci, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biol Psychiat, John Umstead Hosp, Durham, NC 27710 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Inst Neuropsychiat, Res Triangle Pk, NC USA. Quintiles Inc, Res Triangle Pk, NC USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIMH, Adult Psychopharmacol Program, Adult Treatment & Prevent Intervent Res Branch, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Keefe, RSE (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3270, Durham, NC 27710 USA. EM richard.keefe@duke.edu RI Bilder, Robert/A-8894-2008; Meltzer, Herbert/E-8131-2013; Stroup, Thomas/F-9188-2014 OI Bilder, Robert/0000-0001-5085-7852; Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH90001] NR 94 TC 567 Z9 575 U1 7 U2 38 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2007 VL 64 IS 6 BP 633 EP 647 DI 10.1001/archpsyc.64.6.633 PG 15 WC Psychiatry SC Psychiatry GA 175HQ UT WOS:000247005100003 PM 17548746 ER PT J AU Di Prospero, NA Sumner, CJ Penzak, SR Ravina, B Fischbeck, KH Taylor, JP AF Di Prospero, Nicholas A. Sumner, Charlotte J. Penzak, Scott R. Ravina, Bernard Fischbeck, Kenneth H. Taylor, J. Paul TI Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia SO ARCHIVES OF NEUROLOGY LA English DT Article ID BRAIN MITOCHONDRIA; CONTROLLED TRIAL; DISEASE; HYPERTROPHY; CV-2619; MODEL; STAGE AB Background: Friedreich ataxia ( FA) is a progressive, multisystem degenerative disorder in which oxidative stress is believed to have a role. Recent clinical studies indicate that the antioxidant idebenone, administered at 5 mg/ kg per day, reduces the cardiac hypertrophy that occurs in FA, but improvement in neurologic measures is unclear. Some studies suggest that higher doses of idebenone may be more effective, but pharmacology and toxicology at higher doses have not been investigated in human beings. Objective: To determine the safety, tolerability, and pharmacokinetics of increasing doses of idebenone in subjects with FA. Design: Open-label, phase 1A dose-escalation trial followed by an open-label, 1-month phase 1B trial. Setting: National Institutes of Health Clinical Center, Bethesda, Md. Patients: Phase 1A included 78 subjects with FA ( 24 adults, 27 adolescents, and 27 children), and phase 1B included 15 subjects with FA ( 5 adults, 5 adolescents, and 5 children). Interventions: Oral idebenone was administered to groups of 3 subjects in each age cohort during day 1. In phase 1A, the dose was increased in 10-mg/ kg increments in each successive dose group to a maximum of 75 mg/ kg. In phase 1B, oral idebenone was administered at 60 mg/ kg divided in 3 doses per day for 1 month. Main Outcome Measures: We studied the type, number, and frequency of adverse events, and pharmacokinetic parameters including maximum drug concentration, time to maximum drug concentration, area under the curve, and half- life. Results: In the first phase of the study, no doselimiting toxicity was observed and the maximum allowed dose of 75 mg/ kg was achieved in all cohorts. Plasma levels of total idebenone were found to increase proportional to drug dose up to 55 mg/ kg. Variability in absorption of the drug was observed, but drug half- life was relatively consistent across dose levels. In the second phase of the study, 14 of 15 subjects with FA tolerated idebenone at a dose of 60 mg/ kg per day for 1 month. All adverse events were mild, and pharmacokinetic parameters including maximum drug concentration, time to maximum drug concentration, and half- life did not differ significantly across age cohorts. Conclusions: These findings indicate that higher doses of idebenone lead to a proportional increase in plasma levels up to 55 mg/ kg per day and that high- dose idebenone is well- tolerated in patients with FA. These findings are essential to planning efficacy trials of high- dose idebenone in FA and other degenerative diseases in which oxidative damage has been implicated. C1 Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Clin Ctr, Clin Pharmacokinet Res Lab, Dept Pharm, NIH, Bethesda, MD USA. Univ Rochester, Dept Neurol, Med Ctr, Rochester, NY USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Di Prospero, NA (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, 35 Convent Dr,Room 2A-1008, Bethesda, MD 20892 USA. EM diprospern@ninds.nih.gov FU Intramural NIH HHS NR 24 TC 51 Z9 53 U1 0 U2 3 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 JUN PY 2007 VL 64 IS 6 BP 803 EP 808 DI 10.1001/archneur.64.6.803 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 177HF UT WOS:000247143500004 PM 17562928 ER PT J AU Ichihara, S Yamada, Y Ichihara, G Nakajima, T Li, P Kondo, T Gonzalez, FJ Murohara, T AF Ichihara, Sahoko Yamada, Yoshiji Ichihara, Gaku Nakajima, Tamie Li, Ping Kondo, Takahisa Gonzalez, Frank J. Murohara, Toyoaki TI A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiogenesis; hypoxia; ischemia; peripheral vascular disease; smoking ID HYPOXIA-INDUCIBLE FACTOR-1; AH-RECEPTOR; IN-VIVO; THERAPEUTIC ANGIOGENESIS; TRANSCRIPTION FACTOR; DEFICIENT MICE; DNA-BINDING; ACTIVATION; MECHANISMS; PROTEIN AB Objective-The aryl hydrocarbon receptor (AHR) is a transcription factor that binds to DNA as a heterodimer with the AHR nuclear translocator (ARNT) after interaction with ligands such as polycyclic and halogenated aromatic hydrocarbons found in tobacco smoke and the environment. We have investigated the interaction between AHR and hypoxia signaling pathways in regulation of angiogenesis with the use of a surgical model of ischemia. Methods and Results-Ischemia was induced by femoral artery occlusion in wild-type and AHR-null mice. Ischemia-induced angiogenesis was markedly enhanced in AHR-null mice compared with that in wild-type animals. Ischemia-induced upregulation of the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and ARNT as well as that of target genes for these transcription factors, such as that for vascular endothelial growth factor (VEGF), were also enhanced in AHR-null mice. Furthermore, the DNA binding activity of the HIF-1 alpha-ARNT complex as well as the association of HIF-1 alpha and ARNT with the VEGF gene promoter were increased by ischemia to a greater extent in AHR-null mice than in wild-type animals. Conclusions-Ablation of AHR resulted in enhancement of ischemia-induced angiogenesis. This effect was likely attributable in part to the associated enhancement of ischemia-induced VEGF expression, which in turn may be caused by an increased abundance and activity of the HIF-1 alpha-ARNT heterodimer. C1 Mie Univ, Life Sci Res Ctr, Dept Human Funct Genom, Tsu, Mie 5148507, Japan. Nagoya Univ, Grad Sch Med, Dept Cardiol, Nagoya, Aichi, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Ichihara, S (reprint author), Mie Univ, Life Sci Res Ctr, Dept Human Funct Genom, 1577 Kurimamachiya Cho, Tsu, Mie 5148507, Japan. EM saho@gene.mie-u.ac.jp RI Murohara, Toyoaki/M-4958-2014; Kondo, Takahisa/M-4918-2014 NR 32 TC 24 Z9 27 U1 0 U2 1 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 JUN PY 2007 VL 27 IS 6 BP 1297 EP 1304 DI 10.1161/ATVBAHA.106.138701 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600011 PM 17413038 ER PT J AU Buono, C Waldo, SW Chang, J Li, YF Kruth, HS AF Buono, Chiara Waldo, Stephen W. Chang, Janet Li, Yifu Kruth, Howard S. TI Macrophage phenotype in atherosclerotic human coronary arteries is different from macrophage phenotype in normal human coronary arteries SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Bethesda, MD 20817 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E46 EP E46 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600096 ER PT J AU Frazier, WA Isenberg, JS Roberts, DD AF Frazier, William A. Isenberg, Jeff S. Roberts, David D. TI Thrombospondin-1 and CD47 promote platelet aggregation by opposing NO signaling SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Washington Univ, St Louis, MO USA. Natl Inst Hlth, Bethesda, MD USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E50 EP E51 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600119 ER PT J AU Freeman, LA Amar, MJ Aponte, A Wu, W Shen, RF Shamburek, RT Remaley, AT Santamarina-Fojo, S AF Freeman, Lita A. Amar, Marcelo J. Aponte, Angel Wu, Wells Shen, Rong-Fong Shamburek, Robert T. Remaley, Alan T. Santamarina-Fojo, Silvia TI Native 2D gel analysis of HDL subpopulations: A proteomics approach SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E91 EP E91 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600331 ER PT J AU Freeman, LA Nong, Z Wagner, EM Walts, A Gonzalez-Navarro, H Rhodes, H Kennedy, AJ Remaley, AT Santamarina-Fojo, S AF Freeman, Lita A. Nong, Zengxuan Wagner, Elike M. Walts, Avram Gonzalez-Navarro, Herminia Rhodes, Hope Kennedy, Arlon J. Remaley, Alan T. Santamarina-Fojo, Silvia TI Alternative transcript variants of the mouse hepatic lipase gene in macrophages SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E65 EP E65 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600196 ER PT J AU Ganesh, SK Skelding, K Joo, JN Zheng, G Yu, A Geller, N Pan, S Billings, E Mehta, L O'Neill, K Simari, R Holmes, D O'Neill, W Kennedy, G Nabel, EG AF Ganesh, Santhi K. Skelding, Kimberly Joo, Jungnam Zheng, Gang Yu, Adong Geller, Nancy Pan, Stephen Billings, Eric Mehta, Laxmi O'Neill, Kathleen Simari, Robert Holmes, David, Jr. O'Neill, William Kennedy, Giulia Nabel, Elizabeth G. TI Candidate susceptibility loci for vascular remodeling identified through a genome-wide association study of in-stent restenosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 NIH, NHGRI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NHLBI, Bethesda, MD 20892 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Affymetrix Inc, Santa Clara, CA USA. NIH, NHGRI, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E38 EP E39 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600056 ER PT J AU Lee, JS Howard, BV Zhang, Y Fabsitz, RR AF Lee, Jennifer S. Howard, Barbara V. Zhang, Ying Fabsitz, Richard R. TI Elevated triglyceride with low HDL-C and risk of coronary heart disease in diabetics: The strong heart study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. MedStart Rsch Inst, Hyattsville, MD USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E84 EP E84 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600293 ER PT J AU Sen, S Chow, CC Ricks, M Sebring, NG Frempong, BA Sumner, AE AF Sen, Salbyasachi Chow, Carson C. Ricks, Madia Sebring, Nancy G. Frempong, Barbara A. Sumner, Anne E. TI Testing national cholesterol education program-adult treatment panel III (NCEP-ATP III) guidelines for central obesity in African Americans SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 NIH, NIDDK, Bethesda, MD 20892 USA. RI Chow, Carson/A-7970-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E113 EP E114 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600449 ER PT J AU Wagner, EM Kennedy, MA Choi, YH Schimel, DM Dulin, A Santamarina-Fojo, S Remaley, AT AF Wagner, Elike M. Kennedy, Matthew A. Choi, Young-Hun Schimel, Dan M. Dulin, Ashley Santamarina-Fojo, Silvia Remaley, Alan T. TI Inactivation of ABCG1 in C57BI/6 mice results in reduced adipose tissue mass development when challenged with a High-fat/High-cholesterol diet SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Columbus Childrens Res Inst, Columbus, OH USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E43 EP E43 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600083 ER PT J AU Nandula, SR Amarnath, S Molinolo, A Bandyopadhyay, BC Hall, B Goldsmith, CM Zheng, CY Larsson, J Sreenath, T Chen, WJ Ambudkar, IS Karlsson, S Baum, BJ Kulkarni, AB AF Nandula, Seshagiri R. Amarnath, Shoba Molinolo, Alfredo Bandyopadhyay, Bidhan C. Hall, Bradford Goldsmith, Corinne M. Zheng, Changyu Larsson, Jonas Sreenath, Taduru Chen, WanJun Ambudkar, Indu S. Karlsson, Stefan Baum, Bruce J. Kulkarni, Ashok B. TI Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PRIMARY SJOGRENS-SYNDROME; NOD MOUSE MODEL; MESSENGER-RNA EXPRESSION; TGF-BETA; FACTOR-BETA-1-DEFICIENT MICE; ABNORMAL DISTRIBUTION; AUTOIMMUNE-DISEASE; EPITHELIAL-CELLS; TRANSGENIC MICE; KNOCKOUT MICE AB Objective. Transforming growth factor 13 (TGF)3) plays a key role in the onset and resolution of autoimmune diseases and chronic inflammation. The aim of this study was to delineate the precise function of TGF beta signaling in salivary gland inflammation. Methods. We impaired TGF beta signaling in mouse salivary glands by conditionally inactivating expression of TGF beta receptor type I (TGF beta RI), either by using mouse mammary tumor virus-Cre mice or by delivering adenoviral vector containing Cre to mouse salivary glands via retrograde infusion of the cannulated main excretory ducts of submandibular glands. Results. TGF beta RI-conditional knockout (TGF beta RI-coko) mice were born normal; however, female TGF beta RI-coko mice developed severe multifocal inflammation in salivary and mammary glands and in the heart. The inflammatory disorder affected normal growth and resulted in the death of the mice at ages 4-5 weeks. Interestingly, male TGF beta RI-coko mice did not exhibit any signs of inflammation. The female TGF beta RI-coko mice also showed an increase in Th1 proinflammatory cytokines in salivary glands and exhibited an up-regulation of peripheral T cells. In addition, these mice showed an atypical distribution of aquaporin 5 in their salivary glands, suggesting likely secretory impairment. Administration of an adenoviral vector encoding Cre recombinase into the salivary glands resulted in inflammatory foci only in the glands of female TGF beta RI-loxP-flanked (floxed) mice (TGF beta RI-f/f mice), but not in those of male and female wild-type mice or male TGF beta RI-f/f mice. Conclusion. These results suggest that female mice are uniquely more susceptible to developing inflammatory disorders due to impaired TGF beta signaling in their salivary glands. C1 NIDCR, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. Univ Lund Hosp, S-22185 Lund, Sweden. RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov FU Intramural NIH HHS NR 40 TC 20 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2007 VL 56 IS 6 BP 1798 EP 1805 DI 10.1002/art.22715 PG 8 WC Rheumatology SC Rheumatology GA 177PF UT WOS:000247164300009 PM 17530708 ER PT J AU Chakravarty, EF Bush, TM Manzi, S Clarke, AE Ward, MM AF Chakravarty, Eliza F. Bush, Thomas M. Manzi, Susan Clarke, Ann E. Ward, Michael M. TI Prevalence of adult systemic lupus erythematosus in California and Pennsylvania in 2000: estimates obtained using hospitalization data SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID UNITED-STATES; HEALTH; EPIDEMIOLOGY C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. Univ Pittsburgh, Pittsburgh, PA USA. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. NIH, Bethesda, MD 20892 USA. RP Chakravarty, EF (reprint author), Stanford Univ, Sch Med, Stanford, CA 94305 USA. FU Intramural NIH HHS [Z99 AR999999]; NIAMS NIH HHS [K24 AR002213, K24-AR-00221305, R01 AR046588, R01-AR-4658805] NR 9 TC 76 Z9 79 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2007 VL 56 IS 6 BP 2092 EP 2094 DI 10.1002/art.22641 PG 3 WC Rheumatology SC Rheumatology GA 177PF UT WOS:000247164300039 PM 17530651 ER PT J AU Goldbach-Mansky, R Pucino, F Kastner, DL AF Goldbach-Mansky, Raphaela Pucino, Frank Kastner, Daniel L. TI Treatment of patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome: Comment on the article by Matsubara et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID RECEPTOR ANTAGONIST; METHOTREXATE; ARTHROPATHY; IMPROVEMENT; INDUCTION; ARTHRITIS; TRIAL; IL-1 C1 NIAMSD, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 11 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2007 VL 56 IS 6 BP 2099 EP 2101 DI 10.1002/art.22561 PG 3 WC Rheumatology SC Rheumatology GA 177PF UT WOS:000247164300045 PM 17530657 ER PT J AU Zuliani, G Volpato, S Ble, A Bandinelli, S Corsi, AM Lauretani, F Paolisso, G Fellin, R Ferrucci, L AF Zuliani, Giovanni Volpato, Stefano Ble, Alessando Bandinelli, Stefania Corsi, Anna Maria Lauretani, Fulvio Paolisso, Giuseppe Fellin, Renato Ferrucci, Luigi TI High interleukin-6 plasma levels are associated with low HDL-C levels in community-dwelling older adults: The InChianti study SO ATHEROSCLEROSIS LA English DT Article DE HDL-cholesterol; inflammation; interleukin 6; metabolic syndrome ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; INSULIN-RESISTANCE; HEART-DISEASE; ENDOTHELIAL LIPASE; LIPID-METABOLISM; RISK-FACTORS; CHOLESTEROL; APOLIPOPROTEIN; CYTOKINES AB Background: Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased incidence of coronary heart disease (CHID). A better understanding of the mechanisms leading to low HDL-C and CHD is essential for planning treatment strategies. Clinical studies have demonstrated that cytokines might affect both concentration and composition of plasma lipoproteins, including HDLs. Methods: We investigated the possible association between low HDL-C levels, defined as <= 10th gender specific percentile, and circulating markers of inflammation (IL-1 beta, TNF-alpha, IL-6, IL-10, IL-18, and CRP) in a population of 1044 community dwelling older Italian subjects from the InChianti study. Results: Using logistic regression analysis we demonstrated that IL-6 levels (111 versus I tertile, OR: 2.10; 1.10-3.75), TG (III versus I tertile OR: 27.45; 8.47-88.93), fasting insulin (III versus I tertile OR: 2.84; 1.50-5.42), and age (OR: 1.038; 1.002-1.075) were associated with low HDL-C independent of smoking, BMI, waist circumference, hypertension, diabetes, physical activity, alcohol intake, oral hypoglycaemics, CRP, IL-18, and TNF-alpha levels. The adjusted attributable risk of low HDL-C in the exposed group (III tertile of IL-6) was 54%. Conclusions: The present study provides the epidemiological evidence that besides triglycerides, fasting insulin, and age, IL-6 is one of the main correlates of low HDL-C levels in older individuals. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy. ASF Geriatr Rehabil, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Univ Florence, Ctr Study Mol Level Chron Degenerat, Dept Med & Surg Crit Care, Florence, Italy. Univ Florence, Neoplast Dis Develop Novel Therapies, Florence, Italy. Dept Geriatr Med & Metab Dis 6, Naples, Italy. NIA, Clin Res Branch, Longitudinal Studies Sect, NIH, Baltimore, MD USA. RP Zuliani, G (reprint author), Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, Via Savonarola 9, I-44100 Ferrara, Italy. EM gzuliani@hotmail.com RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016 OI VOLPATO, STEFANO/0000-0003-4335-6034; Paolisso, Giuseppe/0000-0002-2137-455X; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999] NR 33 TC 28 Z9 28 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUN PY 2007 VL 192 IS 2 BP 384 EP 390 DI 10.1016/j.atherosclerosis.2006.05.024 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178MX UT WOS:000247225900022 PM 16787648 ER PT J AU Fornage, M Carr, JJ Jacobs, DR Loria, CM Steffen, LM Williams, OD AF Fornage, M. Carr, J. J. Jacobs, D. R. Loria, C. M. Steffen, L. M. Williams, O. D. TI Association of ALOX15 gene polymorphisms with prevalence and progression of coronary artery calcification: The cardia study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Texas, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 12 EP 13 DI 10.1016/S1567-5688(07)70992-3 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100047 ER PT J AU Sethi, AA Stonik, JA Demosky, SJ Remaley, AT AF Sethi, A. A. Stonik, J. A. Demosky, S. J. Remaley, A. T. TI Complexation of an APOA-I mimetic peptide with phospholipid increases ABCA1-specific cholesterol efflux SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 NHLBI, NIH, Vasc Med Branch, Lipoprot Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 13 EP 13 DI 10.1016/S1567-5688(07)70995-9 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100050 ER PT J AU Amar, MJA Spinner, J Remaley, A AF Amar, M. J. A. Spinner, J. Remaley, A. TI Moderate increase in plasma PLTP leads to elevation of pre-beta and alpha-HDL and is coadjuvant of ApoA-I/ABCA1 in HDL formation SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 NIH, NHLBI, Vasc Med Branch, Lipoprotein Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 29 EP 29 DI 10.1016/S1567-5688(07)71056-5 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100111 ER PT J AU Janket, S Meurman, JH Baird, AE Qvarnstrom, M Nuutinen, P Van Dyke, TE AF Janket, S. Meurman, J. H. Baird, A. E. Qvarnstrom, M. Nuutinen, P. Van Dyke, T. E. TI Salivary immunoglobulins and risk of coronary artery disease SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 76th Congress of the European-Atherosclerosis-Society CY JUN 10-13, 2007 CL Helsinki, FINLAND SP European Atherosclerosis Soc C1 Boston Univ, Boston, MA 02215 USA. Univ Helsinki, Cent Hosp, Inst Dent, Helsinki, Finland. NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. Kuopio Univ Hosp, Dept Otorhinolaryngol, SF-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Cardiothorac Surg, SF-70210 Kuopio, Finland. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2007 VL 8 IS 1 BP 162 EP 162 DI 10.1016/S1567-5688(07)71603-3 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 187SP UT WOS:000247869100652 ER PT J AU Barbey, AK Sloman, SA AF Barbey, Aron K. Sloman, Steven A. TI Base-rate respect: From ecological rationality to dual processes SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article DE base-rate neglect; Bayesian reasoning; dual process theory; nested set hypothesis; probability judgment ID COGNITIVE ILLUSIONS; CONDITIONAL-PROBABILITY; INDIVIDUAL-DIFFERENCES; CATEGORICAL INFERENCE; CONJUNCTION FALLACY; FREQUENCY FORMATS; JUDGMENT; INFORMATION; MEMORY; UNCERTAINTY AB The phenomenon of base-rate neglect has elicited much debate. One arena of debate concerns how people make judgments under conditions of uncertainty. Another more controversial arena concerns human rationality. In this target article, we attempt to unpack the perspectives in the literature on both kinds of issues and evaluate their ability to explain existing data and their conceptual coherence. Front this evaluation we conclude that the best account of the data should be framed in terms of a dual-process model of judgment, which attributes base-rate neglect to associative judgment strategies that fail to adequately represent the set structure of the problem. Base-rate neglect is reduced when problems are presented in a format that affords accurate representation in terms of nested sets of individuals. C1 [Sloman, Steven A.] Brown Univ, Providence, RI 02912 USA. [Barbey, Aron K.] Emory Univ, Cognit & Dev Program, Atlanta, GA 30322 USA. RP Barbey, AK (reprint author), NINDS, Cognit Neurosci Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM barbeya@ninds.nih.gov; Steven_Sloman@brown.edu RI Barbey, Aron/L-7312-2015 OI Barbey, Aron/0000-0002-6092-0912 FU National Science Foundation [DGE-0536941, DGE-0231900] FX This work was supported by National Science Foundation Grants DGE-0536941 and DGE-0231900 to Aron K. Barbey. We are grateful to Gary Brase, Jonathan Evans, Vittorio Girotto, Philip Johnson-Laird, Gernot Kleiter, and David Over for their very helpful comments on prior drafts of this paper. Barbey would also like to thank Lawrence W. Barsalou, Sergio Chaigneau, Brian R. Cornwell, Pablo A. Escobedo, Shlomit R. Finkelstein, Carla Harenski, Corey Kallenberg, Patricia Marsteller, Robert N. McCauley, Richard Patterson, Diane Pecher, Philippe Rochat, Ava Santos, W Kyle Simmons, Irwin Waldman, Christine D. Wilson, and Phillip Wolff for their encouragement and support while writing this paper. NR 83 TC 128 Z9 130 U1 4 U2 26 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2007 VL 30 IS 3 BP 241 EP + DI 10.1017/S0140525X07001653 PG 20 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 286LQ UT WOS:000254847800001 PM 17963533 ER PT J AU Berman, CM Lonica, C Li, J AF Berman, Carol M. Lonica, Consuel Li, Jinhua TI Supportive and tolerant relationships among male Tibetan macaques at Huangshan, China SO BEHAVIOUR LA English DT Article DE Macaca thibetana; male cooperation; agonistic support; reciprocity; male tolerance ID MALE BONNET MACAQUES; MACACA-THIBETANA; RECIPROCAL ALTRUISM; SOCIAL RELATIONSHIPS; BRIDGING BEHAVIOR; MT. HUANGSHAN; MATING SYSTEM; CHIMPANZEES; COALITIONS; COMPETITION AB Tibetan macaque males at Huangshan (Macaca thibetana huangshanensis) display highly skewed mating success and highly asymmetric patterns of aggression, but also high levels of tolerance. We examined affiliation, tolerance and agonistic support to test the hypothesis that increased tolerance in otherwise despotic males may occur when high-ranking males require support from other males to prevent (1) potentially destabilizing revolutionary coalitions against them, or (2) young adult males from usurping the alpha position. Several predictions of the first hypothesis were supported: Support was unrelated to kinship or affiliation and was Generally conservative, serving to reinforce the current hierarchy. Nevertheless revolutionary coalitions posed a threat, particularly to alpha males. High-ranking males displayed tolerance in the form of co-feeding toward lower ranking males that supported them, and alpha males showed the most cooperation with the males that targeted them in revolutionary coalitions. Predictions of the second hypothesis were not consistently supported; male coalitions targeted young potential usurpers of the alpha position during only one of two periods of hierarchical stability. We suggest that high ranking males discourage revolutionary alliances by using two strategies. They primarily rely on conservative alliances, but also offer tolerance in cases in which conservative coalitions are less effective. C1 SUNY Buffalo, Dept Anthropol, Buffalo, NY 14261 USA. SUNY Buffalo, Grad Program Evolut Ecol & Behav, Buffalo, NY 14261 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. Anhui Univ, Sch Life Sci, Hefei 230039, Anhui, Peoples R China. RP Berman, CM (reprint author), SUNY Buffalo, Dept Anthropol, Buffalo, NY 14261 USA. EM cberman@buffalo.edu RI Ionica, Consuel/A-5186-2009 NR 70 TC 20 Z9 21 U1 2 U2 16 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD JUN PY 2007 VL 144 BP 631 EP 661 DI 10.1163/156853907781347790 PN 6 PG 31 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 199VV UT WOS:000248724200002 ER PT J AU Oetting, A Yen, PM AF Oetting, Alexis Yen, Paul M. TI New insights into thyroid hormone action SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE non-genomic; nuclear hormone receptor; thyroid hormone receptor; thyroid hormone; transcription ID II IODOTHYRONINE 5-DEIODINASE; TRANSCRIPTION FACTOR TFIIB; DEPENDENT PROTEIN-KINASE; RECEPTOR-BINDING PROTEIN; RETINOID-X-RECEPTOR; NUCLEAR RECEPTOR; RESPONSIVE PROMOTERS; ERBA-ALPHA; HISTONE ACETYLATION; COACTIVATOR-BINDING AB Thyroid hormones (THs) have important effects on cellular development, growth, and metabolism. They bind to thyroid hormone receptors (TRs), TR alpha and TR beta, which belong to the nuclear hormone receptor superfamily. These receptors also bind to enhancer elements in the promoters of target genes, and can regulate both positive and negative transcription. Recent emerging evidence has characterized some of the molecular mechanisms by which THs regulate transcription as co-repressors, and co-activators have been identified and their effects on histone acetylation examined. THs also have rapid effects that do not require transcription. These can occur via TRs or other cellular proteins, and typically occur outside the nucleus. It appears that THs regulate multiple cellular functions using a diverse array of receptors and signaling systems. TR isoform- or pathway-specific drugs might provide the therapeutic benefits of TH action such as decreasing obesity or lowering cholesterol levels without some of the side effects of hyperthyroidism. C1 Johns Hopkins Univ, Dept Med,Sch Med, Div Endocrinol, Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. NIH, Natl Inst Child Hlth & Dev, Lab Gene Regulat & Dev, Bethesda, MD USA. RP Yen, PM (reprint author), Johns Hopkins Univ, Dept Med,Sch Med, Div Endocrinol, Johns Hopkins Bayview Med Ctr, 5200 Eastern Ave,Room 432, Baltimore, MD 21224 USA. EM pyen3@jhmi.edu FU Intramural NIH HHS NR 100 TC 114 Z9 123 U1 0 U2 10 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2007 VL 21 IS 2 BP 193 EP 208 DI 10.1016/j.beem.2007.04.004 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 188GY UT WOS:000247909300003 PM 17574003 ER PT J AU Zhang, Y Ni, J Huang, Q Ren, WH Yu, L Zhao, SY AF Zhang, Yue Ni, Jun Huang, Qiang Ren, Weihua Yu, Long Zhao, Shouyuan TI Identification of the auto-inhibitory domains of Aurora-A kinase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Aurora-A; autoinhibitory regulation; protein interaction; protein kinase ID LIM PROTEIN AJUBA; CELL-DIVISION; SERINE/THREONINE KINASE; MITOTIC SPINDLE; PHOSPHORYLATION; CHECKPOINT; DROSOPHILA; MITOSIS; CYCLE; TPX2 AB Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. Here, we report an intramolecular inhibitory regulation in Aurora-A between its N-terminal regulatory domain (aa 1-128, Nt) and the C-terminal catalytic domain (aa 129-403, Cd). Removal of Nt results in a significant increase in kinase activity. Nt inhibited the activity of the single C-terminal kinase domain, but had little effect on the activity of the full-length of Aurora-A. PP1 is not involved in this regulation, instead, Nt interacts Cd directly in vitro and in vivo. The non-Aurora box (aa 64-128) in the N-terminal negatively regulated the kinase activity of the C-terminal kinase domain by intramolecular interaction with aa 240-300 within the C-terminal. (c) 2007 Elsevier Inc. All rights reserved. C1 Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Yu, L (reprint author), Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. EM longyu@fudan.edu.cn NR 24 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 1 PY 2007 VL 357 IS 2 BP 347 EP 352 DI 10.1016/j.bbrc.2007.03.129 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 164SE UT WOS:000246253700004 PM 17433255 ER PT J AU Ahmad, F Lindh, R Tang, Y Weston, M Degerman, E Manganiello, VC AF Ahmad, Faiyaz Lindh, Rebecka Tang, Yan Weston, Marie Degerman, Eva Manganiello, Vincent C. TI Insulin-induced formation of macromolecular complexes involved in activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and its interaction with PKB SO BIOCHEMICAL JOURNAL LA English DT Article DE confocal microscopy; gel filtration; insulin; macromolecular complex; phosphodiesterase 3B (PDE3B); phosphorylation ID PROTEIN-KINASE-B; RAT ADIPOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; GLUCOSE; CAVEOLAE; CELLS; IDENTIFICATION; LOCALIZATION AB Fractionation of 3T3-L1 adipocyte membranes revealed that PDE3B (phosphodiesterase 3B) was associated with PM (plasma membrane) and ER (endoplasmic reticulum)/Golgi fractions, that insulin-induced phosphorylation/activation of PDE3B was greater in internal membranes than PM fractions, and that there was no significant translocation of PDE3B between membrane fractions. Insulin also induced formation of large macromolecular complexes, separated during gel filtration (Superose 6 columns) of solubilized membranes, which apparently contain phosphorylated/activated PDE3B and signalling molecules potentially involved in its activation by insulin, e.g. IRS-1 (insulin receptor substrate-1), IRS-2, PI3K p85 [p85-subunit of PI3K (phospho-inosifide 3-kinase)], PKB (protein kinase B), HSP-90 (heat-shock protein 90) and 14-3-3. Expression of full-length recombinant FLAG-tagged murine (M) PDE3B and M3B Delta 604 (MPDE3B lacking N-terminal 604 amino acids) indicated that the N-terminal region of MPDE3B was necessary for insulin-induced activation and recruitment of PDE3B. siRNA (small interfering RNA) knock-down of PDE3B indicated that PDE3B was not required for formation of insulin-induced complexes. Wortmannin inhibited insulin-induced assembly of macromolecular complexes, as well as phosphorylation/activation of PKB and PDE3B, and their coimmunoprecipitation. Another PI3K inhibitor, LY294002, and the tyrosine kinase inhibitor, Genistein, also inhibited insulin-induced activation of PDE3B and its co-immunoprecipitation with PKB. Confocal microscopy indicated co-localization of PDE3B and PKB. Recombinant MPDE3B co-immunoprecipitated, and co-eluted during Superose 12 chromatography, to a greater extent with recombinant pPKB (phosphorylated/activated PKB) than dephospho-PKB or p-Delta PKB [pPKB lacking its PH domain (pleckstrin homology domain)]. Truncated recombinant MPDE3B proteins and pPKB did not efficiently co-immunoprecipitate, suggesting that structural determinants for their interaction reside in, or are regulated by, the N-terminal portion of MPDE3B. Recruitment of PDE3B in macromolecular complexes may be critical for regulation of specific cAMP pools and signalling pathways by insulin, e.g. lipolysis. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Lund Univ, Dept Expt Med Sci, S-22184 Lund, Sweden. RP Ahmad, F (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5N307, Bethesda, MD 20892 USA. EM Ahmadf@nhlbi.nih.gov FU Intramural NIH HHS NR 37 TC 37 Z9 38 U1 3 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2007 VL 404 BP 257 EP 268 DI 10.1042/BJ20060960 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175LI UT WOS:000247014700010 PM 17324123 ER PT J AU Stein, WD Litman, T Fojo, T Bates, SE AF Stein, Wilfred D. Litman, Thomas Fojo, Tito Bates, Susan E. TI A database study that identifies genes whose expression correlates, negatively or positively, with 5-year survival of cancer patients SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE microarray; SEER survivals; cell adhesion; drug resistance; adhesion-mediated resistance ID ANCHORAGE-INDEPENDENT GROWTH; CELL-ADHESION; BREAST-CANCER; MOLECULAR CLASSIFICATION; MULTIDRUG-RESISTANCE; SERIAL ANALYSIS; SOLID TUMORS; MODEL; LINES; PREDICTION AB A published microarray gene expression database containing data on 174 tumor samples from ten tissues was mined, enabling the identification of classes of genes whose expression correlates significantly with the intractability, or tractability, to therapy of tumors derived from such tissues. As a measure of tractability, the 5-year survival of patients presenting with distant (metastatic) tumors was used. Genes that encode proteins related to cell adhesion, and enzymes involved in metabolic oxidation or reduction, were upregulated in intractable cancers. Genes that encode proteins implicated in the control of DNA transcription were downregulated in the intractable cancers. We describe hypotheses with regard to cell functions that may help in designing new therapeutic modalities, aimed at improving survival of cancer patients. Published by Elsevier B.V. C1 NCI, Bethesda, MD 20896 USA. Hebrew Univ Jerusalem, IL-91905 Jerusalem, Israel. Univ Copenhagen, Bioinformat Ctr, DK-1168 Copenhagen, Denmark. RP Stein, WD (reprint author), NCI, Bethesda, MD 20896 USA. EM wdstein@gmail.com NR 56 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JUN PY 2007 VL 1770 IS 6 BP 857 EP 871 DI 10.1016/j.bbagen.2006.12.013 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 170HP UT WOS:000246654000002 PM 17398010 ER PT J AU Schulz, TA Prinz, WA AF Schulz, Timothy A. Prinz, William A. TI Sterol transport in yeast and the oxysterol binding protein homologue (OSH) family SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE yeast; oxysterol binding protein; sterol; lipid; menibranc transport; lipid binding protein ID OSBP-RELATED PROTEINS; PHOSPHATIDYLINOSITOL TRANSFER PROTEINS; INTRACELLULAR CHOLESTEROL TRANSPORT; OXIDOSQUALENE CYCLASE ERG7P; NUCLEUS-VACUOLE JUNCTIONS; CELLULAR LIPID-METABOLISM; NIEMANN-PICK-DISEASE; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM AB Sterols such as cholesterol are a significant component of eukaryotic cellular membranes, and their unique physical properties influence a wide variety of membrane processes. It is known that the concentration of sterol within the membrane varies widely between organelles, and that the cell actively maintains this distribution through various transport processes. Vesicular pathways such as secretion or endocytosis may account for this traffic, but increasing evidence highlights the importance of nonvesicular routes as well. The structure of an oxysterol-binding protein homologue (OSH) in yeast (Osh4p/Kes1p) has recently been solved, identifying it as a sterol binding protein, and there is evidence consistent with the role of a cytoplasmic, nonvesicular sterol transporter. Yeast have seven such proteins, which appear to have distinct but overlapping functions with regard to maintaining intracellular sterol distribution and homeostasis. Control of sterol distribution can have far-reaching effects on membrane-related functions, and Osh proteins have been implicated in a variety of processes such as secretory vesicle budding from the Golgi and establishment of cell polarity. This review summarizes the current body of knowledge regarding this family and its potential functions, placing it in the context of known and hypothesized pathways of sterol transport in yeast. Published by Elsevier B.V. C1 US Dept HHS, NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Prinz, WA (reprint author), US Dept HHS, NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov FU Intramural NIH HHS [Z01 DK060004-06] NR 127 TC 50 Z9 50 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JUN PY 2007 VL 1771 IS 6 BP 769 EP 780 DI 10.1016/j.bbalip.2007.03.003 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 183EG UT WOS:000247554900013 PM 17434796 ER PT J AU Gillet, JP Efferth, T Remacle, J AF Gillet, Jean-Pierre Efferth, Thomas Remacle, Jose TI Chemotherapy-induced resistance by ATP-binding cassette transporter genes SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE ABC transporter genes; multidrug resistance ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; X-LINKED ADRENOLEUKODYSTROPHY; P-GLYCOPROTEIN EXPRESSION; ORGANIC ANION TRANSPORTER; SALT EXPORT PUMP; CANCER CELL-LINE; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; SINGLE NUCLEOTIDE POLYMORPHISMS; PEROXISOMAL ABC TRANSPORTER AB A key issue in the treatment of many cancers is the development of resistance to chemotherapeutic drugs. Resistance mechanisms are numerous and complex. One of them is mediated by the overexpression of ATP-binding cassette (ABC) transporters able to efflux drugs out of the tumor cell. The last two decades have seen notable growth of knowledge concerning the involvement of ABC transporters in resistance to chemotherapy. This review emphasizes these transporters, their clinical relevance and the diagnostic methods and strategies to circumvent multidrug resistance (MDR) mediated by ABC transporters. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Namur, Dept Biol, B-5000 Namur, Belgium. German Canc Res Ctr, D-69120 Heidelberg, Germany. RP Gillet, JP (reprint author), NCI, Ctr Canc Res, Cell Biol Lab, NIH, 37 Convent Dr,Rm 2112, Bethesda, MD 20892 USA. EM gilletjp@mail.nih.gov RI gillet, jean-pierre/A-3714-2012 NR 381 TC 201 Z9 214 U1 2 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD JUN PY 2007 VL 1775 IS 2 BP 237 EP 262 DI 10.1016/j.bbcan.2007.05.002 PG 26 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 187OR UT WOS:000247858100001 PM 17572300 ER PT J AU Khabar, KSA Young, HA AF Khabar, Khalid S. A. Young, Howard A. TI Post-transcriptional control of the interferon system SO BIOCHIMIE LA English DT Article DE interferons; post-transcriptional; 3 ' untranslated regions; mRNA stability; AU-rich elements ID MESSENGER-RNA STABILITY; PROTEIN-KINASE PKR; 3' UNTRANSLATED REGION; AU-RICH TRANSCRIPTOME; CARCINOMA CELL-LINE; C-MYC EXPRESSION; HUMAN NK CELLS; GENE-EXPRESSION; IFN-GAMMA; ANTIVIRAL RESPONSE AB The interferon (IFN) system is a well-controlled network of signaling, transcriptional, and post-transcriptional processes that orchestrate host defense against microbes. The IFN response comprises a multi-array of IFN-stimulated gene products that mediate a variety of biological processes designed to control infection and regulate specific immune responses. In this review, we focus on post-transcriptional mechanisms of gene regulation that occur during the course of IFN induction and during the response of cells to IFN. Post-transcriptional mechanisms involve different levels of regulation such as mRNA stability, alternative splicing, and translation. Such controls offer a fine tuning mechanism for efficient and rapid response and as a negative feedback control in IFN biosynthesis and response. (C) 2007 Elsevier Masson SAS. All rights reserved. C1 King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, Riyadh 11211, Saudi Arabia. Natl Canc Inst, Canc Res Ctr, Expt Immunol Lab, Ft Detrick, MD 21702 USA. RP Khabar, KSA (reprint author), King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, P3354,MBC-03,Takhasusi Rd, Riyadh 11211, Saudi Arabia. EM khabar@kfshrc.edu.sa RI Young, Howard/A-6350-2008; Khabar, Khalid/A-4772-2011 OI Young, Howard/0000-0002-3118-5111; Khabar, Khalid/0000-0003-1003-9788 FU Intramural NIH HHS [Z01 BC009283-22] NR 86 TC 39 Z9 39 U1 0 U2 6 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JUN-JUL PY 2007 VL 89 IS 6-7 BP 761 EP 769 DI 10.1016/j.biochi.2007.02.008 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196SK UT WOS:000248502100009 PM 17408842 ER PT J AU Deng, XL Ladenheim, B Jayanthi, S Cadet, JL AF Deng, Xiaolin Ladenheim, Bruce Jayanthi, Subramaniam Cadet, Jean Lud TI Methamphetamine administration causes death of dopaminergic neurons in the mouse olfactory bulb SO BIOLOGICAL PSYCHIATRY LA English DT Article DE caspase-3; dopamine; neurodegeneration; neuronal apoptosis; olfactory bulb ID TYROSINE-HYDROXYLASE EXPRESSION; DISMUTASE TRANSGENIC MICE; APOPTOSIS-INDUCING FACTOR; RAT SOMATOSENSORY CORTEX; CELL-DEATH; PARKINSONS-DISEASE; TERMINAL MARKERS; POSITIVE-NEURONS; NEUROTOXICITY; BRAIN AB Background: Methamphetamine (METH) is an addictive drug that can cause neurological and psychiatric disorders. In the rodent brain, toxic doses of METH cause damage of dopaminergic terminals and apoptosis of nondopaminergic neurons. The olfactory bulb (013) isa brain region that is rich with dopaminergic neurons and terminals. Methods: Rats were given a single injection of METH (40 mg/kg) and sacrificed at various time points afterward. The toxic effects of this injection on the OB were assessed by measuring monoamine levels, tyrosine hydroxylase (TH) immunocytochemistry, terminal deoxynucleotidyl transferase-mediated deoxyribonucleoticle triphosphate (dNTP) nick end labeling (TUNEL) histochemistry, and caspase-3 immunochemistry. Results: Methamphetamine administration caused marked decreases in dopamine (DA) levels and TH-like immunostaining in the mouse OB. The drug also caused increases in TUNEL-labeled OB neurons, some of which were also positive for TH expression. Moreover, there was METH-induced expression of activated caspase-3 in TH-positive cells. Finally, the METH injection was associated with increased expression of the proapoptotic proteins, Bax and Bid, but with decreased expression of the antideath protein, Bcl2. Conclusions: These observations show, for the first time, that METH can cause loss of OB DA terminals and death of DA neurons, in part, via mechanisms that are akin to an apoptotic process. C1 NIDA, Mol Neuropsychiat Branch, IRP, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Deng, XL (reprint author), NIDA, Mol Neuropsychiat Branch, IRP, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural NIH HHS NR 83 TC 33 Z9 34 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2007 VL 61 IS 11 BP 1235 EP 1243 DI 10.1016/j.biopsych.2006.09.010 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 172UK UT WOS:000246829700003 PM 17161385 ER PT J AU Szczesny, RJ Obriot, H Paczkowska, A Jedrzejczak, R Dmochowska, A Bartnik, E Formstecher, P Polakowska, R Stepien, PP AF Szczesny, Roman J. Obriot, Helene Paczkowska, Aleksandra Jedrzejczak, Robert Dmochowska, Aleksandra Bartnik, Ewa Formstecher, Pierre Polakowska, Renata Stepien, Piotr P. TI Down-regulation of human RNA/DNA helicase SUV3 induces apoptosis by a caspase- and AIF-dependent pathway SO BIOLOGY OF THE CELL LA English DT Article DE apoptosis; apoptosis-inducing factor (AIF); caspase; helicase; human SUV3 ID INDEPENDENT CELL-DEATH; MITOCHONDRIAL RELEASE; RNA HELICASE; SACCHAROMYCES-CEREVISIAE; P53; DNA; ACTIVATION; SURVIVIN; DEGRADATION; DOWNSTREAM AB Background information. The nuclear gene hSUV3 (human SUV3) encodes an ATIP-dependent DNA/RNA helicase. In the yeast Saccharomyces cerevisiae the orthologous Suv3 protein is localized in mitochondria, and is a subunit of the degradosome complex which regulates RNA surveillance and turnover. In contrast, the functions of human SUV3 are not known to date. Results. In the present study, we show that a fraction of human SUV3 helicase is localized in the nucleus. Using small interfering RNA gene silencing in HeLa cells, we demonstrate that down-regulation of hSUV3 results in cell cycle perturbations and in apoptosis, which is both AIF- and caspase-dependent, and proceeds with the induction of p53. Conclusions. In addition to its mitochondrial localization, human SUV3 plays an important role in the nucleus and is probably involved in chromatin maintenance. C1 Univ Lille 2, INSERM, Fac Med, U814, F-59045 Lille, France. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. Warsaw Univ, Dept Genet & Biotechnol, PL-02106 Warsaw, Poland. NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA. RP Polakowska, R (reprint author), Univ Lille 2, INSERM, Fac Med, U814, 1 Pl Verdun, F-59045 Lille, France. EM renata.polakowska@lille.inserm.fr FU Intramural NIH HHS NR 40 TC 21 Z9 24 U1 0 U2 8 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD JUN PY 2007 VL 99 IS 6 BP 323 EP 332 DI 10.1042/BC20060108 PG 10 WC Cell Biology SC Cell Biology GA 180RB UT WOS:000247382100003 PM 17352692 ER PT J AU Brown, PH Balbo, A Schuck, P AF Brown, Patrick H. Balbo, Andrea Schuck, Peter TI Using prior knowledge in the determination of macromolecular size-distributions by analytical ultracentrifugation SO BIOMACROMOLECULES LA English DT Article ID SEDIMENTATION COEFFICIENT DISTRIBUTIONS; VELOCITY ANALYTICAL ULTRACENTRIFUGATION; PROTEIN-PROTEIN INTERACTIONS; FREDHOLM INTEGRAL-EQUATIONS; LAMM EQUATION; CONCENTRATION PROFILES; BOUNDARY ANALYSIS; INVERSE PROBLEMS; 1ST KIND; EQUILIBRIUM AB Analytical ultracentrifugation has reemerged as a widely used tool for the study of ensembles of biological macromolecules to understand, for example, their size-distribution and interactions in free solution. Such information can be obtained from the mathematical analysis of the concentration and signal gradients across the solution column and their evolution in time generated as a result of the gravitational force. In sedimentation velocity analytical ultracentrifugation, this analysis is frequently conducted using high resolution, diffusion-deconvoluted sedimentation coefficient distributions. They are based on Fredholm integral equations, which are ill-posed unless stabilized by regularization. In many fields, maximum entropy and Tikhonov-Phillips regularization are well-established and powerful approaches that calculate the most parsimonious distribution consistent with the data and prior knowledge, in accordance with Occam's razor. In the implementations available in analytical ultracentrifugation, to date, the basic assumption implied is that all sedimentation coefficients are equally likely and that the information retrieved should be condensed to the least amount possible. Frequently, however, more detailed distributions would be warranted by specific detailed prior knowledge on the macromolecular ensemble under study, such as the expectation of the sample to be monodisperse or paucidisperse or the expectation for the migration to establish a bimodal sedimentation pattern based on Gilbert-Jenkins' theory for the migration of chemically reacting systems. So far, such prior knowledge has remained largely unused in the calculation of the sedimentation coefficient or molecular weight distributions or was only applied as constraints. In the present paper, we examine how prior expectations can be built directly into the computational data analysis, conservatively in a way that honors the complete information of the experimental data, whether or not consistent with the prior expectation. Consistent with analogous results in other fields, we find that the use of available prior knowledge can have a dramatic effect on the resulting molecular weight, sedimentation coefficient, and size-and-shape distributions and can significantly increase both their sensitivity and their resolution. Further, the use of multiple alternative prior information allows us to probe the range of possible interpretations consistent with the data. C1 Natl Inst Biomed Imaging & Bioengn, Prot Biophys Resource, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Prot Biophys Resource, NIH, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS [Z01 OD010485-08] NR 81 TC 37 Z9 37 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD JUN PY 2007 VL 8 IS 6 BP 2011 EP 2024 DI 10.1021/bm070193j PG 14 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 176TN UT WOS:000247107900034 PM 17521163 ER PT J AU Wally, J Buchanan, SK AF Wally, Jeremy Buchanan, Susan K. TI A structural comparison of human serum transferrin and human lactoferrin SO BIOMETALS LA English DT Article; Proceedings Paper CT 5th International Biometals Symposium (Biometals 2006) CY JUL 30-AUG 06, 2006 CL Welches, OR DE transferrin; lactoferrin; iron transport; human transferrin receptor; bacterial transferrin receptor ID BINDING PROTEIN-B; MEMBRANE TRANSPORTER FECA; CARBOXYL-TERMINAL LOBES; 2.8 ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; IRON-RELEASE; N-LOBE; NEISSERIA-MENINGITIDIS; C-LOBE; INTERLOBE COMMUNICATION AB The transferrins are a family of proteins that bind free iron in the blood and bodily fluids. Serum transferrins function to deliver iron to cells via a receptor-mediated endocytotic process as well as to remove toxic free iron from the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins (found in bodily secretions such as milk) are only known to have an anti-bacterial function, via their ability to tightly bind free iron even at low pH, and have no known transport function. Though these proteins keep the level of free iron low, pathogenic bacteria are able to thrive by obtaining iron from their host via expression of outer membrane proteins that can bind to and remove iron from host proteins, including both serum transferrin and lactoferrin. Furthermore, even though human serum transferrin and lactoferrin are quite similar in sequence and structure, and coordinate iron in the same manner, they differ in their affinities for iron as well as their receptor binding properties: the human transferrin receptor only binds serum transferrin, and two distinct bacterial transport systems are used to capture iron from serum transferrin and lactoferrin. Comparison of the recently solved crystal structure of iron-free human serum transferrin to that of human lactoferrin provides insight into these differences. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDKD, NIH, 50 S Dr, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU Intramural NIH HHS [Z01 DK036143-01] NR 72 TC 42 Z9 47 U1 2 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD JUN PY 2007 VL 20 IS 3-4 BP 249 EP 262 DI 10.1007/s10534-006-9062-7 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169RZ UT WOS:000246610700004 PM 17216400 ER PT J AU Tong, WH Rouault, TA AF Tong, Wing-Hang Rouault, Tracey A. TI Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis SO BIOMETALS LA English DT Article; Proceedings Paper CT 5th International Biometals Symposium (Biometals 2006) CY JUL 30-AUG 06, 2006 CL Welches, OR DE iron-sulfur cluster biogenesis; aconitase; citrate metabolism; iron metabolism ID ERYTHROID 5-AMINOLEVULINATE SYNTHASE; NUCLEAR-MAGNETIC-RESONANCE; PROSTATE EPITHELIAL-CELLS; INDUCED OXIDANT STRESS; RNA-BINDING ACTIVITY; CITRIC-ACID CYCLE; FE-S CLUSTER; MITOCHONDRIAL ACONITASE; RAT-LIVER; RESPONSIVE ELEMENT AB Iron and citrate are essential for the metabolism of most organisms, and regulation of iron and citrate biology at both the cellular and systemic levels is critical for normal physiology and survival. Mitochondrial and cytosolic aconitases catalyze the interconversion of citrate and isocitrate, and aconitase activities are affected by iron levels, oxidative stress and by the status of the Fe-S cluster biogenesis apparatus. Assembly and disassembly of Fe-S clusters is a key process not only in regulating the enzymatic activity of mitochondrial aconitase in the citric acid cycle, but also in controlling the iron sensing and RNA binding activities of cytosolic aconitase (also known as iron regulatory protein IRP1). This review discusses the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe-S cluster biogenesis regulate the Fe-S cluster switch and modulate intracellular citrate flux. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18,Room 101, Bethesda, MD 20892 USA. EM trou@helix.nih.gov NR 161 TC 56 Z9 57 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD JUN PY 2007 VL 20 IS 3-4 BP 549 EP 564 DI 10.1007/s10534-006-9047-6 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169RZ UT WOS:000246610700026 PM 17205209 ER PT J AU Norgate, M Southon, A Zou, SG Zhan, M Sun, Y Batterham, P Camakaris, J AF Norgate, Melanie Southon, Adam Zou, Sige Zhan, Ming Sun, Yu Batterham, Phil Camakaris, James TI Copper homeostasis gene discovery in Drosophila melanogaster SO BIOMETALS LA English DT Article; Proceedings Paper CT 5th International Biometals Symposium (Biometals 2006) CY JUL 30-AUG 06, 2006 CL Welches, OR DE copper; Drosophila melanogaster; mutagenesis; microarray; screen ID METALLOTHIONEIN GENE; EXPRESSION; TRANSPORT; PROTEIN; RESISTANCE; CDNA; TRANSCRIPTION; PIGMENTATION; POPULATIONS; METABOLISM AB Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery. C1 Univ Melbourne, Dept Genet, Parkville, Vic 3010, Australia. Univ Melbourne, Ctr Environm Stress & Adaptat Res, Parkville, Vic 3010, Australia. NIA, Gerontol Res Ctr, Lab Expt Gerontol, Baltimore, MD 21224 USA. NIA, Bioinformat Unit, Res Resouces Branch, Baltimore, MD 21224 USA. RP Camakaris, J (reprint author), Univ Melbourne, Dept Genet, Parkville, Vic 3010, Australia. EM j.camakaris@unimelb.edu.au RI Batterham, Philip/G-5914-2012 OI Batterham, Philip/0000-0001-9840-9119 FU Intramural NIH HHS NR 45 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD JUN PY 2007 VL 20 IS 3-4 BP 683 EP 697 DI 10.1007/s10534-006-9075-2 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169RZ UT WOS:000246610700037 PM 17216353 ER PT J AU Korn, EL Freidlin, B AF Korn, Edward L. Freidlin, Boris TI A posterior tale SO BIOMETRICAL JOURNAL LA English DT Article DE Bayesian analysis; data monitoring; posterior distribution; predictive distribution ID TRIALS AB A vignette is presented that naively suggests that the posterior distribution of a parameter may not always contain everything that is needed for inference about that parameter. The resolution of this apparent paradox is discussed as well as its relation to real-life problems involving data monitoring of clinical trials. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN-8129, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD JUN PY 2007 VL 49 IS 3 BP 346 EP 350 DI 10.1002/bimj.200510264 PG 5 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 185MT UT WOS:000247715800002 PM 17623340 ER PT J AU Fay, MP Halloran, ME Follmann, DA AF Fay, Michael P. Halloran, M. Elizabeth Follmann, Dean A. TI Accounting for variability in sample size estimation with applications to nonadherence and estimation of variance and effect size SO BIOMETRICS LA English DT Article DE binomial; compliance; normal; poisson; power; sample size ID INTENT-TO-TREAT; TRIALS; EFFICACY AB We consider sample size calculations for testing differences in means between two samples and allowing for different variances in the two groups. Typically, the power functions depend on the sample size and a set of parameters assumed known, and the sample size needed to obtain a prespecified power is calculated. Here, we account for two sources of variability: we allow the sample size in the power function to be a stochastic variable, and we consider estimating the parameters from preliminary data. An example of the first source of variability is nonadherence (noncompliance). We assume that the proportion of subjects who will adhere to their treatment regimen is riot known before the study, but that the proportion is a stochastic variable with a known distribution. Under this assumption, we develop simple closed form sample size calculations based on asymptotic normality. The second source of variability is in parameter estimates that are estimated from prior data. For example, we account for variability in estimating the variance of the normal response from existing data which are assumed to have the same variance as the study for which we are calculating the sample size. We show that we can account for the variability of the variance estimate by simply using a slightly larger nominal power in the usual sample size calculation, which we call the calibrated power. We show that the calculation of the calibrated power depends only on the sample size of the existing data, and we give a table of calibrated power by sample size. Further, we consider the calculation of the sample size in the rarer situation where we account for the variability in estimating the standardized effect size from some existing data. This latter situation, as well as several of the previous ones, is motivated by sample size calculations for a Phase 11 trial of a malaria vaccine candidate. C1 NIAID, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. RP Fay, MP (reprint author), NIAID, 6700-B Rockledge Dr, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 FU NIAID NIH HHS [R01 AI32042] NR 19 TC 15 Z9 16 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2007 VL 63 IS 2 BP 465 EP 474 DI 10.1111/j.1541-0420.2006.00703.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 172ZS UT WOS:000246843900018 PM 17688499 ER PT J AU Albert, PS AF Albert, Paul S. TI Random effects modeling approaches for estimating ROC curves from repeated ordinal tests without a gold standard SO BIOMETRICS LA English DT Article DE diagnostic accuracy; latent class analysis; mixture models; random effects models for repeated ordinal data; ROC curves ID LATENT CLASS ANALYSIS; REGRESSION-MODELS; DIAGNOSTIC ERROR; BOOTSTRAP; ABSENCE AB Estimating diagnostic accuracy without a gold standard is an important problem in medical testing. Although there is a fairly large literature on this problem for the case of repeated binary tests, there is substantially less work for the case of ordinal tests. A noted exception is the work by Zhou, Castelluccio, and Zhou (2005, Biometrics 61, 600-609), which proposed a methodology for estimating receiver operating characteristic (ROC) curves without a gold standard from multiple ordinal tests. A key assumption in their work was that the test results are independent conditional on the true test result. I propose random effects modeling approaches that incorporate dependence between the ordinal tests, and I show through asymptotic results and simulations the importance of correctly accounting for the dependence between tests. These modeling approaches, along with the importance of accounting for the dependence between tests, are illustrated by analyzing the uterine cancer pathology data analyzed by Zhou et al. (2005). C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov NR 31 TC 12 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2007 VL 63 IS 2 BP 593 EP 602 DI 10.1111/j.1541-0420.2006.00712.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 172ZS UT WOS:000246843900032 PM 17688512 ER PT J AU Kulkarni, SS Newman, AH AF Kulkarni, Santosh S. Newman, Amy Hauck TI Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MGLUR5 ANTAGONIST; NONCOMPETITIVE ANTAGONISTS; ANXIOLYTIC ACTIVITY; MPEP; POTENT; DERIVATIVES; DISORDERS; CATALYSTS; DESIGN; MODEL AB Investigation of a series of heterobicyclic compounds with essential pharmacophoric features of the metabotropic glutamate receptor 5 (mGluR5) antagonists MPEP and MTEP provided novel structural templates with sub-micromolar affinities at the mGluR5. Published by Elsevier Ltd. C1 NIH, Med Chem Sect, NIDA, DHHS, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIH, Med Chem Sect, NIDA, DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000488-02] NR 31 TC 36 Z9 37 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 1 PY 2007 VL 17 IS 11 BP 2987 EP 2991 DI 10.1016/j.bmcl.2007.03.066 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 175ZQ UT WOS:000247052900006 PM 17446071 ER PT J AU Dudko, OK Mathe, J Szabo, A Meller, A Hummer, G AF Dudko, Olga K. Mathe, Jerome Szabo, Attila Meller, Amit Hummer, Gerhard TI Extracting kinetics from single-molecule force spectroscopy: Nanopore unzipping of DNA hairpins SO BIOPHYSICAL JOURNAL LA English DT Article ID MEMBRANE CHANNEL; NUCLEIC-ACID; POLYNUCLEOTIDE MOLECULES; POLYMER TRANSLOCATION; ADHESION BONDS; RNA MOLECULES; DISCRIMINATION; DETACHMENT; TRANSPORT; DYNAMICS AB Single-molecule force experiments provide powerful new tools to explore biomolecular interactions. Here, we describe a systematic procedure for extracting kinetic information from force-spectroscopy experiments, and apply it to nanopore unzipping of individual DNA hairpins. Two types of measurements are considered: unzipping at constant voltage, and unzipping at constant voltage-ramp speeds. We perform a global maximum-likelihood analysis of the experimental data at low-to-intermediate ramp speeds. To validate the theoretical models, we compare their predictions with two independent sets of data, collected at high ramp speeds and at constant voltage, by using a quantitative relation between the two types of measurements. Microscopic approaches based on Kramers theory of diffusive barrier crossing allow us to estimate not only intrinsic rates and transition state locations, as in the widely used phenomenological approach based on Bell's formula, but also free energies of activation. The problem of extracting unique and accurate kinetic parameters of a molecular transition is discussed in light of the apparent success of the microscopic theories in reproducing the experimental data. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Evry Val Essonne, Lab MPI, Evry, France. Boston Univ, Dept Phys & Biomed Engn, Boston, MA 02215 USA. RP Hummer, G (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI MATHE, JEROME/B-6221-2008; Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013; OI Hummer, Gerhard/0000-0001-7768-746X; Meller, Amit/0000-0001-7082-0985 FU Intramural NIH HHS; NHGRI NIH HHS [HG003574, R21 HG003574]; NIGMS NIH HHS [R21 GM072893, GM072893] NR 39 TC 112 Z9 112 U1 3 U2 37 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2007 VL 92 IS 12 BP 4188 EP 4195 DI 10.1529/biophysj.106.102855 PG 8 WC Biophysics SC Biophysics GA 172NT UT WOS:000246811700012 PM 17384066 ER PT J AU Hu, J Asbury, T Achuthan, S Li, CG Bertram, R Quine, JR Fu, RQ Cross, TA AF Hu, Jun Asbury, Tom Achuthan, Srisairam Li, Conggang Bertram, Richard Quine, Jack R. Fu, Riqiang Cross, Timothy A. TI Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from influenza A virus SO BIOPHYSICAL JOURNAL LA English DT Article ID STATE NMR-SPECTROSCOPY; PLANAR LIPID-BILAYERS; ION-CHANNEL; PROTEIN-STRUCTURE; CHEMICAL-SHIFT; SEQUENCE DETERMINANTS; TRANSMEMBRANE DOMAIN; DIPOLAR WAVES; M(2) PROTEIN; HELIX TILT AB Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine. C1 Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Natl High Magnet Field Lab, Tallahassee, FL USA. RP Cross, TA (reprint author), Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. EM cross@magnet.fsu.edu OI li, cong gang/0000-0002-5798-1722 FU NIAID NIH HHS [R01 AI073891, R01 AI023007, R01-AI23007]; NIGMS NIH HHS [P01 GM064676, P01-GM064676] NR 49 TC 139 Z9 142 U1 0 U2 26 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2007 VL 92 IS 12 BP 4335 EP 4343 DI 10.1529/biophysj.106.090183 PG 9 WC Biophysics SC Biophysics GA 172NT UT WOS:000246811700025 PM 17384070 ER PT J AU Martyn, DA Smith, L Kreutziger, KL Xu, S Yu, LC Regnier, M AF Martyn, D. A. Smith, L. Kreutziger, K. L. Xu, S. Yu, L. C. Regnier, M. TI The effects of force inhibition by sodium vanadate on cross-bridge binding, force redevelopment, and Ca2+ activation in cardiac muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID RABBIT PSOAS MUSCLE; SLOW SKELETAL-MUSCLE; X-RAY-DIFFRACTION; THIN-FILAMENT; SKINNED FIBERS; TROPONIN-C; INORGANIC-PHOSPHATE; ACTOMYOSIN-ATPASE; DEPENDENT CHANGES; CAGED ATP AB Strongly bound, force-generating myosin cross-bridges play an important role as allosteric activators of cardiac thin filaments. Sodium vanadate (Vi) is a phosphate analog that inhibits force by preventing cross-bridge transition into force-producing states. This study characterizes the mechanical state of cross-bridges with bound Vi as a tool to examine the contribution of cross-bridges to cardiac contractile activation. The K-i of force inhibition by Vi was similar to 40 mu M. Sinusoidal stiffness was inhibited with Vi, although to a lesser extent than force. We used chord stiffness measurements to monitor Vi-induced changes in cross-bridge attachment/detachment kinetics at saturating [Ca2+]. Vi decreased chord stiffness at the fastest rates of stretch, whereas at slow rates chord stiffness actually increased. This suggests a shift in cross-bridge population toward low force states with very slow attachment/detachment kinetics. Low angle x-ray diffraction measurements indicate that with Vi cross-bridge mass shifted away from thin filaments, implying decreased cross-bridge/thin filament interaction. The combined x-ray and mechanical data suggest at least two cross-bridge populations with Vi; one characteristic of normal cycling cross-bridges, and a population of weak-binding cross-bridges with bound Vi and slow attachment/detachment kinetics. The Ca2+ sensitivity of force (pCa(50)) and force redevelopment kinetics (k(TR)) were measured to study the effects of Vi on contractile activation. When maximal force was inhibited by 40% with Vi pCa50 decreased, but greater force inhibition at higher [Vi] did not further alter pCa(50). In contrast, the Ca2+ sensitivity of k(TR) was unaffected by Vi. Interestingly, when force was inhibited by Vi k(TR) increased at submaximal levels of Ca2+-activated force. Additionally, k(TR) is faster at saturating Ca2+ at [Vi] that inhibit force by >similar to 70%. The effects of Vi on k(TR) imply that k(TR) is determined not only by the intrinsic properties of the cross-bridge cycle, but also by cross-bridge contribution to thin filament activation. C1 Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Martyn, DA (reprint author), Univ Washington, Dept Bioengn, Box 355061, Seattle, WA 98195 USA. EM dmartyn@u.washington.edu FU Intramural NIH HHS; NHLBI NIH HHS [HL61683, R01 HL061683, HL 67071, R01 HL067071] NR 60 TC 17 Z9 18 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2007 VL 92 IS 12 BP 4379 EP 4390 DI 10.1529/biophysj.106.096768 PG 12 WC Biophysics SC Biophysics GA 172NT UT WOS:000246811700029 PM 17400698 ER PT J AU Manji, HK Chen, G Du, J Zarate, CA AF Manji, H. K. Chen, G. Du, J. Zarate, C. A., Jr. TI Neuronal plasticity cascades: genes to behavior pathways in the pathophysiology and treatment of bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD C1 [Manji, H. K.; Chen, G.; Du, J.; Zarate, C. A., Jr.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 2 EP 2 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000006 ER PT J AU Insel, TR AF Insel, Thomas R. TI Report from the National Institute of Mental Health SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD C1 [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 7 EP 7 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000020 ER PT J AU Zarate, CA Singh, JB Carlson, PJ Quiroz, JA Jolkovsky, L Luckenbaugh, DA Manji, HK AF Zarate, C. A., Jr. Singh, J. B. Carlson, P. J. Quiroz, J. A. Jolkovsky, L. Luckenbaugh, D. A. Manji, H. K. TI Efficacy of a protein kinase C inhibitor in the treatment of acute mania: a double-blind, placebo-controlled study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE antimanic; mania; protein kinase C; tamoxifen C1 [Zarate, C. A., Jr.; Singh, J. B.; Carlson, P. J.; Quiroz, J. A.; Jolkovsky, L.; Luckenbaugh, D. A.; Manji, H. K.] Natl Inst Hlth, Mol Pathophysiol Lab, Bethesda, MD USA. [Zarate, C. A., Jr.; Singh, J. B.; Carlson, P. J.; Quiroz, J. A.; Jolkovsky, L.; Luckenbaugh, D. A.; Manji, H. K.] Natl Inst Hlth, NIMH, Dept Human & Hlth Serv, Expt Therapeut Mood Anxiety Diorders Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 11 EP 11 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000032 ER PT J AU Abulseoud, OA Hellemann, G Frye, MA Altshuler, LL Keck, PE Mcelroy, SL Suppes, T Nolen, WA Kupka, RW Grunze, H Leverich, GS Post, RM AF Abulseoud, O. A. Hellemann, G. Frye, M. A. Altshuler, L. L. Keck, P. E., Jr. Mcelroy, S. L. Suppes, T. Nolen, W. A. Kupka, R. W. Grunze, H. Leverich, G. S. Post, R. M. TI Mood stabilizer and subsequent need for adjunctive antidepressant: naturalistic follow up of the SFBN SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar; depression; antidepressant; mood stabilizer C1 [Abulseoud, O. A.; Hellemann, G.; Frye, M. A.; Altshuler, L. L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Abulseoud, O. A.; Hellemann, G.; Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Frye, M. A.] Mayo Coll Med, Rochester, MN USA. [Mcelroy, S. L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Suppes, T.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kupka, R. W.] Altrech Inst Mental Hlth Care, Utrecht, Netherlands. [Grunze, H.] LMU Munioh, Munich, Germany. [Leverich, G. S.; Post, R. M.] Natl Inst Hlth, NIMH, Bethesda, MD USA. [Post, R. M.] Penn State Coll Med, Hershey, PA USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 13 EP 13 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000034 ER PT J AU Carlson, PJ Bain, E Tinsley, R Nugent, A Luckenbaugh, D Carson, R Manji, HK Drevets, WC AF Carlson, P. J. Bain, E. Tinsley, R. Nugent, A. Luckenbaugh, D. Carson, R. Manji, H. K. Drevets, W. C. TI Serotonin-1A receptor binding in bipolar depression before and after mood stabilizer treatment SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE serotonin-1A; PET; bipolar disorder; depression; divalproex; lithium C1 [Carlson, P. J.; Bain, E.; Tinsley, R.; Nugent, A.; Luckenbaugh, D.; Manji, H. K.; Drevets, W. C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Carson, R.] Yale Univ, Sch Med, PET Dept, New Haven, CT USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 26 EP 27 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000073 ER PT J AU Creson, T Hao, YL Shen, Y Engel, S Gutkind, S Manji, HK Chen, G AF Creson, T. Hao, Y-L Shen, Y. Engel, S. Gutkind, S. Manji, H. K. Chen, G. TI The anterior cingulate ERK pathway plays a critical role in modulating affective-like behavior SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE mood stabilizer; anterior cingulated cortex; mania; animal model C1 [Creson, T.; Hao, Y-L; Shen, Y.; Engel, S.; Manji, H. K.; Chen, G.] NIH, NIMH, MAP, LMP, Bethesda, MD 20892 USA. [Gutkind, S.] NIH, NIDCR, OPCB, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 30 EP 31 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000084 ER PT J AU Kelly, DI Suppes, T Keck, PE McElroy, SL Altshuler, LL Frye, MA Nolen, WA Kupka, RW Grunze, H Leverich, GS Mintz, J Luckenbaugh, DA Fischer, EG Post, RM AF Kelly, D. I. Suppes, T. Keck, P. E., Jr. McElroy, S. L. Altshuler, L. L. Frye, M. A. Nolen, W. A. Kupka, R. W. Grunze, H. Leverich, G. S. Mintz, J. Luckenbaugh, D. A. Fischer, E. G. Post, R. M. TI Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 7th International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar disorder; bipolar depression; cycling; quetiapine C1 [Kelly, D. I.; Suppes, T.; Fischer, E. G.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Keck, P. E., Jr.; McElroy, S. L.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Keck, P. E., Jr.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Altshuler, L. L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Frye, M. A.] Mayo Coll Med, Rochester, MN USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Kupka, R. W.] Altrech Inst Med Hlth Care, Utrecht, Netherlands. [Grunze, H.] Ludwig Maximilians Univ Munchen, Munich, Germany. [Leverich, G. S.; Luckenbaugh, D. A.] NIMH, NIH, Bethesda, MD 20892 USA. [Post, R. M.] Penn State Coll Med, Hershey, PA USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000157 ER PT J AU Langosch, JM Drieling, T Schaerer, LO Biedermann, NC Post, RM AF Langosch, J. M. Drieling, T. Schaerer, L. O. Biedermann, N. C. Post, R. M. TI Social functioning of bipolar patients depends on carefully treated depressive symptoms SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE life functioning questionnaire (LFQ); bipolar disorder; interpersonal and instrumental functioning; depressive symptoms C1 [Langosch, J. M.; Drieling, T.; Schaerer, L. O.; Biedermann, N. C.] Univ Freiburg, Dept Psychiat, D-7800 Freiburg, Germany. [Post, R. M.] NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 63 EP 63 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000173 ER PT J AU Lawson, WB Hipolito, M Nwulia, E Exxum, K AF Lawson, W. B. Hipolito, M. Nwulia, E. Exxum, K. TI Race and psychotic features in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar; genetic; psychosis; race C1 NIMH Bipolar Disorder Genet Initiat, Washington, DC USA. Howard Univ Sch Med & Hosp, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 64 EP 64 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000177 ER PT J AU Maeng, SH Mccammon, J Chen, G Reed, J Manji, HK AF Maeng, S-H Mccammon, J. Chen, G. Reed, J. Manji, H. K. TI A novel role of BAG1 in the modulation of affective resilience SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE mood stabilizers; mania; depression; animal model; BAG1 C1 [Maeng, S-H; Mccammon, J.; Chen, G.; Manji, H. K.] NIMH, LMP, MAP, NIH, Bethesda, MD 20892 USA. [Reed, J.] Burnham Inst Med Res, La Jolla, CA USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 70 EP 70 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000195 ER PT J AU Mallinger, J Koeske, G Frank, E AF Mallinger, J. Koeske, G. Frank, E. TI Social stigma, diagnosis and gender SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE stigma; social rejection; social withdrawal C1 [Mallinger, J.] NIMH, Bethesda, MD 20892 USA. [Koeske, G.] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15260 USA. [Frank, E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 72 EP 72 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000201 ER PT J AU Moral, JR Holmes, MK Cumba, DR Luckenbaugh, DA Manji, HK Zarate, CA AF Moral, J. R. Holmes, M. K. Cumba, D. R. Luckenbaugh, D. A. Manji, H. K. Zarate, C. A., Jr. TI Development of the severity index of psychosocial and environmental stress (SIPES) SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE psychosocial; stress; depression; environmental; rating scale C1 [Moral, J. R.; Holmes, M. K.; Cumba, D. R.; Luckenbaugh, D. A.; Manji, H. K.; Zarate, C. A., Jr.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 79 EP 79 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000221 ER PT J AU Shaltiel, G Maeng, SH Rogawski, M Gasior, M Chen, G Manji, HK AF Shaltiel, G. Maeng, S-H Rogawski, M. Gasior, M. Chen, G. Manji, H. K. TI GRIK2 (GluR6), a putative bipolar susceptibility gene, plays a critical role in aggression, exploration and behavioral excitement SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE bipolar; mania; lithium; GRIK2; animal model C1 [Shaltiel, G.; Maeng, S-H; Chen, G.; Manji, H. K.] NIH, NIMH, Lab Mol Pathophysiol, Bethesda, MD 20892 USA. [Rogawski, M.; Gasior, M.] NIH, NIMH, Epilepsy Res Sect, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009; Chen, Guang/A-2570-2017 OI Rogawski, Michael/0000-0002-3296-8193; NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 MA P235 BP 96 EP 96 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000267 ER PT J AU Yuan, PX Maeng, SH Schloesser, R Mccammon, J Du, J Chen, G Manji, HK AF Yuan, P-X Maeng, S-H Schloesser, R. Mccammon, J. Du, J. Chen, G. Manji, H. K. TI Evidence for the critical role of Bcl-2 in behavioral responses to severe stress and the actions of antidepressants SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE citalopram; mood stabilizers; depression; animal model C1 [Yuan, P-X; Maeng, S-H; Schloesser, R.; Mccammon, J.; Du, J.; Chen, G.; Manji, H. K.] NIMH, NIH, MAP, LMP, Bethesda, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 113 EP 113 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000313 ER PT J AU Kogan, JN Kupfer, DJ Manji, H Frank, E Calabrese, JR Drevets, W Axelson, DA Marangell, LB Chavez, M AF Kogan, J. N. Kupfer, D. J. Manji, H. Frank, E. Calabrese, J. R. Drevets, W. Axelson, D. A. Marangell, L. B. Chavez, M. TI Growing the next generation of bipolar researchers: the Career Development Institute for bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT International Conference on Bipolar Disorder CY JUN 07-09, 2007 CL Pittsburgh, PA SP ICBD DE career development; mentorship; training C1 [Kogan, J. N.; Kupfer, D. J.; Frank, E.; Axelson, D. A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Manji, H.; Drevets, W.] NIMH, Bethesda, MD 20892 USA. [Calabrese, J. R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Calabrese, J. R.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Marangell, L. B.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 SU 1 BP 115 EP 116 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264JQ UT WOS:000253284000320 ER PT J AU McElroy, SL Frye, MA Altshuler, LL Suppes, T Hellemann, G Black, D Mintz, J Kupka, R Nolen, W Leverich, GS Denicoff, KD Post, RM Keck, PE AF McElroy, Susan L. Frye, Mark A. Altshuler, Lori L. Suppes, Trisha Hellemann, Gerhard Black, David Mintz, Jim Kupka, Ralph Nolen, Willem Leverich, Gabriele S. Denicoff, Kirk D. Post, Robert M. Keck, Paul E., Jr. TI A 24-week, randomized, controlled trial of adjunctive sibutramine versus topiramate in the treatment of weight gain in overweight or obese patients with bipolar disorders SO BIPOLAR DISORDERS LA English DT Article; Proceedings Paper CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar disorder; obesity; sibutramine; topiramate; weight gain ID BINGE-EATING DISORDER; PLACEBO-CONTROLLED TRIAL; 1-YEAR FOLLOW-UP; OPEN-LABEL; DOUBLE-BLIND; I-DISORDER; PHARMACOLOGICAL-TREATMENT; MANIC EPISODE; MOOD; EFFICACY AB Objectives: Patients with bipolar disorder (BD) have an increased risk of obesity as well as psychotropic-associated weight gain. The objective of this study was to compare sibutramine and topiramate as adjunctive treatments for psychotropic-associated weight gain in overweight or obese outpatients with BD. Methods: In this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with bipolar disorders who had a body mass index (BMI) >= 30 kg/m(2), or >= 27 kg/m(2) with obesity-related comorbidities, and psychotropic-associated weight gain were randomly assigned to receive sibutramine (n = 18; 5-15 mg/day) or topiramate (n = 28; 25-600 mg/day). The primary outcome measure was weight loss. Secondary measures included changes in BMI, percent body weight loss, and mood symptoms. Results: Patients randomized either to sibutramine or topiramate lost comparable amounts of weight (4.1 +/- 5.7 and 2.8 +/- 3.5 kg, respectively) and displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively). However, only four (22%) patients receiving sibutramine and six (21%) patients receiving topiramate completed the 24-week trial. In addition, the attrition patterns for the two drugs were different, with patients discontinuing topiramate doing so early in treatment and patients discontinuing sibutramine doing so throughout treatment. Also, higher ratings of manic and depressive symptoms significantly increased risk for early topiramate discontinuation compared to that for sibutramine. Conclusons: Adjunctive sibutramine and topiramate may have comparable weight loss effects in overweight or obese bipolar patients with psychotropic-associated weight gain, but are each associated with similarly high discontinuation rates. In addition, they may have different attrition profiles. Compared to sibutramine, discontinuation of topiramate may be more likely to occur early in treatment and may be more dependent upon manic and depressive symptoms. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. Univ Calif Los Angeles, Mood Disorder Clin, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Bipolar Disorder Res Program, Dallas, TX USA. Univ Calif Los Angeles, Inst Neuropsychiat, Biostat Core, Los Angeles, CA 90024 USA. Boston Univ, Boston, MA 02215 USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Bipolar Collaborat Network, Hershey, PA USA. Vet Affairs Med Ctr, Gen Clin Res Ctr, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr, Mental Hlth Care Line, Cincinnati, OH 45267 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, 231 Albert Sabin Way,ML 559, Cincinnati, OH 45267 USA. EM susan.mcelroy@uc.edu RI Nolen, Willem/E-9006-2014 NR 61 TC 44 Z9 44 U1 3 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2007 VL 9 IS 4 BP 426 EP 434 DI 10.1111/j.1399-5618.2007.00488.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 176UO UT WOS:000247110600012 PM 17547588 ER PT J AU Parker, C Sydes, MR Catton, C Kynaston, H Logue, J Murphy, C Morgan, RC Mellon, K Morash, C Parulekar, W Parmar, MKB Payne, H Savage, C Stansfeld, J Clarke, NW AF Parker, Chris Sydes, Matthew R. Catton, Charles Kynaston, Howard Logue, John Murphy, Claire Morgan, Rachel C. Mellon, Kilian Morash, Chris Parulekar, Wendy Parmar, Mahesh K. B. Payne, Heather Savage, Colleen Stansfeld, Jim Clarke, Noel W. CA RADICALS Trial Management Grp TI Radiotherapy and androgen deprivation in combination after local surgery (RADICALS): A new Medical Research Council/National Cancer Institute of Canada phase III trial of adjuvant treatment after radical prostatectomy SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; radiotherapy; clinical trial ID RANDOMIZED CONTROLLED-TRIAL; RADIATION-THERAPY; SALVAGE TREATMENT; SUPPRESSION; IRRADIATION; CARCINOMA; EORTC C1 Canc Res Inst, Acad Unit Radiotherapy & Oncol, Sutton SM2 5PT, Surrey, England. Royal marsden NHS Fdn Trust, Sutton, Surrey, England. MRC, Clin Trials Unit, London, England. Princess Margaret Hosp, Toronto, ON, Canada. Univ Wales Hosp, Dept Urol, Cardiff, S Glam, Wales. Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. Univ Leicester, Urol Sect, Leicester, Leics, England. Univ Ottawa, Ottawa Hosp, Ottawa, ON, Canada. NCI, Clin Trials Grp, Kingston, ON, Canada. Univ Coll Hosp, Dept Oncol, London, England. PCaSO Prostate Canc Network, Emsworth, Hants, England. Salford Royal Hosp NHS Trust, Salford, Lancs, England. RP Parker, C (reprint author), Canc Res Inst, Acad Unit Radiotherapy & Oncol, Downs Rd, Sutton SM2 5PT, Surrey, England. EM chris.parker@icr.ac.uk RI Sydes, Matthew/C-3373-2008; OI Clarke, Noel/0000-0001-7776-8059 FU Cancer Research UK [6381]; Medical Research Council [MC_U122861330, G0501019] NR 13 TC 64 Z9 64 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JUN PY 2007 VL 99 IS 6 BP 1376 EP 1379 DI 10.1111/j.1464-410X.2007.06844.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 172FU UT WOS:000246790300013 PM 17428247 ER PT J AU Wiestner, A Tehrani, M Chiorazzi, M Wright, G Gibellini, F Nakayama, K Liu, H Rosenwald, A Muller-Hermelink, HK Ott, G Chan, WC Greiner, TC Weisenburger, DD Vose, J Armitage, JO Gascoyne, RD Connors, JM Campo, E Montserrat, E Bosch, F Smeland, EB Kvaloy, S Holte, H Delabie, J Fisher, RI Grogan, TM Miller, TP Wilson, WH Jaffe, ES Staudt, LM AF Wiestner, Adrian Tehrani, Mahsa Chiorazzi, Michael Wright, George Gibellini, Federica Nakayama, Kazutaka Liu, Hui Rosenwald, Andreas Muller-Hermelink, H. Konrad Ott, German Chan, Wing C. Greiner, Timothy C. Weisenburger, Dennis D. Vose, Julie Armitage, James O. Gascoyne, Randy D. Connors, Joseph M. Campo, Elias Montserrat, Emilio Bosch, Francesc Smeland, Erlend B. Kvaloy, Stein Holte, Harald Delabie, Jan Fisher, Richard I. Grogan, Thomas M. Miller, Thomas P. Wilson, Wyndham H. Jaffe, Elaine S. Staudt, Louis M. CA LymphomaLeukemia Mol Pr TI Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival SO BLOOD LA English DT Article ID MANTLE-CELL LYMPHOMA; GENE-EXPRESSION; BREAST CANCERS; POLYMORPHISM; REARRANGEMENT; MICRORNAS; GROWTH; REGION; BCL-1; OVEREXPRESSION AB A gene expression signature of tumor proliferation rate in mantle cell lymphoma (MCL) is an overriding molecular predictor of the length of survival following diagnosis. Many strongly proliferative MCL tumors have exceptionally high cyclin D1 mRNA levels and preferentially express short cyclin D1 mRNA isoforms. We demonstrate here that these short mRNAs are cyclin D1a isoforms with truncated UTRs, not alternatively spliced cyclin D1b mRNA isoforms. Among 15 MCL tumors with truncated cyclin D1 mRNAs, 7 had genomic deletions in the CCND1 3'UTR region. In 3 others, CCND1 contained point mutations that created premature polyadenylation signals, giving rise to 1.5-kb mRNAs lacking most of the 3'UTR. Both types of genomic alteration created transcripts lacking mRNA destabilization elements present in the wild-type cyclin D1a mRNA. Premature polyadenylation due to a 3'UTR mutation also was present in the Z-138 MCL cell line, which expressed both truncated and full-length cyclin D1a mRNAs. In these cells, the half-life of the short cyclin D1a mRNA was much longer than that of the full-length mRNA. We conclude that alterations of CCND1 3'UTR structure can significantly increase its oncogenic effect and worsen the clinical course of MCL patients. C1 NCI, CCR, Metab Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. British Columbia Canc Ctr, Vancouver, BC, Canada. Univ Barcelona, Hosp Clin Barcelona, E-08007 Barcelona, Spain. Norwegian Radium Hosp, N-0310 Oslo, Norway. SW Oncol Grp, San Antonio, TX 78229 USA. RP Staudt, LM (reprint author), NCI, CCR, Metab Branch, NIH, Bldg 10,Rm 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU Intramural NIH HHS NR 44 TC 102 Z9 103 U1 3 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2007 VL 109 IS 11 BP 4599 EP 4606 DI 10.1182/blood-2006-08-039859 PG 8 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100008 PM 17299095 ER PT J AU Patel, KV Harris, TB Faulhaber, M Angleman, SB Connelly, S Bauer, DC Kuller, LH Newman, AB Guralnik, JM AF Patel, Kushang V. Harris, Tamara B. Faulhaber, Marion Angleman, Sara B. Connelly, Stephanie Bauer, Douglas C. Kuller, Lewis H. Newman, Anne B. Guralnik, Jack M. CA Hlth, Aging, Body Compositon Study TI Racial variation in the relationship of anemia with mortality and mobility disability among older adults SO BLOOD LA English DT Article ID GLOMERULAR-FILTRATION-RATE; HEMOGLOBIN CONCENTRATION; IRON-DEFICIENCY; KIDNEY-FUNCTION; CYSTATIN-C; DISEASE; HEALTH; WHITES; WOMEN; AGE AB Anemia is more common among older blacks than older whites. However, it is unclear whether anemia predicts adverse events similarly in both races. Data on 1018 black and 1583 white adults aged 71 to 82 years were analyzed. Anemia, as defined by World Health Organization (WHO) criteria, was used to predict mortality over 6 years and incidence of mobility disability over 4 years. In proportional hazards models of mortality in whites, the age-adjusted hazard ratio (HR) for anemia in men was 1.96 (95% confidence interval [Cl]: 1.35, 2.83) and in women was 2.86 (95% Cl: 1.69, 4.82). In contrast, anemia was not associated with mortality in black men (HR = 1.15 [95% CI: 0.77, 1.72]) or women (HR = 1.39 [95% CI: 0.91, 2.14]). Higher mortality rate was observed only in black men with hemoglobin values more than 20 g/L (2.0 g/dL) below the WHO cutoff, whereas mortality rates were elevated in white men with hemoglobin values 1 to 10, 11 to 20, and more than 20 g/L below the WHO cutoff. In conclusion, anemia was significantly associated with increased risk of death and mobility disability in community-dwelling older whites. Conversely, older blacks classified as anemic by WHO criteria were not at risk for adverse events, indicating that alternative criteria are warranted. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. RP Patel, KV (reprint author), 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM patelku@mail.nih.gov RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716 FU NIA NIH HHS [N01 AG 62101, N01 AG 62103, N01 AG 62106] NR 30 TC 62 Z9 64 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2007 VL 109 IS 11 BP 4663 EP 4670 DI 10.1182/blood-2006-10-055384 PG 8 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100018 PM 17284526 ER PT J AU Withers, DR Fiorini, C Fischer, RT Ettinger, R Lipsky, PE Grammer, AC AF Withers, David R. Fiorini, Claudia Fischer, Randy T. Ettinger, Rachel Lipsky, Peter E. Grammer, Amrie C. TI T cell-dependent survival of CD20(+) and CD20(-) plasma cells in human secondary lymphoid tissue SO BLOOD LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MEMORY B-CELLS; GERMINAL CENTER FORMATION; BONE-MARROW; STROMAL CELLS; TERMINAL DIFFERENTIATION; RHEUMATOID-ARTHRITIS; HUMORAL IMMUNITY; HUMAN SPLEEN; NZB/W MICE AB The signals mediating human plasma cell survival in vivo, particularly within secondary lymphoid tissue, are unclear. Human tonsils grafted into immunodeficient mice were therefore used to delineate the mechanisms promoting the survival of plasma cells. Tonsillar plasma cells were maintained within the grafts and the majority were nonproliferating, indicating a long-lived phenotype. A significant depletion of graft plasma cells was observed after anti-CD20 treatment, consistent with cells. Moreover, anti-CD52 treatment caused the complete loss of all graft lymphocytes, including plasma cells. Unexpectedly, anti-CD3, but not anti-CD154, treatment caused the complete loss of plasma cells, indicating an essential role for T cells, but not CD40-CD154 interactions in plasma cell survival. The in vitro coculture of purified tonsillar plasma cells and T cells revealed a T-cell survival signal requiring cell contact. Furthermore, immunofluorescence studies deman plasma cells and T cells in vivo. These data reveal that human tonsil contains long-lived plasma cells, the majority of which express CD20 and can be deleted with anti-CD20 therapy. In addition, an important role for contact-dependent interactions with T cells in human plasma cell survival within secondary lymphoid tissue was identified. C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIAMS, B Cell Biol Grp, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMS, Autoimmun Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov RI Withers, David/C-7055-2015 OI Withers, David/0000-0003-3757-7594 FU Intramural NIH HHS NR 52 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2007 VL 109 IS 11 BP 4856 EP 4864 DI 10.1182/blood-2006-08043414 PG 9 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100044 PM 17299094 ER PT J AU Zhan, FH Colla, S Wu, XS Chen, BZ Stewart, JP Kuehl, WM Barlogie, B Shaughnessy, JD AF Zhan, Fenghuang Colla, Simona Wu, Xiaosong Chen, Bangzheng Stewart, James P. Kuehl, W. Michael Barlogie, Bart Shaughnessy, John D., Jr. TI CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27(Kip1)-dependent and -independent mechanisms SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; GLOBAL GENE-EXPRESSION; IN-SITU HYBRIDIZATION; UNDETERMINED SIGNIFICANCE; INDEPENDENT FUNCTION; UBIQUITIN LIGASE; P27 DEGRADATION; PLASMA-CELLS; PROGRESSION; P16(INK4A) AB Overexpression of CKS1B, a gene mapping within a minimally amplified region between 153 to 154 Mb of chromosome 1q21, is linked to a poor prognosis in multiple myeloma (MM). CKS1B binds to and activates cyclin-dependent kinases and also interacts with SKP2 to promote the ubiquitination and proteasomal degradation of P27(Kip1). Overexpression of CKS1B or SKP2 contributes to increased p27(KIP1) turnover, cell proliferation, and a poor prognosis in many tumor types. Using 4 MM cell lines harboring MAF-, FGFR3/MMSET-, or CCND1-activating translocations, we show that lentiviral delivery of shRNA directed against CKS1 B resulted in ablation of CKS1B mRNA and protein with concomitant stabilization of P27(Kip1), cell cycle arrest, and apoptosis. Although shRNA-medlated knockdown of SKP2 and forced expression of a nondegradable form of p27(Kip1) (p27(T187A)) led to cell cycle arrest, apoptosis was modest. Of importance, while knockdown of SKP2 or overexpression of p27T187A induced cell cycle arrest in KMS28PE, an MM cell line with biallelic deletion of CDKN1B/p27(Kip1), CKS1B ablation induced strong apoptosis. These data suggest that CKS1B influences myeloma cell growth and survival through SKP2- and p27(KiP1)-dependent and -independent mechanisms and that therapeutic strategies aimed at abolishing CKS1B function may hold promise for the treatment of high-risk disease for which effective therapies are currently lacking. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. NCI, Canc Res Ctr, Genet Branch, Bethesda, MD 20892 USA. RP Shaughnessy, JD (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, 4301 W Markham St,Slot 776, Little Rock, AR 72205 USA. EM zhanfenghuang@uams.edu; shaughnessyjohn@uams.edu OI Colla, Simona/0000-0001-6583-8910 FU NCI NIH HHS [P01 CA055819, CA 55819, CA 97513, R33 CA097513] NR 35 TC 68 Z9 79 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2007 VL 109 IS 11 BP 4995 EP 5001 DI 10.1182/blood-2006-07-038703 PG 7 WC Hematology SC Hematology GA 174MJ UT WOS:000246946100061 PM 17303695 ER PT J AU Brillante, BA Kelly, MH Collins, MT AF Brillante, B. A. Kelly, M. H. Collins, M. T. TI Age-related changes in pain prevalence and the anatomical distribution of skeletal lesions in fibrous dysplasia SO BONE LA English DT Meeting Abstract CT 4th International Conference on Childrens Bone Health CY JUN 21-24, 2007 CL Montreal, CANADA C1 NIH, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Skeletal Clin Studies Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 1 BP S30 EP S30 DI 10.1016/j.bone.2007.04.018 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GU UT WOS:000247426000045 ER PT J AU Marini, JC Chang, W Cabral, WA Barnes, AM Eyre, DR Weis, M Morello, R Lee, B Leikin, S Rosenbaum, K Tifft, C Bulas, DI Kozma, C Smith, P Mulvihill, JJ Sundaram, U AF Marini, J. C. Chang, W. Cabral, W. A. Barnes, A. M. Eyre, D. R. Weis, M. Morello, R. Lee, B. Leikin, S. Rosenbaum, K. Tifft, C. Bulas, D. I. Kozma, C. Smith, P. Mulvihill, J. J. Sundaram, U. TI Recessive severe/lethal Osteogenesis Imperfecta is caused by deficiency of proteins comprising the collagen 3-hydroxylation complex SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 NICHD, BEMB, NIH, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. Baylor Coll Med, Houston, TX 77030 USA. NICHD, SPB, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Shriners Hosp Children, Chicago, IL USA. Univ Oklahoma, Oklahoma City, OK USA. VCU MCV, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S128 EP S128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100055 ER PT J AU Mckie, JE Collins, MT Reynolds, JC Winer, KK AF Mckie, J. E. Collins, M. T. Reynolds, J. C. Winer, K. K. TI Comparison of bone mineral density in children and adults with hypoparathyroidism SO BONE LA English DT Meeting Abstract CT 4th International Conference on Childrens Bone Health CY JUN 21-24, 2007 CL Montreal, CANADA C1 Natl Inst Hlth, Craniofac & Skeletal Dis Branch, Bethesda, MD USA. Natl Inst Hlth, Nucl Med, Bethesda, MD USA. NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 JUN PY 2007 VL 40 IS 6 SU 1 BP S64 EP S64 DI 10.1016/j.bone.2007.04.085 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GU UT WOS:000247426000112 ER PT J AU Qiang, Y Chen, Y Brown, N Rudikoff, S Barlogie, B Shaughnessy, JD AF Qiang, Y. Chen, Y. Brown, N. Rudikoff, S. Barlogie, B. Shaughnessy, J. D., Jr. TI Dkk1 blocks Wnt-induced osteoprotegerin production in osteoblast progenitors in multiple myeloma SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 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 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 2 BP S144 EP S144 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100084 ER PT J AU Shepherd, JA Zhao, S Fan, B Zemel, B Kalkwarf, H Lappe, J Wang, L Gilsanz, V Wren, TA Winer, K Lu, Y AF Shepherd, J. A. Zhao, S. Fan, B. Zemel, B. Kalkwarf, H. Lappe, J. Wang, L. Gilsanz, V. Wren, T. A. Winer, K. Lu, Y. TI "P-Score" to estimate fracture risk in children SO BONE LA English DT Meeting Abstract CT 4th International Conference on Childrens Bone Health CY JUN 21-24, 2007 CL Montreal, CANADA C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Cincinnati Childrens Med Ctr, Cincinnati, OH USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Childrens Hosp, Los Angeles, CA 90027 USA. NICHD, Bethesda, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 1 BP S78 EP S78 DI 10.1016/j.bone.2007.04.113 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GU UT WOS:000247426000140 ER PT J AU Sigurdsson, G Chang, M Aspelund, T Siggeirsdottir, K Sigurdsson, S Eiriksdottir, G Launer, L Harris, T Gudnason, V Lang, TF AF Sigurdsson, G. Chang, M. Aspelund, T. Siggeirsdottir, K. Sigurdsson, S. Eiriksdottir, G. Launer, L. Harris, T. Gudnason, V. Lang, T. F. TI Gender comparison in muscle-bone relationship in mid-thigh in old age SO BONE LA English DT Meeting Abstract CT 17th Scientific Meeting of the International-Bone-and-Mineral-Society CY JUN 24-29, 2007 CL Montreal, CANADA SP Int Bone & Mineral Soc C1 Univ Hosp Reykjavik, Landspitali, Icelandic Heart Assoc, Reykjavik, Iceland. Icelandic Heart Assoc, Kopavogur, Iceland. NIA, Intramural Res Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 1 PU 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 JUN PY 2007 VL 40 IS 6 SU 2 BP S138 EP S139 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GV UT WOS:000247426100074 ER PT J AU Zemel, B Kalkwarf, H Mahboubi, S Gilsanz, V Shepherd, J Oberfield, S Lappe, J Frederick, M Winer, K AF Zemel, B. Kalkwarf, H. Mahboubi, S. Gilsanz, V. Shepherd, J. Oberfield, S. Lappe, J. Frederick, M. Winer, K. TI Effect of bone age on bone density Z-scores in childhood. Results from the bone mineral density in childhood study SO BONE LA English DT Meeting Abstract CT 4th International Conference on Childrens Bone Health CY JUN 21-24, 2007 CL Montreal, CANADA C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Med Ctr, Cincinnati, OH USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, New York, NY 10027 USA. Creighton Univ, Omaha, NE 68178 USA. Clin Trials & Survey Corp, Baltimore, MD USA. NICHD, Bethesda, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2007 VL 40 IS 6 SU 1 BP S88 EP S88 DI 10.1016/j.bone.2007.04.132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181GU UT WOS:000247426000159 ER PT J AU Walshe, JM Berman, AW Vatas, U Steinberg, SM Anderson, WF Lippman, ME Swain, SM AF Walshe, Janice M. Berman, Arlene W. Vatas, Ujala Steinberg, Seth M. Anderson, William F. Lippman, Marc E. Swain, Sandra M. TI A prospective study of adjuvant CMF in males with node positive breast cancer: 20-year follow-up SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE adjuvant chemotherapy; CMF chemotherapy; male breast cancer ID BRCA2 GENES; CARCINOMA; CHEMOTHERAPY; RISK; EPIDEMIOLOGY; PROGNOSIS; FAMILIES; MEN; EXPERIENCE; INSTITUTE AB Purpose To determine the long-term overall survival of male patients with stage II node positive breast cancer treated with adjuvant chemotherapy. Patients and methods Between 1974 and 1988, 31 male breast cancer patients were prospectively enrolled on study MB-82 in the National Cancer Institute. Following mastectomy, patients were treated with 12 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. Results Median patient age was 61 years (38-74 years). Twenty-one patients (68%) had 1-3 positive axillary lymph nodes while ten patients (32%) had four or more positive nodes. Estrogen receptor status was positive in 22 (71%), negative in 1 (3%), and unknown in 8 (26%) tumors. Progesterone receptor status was positive in 18 (58%), negative in 3 (10%), and unknown in 10 (32%) tumors. Median potential follow-up for all patients is 22.5 years with a median survival of 16.3 years. Twenty-one of 31 patients have died; one from a treatment-related complication, nine patients from recurrent breast cancer, five from other cancers, one from non-cancer related causes, and five from unknown causes. Ten patients remain alive at a median of 19.2 years. The overall survival probability at 10 years is 64.5% (95% CI: 46.9-78.9%), at 15 years is 51.6% (95% CI: 34.8-68%), and at 20 years is 42.4% (95% CI: 25.8-60.8%). Conclusion To our knowledge, 20-year prospective data with adjuvant chemotherapy in male breast cancer has never been reported. Adjuvant chemotherapy may benefit male breast cancer patients with positive nodes. C1 NCI, Brest Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20889 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20889 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Swain, SM (reprint author), NCI, Brest Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 49 TC 14 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2007 VL 103 IS 2 BP 177 EP 183 DI 10.1007/s10549-006-9363-0 PG 7 WC Oncology SC Oncology GA 169SC UT WOS:000246611000005 PM 17039267 ER PT J AU Hasnie, FS Wallace, VCJ Hefner, K Holmes, A Rice, ASC AF Hasnie, F. S. Wallace, V. C. J. Hefner, K. Holmes, A. Rice, A. S. C. TI Mechanical and cold hypersensitivity in nerve-injured C57BL/6J mice is not associated with fear-avoidance- and depression-related behavior SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE mouse; pain, chronic; pain, neuropathic; pain, psychological variables; research, animal ID TAIL SUSPENSION TEST; NEUROPATHIC PAIN; EXPERIMENTAL-MODEL; MOUSE STRAINS; ANXIETY; LIGATION; ANTIDEPRESSANTS; RATS AB Background. Neuropathic pain is associated with significant co-morbidity, including anxiety and depression, which impact considerably on the overall patient experience. However, pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. To improve the clinical validity of a widely used rodent model of traumatic peripheral neuropathy, we have investigated fear-avoidance- and depression-related behaviours in nerve-injured and sham-operated mice over a 4 week period. Methods. Male C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) or sham surgery and were assessed on days 7, 14, and 28 after operation. Withdrawal thresholds to punctate mechanical and cooling stimuli were measured. Mice were tested on the novel open-field and elevated plus-maze tests for fear-avoidance behaviour, and on the tail suspension test for depression-related behaviour. R Results. Hypersensitivity to punctate mechanical and cool stimuli was evident up to day 28 after PSNL. However, there was no change in fear-avoidance- or depression-related behaviours regardless of interval after-surgery. Conclusion. These data demonstrate that pain behaviour in nerve-injured C57BL/6J mice was not associated with alterations in emotion-related behaviours. C1 Univ London Imperial Coll Sci Technol & Med, Pain Res Grp, Dept Anaesthet, Fac Med, London SW10 9NH, England. Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, Bethesda, MD USA. RP Rice, ASC (reprint author), Univ London Imperial Coll Sci Technol & Med, Pain Res Grp, Dept Anaesthet, Fac Med, Chelsea & Westminster Hosp Campus,369 Fulham Rd, London SW10 9NH, England. EM a.rice@imperial.ac.uk RI Rice, Andrew/I-7501-2012 FU Intramural NIH HHS; Wellcome Trust [, 065374] NR 27 TC 27 Z9 27 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 2007 VL 98 IS 6 BP 816 EP 822 DI 10.1093/bja/aem087 PG 7 WC Anesthesiology SC Anesthesiology GA 178GD UT WOS:000247208300018 PM 17478455 ER PT J AU Giralt, SA Arora, M Goldman, JM Lee, SJ Maziarz, RT McCarthy, PL Sobocinski, KA Horowitz, MM AF Giralt, Sergio A. Arora, Mukta Goldman, John M. Lee, Stephanie J. Maziarz, Richard T. McCarthy, Philip L. Sobocinski, Kathleen A. Horowitz, Mary M. CA Chronic Leukemia Working Comm TI Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE imatinib; chronic myeloid leukaemia; haematopoietic cell transplantation; STI571; IRIS ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; 1ST CHRONIC PHASE; ABL TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; BCR-ABL; INTERFERON-ALPHA; CYTOGENETIC RESPONSES; PROGNOSTIC-FACTORS AB The discovery and approval of imatinib drastically changed the therapeutic algorithm for chronic myeloid leukaemia (CML). Imatinib is now considered the therapy of choice for patients with newly diagnosed CML, including those previously considered candidates for allogeneic haematopoietic cell transplantation (HCT). We compared numbers and types of allogeneic HCTs performed for CML in North America before and after the introduction of imatinib, and publication of the International Randomized Trial of Interferon and STI571 (IRIS) using transplants reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The number of HCTs for CML registered with the CIBMTR in 1998 was 617; 62% were performed in first chronic phase (CP1). Only 1% of patients had received imatinib prior to transplantation. In 2003, the number of HCTs reported was 223; 44% were performed in CP1 and 77% of patients received imatinib prior to transplantation. The introduction of imatinib therapy has had a profound impact on the use of allogeneic transplantation for CML, with a marked decrease in the number of transplants for CML and an accompanying decrease in the proportion done in CP1. Most patients now receive a trial of imatinib before proceeding to HCT. C1 MD Anderson Canc Ctr, Houston, TX 77230 USA. Univ Minnesota, Minneapolis, MN USA. Natl Inst Hlth, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Med Coll Wisconsin, CIBMTR, Hlth Policy Inst, Milwaukee, WI 53226 USA. RP Giralt, SA (reprint author), MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 423, Houston, TX 77230 USA. EM sgiralt@mdanderson.org FU NCI NIH HHS [U24 CA 76518] NR 35 TC 57 Z9 58 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2007 VL 137 IS 5 BP 461 EP 467 DI 10.1111/j.1365-2141.2007.06582.x PG 7 WC Hematology SC Hematology GA 163TT UT WOS:000246186800011 PM 17459051 ER PT J AU Hall, KD AF Hall, Kevin D. TI Body fat and fat-free mass inter-relationships: Forbes's theory revisited SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE body composition; weight loss; weight gain; mathematical model ID ENERGY-EXPENDITURE; WEIGHT-LOSS; MORBID-OBESITY; METABOLISM; ADAPTATION; SURGERY; PROTEIN; WOMEN; MEN AB A theoretical equation was developed by Forbes that quantifies the fat-free proportion of a weight change as a function of the initial body fat. However, Forbes's equation was strictly valid only for infinitesimal weight changes. Here, I extended Forbes's equation to account for the magnitude and direction of macroscopic body weight changes. The new equation was also re-expressed in terms of an alternative representation of body composition change defined by an energy partitioning parameter called the P-ratio. The predictions of the resulting equations compared favourably with data from human underfeeding and overfeeding experiments and accounted for previously unexplained trends in the data. The magnitude of the body weight change had a relatively weak effect on the predicted body composition changes and the results were very similar to Forbes's original equation for modest weight changes. However, for large weight changes, such as the massive weight losses found in patients following bariatric surgery, Forbes's original equation consistently underestimated the fat-free mass loss, as expected. The new equation that accounts for the magnitude of the weight loss provides better predictions of body composition changes in such patients. C1 NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Hall, KD (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU Intramural NIH HHS [Z01 DK013036-01] NR 22 TC 50 Z9 51 U1 0 U2 10 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD JUN PY 2007 VL 97 IS 6 BP 1059 EP 1063 DI 10.1017/S0007114507691946 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 182VA UT WOS:000247530900007 PM 17367567 ER PT J AU Harden, VA AF Harden, Victoria A. TI James Harvey Young, 1915-2006 - In memoriam SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. RP Harden, VA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 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 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SUM PY 2007 VL 81 IS 2 BP 432 EP 433 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 179HO UT WOS:000247280600005 ER PT J AU MacDonald, IM Sauve, Y Sieving, PA AF MacDonald, Ian M. Sauve, Yves Sieving, Paul A. TI Preventing blindness in retinal disease: ciliary neurotrophic factor intraocular implants SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article; Proceedings Paper CT International Ocular Neuroprotection Symposium CY OCT 14, 2006 CL Toronto, CANADA DE neuroprotection; retina; retinitis pigmentosa; ciliary neurotrophic factor; encapsulated cell therapy; macular degeneration ID PHOTORECEPTOR DEGENERATION; GROWTH-FACTOR; TRIAL; INFUSION; DAMAGE; CNTF AB A recent phase I trial of an encapsulated cell therapy device that delivers ciliary neurotrophic factor has shown the potential of this approach in the treatment of retinitis pigmentosa. As experience with this device is gained, other retinal degenerative disorders may be potential targets of a similar therapeutic approach. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Ophthalmol, Edmonton, AB T6G 2M7, Canada. RP MacDonald, IM (reprint author), NEI, NIH, Bldg 10,Rm 10N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM macdonaldi@mail.nih.gov OI MacDonald, Ian/0000-0001-7472-8385 FU Intramural NIH HHS; NEI NIH HHS [N01-EY-1-2113] NR 17 TC 26 Z9 29 U1 0 U2 5 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 EI 1715-3360 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD JUN PY 2007 VL 42 IS 3 BP 399 EP 402 DI 10.3129/canjophthalmol.i07-039 PG 4 WC Ophthalmology SC Ophthalmology GA 179LO UT WOS:000247291300003 PM 17508034 ER PT J AU Ramsey, SD Howlader, N Etzioni, R Brown, ML Warren, JL Newcomb, P AF Ramsey, Scott D. Howlader, Nadia Etzioni, Ruth Brown, Martin L. Warren, Joan L. Newcomb, Polly TI Surveillance endoscopy does not improve survival for patients with local and regional stage colorectal cancer SO CANCER LA English DT Article DE colorectal cancer; surveillance endoscopy; survival; case-control ID FOLLOW-UP; CURATIVE RESECTION; COLONOSCOPY; SURGERY; METAANALYSIS; GUIDELINES; CARCINOMA; SOCIETY AB BACKGROUND. Endoscopic surveillance is recommended and widely practiced after definitive treatment for colorectal cancer, yet to the authors' knowledge there is little evidence supporting its benefit. The purpose of the current study was to estimate the impact of endoscopic surveillance on colorectal cancer-specific survival for persons with localized or regional colorectal cancer. The population included Medicare patients (age >= 65 years) who were diagnosed with local or regional stage colorectal cancer between 1986 and 1996. METHODS. The current study was a retrospective case-control study. Cases were defined as those individuals who died of colorectal cancer and controls were defined as those with colorectal cancer who did not die of colorectal cancer; controls were frequency matched to cases. Surveillance was defined as the use of colonoscopy, flexible sigmoidoscopy, or barium enema >= 6 months after diagnosis. Logistic regression was used to control for endoscopic procedure, race, comorbidity index at the time of diagnosis, and types of initial treatments after surgery. RESULTS. The analysis group contained 8130 cases (29%) and 20,079 controls (71%). The average time to first bowel surveillance for those with at least 1 surveillance examination was 15.9 months after the diagnosis (median, 13 months). In the regression analysis, surveillance endoscopy was not found to be associated with improved colorectal cancer-specific survival (odds ratio of 1.01; 95% confidence interval, 0.95-1.06 [P = 0.85]). Setting the surveillance interval to 12 months and 15 months rather than 6 months after diagnosis did not appear to influence the results. CONCLUSIONS. Surveillance endoscopy does not appear to influence colorectal cancer-specific mortality in patients age >= 65 years who are diagnosed with localized or regional stage colorectal cancer. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,POB 19024,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU NCI NIH HHS [U01 CA074794]; NHGRI NIH HHS [R01 HG002941] NR 24 TC 11 Z9 11 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2007 VL 109 IS 11 BP 2222 EP 2228 DI 10.1002/cncr.22673 PG 7 WC Oncology SC Oncology GA 170QN UT WOS:000246679100009 PM 17410533 ER PT J AU Melillo, G AF Melillo, Giovanni TI Targeting hypoxia cell signaling for cancer therapy SO CANCER AND METASTASIS REVIEWS LA English DT Review DE hypoxia inducible factors; solid tumors; cancer therapy; molecular target ID ENDOTHELIAL-GROWTH-FACTOR; INDUCIBLE-FACTOR-I; SMALL-MOLECULE INHIBITORS; RECEPTOR NUCLEAR TRANSLOCATOR; BREAST-TUMOR CELLS; FACTOR EXPRESSION; FACTOR 1-ALPHA; DNA-BINDING; VEGF EXPRESSION; GENE-EXPRESSION AB Hypoxia, a decrease in oxygen levels, is a hallmark of solid tumors. Hypoxic cells are more resistant to killing by ionizing radiation and chemotherapy, are more invasive and metastatic, resistant to apoptosis, and genetically unstable. Over the last two decades, the discovery of Hypoxia Inducible Factors, a family of transcription factors crucially involved in the response of mammalian cells to oxygen deprivation, has led to the identification of a molecular target associated with hypoxia suitable for the development of cancer therapeutics. These features of solid tumors may offer a unique opportunity for selective therapeutic approaches. A number of strategies targeting hypoxia and/or Hypoxia Inducible Factors (HIF) have been developed over the last several years and will be described. The exponentially growing interest in therapeutic strategies targeting hypoxia/HIF will undoubtedly generate more active compounds for preclinical and clinical development. A rational development plan aimed to validate target inhibition in preclinical models and early clinical trials is essential for a rapid translation of these agents to the treatment of human cancers. C1 Natl Canc Inst, Tumor Hypoxia Lab, Frederick, MD 21702 USA. SAIC Frederick Inc, Dev Therapeut Program, Natl Canc Inst, Frederick, MD 21702 USA. RP Melillo, G (reprint author), Natl Canc Inst, Tumor Hypoxia Lab, Bldg 432,Rm 218, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 111 TC 150 Z9 154 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2007 VL 26 IS 2 BP 341 EP 352 DI 10.1007/s10555-007-9059-x PG 12 WC Oncology SC Oncology GA 193UH UT WOS:000248300100013 PM 17415529 ER PT J AU Song, EY Rizvi, SMA Qu, CF Raja, C Brechbiel, MW Morgenstern, A Apostolidis, C Allen, BJ AF Song, Emma Y. Rizvi, Syed M. Abbas Qu, Chang F. Raja, Chand Brechbiel, Martin W. Morgenstern, Alfred Apostolidis, Christos Allen, Barry J. TI Pharmacokinetics and toxicity of Bi-213-labeled PAI2 in preclinical targeted alpha therapy for cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE radioimmunotherapy; a radiation; maximum tolerance dose; plasminogen activator inhibitor 2 (PAI2); pharmacokinetics; acute toxicity; 213Bismuth ID ACTIVATOR INHIBITOR TYPE-2; RADIOLABELED ANTIBODY FRAGMENTS; ANIMAL-MODEL; RENAL UPTAKE; BI-213; CYTOTOXICITY; CELLS; MICRODOSIMETRY; IRRADIATION; SYSTEM AB Objectives: The plasminogen activator inhibitor type 2 (PAI2) when labelled with B-213 forms the Bi-213-PAI2 alpha conjugate (AC). This AC has been shown to be efficacious in preclinical studies with breast, ovarian, prostate and pancreatic cancers. T of this study were to investigate the pharmacokinetics and in vivo stability of Bi-213-PAI2 mice its toxicity in mice and rabbits; and to determine whether a prior injection of metal chelator (Ca-DTPA) or lysine can reduce toxicity by decreasing renal uptake. Methods: Two chelators (CHX-A"-DTPA and cDTPA) were used for preparation of the A Bi-213-PAI2 conjugate, for intraperitoneal administration in mice and ear vein injection in rabbits. The mice were sacrificed at different time points for pharmacokinetic studies Blood and organs were collected for toxicity studies for all groups. Results: Both chelators were found to have similar %ID/g in the kidneys over four hours. Mice and rabbits did not show any short term toxicity over 1 3 weeks at 142 MBq/kg and 120 MBq/kg 213Bi-PAI2 respectively. Kidney uptake was decreased three fold by lysine. Radiation nephropathy was observed at 20-30 weeks in mice, leading to severe weight loss whereas severe and widespread renal tubular necrosis was observe at 13 weeks in rabbits. Conclusions: Radiation nephropathy is the dose limiting toxicity observed in mice an rabbits. Lysine can reduce kidney uptake by three fold. Based on long-term monitoring the maximum tolerance doses (MTD) are 350 and 120 MBq/kg for mice and rabbi respectively. C1 Gen Hosp St Georg, Canc Care Ctr, Expt Radiat Oncol, Gray St Kogarah, NSW, Australia. Univ New S Wales, Sydney, NSW, Australia. Commiss European Communities, Joint Res Ctr, European Inst Transuranium Elements, D-7500 Karlsruhe, Germany. Natl Inst Hlth, Natl Canc Ctr, Canc Res Ctr, Natl Canc Inst, Bethesda, MD USA. RP Rizvi, SMA (reprint author), Gen Hosp St Georg, Canc Care Ctr, Expt Radiat Oncol, Gray St Kogarah, NSW, Australia. EM syed.rizvi@sesiahs.health.nsw.gov.au NR 38 TC 9 Z9 10 U1 0 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2007 VL 6 IS 6 BP 898 EP 904 PG 7 WC Oncology SC Oncology GA 222PF UT WOS:000250308700025 PM 17582216 ER PT J AU Hunter, DJ Thomas, G Hoover, RN Chanock, SJ AF Hunter, D. J. Thomas, G. Hoover, R. N. Chanock, S. J. TI Scanning the horizon: What is the future of genome-wide association studies in accelerating discoveries in cancer etiology and prevention? SO CANCER CAUSES & CONTROL LA English DT Article DE genetic linkage; neoplasms; epidemiologic methods; genomics; heredity ID PROSTATE-CANCER; SUSCEPTIBILITY; VARIANTS; BREAST; GENE AB Genome-wide association studies using recently developed large scale single nucleotide polymorphism platforms are beginning to be performed, and results reported. Initial indications are that these studies are capable of discovering loci associated with relative risks too modest to have been detectable through family-based linkage studies. However, as these studies initially test 500,000 or more polymorphisms in a first series of cases and controls, the need for robust replication in one, or preferably, several independent studies is paramount to winnow out the true positive results from the large number of expected false positives. We discuss the need for the formation of consortia to conduct these multi-stage studies, and stress the importance of full disclosure of allele frequencies in cases and controls from these studies in order to facilitate joint analyses across datasets to speed discovery of reproducible associations, and to explore more complex associations such as gene-gene interactions. Desirable characteristics of studies in which genome-wide association studies will be most informative are discussed. The validation of genetic variants that alter risk of specific cancers may be relevant to screening, the identification of high risk persons for risk-reducing interventions, and the discovery of new biological mechanisms that may provide insight into cancer causes and preventive strategies. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hunter, DJ (reprint author), Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. EM david.hunter@channing.harvard.edu NR 20 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2007 VL 18 IS 5 BP 479 EP 484 DI 10.1007/s10552-007-0118-y PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 163PW UT WOS:000246174700002 PM 17440825 ER PT J AU Calton, BA Chang, SC Wright, ME Kipnis, V Lawson, K Thompson, FE Subar, AF Mouw, T Campbell, DS Hurwitz, P Hollenbeck, A Schatzkin, A Leitzmann, MF AF Calton, Brook A. Chang, Shih Chen Wright, Margaret E. Kipnis, Victor Lawson, Karla Thompson, Frances E. Subar, Amy F. Mouw, Traci Campbell, David S. Hurwitz, Paul Hollenbeck, Albert Schatzkin, Arthur Leitzmann, Michael F. TI History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE prostate cancer; diabetes mellitus; prospective; cohort; incidence; AARP ID IMPAIRED GLUCOSE-TOLERANCE; NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; US ADULTS; PHYSICAL-ACTIVITY; FASTING GLUCOSE; PLASMA-GLUCOSE; UNITED-STATES; LARGE COHORT; MEN AB Objective A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors. Methods We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50-71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression. Results During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI = 0.64, 0.74) and 0.71 (95% CI = 0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR = 0.41; 95% CI = 0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer. Conclusion Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk. C1 NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Biometry Res Grp, US Dept HHS,NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. WESTAT Corp, Rockville, MD 20850 USA. AARP, Washington, DC USA. RP Calton, BA (reprint author), NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, 6120 Execut Blvd,EPS-MSC 7232, Bethesda, MD 20892 USA. EM brook.calton@ucsf.edu FU Intramural NIH HHS NR 63 TC 50 Z9 53 U1 0 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 JUN PY 2007 VL 18 IS 5 BP 493 EP 503 DI 10.1007/s10552-007-0126-y PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 163PW UT WOS:000246174700004 PM 17450441 ER PT J AU Seaman, S Stevens, J Yang, MY Logsdon, D Graff-Cherry, C Croix, BS AF Seaman, Steven Stevens, Janine Yang, Mi Young Logsdon, Daniel Graff-Cherry, Cari Croix, Brad St. TI Genes that distinguish physiological and pathological angiogenesis SO CANCER CELL LA English DT Article ID BLOOD-BRAIN-BARRIER; ORGANIC ANION TRANSPORTER; ENDOTHELIAL GROWTH-FACTOR; GLUCOSE-TRANSPORTER; MONOCLONAL-ANTIBODY; LIVER-REGENERATION; ABLUMINAL MEMBRANE; VESSEL WALLS; EXPRESSION; CELLS AB To unravel the normal vasculature transcriptome and determine how it is altered by neighboring malignant cells, we compared gene expression patterns of endothelial cells derived from the blood vessels of eight normal resting tissues, five tumors, and regenerating liver. Organ-specific endothelial genes were readily identified, including 27 from brain. We also identified 25 transcripts overexpressed in tumor versus normal endothelium, including 13 that were not found in the angiogenic endothelium of regenerating liver. Most of the shared angiogenesis genes have expected roles in cell-cycle control, but those specific for tumor endothelium were primarily cell surface molecules of uncertain function. These studies reveal striking differences between physiological and pathological angiogenesis potentially important for the development of tumor-specific, vascular-targeted therapies. C1 Natl Canc Inst, Tumor Angiogenesis Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA. Natl Canc Inst, Basic Res Program, SAIC, Frederick, MD 21702 USA. RP Croix, BS (reprint author), Natl Canc Inst, Tumor Angiogenesis Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM stcroix@ncifcrf.gov RI Seaman, Steven/A-2755-2013 OI Seaman, Steven/0000-0003-3349-3334 FU Intramural NIH HHS [Z01 BC010486-04] NR 52 TC 199 Z9 200 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2007 VL 11 IS 6 BP 539 EP 554 DI 10.1016/j.ccr.2007.04.017 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 179MB UT WOS:000247292800008 PM 17560335 ER PT J AU Morgan, GD Backinger, CL Leischow, SJ AF Morgan, Glen D. Backinger, Cathy L. Leischow, Scott J. TI The future of tobacco-control research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SMOKING-CESSATION; PUBLIC-HEALTH; UNITED-STATES; DEPENDENCE; ADULTS; CARE AB Recent epidemiologic data on the stabilization of adult and youth smoking rates underscore the need for vigorous research across the cancer control spectrum on tobacco use interventions. The steady decline in adult rates of smoking has stalled for the first time in 8 years, and certain race, ethnic, and population groups are disproportionately at risk to tobacco-related cancers because of disparities in tobacco use or access to effective interventions. Although substantial progress has been made across levels of basic through applied research, tobacco-control research across the discovery and delivery continuum must be accelerated to further reduce the cancer burden. Following a brief review of the prevalence and trends affecting tobacco use initiation and cessation, we identify and describe four domains of extraordinary research opportunities: genetics and gene-environment interactions, bioinformatics and health informatics, disparities and disproportionate risk, and prevention and treatment. Evolutionary scientific changes, like rapidly advancing technology and emphasis on the paradigm of team science research approaches, provide both a challenge as well as unparalleled opportunities for scientific advancement and public health progress. C1 NCI, Tobacco Control Res Branch, Rockville, MD 20852 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. RP Morgan, GD (reprint author), NCI, Tobacco Control Res Branch, 6130 Execut Blvd,EPN 4034, Rockville, MD 20852 USA. EM gmorgan@nih.gov NR 27 TC 17 Z9 17 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 JUN PY 2007 VL 16 IS 6 BP 1077 EP 1080 DI 10.1158/1055-9965.EPI-06-0928 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100006 PM 17548666 ER PT J AU Wright, ME Weinstein, SJ Lawson, KA Albanes, D Subar, AF Dixon, LB Mouw, T Schatzkin, A Leitzmann, MF AF Wright, Margaret E. Weinstein, Stephanie J. Lawson, Karla A. Albanes, Demetrius Subar, Amy F. Dixon, L. Beth Mouw, Traci Schatzkin, Arthur Leitzmann, Michael F. TI Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALPHA-TOCOPHEROL; BETA-CAROTENE; GAMMA-TOCOPHEROL; CONTROLLED-TRIAL; ANTIOXIDANT VITAMIN; LARGE COHORT; ASSOCIATION; PREVENTION; RETINOL; SELENIUM AB Supplemental vitamin E (alpha-tocopherol) has been linked to lower prostate cancer incidence in one randomized trial and several, although not all, observational studies. The evidence regarding dietary intake of individual vitamin E isoforms and prostate cancer is limited and inconclusive, however. We prospectively examined the relations of supplemental vitamin E and dietary intakes of alpha-, beta-, gamma-, and delta- tocopherols to prostate cancer risk among 295,344 men, ages 50 to 71 years and cancer-free at enrollment in 1995 to 1996, in the NIH-AARP Diet and Health Study. At baseline, participants completed a questionnaire that captured information on diet, supplement use, and other factors. Proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (95% CI) of prostate cancer. During 5 years of follow-up, 10,241 incident prostate cancers were identified. Supplemental vitamin E intake was not related to prostate cancer risk (for >0-99, 100-199, 200-399, 400-799, and >= 800 IU/d versus never use: RR, 0.97, 0.89, 1.03, 0.99, and 0.97 (95% CI, 0.87-1.07) respectively; P-trend = 0.90). However, dietary gamma-tocopherol, the most commonly consumed form of vitamin E in the United States, was significantly inversely related to the risk of advanced prostate cancer (for highest versus lowest quintile: RR, 0.68; 95% CI, 0.56-0.84; P-trend = 0.001). These results suggest that supplemental vitamin E does not protect against prostate cancer, but that increased consumption of gamma-tocopherol from foods is associated with a reduced risk of clinically relevant disease. The potential benefit of gamma-tocopherol for prostate cancer prevention deserves further attention. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD USA. NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD USA. NYU, Dept Nutr Food Studies & Publ Hlth, New York, NY USA. RP Wright, ME (reprint author), Univ Illinois, Coll Med, Dept Pathol, Room 130,840 S Wood St, Chicago, IL 60612 USA. EM mewright@uic.edu RI Albanes, Demetrius/B-9749-2015 FU Intramural NIH HHS NR 40 TC 63 Z9 66 U1 0 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 JUN PY 2007 VL 16 IS 6 BP 1128 EP 1135 DI 10.1158/1055-9965.EPI-06-1071 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100014 PM 17548674 ER PT J AU Yang, G Shu, XO Li, HL Chow, WH Ji, BT Zhang, XL Gao, YT Zheng, W AF Yang, Gong Shu, Xiao-Ou Li, Honglan Chow, Wong-Ho Ji, Bu-Tian Zhang, Xianglan Gao, Yu-Tang Zheng, Wei TI Prospective cohort study of green tea consumption and colorectal cancer risk in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BLACK TEA; STOMACH-CANCER; RECTAL-CANCER; REDUCED RISK; SHANGHAI; COLON; JAPAN; POLYPHENOLS; COFFEE; CHINA AB Tea and its constituents have shown anticarcinogenic activities in in vitro and animal studies. Epidemiologic studies, however, have been inconsistent. We prospectively evaluated the association between green tea consumption and colorectal cancer (CRC) risk in a cohort of 69,710 Chinese women aged 40 to 70 years. Information on tea consumption was assessed through in-person interviews at baseline and reassessed 2 to 3 years later in a follow-up survey. During 6 years of follow-up, 256 incident cases of CRC were identified. The multivariate relative risk of CRC was 0.63 (95% confidence interval, 0.45-0.88) for women who reported drinking green tea regularly at baseline compared with nonregular tea drinkers. A significant dose-response relationship was found for both the amount of tea consumed (P-trend = 0.01) and duration in years of lifetime tea consumption (P-trend = 0.006). The reduction in risk was most evident among those who consistently reported to drink tea regularly at both the baseline and follow-up surveys (relative risk, 0.43; 95% confidence interval, 0.24-0.77). The inverse association with regular tea drinking was observed for both colon and rectal cancers. This study suggests that regular consumption of green tea may reduce CRC risk in women. C1 Vanderbilt Univ, Ctr Med, Sch Med, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37232 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. RP Yang, G (reprint author), Vanderbilt Univ, Ctr Med, Sch Med, Dept Med,Vanderbilt Epidemiol Ctr, S-1118 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM Gong.Yang@vanderbilt.edu FU Intramural NIH HHS; NCI NIH HHS [R01CA70867] NR 31 TC 58 Z9 63 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2007 VL 16 IS 6 BP 1219 EP 1223 DI 10.1158/1055-9965.EPI-07-0097 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100028 PM 17548688 ER PT J AU Boocock, DJ Faust, GES Patel, KR Schinas, AM Brown, VA Ducharme, MP Booth, TD Crowell, JA Perloff, M Gescher, AJ Steward, WP Brenner, DE AF Boocock, David J. Faust, Guy E. S. Patel, Ketan R. Schinas, Anna M. Brown, Victoria A. Ducharme, Murray P. Booth, Tristan D. Crowell, James A. Perloff, Marjorie Gescher, Andreas J. Steward, William P. Brenner, Dean E. TI Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INTESTINAL TUMORIGENESIS; DIETARY RESVERATROL; LOW BIOAVAILABILITY; TRANS-RESVERATROL; GENE-EXPRESSION; TUMOR-CELLS; RATS; POLYPHENOLS; WINE; INHIBITION AB The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents. The hypothesis was tested that, in healthy humans, p.o. administration of resveratrol is safe and results in measurable plasma levels of resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry and quantitated by highperformance liquid chromatography-UV. Consumption of resveratrol did not cause serious adverse events. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4 mu mol/L, mean +/- SD; n = 10), which occurred 1.5 h post-dose. Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3-to 8-fold higher. The area under the plasma concentration curve (AUC) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol. Urinary excretion of resveratrol and its metabolites was rapid, with 77% of all urinary agent-derived species excreted within 4 h after the lowest dose. Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 mu mol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy. However, the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation. C1 Univ Leicester, Leicester Royal Infirm, Dept Canc Studies & Mol Med, Canc Biomarkers & Prevent Grp, Leicester LE2 7LX, Leics, England. MDS Pharma Serv, Montreal, PQ, Canada. Royalmt Pharma, Montreal, PQ, Canada. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. VA Med Ctr, Ann Arbor, MI USA. RP Gescher, AJ (reprint author), Univ Leicester, Leicester Royal Infirm, Dept Canc Studies & Mol Med, Canc Biomarkers & Prevent Grp, Robert Kilpatrick Clin Sci Bldg, Leicester LE2 7LX, Leics, England. EM ag15@le.ac.uk RI Boocock, David/I-4666-2015 OI Boocock, David/0000-0002-7333-3549 FU Medical Research Council [G0100874]; NCI NIH HHS [N01-CN-25025] NR 40 TC 411 Z9 416 U1 4 U2 43 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2007 VL 16 IS 6 BP 1246 EP 1252 DI 10.1158/1055-9965.EPI-07-0022 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100032 PM 17548692 ER PT J AU Weinstein, SJ Wright, ME Lawson, KA Snyder, K Mannisto, S Taylor, PR Virtamo, J Albanes, D AF Weinstein, Stephanie J. Wright, Margaret E. Lawson, Karla A. Snyder, Kirk Mannisto, Satu Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI Serum and dietary vitamin E in relation to prostate cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BETA-CAROTENE; ALPHA-TOCOPHEROL; CONTROLLED-TRIAL; FOLLOW-UP; ANTIOXIDANT VITAMIN; GAMMA-TOCOPHEROL; UNITED-STATES; RETINOL; SUPPLEMENTATION; MICRONUTRIENTS AB alpha-Tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. We investigated whether serum alpha-tocopherol or intake of vitamin E (eight tocopherols and tocotrienols) was associated with prostate cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency questionnaire and food chemistry analyses. Proportional hazard models were used to determine multivariate-adjusted relative risks MR) and 95% confidence intervals (95% Cb. Higher serum alpha-tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest quintile; P-trend = 0.03) and was strongly and inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; P-trend = 0.002). The inverse serum alpha-tocopherol-prostate cancer association was greater among those who were supplemented with either alpha-tocopherol or beta-carotene during the trial. There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols. In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron & Dis Prevent, Helsinki, Finland. RP Weinstein, SJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Room 320,6120 Execut Blvd, Bethesda, MD 20892 USA. EM weinstes@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 51 TC 46 Z9 47 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2007 VL 16 IS 6 BP 1253 EP 1259 DI 10.1158/1055-9965.EPI-06-1084 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100033 PM 17548693 ER PT J AU Goedert, JJ Purdue, MP McNeel, TS McGlynn, KA Engels, EA AF Goedert, James J. Purdue, Mark P. McNeel, Timothy S. McGlynn, Katherine A. Engels, Eric A. CA HIV AIDS Canc Match Study TI Risk of germ cell tumors among men with HIV/acquired immunodeficiency syndrome SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INFILTRATING LYMPHOCYTES; TESTICULAR SEMINOMA; CANCER-RISK; AIDS; TRANSPLANTATION; DISORDERS; SPECTRUM; PEOPLE; HIV AB Background: Men with HIV/acquired immunodeficiency syndrome (AIDS) are reported to be at increased risk for germ cell tumors (GCT), particularly testicular seminoma. We investigated correlates of this association to improve understanding of GCTs. Methods: Testicular and extratesticular seminoma and nonseminoma cases were found by linking population-based cancer and HIV/AIDS registry data for 268,950 men who developed AIDS in 1980 to 2003. Standardized incidence ratios (SIR) with 95% confidence intervals (95% CD were used to compare these cases with the number of cases expected in the demographically matched population. Results: Overall, seminoma risk (161 cases: SIR, 1.9; 95% CI, 1.6-2.2) was increased significantly with HIV/AIDS, whereas nonseminoma risk was not (56 cases: SIR, 1.3; 95% CI, 0.96-1.7). Extratesticular GCT risk also was increased (11 cases: SIR, 2.1; 95% CI, 1.1-3.7). Seminoma risk was elevated regardless of age, race, or HIV/AIDS transmission group. It was highest for disseminated disease (SIR, 4.7; 95% CI, 2.97.2) and within 9 months of AIDS onset (SIR, 7.6; 95% CI, 5.8-9.6), but it was unrelated to CD4 count and duration of HIV/ AIDS. The excess risk of seminoma declined in more recent calendar periods, and it was no longer elevated (SIR, 1.4; 95% CI, 0.9-1.9) in the highly active antiretroviral treatment era. Conclusions: Men with HIV/AIDS had an increased risk of seminoma, but this risk may have attenuated with improving anti-HIV/AIDS treatments. Although detection bias could partly explain the excess of this cancer, various lines of evidence support a causal relationship. Possible mechanisms underlying this association include impaired tumor immunosurveillance or AIDS-related testicular atrophy. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS NR 26 TC 15 Z9 17 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 JUN PY 2007 VL 16 IS 6 BP 1266 EP 1269 DI 10.1158/1055-9965.EPI-07-0042 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100035 PM 17548695 ER PT J AU Welzel, TM Katki, HA Sakoda, LC Evans, AA London, WT Chen, G O'Broin, S Shen, FM Lin, WY McGlynn, KA AF Welzel, Tania M. Katki, Hormuzd A. Sakoda, Lori C. Evans, Alison A. London, W. Thomas Chen, Gang O'Broin, Sean Shen, Fu-Min Lin, Wen-Yao McGlynn, Katherine A. TI Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TANDEM MASS-SPECTROMETRY; HAIMEN-CITY; MICROBIOLOGIC ASSAY; OXIDATIVE STRESS; CANCER INCIDENCE; SERUM; MORTALITY; FIBROSIS; CARRIERS; CHINA AB Background: Studies in experimental animals suggest that low folate levels may play a role in liver damage and hepatocarcinogenesis. To examine this association in humans, folate levels in blood and risk for subsequent liver damage and hepatocellular carcinoma (HCC) were assessed in a population at high risk of liver cancer in China. Methods: Four hundred fifteen hepatitis B surface antigen-positive participants of the Haimen City Cohort were prospectively followed between 1998 and 2002. Serum and RBC folate levels were determined at baseline. Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured semiannually. Logistic regression modeling was used to examine the presence of hepatitis B virus DNA and HCC, whereas linear regression with a log-link function was used to examine ALT levels. Results: There was a statistically significant inverse association between serum folate level and ALT level. ALT levels decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86; 95% confidence interval, 0.76-0.97 for the highest compared with the lowest quartile; P-trend = 0.002). After exclusion of three persons with prevalent HCC, 20 (4.9%) of the 412 study participants developed HCC during follow-up, with a median time between enrollment and HCC diagnosis of 2.66 years (interquartile range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to persons in all other quartiles, the analysis found that higher RBC folate levels were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95% confidence interval, 0.13-0.86; P-trend = 0.02). Conclusions: This study suggests that increased folate levels in humans may be inversely associated with the development of liver damage and HCC. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH,EPS, Bethesda, MD 20892 USA. Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. St James Hosp, Dublin 8, Ireland. Fudan Univ, Shanghai 200433, Peoples R China. Haimen City Ctr Dis Control, Haimen City, Peoples R China. RP Welzel, TM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH,EPS, Suite 550,6120 Execut Blvd, Bethesda, MD 20892 USA. EM welzelt@mail.nih.gov RI Evans, Alison/I-4970-2013; Katki, Hormuzd/B-4003-2015 FU Intramural NIH HHS NR 26 TC 20 Z9 21 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2007 VL 16 IS 6 BP 1279 EP 1282 DI 10.1158/1055-9965.EPI-06-0853 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100037 PM 17548697 ER PT J AU Hung, RJ Moore, L Boffetta, P Feng, BJ Toro, JR Rothman, N Zaridze, D Navratilova, M Bencko, V Janout, V Kollarova, H Szeszenia-Dabrowska, N Mates, D Chow, WH Brennan, P AF Hung, Rayjean J. Moore, Lee Boffetta, Paolo Feng, Bing-Jian Toro, Jorge R. Rothman, Nathanial Zaridze, David Navratilova, Marie Bencko, Vladimir Janout, Vladimir Kollarova, Helena Szeszenia-Dabrowska, Neonila Mates, Dana Chow, Wong-Ho Brennan, Paul TI Family history and the risk of kidney cancer: A multicenter case-control study in Central Europe SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RENAL-CELL CARCINOMA; PHENOTYPE AB An elevated familial relative risk may indicate either an important genetic component in etiology or shared environmental exposures within the family. Incidence rates of kidney cancer are particularly high in Central Europe, although no data were available on the familial aggregation or genetic background of kidney cancer in this region. We have, therefore, investigated the role of family history in first-degree relatives in a large multicenter case-control study in Central Europe. A total number of 1,097 cases of kidney cancer and 1,555 controls were recruited from 2000 to 2003 from seven centers in Czech Republic, Poland, Romania, and Russia. The risk of kidney cancer increased with the increasing number of relatives with history of any cancer [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.00-1.31 per affected relative], and this association seemed to be more prominent among subjects with young onset (OR, 1.55; 95% CI, 1.09-2.20 per affected relative). Overall, the OR was 1.40 (95% CI, 0.71-2.76) for the subjects who had at least one first-degree relative with kidney cancer after adjusting for tobacco smoking, body mass index, and medical history of hypertension, and this association was most apparent among subjects with affected siblings (OR, 4.09; 95% CI, 1.09-15.4). Based on the relative risk to siblings in our study population, we estimated that 80% of the kidney cancer cases are likely to occur in 20% of the population with the highest genetic risk, which indicate the importance of further investigation of genetic factors in cancer prevention for kidney cancer. C1 IARC, F-69372 Lyon 08, France. Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Inst Cardinogenesis, Canc Res Ctr, Moscow, Russia. Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, CR-11636 Prague 1, Czech Republic. Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. Inst Occupat Med, Dept Epidemiol, Lodz, Poland. Inst Publ Hlth, Bucharest, Romania. RP Hung, RJ (reprint author), IARC, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM hung@iarc.fr RI Feng, Bing-Jian/C-6974-2009; Hung, Rayjean/A-7439-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 FU Intramural NIH HHS NR 17 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2007 VL 16 IS 6 BP 1287 EP 1290 DI 10.1158/1055-9965.EPI-06-0963 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100039 PM 17548699 ER PT J AU Kang, D Lee, KM Park, SK Berndt, SI Reding, D Chatterjee, N Welch, R Chanock, S Huang, WY Hayes, RB AF Kang, Daehee Lee, Kyoung-Mu Park, Sue Kyung Berndt, Sonja I. Reding, Douglas Chatterjee, Nilanjan Welch, Robert Chanock, Stephen Huang, Wen-Yi Hayes, Richard B. TI Lack of association of transforming growth factor-beta 1 polymorphisms and haplotypes with prostate cancer risk in the prostate, lung, colorectal, and ovarian trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; MYOCARDIAL-INFARCTION; IN-VITRO; TGF-BETA; SUSCEPTIBILITY; JAPANESE C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 151, South Korea. Marshfield Clin Res Fdn, Marshfield, WI USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Gaithersburg, MD USA. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, Seoul 110799, South Korea. EM dhkang@snu.ac.kr RI Kang, Dae Hee/E-8631-2012; Park, Sue Kyung/J-2757-2012; OI Hayes, Richard/0000-0002-0918-661X NR 15 TC 9 Z9 9 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 JUN PY 2007 VL 16 IS 6 BP 1303 EP 1305 DI 10.1158/1055-9965.EPI-06-0895 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100043 PM 17548703 ER PT J AU Moore, SC Leitzmann, MF Weinstein, SJ Snyder, K Albanes, D Virtamo, J Graubard, BI Mayne, ST Yu, H Peters, U Gunter, MJ AF Moore, Steven C. Leitzmann, Michael F. Weinstein, Stephanie J. Snyder, Kirk Albanes, Demetrius Virtamo, Jarmo Graubard, Barry I. Mayne, Susan T. Yu, Herbert Peters, Ulrike Gunter, Marc J. TI Insulin resistance-related gene polymorphisms and risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID RECEPTOR SUBSTRATE-1; BETA-CAROTENE; LUNG-CANCER; POPULATION; MEN; ASSOCIATION; OBESITY; VARIANT C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. Univ Washington, Sch Publ Hlth, Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Moore, SC (reprint author), 6120 Execut Blvd, Bethesda, MD 20892 USA. EM moorest@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016 OI Moore, Steven/0000-0002-8169-1661 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165, TU2CA105666] NR 23 TC 6 Z9 6 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 JUN PY 2007 VL 16 IS 6 BP 1315 EP 1317 DI 10.1158/1055-9965.EPI-07-0191 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100047 PM 17548707 ER PT J AU Freedman, LS Schatzkin, A Thiebaut, ACM Potischman, N Subar, AF Thompson, FE Kipnis, V AF Freedman, Laurence S. Schatzkin, Arthur Thiebaut, Anne C. M. Potischman, Nancy Subar, Amy F. Thompson, Frances E. Kipnis, Victor TI Abandon neither the food frequency questionnaire nor the dietary fat-breast cancer hypothesis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID RATS C1 Gertner Inst Epidemiol, Tel Hashomer, Israel. NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. NCI, Div Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol, Tel Hashomer, Israel. NR 9 TC 9 Z9 9 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 JUN PY 2007 VL 16 IS 6 BP 1321 EP 1322 DI 10.1158/1055-9965.EPI-07-0179 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 177OT UT WOS:000247163100049 PM 17548709 ER PT J AU Slape, C Hartung, H Lin, YW Bies, J Wolff, L Aplan, PD AF Slape, Christopher Hartung, Helge Lin, Ying-Wei Bies, Juraj Wolff, Linda Aplan, Peter D. TI Retroviral Insertional mutagenesis identifies genes that collaborate with NUP98-HOXD13 during leukemic transformation SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTOR; BETHESDA PROPOSALS; LYMPHOID NEOPLASMS; MICE DEVELOP; CELL-LINES; EXPRESSION; CANCER; FUSION; MEIS1 AB The t(2;11)(q31;p15) chromosomal translocation results in a fusion between the NUP98 and HOXD13 genes and has been observed in patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia. We previously showed that expression of the NUP98-HOXD13 (NHD13) fusion gene in transgenic mice results in an invariably fatal MDS; approximately one third of mice die due to complications of severe pancytopenia, and about two thirds progress to a fatal acute leukemia. In the present study, we used retroviral insertional mutagenesis to identify genes that might collaborate with NHD13 as the MDS transformed to an acute leukemia. Newborn NHD13 transgenic mice and littermate controls were infected with the MOL407OLTR retrovirus. The onset of leukemia was accelerated, suggesting a synergistic effect between the NHD13 transgene and the genes neighboring retroviral insertion events. We identified numerous common insertion sites located near protein-coding genes and confirmed dysregulation of a subset of these by expression analyses. Among these genes were Meis1, a known collaborator of HOX and NUP98-HOX fusion genes, and Mn-1, a transcriptional coactivator involved in human leukemia through fusion with the TEL gene. Other putative collaborators included Gata2, Erg, and Epor. Of note, we identified a common insertion site that was > 100 kb from the nearest coding gene, but within 20 kb of the miR29almiK29b1 microRNA locus. Both of these miRNA were up-regulated, demonstrating that retroviral insertional mutagenesis can target miRNA loci as well as protein-coding loci. Our data provide new insights into AWD13-mediated leakemogenesis as well as retroviral insertional mutagenesis mechanisms. C1 NCI, Genet Branch, Canc Res Ctr, NIH,Natl Naval Med Ctr, Bethesda, MD 20889 USA. NCI, Leukemogenesis Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH,Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; FU Intramural NIH HHS [Z01 SC010378-06] NR 49 TC 51 Z9 55 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5148 EP 5155 DI 10.1158/0008-5472.CAN-07-0075 PG 8 WC Oncology SC Oncology GA 175NS UT WOS:000247020900015 PM 17545593 ER PT J AU Engel, LS Laden, F Andersen, A Strickland, PT Blair, A Needham, LL Barr, DB Wolff, MS Helzlsouer, K Hunter, DJ Lan, Q Cantor, KP Comstock, GW Brock, JW Bush, D Hoover, RN Rothman, N AF Engel, Lawrence S. Laden, Francine Andersen, Aage Strickland, Paul T. Blair, Aaron Needham, Larry L. Barr, Dana B. Wolff, Mary S. Helzlsouer, Kathy Hunter, David J. Lan, Qing Cantor, Kenneth P. Comstock, George W. Brock, John W. Bush, David Hoover, Robert N. Rothman, Nathaniel TI Polychlorinated biphenyl levels in peripheral blood and non-hodgkin's lymphoma: A report from three cohorts SO CANCER RESEARCH LA English DT Article ID CAPACITOR MANUFACTURING WORKERS; AGRICULTURAL PESTICIDE USE; UNITED-STATES; CANCER MORTALITY; RISK-FACTORS; ORGANOCHLORINE RESIDUES; CHLORINATED PESTICIDES; BREAST-CANCER; HUMAN-SERUM; PCBS AB The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE 1 (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% Cl) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE 1), ORs and 95% Cls for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8) (P-trend < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8) (P-trend < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-clilorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL. C1 Mem Sloan Kettering Canc Ctr, Epidemiol Serv, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Norwegian Canc Registry, Oslo, Norway. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. RP Engel, LS (reprint author), Mem Sloan Kettering Canc Ctr, Epidemiol Serv, Dept Epidemiol & Biostat, 307 E 63rd St,3rd Floor, New York, NY 10021 USA. EM engell@mskcc.org RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013; OI Engel, Lawrence/0000-0001-9268-4830 FU Intramural NIH HHS; NCI NIH HHS [CA/ES62984, CA60754, CA98122]; NHLBI NIH HHS [HL21670]; NIEHS NIH HHS [ES03819] NR 53 TC 51 Z9 52 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2007 VL 67 IS 11 BP 5545 EP 5552 DI 10.1158/0008-5472.CAN-06-3906 PG 8 WC Oncology SC Oncology GA 175NS UT WOS:000247020900061 PM 17545638 ER PT J AU Lim, U Gayles, T Katki, HA Stolzenberg-Solomon, R Weinstein, SJ Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Lim, Unhee Gayles, Travis Katki, Hormuzd A. Stolzenberg-Solomon, Rachael Weinstein, Stephanie J. Pietinen, Pirjo Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI Serum high-density lipoprotein cholesterol and risk of non-Hodgkin lymphoma SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; BLOOD-PRESSURE; ACUTE-INFLAMMATION; HDL CHOLESTEROL; MALE SMOKERS; STATIN USE; FOLLOW-UP; MORTALITY; COHORT; WOMEN AB Lymphoma patients often exhibit abnormal lipid metabolism. Recent evidence, however, suggests that a decrease in circulating high-density lipoprotein cholesterol (HDL-C) may occur during lymphomagenesis, reflecting underlying etiology such as inflammation. We investigated the relationship between prediagnostic HDL-C and non-Hodgkin lymphoma (NHL) in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. At baseline, serum HDL-C and total cholesterol concentrations from fasting blood, information on diet and lifestyle, and direct measurements of height, weight, and blood pressure were obtained from 27,074 healthy male smokers of ages 50 to 69 years. Cox proportional hazards models with age as underlying time metric was used to estimate relative risks (RR) and 95% confidence intervals (95% Cl). We found no association between total or non-HDL cholesterol and the 201 incident NHL cases ascertained during the follow-up (1985-2002), but observed an inverse association between HDL-C and NHL, which changed with length of follow-up. High HDL-C was associated with lower risk of all NHL during the first 10 years (n = 148; RR for 5th versus 1st quintile, 0.35; 95% CI, 0.19-0.62; P-trend < 0.0001), but not with diagnoses during later follow-up (n = 53; RR, 1.31; 95% Cl, 0.55-3.10). The inverse association was similar for NHL subtypes and was not modified by obesity, blood pressure, physical activity, or alcohol intake, but seemed to be stronger in men with lower duration of smoking (P-interaction = 0-06). Our findings implicate HDL-C as a preclinical indicator of NHL and warrant further prospective investigations for its etiologic contribution. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Illinois, Coll Med, Urbana, IL 61801 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Lim, U (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 320, Rockville, MD 20852 USA. EM limu@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 49 TC 23 Z9 23 U1 1 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 JUN 1 PY 2007 VL 67 IS 11 BP 5569 EP 5574 DI 10.1158/0008-5472.CAN-07-0212 PG 6 WC Oncology SC Oncology GA 175NS UT WOS:000247020900064 PM 17522388 ER PT J AU Patel, V Rosenfeldt, HM Lyons, R Servitja, JM Bustelo, XR Siroff, M Gutking, JS AF Patel, Vyomesh Rosenfeldt, Hans M. Lyons, Ruth Servitja, Joan-Marc Bustelo, Xose R. Siroff, Mary Gutking, J. Silvio TI Persistent activation of Rac1 in squamous carcinomas of the head and neck: evidence for an EGFR/Vav2 signaling axis involved in cell invasion SO CARCINOGENESIS LA English DT Article ID CANCER STATISTICS; RHO-GTPASES; ORAL-CANCER; H-RAS; EXPRESSION; OVEREXPRESSION; METASTASIS; ONCOGENES; APOPTOSIS; MIGRATION AB The poor prognosis associated with head and neck squamous cell carcinoma (HNSCC) is primarily due to both local invasion and the regional and/or distant metastatic spread. Recent findings have provided evidence that the acquisition of a motile and invasive phenotype by cancer cells involves the dysregulated function of key intracellular molecular mechanisms together with aberrant signaling events initiated by the surrounding microenvironment. These intrinsic and extrinsic biochemical pathways in turn often converge to stimulate the activity of members of the Rho family of Ras-related guanosine triphosphate (GTP)-binding proteins, including RhoA, Rac and Cdc42, which control the organization of the actin cytoskeleton thereby regulating cell adhesion, polarity and motility. In this study, we examined the status of activation of these GTPases in a representative collection of HNSCC cell lines. Surprisingly, we found that most HNSCC cells exhibit remarkably high levels of GTP-bound Rac1. Further analysis revealed that the activation of Rac1 in these HNSCC cells could be due to two independent signaling events, an epidermal growth factor receptor (EGFR)-based autocrine loop that leads to the activation of the Rac1 exchange factor Vav2 and an EGFR/Vav2-independent pathway that arises as a consequence of the oncogenic mutation of the H-ras proto-oncogene. Indeed, we provide evidence that the EGFR[Vav2/Rac1 axis is a crucial pathway for the acquisition of motile and invasive properties of most HNSCC cells. These findings shed light onto the molecular mechanisms involved in HNSCC cell invasion, and may reveal new therapeutic opportunities to halt the metastatic spread of these aggressive malignancies. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Univ Salamanca, CSIC, Ctr Invest Canc, E-37007 Salamanca, Spain. Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37007 Salamanca, Spain. RP Gutking, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. EM sg39v@nih.gov OI SERVITJA DUQUE, JOAN-MARC/0000-0002-1241-8004 NR 39 TC 44 Z9 47 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2007 VL 28 IS 6 BP 1145 EP 1152 DI 10.1093/carcin/bgm008 PG 8 WC Oncology SC Oncology GA 189OZ UT WOS:000247999700003 PM 17234718 ER PT J AU Yang, Q Ito, S Gonzalez, FJ AF Yang, Qian Ito, Shinji Gonzalez, Frank J. TI Hepatocyte-restricted constitutive activation of PPAR alpha induces hepatoproliferation but not hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID PEROXISOME PROLIFERATOR WY-14,643; RECEPTOR-ALPHA; KUPFFER CELLS; GENE-EXPRESSION; RAT HEPATOCYTES; MAMMALIAN-CELLS; TRANSGENIC MICE; DNA-SYNTHESIS; CLOFIBRATE; LIVER AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) is responsible for peroxisome proliferator-induced pleiotropic responses, including the development of hepatocellular carcinoma in rodents. However, it remains to be determined whether activation of PPAR alpha only in hepatocytes is sufficient to induce hepatocellular carcinomas. To address this issue, transgenic mice were generated that target constitutively activated PPAR alpha specifically to hepatocytes. The transgenic mice exhibited various responses that mimic wild-type mice treated with peroxisorne proliferators, including significantly decreased serum fatty acids and marked induction of PPAR alpha target genes encoding fatty acid oxidation enzymes, suggesting that the transgene functions in the same manner as peroxisome proliferators to regulate fatty acid metabolism. However, the transgenic mice did not develop hepatocellular carcinomas, even though they exhibited peroxisome proliferation and hepatocyte proliferation, indicating that these events are not sufficient to induce liver cancer. In contrast to the transgenic mice, peroxisome proliferators activate proliferation of hepatic nonparenchymal cells (NPCs). Thus, activation of hepatic NPCs and/ or associated molecular events is an important step in peroxisome proliferators-induced hepatocarcinogenesis. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS [Z01 BC005708-14] NR 37 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2007 VL 28 IS 6 BP 1171 EP 1177 DI 10.1093/carcin/bgm046 PG 7 WC Oncology SC Oncology GA 189OZ UT WOS:000247999700006 PM 17331954 ER PT J AU Ward, MH Cross, AJ Divan, H Kulldorff, M Nowell-Kadlubar, S Kadlubar, FF Sinha, R AF Ward, Mary H. Cross, Amanda J. Divan, Hozefa Kulldorff, Martin Nowell-Kadlubar, Susan Kadlubar, Fred F. Sinha, Rashmi TI Processed meat intake, CYP2A6 activity and risk of colorectal adenoma SO CARCINOGENESIS LA English DT Article ID N-NITROSO COMPOUNDS; HETEROCYCLIC AMINES; CANCER RISK; RED MEAT; WELL-DONE; NITROSAMINES; DIETARY; NITRITE; PRODUCTS; EXPOSURE AB Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02115 USA. Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. RP Ward, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993 NR 42 TC 30 Z9 31 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2007 VL 28 IS 6 BP 1210 EP 1216 DI 10.1093/carcin/bgm009 PG 7 WC Oncology SC Oncology GA 189OZ UT WOS:000247999700011 PM 17277235 ER PT J AU Yang, J Ambrosone, CB Hong, CC Ahn, JY Rodriguez, C Thun, MJ Calle, EE AF Yang, Jun Ambrosone, Christine B. Hong, Chi-Chen Ahn, Jiyoung Rodriguez, Carmen Thun, Michael J. Calle, Eugenia E. TI Relationships between polymorphisms in NOS3 and MPO genes, cigarette smoking and risk of post-menopausal breast cancer SO CARCINOGENESIS LA English DT Article ID NITRIC-OXIDE SYNTHASE; MYELOPEROXIDASE (-463)G->A POLYMORPHISM; DNA ADDUCT LEVELS; LUNG-CANCER; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; TUMOR PROGRESSION; PROSTATE-CANCER; OVARIAN-CANCER; FREE-RADICALS AB NOS3 and MPO genes encode endothelial nitric oxide synthase and myeloperoxidase (MPO), respectively, which generate nitric oxide and reactive oxygen species. Because cigarette smoking generates reactive species, we hypothesized that NOS3 and MPO polymorphisms could influence susceptibility to breast cancer, particularly among smokers. We examined the associations between NOS3 Glu298Asp and MPO G-463A polymorphisms and breast cancer risk by cigarette smoking among post-menopausal women in the American Cancer Society's Cancer Prevention Study II Nutrition Cohort. Included in this analysis were 502 women who provided blood samples and were diagnosed with breast cancer between 1992 and 2001 and 505 cancer-free controls who were matched to the cases by age, race/ethnicity and date of blood donation. Genotyping for NOS3 and MPO was performed using TaqMan, and unconditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). No statistically significant relationships were found between NOS3 and MPO genotypes and breast cancer risk. When considering smoking, variant NOS3 genotypes (GT and TT) were significantly associated with reduced breast cancer risk among never smokers (OR = 0.67, 95 % CI = 0.45-0.99), but were associated with higher risk among ever smokers (OR = 1.59, 95 % CI = 1.05-2.41) and 2-fold increase in risk for those who smoked >10 cigarettes per day (OR = 2.19, 95% CI = 1.21-3.97). NOS3 genotypes appeared to be associated with risk of post-menopausal breast cancer among smokers, supporting the hypothesis that subgroups of women based upon genetic profiles may be at higher risk of breast cancer when exposed to tobacco smoke. C1 Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Yang, J (reprint author), Dept Hlth, Off Epidemiol, James Madison Bldg,Room 532A,109 Governor St, Richmond, VA 23219 USA. EM jun.yang@vdh.virginia.gov NR 86 TC 30 Z9 32 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2007 VL 28 IS 6 BP 1247 EP 1253 DI 10.1093/carcin/bgm016 PG 7 WC Oncology SC Oncology GA 189OZ UT WOS:000247999700017 PM 17259657 ER PT J AU Abdelmohsen, K Lal, A Kim, HH Gorospe, M AF Abdelmohsen, Kotb Lal, Ashish Kim, Hyeon Ho Gorospe, Myriam TI Posttranscriptional orchestration of an anti-apoptotic program by HuR SO CELL CYCLE LA English DT Article DE mRNA-binding protein; mRNA turnover; translational control; ELAV; SIRT1; ProT alpha; Bcl-2; Mcl-1 ID RNA-BINDING PROTEIN; AU-RICH ELEMENT; FOXO TRANSCRIPTION FACTORS; FACTOR MESSENGER-RNA; ELAV-LIKE PROTEIN; PROTHYMOSIN-ALPHA; STABILITY FACTOR; GENE-EXPRESSION; CYTOCHROME-C; TNF-ALPHA AB The RNA-binding protein HuR can stabilize and/ or regulate the translation of target mRNAs, thereby affecting the cellular responses to immune, proliferative, and damaging agents. Here, we discuss emerging evidence that HuR elicits a broad anti-apoptotic function through its influence on the expression of multiple target mRNAs. HuR was previously shown to bind to the mRNA encoding the apoptosome inhibitor prothymosin a (ProT alpha) and enhanced its translation and cytoplasmic abundance. More recently, HuR was shown to increase the stability of a target mRNA encoding the pro-survival deacety lase SIRT1. The discovery that HuR likewise binds to and promotes the expression of mRNAs encoding Bcl-2 and Mcl-1, two major anti-apoptotic effectors, strongly supports HuR's role as a key upstream coordinator of a constitutive pro-survival program. C1 NIA, IRP, Cellular & Mol Biol Lab, NIH, Baltimore, MD USA. RP Gorospe, M (reprint author), NIA, LCMB, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS NR 59 TC 139 Z9 140 U1 3 U2 8 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2007 VL 6 IS 11 BP 1288 EP 1292 PG 5 WC Cell Biology SC Cell Biology GA 190SZ UT WOS:000248081700003 PM 17534146 ER PT J AU Petri, ET Errico, A Escobedo, L Hunt, T Basavappa, R AF Petri, Edward T. Errico, Alessia Escobedo, Lourdes Hunt, Tim Basavappa, Ravi TI The crystal structure of human cyclin B SO CELL CYCLE LA English DT Article DE cell cycle; crystallography; cyclin B; Cdk1; mitosis ID CELL-CYCLE; DEPENDENT KINASES; COMPLEX; PHOSPHORYLATION; IDENTIFICATION; RECOGNITION; ACTIVATION; INHIBITOR; CDK2; TRAFFICKING AB Cyclin B is the key regulatory protein controlling mitosis in all eukaryotes, where it binds cyclin-dependent kinase, cdk1, forming a complex which initiates the mitotic program through phosphorylation of select proteins. Cyclin B regulates the activation, subcellular localization, and substrate specificity of cdk1, and destruction of cyclin B is necessary for mitotic exit. Overexpression of human cyclin B1 has been found in numerous cancers and has been associated with tumor aggressiveness. Here we report the crystal structure of human cyclin B1 to 2.9 angstrom. Comparison of the structure with cyclin A and cyclin E reveals remarkably similar N-terminal cyclin box motifs but significant differences among the C-terminal cyclin box lobes. Divergence in sequence gives rise to unique interaction surfaces at the proposed cyclin B/cdk1 interface as well as the ' RxL' motif substrate binding site on cyclin B. Examination of the structure provides insight into the molecular basis for differential affinities of protein based cyclin/cdk inhibitors such as p27, substrate recognition, and cdk interaction. C1 Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY USA. IPN, CINVESTAV, Dept Physiol Biophys & Neurosci, Mexico City 07738, DF, Mexico. RP Basavappa, R (reprint author), Natl Inst Gen Med Sci, 45 Ctr Dr, Bethesda, MD 20892 USA. EM basavapr@nigms.nih.gov FU NIGMS NIH HHS [R01-GM57536] NR 32 TC 18 Z9 19 U1 1 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2007 VL 6 IS 11 BP 1342 EP 1349 PG 8 WC Cell Biology SC Cell Biology GA 190SZ UT WOS:000248081700014 PM 17495533 ER PT J AU Honjo, Y Bian, YS Kawakami, K Molinolo, A Longenecker, G Boppana, R Larsson, J Karlsson, S Gutkind, JS Puri, RK Kulkarni, AB AF Honjo, Yasuyuki Bian, Yansong Kawakami, Koji Molinolo, Alfredo Longenecker, Glenn Boppana, Ramanamurthy Larsson, Jonas Karlsson, Stefan Gutkind, J. Silvio Puri, Raj K. Kulkarni, Ashok B. TI TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma SO CELL CYCLE LA English DT Article DE TGF-beta receptor I; squamous cell carcinoma; IL-13; Cre-lox P system; TGF-beta; cytotoxin; head and neck cancer ID GROWTH-FACTOR-BETA; TARGETED CANCER-THERAPY; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; NECK-CANCER; TUMOR IMMUNOSURVEILLANCE; APOPTOTIC PATHWAYS; ALPHA-2 CHAIN; COLON-CANCER; MERKEL CELL AB We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (T beta RI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/ or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity. To determine whether evasion of the immune response plays any role in this tumorigenesis, we analyzed the expression levels of receptors for interleukin-13 (mIL-13R), a key negative regulator of tumor immunosurveillance, and found that 33% of COKO tumors expressed the IL-13R alpha 2 chain. Primary cultures of the SCCs expressing IL-13R alpha 2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of T beta RI can lead to spontaneous tumor formation. These mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and effect of anti-cancer therapeutics. C1 NIDCR, LCDB, NIH, Funct Genom Sect, Bethesda, MD 20892 USA. NIDCR, Gene Targeting Facil, NIH, Bethesda, MD USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. Univ Lund Hosp, Inst Lab Med, Dept Mol Med & Gene Therapy, S-22185 Lund, Sweden. RP Kulkarni, AB (reprint author), NIDCR, LCDB, NIH, Funct Genom Sect, 30 Convent Dr,Bldg 30,Room 130,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 56 TC 18 Z9 19 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2007 VL 6 IS 11 BP 1360 EP 1366 PG 7 WC Cell Biology SC Cell Biology GA 190SZ UT WOS:000248081700016 PM 17534148 ER PT J AU Koga, F Tsutsumi, S Neckers, LM AF Koga, Fumitaka Tsutsumi, Shinji Neckers, Leonard M. TI Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells SO CELL CYCLE LA English DT Article DE geldanamycin; Hsp90; tumor invasion; VEGF; Met tyrosine kinase; focal adhesions ID FOCAL ADHESION KINASE; INDUCIBLE FACTOR-I; C-MET; PLASMINOGEN-ACTIVATOR; RECEPTOR EXPRESSION; URINARY-BLADDER; PHASE-I; CARCINOMA; PATHWAY; OVEREXPRESSION AB Hepatocyte growth factor (HGF) receptor Met and hypoxia-inducible factor-1 (HIF-1) signaling pathways are commonly activated in aggressive tumors and promote progres sion. Since both Met and HIF-1a proteins are heat shock protein (Hsp) 90 clients, Hsp90 inhibitors might be expected to positively impact tumor progression. Here, we systemati cally evaluated the inhibitory effects of the prototypical Hsp90 inhibitor geldanamycin (GA) on cellular processes involved in invasion and angiogenesis in T24 bladder cancer cells stimulated with HGF and chemical hypoxia. First, we demonstrated the positive feedback loop between Met and HIF-1 pathways, which serves to sustain and amplifies their signaling in T24 cells. GA downregulated Met by inhibiting new protein maturation, thereby dampening HGF signaling. HGF and chemical hypoxia with CoCl2 coopera tively promoted in vitro invasion and vascular endothelial growth factor (VEGF) secretion, while CoCl2 but not HGF activated urokinase-type plasminogen activator and matrix metalloproteinase 2, both of which promote invasion and angiogenesis. Low dose GA (100 nmol/L) inhibited these processes by suppressing both HGF and HIF-1 pathways. Notably, brief GA pretreatment inhibited in vitro invasion and VEGF secretion induced by HGF as effectively as did continuous treatment. Moreover, we found that GA inhibited activation of focal adhesion kinase, focal adhesion assembly, and actin reorganization induced by HGF and integrin engagement by extracellular matrix. Thus, GA widely suppresses extrinsic stimuli-induced signaling that contribute to tumor invasion and angiogenesis in this bladder carcinoma model, suggesting the utility of Hsp90 inhibitors in preventing tumor progression and metastasis. C1 NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Urol, Tokyo, Japan. RP Neckers, LM (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bldg 10,1-5940, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 49 TC 42 Z9 43 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2007 VL 6 IS 11 BP 1393 EP 1402 PG 10 WC Cell Biology SC Cell Biology GA 190SZ UT WOS:000248081700020 PM 17525527 ER PT J AU Young, SF Griffante, C Aguilera, G AF Young, Sharla F. Griffante, Cristiana Aguilera, Greti TI Dimerization between vasopressin V1B and corticotropin releasing hormone type 1 receptors SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE vasopressin V1B receptor; corticotropin releasing hormone type 1 receptor; dimerization; BRET; immunoprecipitation; receptor binding ID PROTEIN-KINASE-C; RESONANCE ENERGY-TRANSFER; OVINE ANTERIOR-PITUITARY; ARGININE VASOPRESSIN; HETERO-OLIGOMERIZATION; FUNCTIONAL-PROPERTIES; AGONIST STIMULATION; GABA(B) RECEPTOR; OPIOID RECEPTORS; LIGAND-BINDING AB 1. Increasing evidence indicates that guanyl protein coupled receptors (GPCRs), including members of the vasopressin (VP) receptor family can act as homo- and heterodimers. Regulated expression and interaction of pituitary VP V1b receptor (V1bR) and corticotropin releasing hormone receptor type 1 (CRHR1) are critical for hypothalamic pituitary adrenal (HPA) axis adaptation, but it is unknown whether this involves physical interaction between these receptors. 2. Bioluminescence resonance energy transfer (BRET) experiments using V1bR and CRHR1 fused to either Renilla luciferase (Rluc) or yellow fluorescent protein (YFP) at the N-terminus, but not the carboxyl-terminus, revealed specific interaction (BRET50 = 0.39 +/- 0.08, V1bR) that was inhibited by untagged V1b or CRHR1 receptors, suggesting homo- and heterodimerization. The BRET data were confirmed by coimmunoprecipitation experiments using fully bioactive receptors tagged at the aminoterminus with c-myc and Flag epitopes, demonstrating specific homodimerization of the V1b receptor and heterodimerization of the V1b receptor with CRHR1 receptors. 3. Heterodimerization between V1bR and CRHR1 is not ligand dependent since stimulation with CRH and AVP had no effect on coimmunoprecipitation. In membranes obtained from cells cotransfected with CRHR1 and V1bR, incubation with the heterologous nonpeptide antagonist did not alter the binding affinity or capacity of the receptor. 4. The data demonstrate that V1bR and CRHR1 can form constitutive homo- and heterodimers and suggests that the heterodimerization does not influence the binding properties of these receptors. C1 NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. GlaxoSmithKline Grp, Psychiat Ctr Excellence Drug Discovery, Med Res Ctr, I-37135 Verona, Italy. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM greti_aguilera@nih.gov FU Intramural NIH HHS NR 51 TC 38 Z9 38 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 2007 VL 27 IS 4 BP 439 EP 461 DI 10.1007/s10571-006-9135-8 PG 23 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 168ZJ UT WOS:000246562200003 PM 17318384 ER PT J AU Burdick, AD Bility, MT Girroir, EE Billin, AN Willson, TM Gonzalez, FJ Peters, JM AF Burdick, Andrew D. Bility, Moses T. Girroir, Elizabeth E. Billin, Andrew N. Willson, Timothy M. Gonzalez, Frank J. Peters, Jeffrey M. TI Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPAR beta/delta) inhibits cell growth of human N/TERT-1 keratinocytes SO CELLULAR SIGNALLING LA English DT Article DE peroxisome proliferator-activated receptor-beta/delta; PPAR beta/delta; Keratinocytes; N/TERT-1 human keratinocytes; differentiation; cell proliferation; apoptosis ID RECEPTOR-DELTA; LIPID-METABOLISM; SKELETAL-MUSCLE; PPAR-BETA/DELTA; ADENOMA GROWTH; TNF-ALPHA; PROLIFERATOR; DIFFERENTIATION; BETA; EXPRESSION AB The functional role of peroxisome proliferator-activated receptor-beta (PPAR beta; also referred to as PPAR delta) in epidermal cell growth remains controversial. Recent evidence suggests that ligand activation of PPAR beta/delta increases cell growth and inhibits apoptosis in epidermal cells. In contrast, other reports suggest that ligand activation of PPAR beta/delta leads to the induction of terminal differentiation and inhibition of cell growth. In the present study, the effect of the highly specific PPAR /6 ligand GW0742 on cell growth was examined using a human keratinocyte cell line (NI TERT-1) and mouse primary keratinocytes. Ligand activation of PPAR beta/delta with GW0742 prevented cell cycle progression from G1 to S phase and attenuated cell proliferation in N/TERT-1 cells. Despite specifically activating PPAR beta/gamma as revealed by target gene induction, no changes in PTEN, PDK and ILK expression or downstream phosphorylation of Akt were found in either N/TERT-1 cells or primary keratinocytes. Further, altered cell growth resulting from serum withdrawal and the induction of caspase-3 activity by ultraviolet radiation were unchanged in the absence of PPAR beta/delta expression and/or the presence of GW0742. While no changes in the expression of mRNAs encoding cell cycle control proteins were found in response to GW0742, a significant decrease in the level of ERK phosphorylation was observed. Results from these studies demonstrate that ligand activation of PPAR beta/delta does not lead to an anti-apoptotic effect in either human or mouse keratinocytes, but rather, leads to inhibition of cell growth likely through the induction of terminal differentiation. (c) 2007 Elsevier Inc. All rights reserved. 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, Huck Inst Life Sci, University Pk, PA 16802 USA. GlaxoSmithKline Inc, Discovery Res, Res Triangle Pk, NC 27709 USA. NCI, Lab Metab, Bethesda, MD 20892 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 Bility, Moses/0000-0001-5153-2718; Burdick, Andrew/0000-0002-4584-1378; Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA89607, CA97999, R01 CA089607, R01 CA097999, CA124533, R01 CA124533] NR 41 TC 62 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2007 VL 19 IS 6 BP 1163 EP 1171 DI 10.1016/j.cellsig.2006.12.007 PG 9 WC Cell Biology SC Cell Biology GA 167FS UT WOS:000246437400007 PM 17254750 ER PT J AU Koh, E Clair, T Hermansen, R Bandle, RW Schiffmann, E Roberts, DD Stracke, ML AF Koh, Eunjin Clair, Timothy Hermansen, Raejean Bandle, Russell W. Schiffmann, Elliott Roberts, David D. Stracke, Mary L. TI Sphingosine-1-phosphate initiates rapid retraction of pseudopodia by localized RhoA activation SO CELLULAR SIGNALLING LA English DT Article DE mDia; ROCK; RhoA; sphingosine-1-phosphate; lysophosphatidic acid; pseudopodia ID PROTEIN-COUPLED RECEPTOR; CELL-MIGRATION; SPHINGOSINE 1-PHOSPHATE; ACTIN CYTOSKELETON; GROWTH-FACTOR; RAC; MOTILITY; ROCK; CHEMOTAXIS; PATHWAYS AB Lysophosphatidic acid (LPA) stimulates sphingosine-1-phosphate (S1P)-sensitive motility in NIH3T3 clone7 cells. S I P inhibits motility only when added to the bottom well of the Boyden chamber, suggesting that pseudopodia can respond to their microenvironment. In order to study and localize this effect, we utilized a Transwell insert system to isolate pseudopodia. LPA stimulates protrusion of pseudopodia that are enriched in RhoA compared to cell bodies. Removal of LPA results in slow retraction with loss of vinculin-rich adhesion complexes and prolonged activation of RhoA. However, RhoA, ROCK and mDia are not required for this process. In contrast, rapid retraction, induced by adding S1P to the bottom well, is associated with a quick spike of activated RhoA and coalescence of adhesion complexes that colocalize with the ends of stress fibers. S1P-induced retraction requires RhoA and ROCK but is only delayed by inhibition of mDia. These data indicate that pseudopodia sense and integrate signals initiated by localized bioactive lipids, affecting both cellular polarity and their own function in motility. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Stracke, ML (reprint author), NCI, Pathol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 2A33, Bethesda, MD 20892 USA. EM stracke@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 43 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JUN PY 2007 VL 19 IS 6 BP 1328 EP 1338 DI 10.1016/j.cellsig.2007.01.005 PG 11 WC Cell Biology SC Cell Biology GA 167FS UT WOS:000246437400024 PM 17307336 ER PT J AU Altamura, C Dell'Acqua, ML Moessner, R Murphy, DL Lesch, KP Persico, AM AF Altamura, C. Dell'Acqua, M. L. Moessner, R. Murphy, D. L. Lesch, K. P. Persico, Antonio M. TI Altered neocortical cell density and layer thickness in serotonin transporter knockout mice: A quantitation study SO CEREBRAL CORTEX LA English DT Article DE apoptosis; cerebral cortex; optical fractionator proliferation; stereology ID PERVASIVE DEVELOPMENTAL DISORDERS; NEURONS IN-VITRO; THALAMIC NEURONS; PLATELET SEROTONIN; MONOAMINE-OXIDASE; BRAIN-SEROTONIN; CORTICAL DEVELOPMENT; HEAD CIRCUMFERENCE; NEURITE OUTGROWTH; INFANTILE-AUTISM AB The neurotransmitter serotonin (5-HT) plays morphogenetic roles during development, and their alteration could contribute to autism pathogenesis in humans. To further characterize 5-HT's contributions to neocortical development, we assessed the thickness and neuronal cell density of various cerebral cortical areas in serotonin transporter (5-HTT) knockout (ko) mice, characterized by elevated extracellular 5-HT levels. The thickness of layer IV is decreased in 5-HTT ko mice compared with wild-type (wt) mice. The overall effect on cortical thickness, however, depends on the genetic background of the mice. Overall cortical thickness is decreased in many cortical areas of 5-HTT ko mice with a mixed c129-CD1-C57BL/6J background. Instead, 5-HTT ka mice backcrossed into the C57BL/6J background display increases in supragranular and infragranular layers, which compensate entirely for decreased layer IV thickness, resulting in unchanged or even enhanced cortical thickness. Moreover, significant increases in neuronal cell density are found in 5-HTT ko mice with a C57BL/6J background (wt:hz:ko ratio = 1.00:1.04:1.17) but not in the mixed c129-CD1-C57BL/6J 5-HTT ko animals. These results provide evidence of 5-HTT gene effects on neocortical morphology in epistatic interaction with genetic variants at other loci and may model the effect of functional 5-HTT gene variants on neocortical development in autism. C1 Univ Rome, Lab Mol Psychiat & Neurogenet, I-00155 Rome, Italy. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. Natl Inst Mental Hlth, Lab Clin Sci, NIH, Bethesda, MD USA. IRCCS Fdz S Lucia, Rome, Italy. RP Persico, AM (reprint author), Univ Rome, Lab Mol Psychiat & Neurogenet, Campus Bio Medico Via Longoni 83, I-00155 Rome, Italy. EM a.persico@unicampus.it RI Forkel, Stephanie/A-4018-2011; Lesch, Klaus-Peter/J-4906-2013; OI Forkel, Stephanie/0000-0003-0493-0283; Lesch, Klaus-Peter/0000-0001-8348-153X; Persico, Antonio/0000-0001-8910-4479; Altamura, Claudia/0000-0002-5934-5535 FU Telethon [E.1215] NR 64 TC 48 Z9 48 U1 4 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2007 VL 17 IS 6 BP 1394 EP 1401 DI 10.1093/cercor/bhl051 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 169VO UT WOS:000246620400015 PM 16905592 ER PT J AU Kagulire, SC Stamper, PD Opendi, P Nakavuma, JL Mills, LA Makumbi, F Gray, RH Serwadda, D Reynolds, SJ AF Kagulire, S. C. Stamper, P. D. Opendi, P. Nakavuma, J. L. Mills, L. A. Makumbi, F. Gray, R. H. Serwadda, D. Reynolds, S. J. TI Performance of two commercial immunochromatographic assays for rapid detection of antibodies specific to human immunodeficiency virus types 1 and 2 in serum and urine samples in a rural community-based research setting (Rakai, Uganda) SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article AB Rapid detection of human immunodeficiency virus (HM antibodies is of great importance in developing and developed countries to diagnose HIV infections quickly and at low cost. In this study, two new immunochromatographic rapid tests for the detection of HIV antibodies (Aware HIV-1/2 BSP and Aware HIV-1/2 U; Calypte Biomedical Corporation) were evaluated in rural Africa to determine the tests' performance and comparability to commercially available conventional enzyme immunoassay (EIA) and Western blot (WB) tests. This prospective study was conducted from March 2005 through May 2005 using serum and urine from respondents in the Rakai Community Cohort Survey. Nine hundred sixty-three serum samples were tested with the Aware blood rapid assay (Aware-BSP) and compared to two independent EIAs for HIV plus confirmatory Calypte WB for any positive EIAs. The sensitivity of Aware-BSP was 98.2%, and the specificity was 99.8%. Nine hundred forty-two urine samples were run using the Aware urine assay (Aware-U) and linked to blood sample results for analysis. The sensitivity of Aware-U was 88.7% and specificity was 99.9% compared to blood EIAs confirmed by WB analysis. These results support the adoption of the Aware-BSP rapid test as an alternative to EIA and WB assays for the diagnosis of HIV in resource-limited settings. However, the low sensitivity of the Aware-U assay with its potential for falsely negative HIV results makes the urine assay less satisfactory. C1 Rakai Hlth Sci Program, Kalisizo, Uganda. Makerere Univ, Kampala, Uganda. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Kagulire, SC (reprint author), Uganda Virus Res Inst, Rakai Hlth Sci Program, PO Box 49, Entebbe, Uganda. EM ckagulire@yahoo.com NR 9 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2007 VL 14 IS 6 BP 738 EP 740 DI 10.1128/CVI.00442-06 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186HK UT WOS:000247769500014 PM 17428950 ER PT J AU Allen, C Duffy, S Teknos, T Islam, M Chen, Z Albert, PS Wolf, G Van Wales, C AF Allen, Clint Duffy, Sonia Teknos, Theodoros Islam, Mozaffarul Chen, Zhong Albert, Paul S. Wolf, Gregory Van Wales, Carter TI Nuclear factor-kappa B-related serum factors as longitudinal biomarkers of response and survival in advanced oropharyngeal carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; NECK-CANCER; LUNG-CANCER; HUMAN HEAD; PROANGIOGENIC CYTOKINES; INTERLEUKIN-8 IL-8; SIGNAL PATHWAYS; FACTOR VEGF AB Purpose: Cytokines and growth factors modulated by transcription factor nuclear factor-kappa B and secreted by tumor and stromal cells are detectable in serum of patients with advanced cancers, including head and neck squamous cell carcinomas (SCC). Longitudinal changes in these serum factors could be early biomarkers of treatment response and survival. Experimental Design: Interleukin (IL)-6, IL-8, growth-related oncogene-1 (GRO-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) concentrations were determined by Luminex multiplex assay using serum obtained at baseline and every 3 months in a prospective study of 30 patients with locally advanced (stage III/IV) oropharyngeal SCC receiving chemoradiation therapy. The relationship between baseline and direction of change in individual and multiple cytokines with cause-specific and disease-free survival was determined by Cox proportional hazards models and Kaplan-Meier survival analysis. Statistical analyses included adjustment for smoking status and response to chemoradiation. Results: Three-year cause-specific and disease-free survival was 74.4% and 68.9%. Nonsmoking history (P = 0.05) and higher baseline VEGF (P = 0.003) correlated with increased survival. Longitudinal increases in levels of individual factors predicted decreased cause-specific survival when adjusted for smoking history [IL-6: relative risk (RR), 3.8; 95% confidence interval (95% CI), 2.0-7.4; P = 0.004; IL-8: RR, 1.6; 95% Cl, 1.2-2.2; P = 0.05; VEGF: RR, 3.0; 95% Cl, 1.6-5.6; P = 0.01; HGF: RR, 2.9; 95% Cl, 1.9-4.4; P = 0.02; and GRO-1: RR, 1.2; 95% Cl, 1.1-1.3; P = 0.02]. For a given individual, large increases in the upper quartile for any three or more factors predicted poorer cause-specific survival compared with patients with two or fewer large increases in factor levels (P = 0.004). Conclusions: Pretreatment VEGF levels and longitudinal change in IL-6, IL-8, VEGF, HGF, and GRO-1 may be useful as biomarkers for response and survival in patients with locally advanced oropharyngeal and head and neck SCC treated with chemoradiation. C1 Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. RP Van Wales, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, 10 Ctr Dr,CRC Room 4-2732, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS; NCI NIH HHS [P50 CA97248] NR 46 TC 74 Z9 77 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2007 VL 13 IS 11 BP 3182 EP 3190 DI 10.1158/1078-0432.CCR-06-3047 PG 9 WC Oncology SC Oncology GA 172FE UT WOS:000246788700012 PM 17545521 ER PT J AU Scott, AM Tebbutt, N Lee, FT Cavicchiolo, T Liu, ZQ Gill, S Poon, AMT Hopkins, W Smyth, FE Murone, C MacGregor, D Papenfuss, AT Chappell, B Saunder, TH Brechbiel, MW Davis, ID Murphy, R Chong, G Hoffman, EW Old, LJ AF Scott, Andrew M. Tebbutt, Niall Lee, Fook-Thean Cavicchiolo, Tina Liu, Zhanqi Gill, Sanjeev Poon, Aurora M. T. Hopkins, Wendie Smyth, Fiona E. Murone, Carmel MacGregor, Duncan Papenfuss, Anthony T. Chappell, Bridget Saunder, Timothy H. Brechbiel, Martin W. Davis, Ian D. Murphy, Roger Chong, Geoffrey Hoffman, Eric W. Old, Lloyd J. TI A phase I biodistribution and pharmacokinetic trial of humanized monoclonal antibody Hu3s193 in patients with advanced epithelial cancers that express the Lewis-Y antigen SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; BR96-DOXORUBICIN CONJUGATE; CARBOHYDRATE DETERMINANTS; TUMOR-ANTIGENS; SOLID TUMORS; NUDE-MICE; BLOOD; CARCINOMA; RADIOIMMUNOTHERAPY; IMMUNOTHERAPY AB Purpose: We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen. Experimental Design: Patients with advanced Le(y)-positive cancers received four infusions of hu3S193 at weekly intervals, with four dose levels (5,10, 20, and 40 mg/m(2)). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients. Results: A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1 non - small-cell lung cancer) were entered into the study. Transient grade 1 to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40mg/m(2) dose level only. There was one episode of dose-limiting toxicity with self-limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of In-111-hu3S193 showed no evidence of any consistent normal tissue uptake, and In-111-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T-1/2 beta = 189.63 +/- 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed. Conclusion: Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le(y)-expressing cancers. C1 Melbourne Tumour Biol Branch, Ludwig Inst Canc Res, Melbourne, Vic, Australia. Austin Hosp, Dept Nucl Med, Melbourne, Vic 3084, Australia. Austin Hosp, Ctr PET, Melbourne, Vic 3084, Australia. Austin Hosp, Canc Clin Trials Ctr, Melbourne, Vic 3084, Australia. Austin Hosp, Dept Anat Pathol, Melbourne, Vic 3084, Australia. NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, New York, NY USA. RP Scott, AM (reprint author), Austin Hosp, Ludwig Inst Canc Res, Level 1,Harold Stokes Bldg,143-165 Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au RI Davis, Ian/A-1430-2012; Papenfuss, Anthony/C-6297-2008 OI Davis, Ian/0000-0002-9066-8244; Papenfuss, Anthony/0000-0002-1102-8506 NR 39 TC 35 Z9 36 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2007 VL 13 IS 11 BP 3286 EP 3292 DI 10.1158/1078-0432.CCR-07-0284 PG 7 WC Oncology SC Oncology GA 172FE UT WOS:000246788700026 PM 17545534 ER PT J AU Fonsatti, E Nicolay, HJM Sigalotti, L Calabro, L Pezzani, L Colizzi, F Altomonte, M Guidoboni, M Marincola, FM Maio, M AF Fonsatti, Ester Nicolay, Hugues J. M. Sigalotti, Luca Calabro, Luana Pezzani, Laura Colizzi, Francesca Altomonte, Maresa Guidoboni, Massimo Marincola, Francesco M. Maio, Michele TI Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2 '-deoxycytidine in cutaneous melanoma: Immunotherapeutic implications SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; CANCER-IMMUNOTHERAPY; GENE-EXPRESSION; IMMUNE ESCAPE; PHASE-I; CELLS; HLA; METHYLATION; RECOGNITION AB Purpose: To investigate the potential of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) to improve the effectiveness of immunotherapeutic approaches against melanocyte differentiation antigens. Experimental Design: The effect of 5-aza-CdR on the constitutive expression of gp100 was investigated in 11 human melanoma cell lines by real-time reverse transcription-PCR and indirect immunofluorescence (IIF) analyses. 5-aza-CdR - mediated changes in the levels of expression of human leukocyte antigen (HLA) class I antigens and HLA-A2 allospecificity, intercellular adhesion molecule-1 (ICAM-1), and leukocyte-function - associated antigen-3 were investigated by IIF analysis on melanoma cells under study. The recognition of gp100-positive Mel 275 melanoma cells, treated or not with 5-aza-CdR, by HLA-A2- restricted gp100((209-217)) -specific CTL was investigated by Cr-51-release assays, IFN-gamma release and IFN-gamma ELISPOT assays. Results: The constitutive expression of gp100 was not affected by 5-aza-CdR on all melanoma cells investigated. Compared with untreated cells, the exposure of Mel 275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up-regulated their expression of HLA class I antigens and of ICAM-1. These phenotypic changes significantly (P < 0.05) increased the lysis of 5-aza-CdR treated Mel 275 melanoma cells by gp100-specific CTL and increased their IFN-gamma release. 5-aza-CdR treatment of Mel 275 cells also induced a higher number of gp100-specific CTL to secrete IFN-gamma. Conclusions: Treatment with 5-aza-CdR improves the recognition of melanoma cells by gp100-specific CTL through the up-regulation of HLA class I antigens expression; ICAM-1 also contributes to this phenomenon. These findings highlight a broader range of therapeutic implications of 5-aza-CdR when used in association with active or adoptive immunotherapeutic approaches against a variety of melanoma-associated antigens. C1 Univ Hosp Siena, Dept Oncol, Div Med Oncol & Immunotherapy, Ist Toscano Tumori, I-53100 Siena, Italy. Ctr Riferimento Oncol, Dept Med Oncol, Ist Ricovero & Cura Carattere Sci, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Maio, M (reprint author), Univ Hosp Siena, Dept Oncol, Div Med Oncol & Immunotherapy, Ist Toscano Tumori, Strada Scotte 14, I-53100 Siena, Italy. EM mmaio@cro.it RI altomonte, maresa/G-7734-2011; Sigalotti, Luca/A-5893-2013; OI Sigalotti, Luca/0000-0003-3362-5026; coral, sandra/0000-0002-1308-3082; Nicolay, Hugues/0000-0001-9264-7001 NR 43 TC 61 Z9 64 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2007 VL 13 IS 11 BP 3333 EP 3338 DI 10.1158/1078-0432.CCR-06-3091 PG 6 WC Oncology SC Oncology GA 172FE UT WOS:000246788700032 PM 17545540 ER PT J AU Lotsch, J Belfer, I Kirchhof, A Mishra, BK Max, MB Doehring, A Costigan, M Woolf, CJ Geisslinger, G Tegeder, I AF Loetsch, Joern Belfer, Inna Kirchhof, Anja Mishra, Bikash K. Max, Mitchell B. Doehring, Alexandrea Costigan, Michael Woolf, Clifford J. Geisslinger, Gerd Tegeder, Irmgard TI Reliable screening for a pain-protective haplotype in the GTP cyclohydrolase 1 gene (GCH1) through the use of 3 or fewer single nucleotide polymorphisms SO CLINICAL CHEMISTRY LA English DT Article ID RECONSTRUCTION; MUTATIONS AB Background: A haplotype in the GTP cyclohydrolase 1 (dopa-responsive dystonia) gene (GCH1) is associated with decreased persistent pain. The aim of the present study was to develop a screening method for the pain-protective haplotype. Methods: Complete genetic information for all 15 GCH1 DNA positions constituting the pain-protective GCH1 haplotype was available from 278 patients. In silico analyses, including discriminant analysis of the most frequent haplotypes, identified distinctive DNA positions that allow detection of the pain-protective haplotype at high sensitivity and specificity with the smallest possible number of DNA positions. Pyrosequencing((TM)) assays were subsequently developed for these DNA positions, established with 662 DNA samples from healthy volunteers, and prospectively validated with a random selection of DNA samples genotyped for all 15 DNA positions. Results: Diagnosis of the pain-protective GCH1 haplotype was possible with 100% sensitivity and specificity by screening for just 3 GCH1 genetic variants that span the entire DNA range of the haplotype: c.-9610G>A (dbSNP rs8007267G>A) in the 5 ' untranslated region, c.343 + 8900A>T (dbSNP rs3783641A>T) in intron 1, and c.*4279 (dbSNP rs10483639C>G) in the 3 ' untranslated region. Test sensitivity and specificity were still >95% with 2 or even just 1 of these GCH1 DNA positions. Conclusions: In silico analysis of complex GCH1 gene haplotypes reduced the requisite number of tested DNA positions from 15 to 3 while maintaining the reliability, specificity, and sensitivity of the genetic diagnosis. This screening method could reduce laboratory diagnostic efforts and facilitate investigations of the pain-protective GCH1 haplotype. (C) 2007 American Association for Clinical Chemistry. C1 Univ Frankfurt, Inst Clin Pharmacol, ZAFES, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany. Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Lotsch, J (reprint author), Univ Frankfurt, Inst Clin Pharmacol, ZAFES, Pharmazentrum Frankfurt, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM j.loetsch@em.uni OI Lotsch, Jorn/0000-0002-5818-6958; Tegeder, Irmgard/0000-0001-7524-8025 FU Intramural NIH HHS NR 10 TC 32 Z9 36 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 BP 1010 EP 1015 DI 10.1373/clinchem.2006.082883 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172UP UT WOS:000246830300005 PM 17363416 ER PT J AU Cecco, SA Yau, Y Bolan, CD Leitman, SF Rehak, NN AF Cecco, S. A. Yau, Y. Bolan, C. D. Leitman, S. F. Rehak, N. N. TI Phosphorus and FGF-23: Effect of routine apheresis procedures with and without Ca prophylaxis. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA D-53 BP A176 EP A177 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000552 ER PT J AU Costello, R Goldbach-Mansky, R Wilson, M Kicker, P Pham, H Csako, G AF Costello, R. Goldbach-Mansky, R. Wilson, M. Kicker, P. Pham, H. Csako, G. TI Effect of cryogelation on laboratory tests SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 NIH CC DLM, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA C68 BP A125 EP A125 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000394 ER PT J AU Hwang, J Choi, J Bang, H Kim, Y Choi, Y Jin, H Lee, I Kim, T Park, S Via, L Barry, C Cho, S Lee, H AF Hwang, J. Choi, J. Bang, H. Kim, Y. Choi, Y. Jin, H. Lee, I. Kim, T. Park, S. Via, L. Barry, C. Cho, S. Lee, H. TI Rapid detection of isoniazid resistant Mycobacterium tuberculosis isolates using reverse blot hybridization assay SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 Mol & Diagnost Inc, Wonju, South Korea. Yonsei Univ, Wonju, South Korea. Natl Masan TB Hosp, Masan, South Korea. NIAID, Bethesda, MD 20892 USA. Yonsei Univ, Seoul 120749, South Korea. RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA B-4 BP A54 EP A54 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000172 ER PT J AU Sethi, AA Sampson, M Warnick, R Muniz, N Nordestgaard, BG Tybjaerg-Hansen, A Remaley, AT AF Sethi, A. A. Sampson, M. Warnick, R. Muniz, N. Nordestgaard, B. G. Tybjaerg-Hansen, A. Remaley, A. T. TI Composition analysis of lipoproteins in patients with ischemic heart disease SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. Berkeley Heart Lab, Burlingame, CA USA. Quantimetrix Corp, Redondo Beach, CA USA. Herlev Univ Hosp, Copenhagen City Heart Study, DK-2730 Herlev, Denmark. Copenhagen Univ Hosp, Copenhagen City Heart Study, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA A143 BP A45 EP A45 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000144 ER PT J AU Sullivan, P Burton, D Costello, R Csako, G AF Sullivan, P. Burton, D. Costello, R. Csako, G. TI Occurrence of falsely high internal standard in an HPLC method for 25-hydroxy-vitamin D2 and D3 (25OH-vitD) measurements. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA A-165 BP A52 EP A53 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000166 ER PT J AU Sviridov, D Drake, SK Hortin, GL AF Sviridov, D. Drake, S. K. Hortin, G. L. TI Variable reactivity of different microalbumin assays with fragmented or modified albumin SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 15-19, 2007 CL San Diego, CA SP Amer Assoc Clin Chem C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2007 VL 53 IS 6 SU S MA B-90 BP A81 EP A81 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 172ZJ UT WOS:000246843000256 ER PT J AU Ho, JT Lewis, JG O'Loughlin, P Bagley, CJ Romero, R Dekker, GA Torpy, DJ AF Ho, Jui T. Lewis, John G. O'Loughlin, Peter Bagley, Christopher J. Romero, Roberto Dekker, Gus A. Torpy, David J. TI Reduced maternal corticosteroid-binding globulin and cortisol levels in pre-eclampsia and gamete recipient pregnancies SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-HORMONE; FETAL-GROWTH RESTRICTION; INSULIN-RESISTANCE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; ADRENAL-FUNCTION; PLASMA-CORTISOL; BIRTH-WEIGHT; HYPERTENSION; ADRENOCORTICOTROPIN; PATHOGENESIS AB Objective To measure and contrast maternal cortisol and corticosteroid-binding globulin (CBG) levels in pregnancies with normal outcomes, pre-eclampsia, intrauterine growth restriction (IUGR) and in gamete recipients. Study design Prospective study of 93 women at high risk of pre-eclampsia, including gamete recipients (n = 22) and 33 controls. Plasma total and free cortisol and CBG were measured every 2 weeks from 16 weeks' gestation until delivery. Results Forty-two per cent of the high-risk group had complications, including pre-eclampsia (n = 11), gestational hypertension (n = 16) and small-for-gestational-age (SGA) neonates (n = 12). There were no complications in the controls. In all groups, plasma CBG concentrations increased progressively across gestation (P < 0.05), in parallel to total cortisol, but fell significantly from 36 weeks' gestation onwards, with a corresponding rise in free cortisol concentrations. In pre-eclampsia and gestational hypertension, plasma CBG, and total and free cortisol concentrations were lower from 36 weeks onwards (P < 0.05). In IUGR, plasma CBG concentrations were suppressed from 28 weeks' gestation until delivery (P < 0.05), but with no significant difference in plasma total and free cortisol. Gamete recipients had significantly lower plasma CBG from 20 weeks' gestation onwards, and plasma total and free cortisol were reduced at 24 and 32 weeks onwards, respectively. Conclusions Maternal plasma CBG, total and free cortisol concentrations are reduced in pre-eclampsia/gestational hypertension, and markedly reduced in gamete recipients. Low CBG may be due to reduced synthesis or enhanced inflammation-driven degradation. Low maternal cortisol may be due to a lack of placental corticotropin-releasing hormone or reduced maternal ACTH, driving cortisol production. Low maternal cortisol may influence the foetal hypothalamic-pituitary-adrenal axis and disease patterns later in life following complicated pregnancy. C1 Royal Adelaide Hosp, Endocrine & Metab Unit, Adelaide, SA 5000, Australia. Hanson Inst, Adelaide, SA, Australia. Univ Adelaide, Adelaide, SA, Australia. Inst Med & Vet Sci, Adelaide, SA 5000, Australia. Womens & Childrens Hosp, Dept Obstet & Gynaecol, Adelaide, SA, Australia. Canterbury Hlth Labs, Christchurch, New Zealand. NICHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA. RP Ho, JT (reprint author), Royal Adelaide Hosp, Endocrine & Metab Unit, N Terrace, Adelaide, SA 5000, Australia. EM jui.ho@imvs.sa.gov.au OI Lewis, John/0000-0003-2757-4111 NR 55 TC 29 Z9 30 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUN PY 2007 VL 66 IS 6 BP 869 EP 877 DI 10.1111/j.1365-2265.2007.02826.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 171TK UT WOS:000246758100017 PM 17437519 ER PT J AU Acton, RT Snively, BM Barton, JC McLaren, CE Adams, PC Rich, SS Eckfeldt, JH Press, RD Sholinsky, P Leiendecker-Foster, C McLaren, GD Speechley, MR Harris, EL Dawkins, FW Gordeuk, VR AF Acton, R. T. Snively, B. M. Barton, J. C. McLaren, C. E. Adams, P. C. Rich, S. S. Eckfeldt, J. H. Press, R. D. Sholinsky, P. Leiendecker-Foster, C. McLaren, G. D. Speechley, M. R. Harris, E. L. Dawkins, F. W. Gordeuk, V. R. CA HIOSS Res Invest TI A genome-wide linkage scan for iron phenotype quantitative trait loci: the HEIRS Family Study SO CLINICAL GENETICS LA English DT Article DE ferritin; hemochromatosis; iron; transferrin saturation; unsaturated iron-binding capacity ID HYPERFERRITINEMIA-CATARACT SYNDROME; TUMOR-NECROSIS-FACTOR; AUSTRALIAN HEMOCHROMATOSIS PATIENTS; MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSFERRIN SATURATION VALUES; SERUM FERRITIN CONCENTRATIONS; HFE C282Y HOMOZYGOSITY; I-LIKE GENE; HEREDITARY HEMOCHROMATOSIS; JUVENILE HEMOCHROMATOSIS AB Iron overload phenotypes in persons with and without hemochromatosis are variable. To investigate this further, probands with hemochromatosis or evidence of elevated iron stores and their family members were recruited for a genome-wide linkage scan to identify potential quantitative trait loci (QTL) that contribute to variation in transferrin saturation (TS), unsaturated iron-binding capacity (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were evaluated from 174 families. After adjusting for age, gender, and race/ethnicity, there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds (LOD) = 2.08, p = 0.001) and of UIBC (LOD = 9.52), TS (LOD = 4.78), and SF (LOD = 2.75) to the chromosome 6p region containing HFE (each p < 0.0001). After adjustments for HFE genotype and other covariates, there was evidence of linkage of SF to chromosome 16p (LOD = 2.63, p = 0.0007) and of UIBC to chromosome 5q (LOD = 2.12, p = 0.002) and to chromosome 17q (LOD = 2.19, p = 0.002). We conclude that these regions should be considered for fine mapping studies to identify QTL that contribute to variation in SF and UIBC. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35209 USA. Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Calif Irvine, Dept Med, Epidemiol Div, Irvine, CA USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA. Natl Heart Lung & Blood Inst, Div Epidemiol & Clin Applicat, Bethesda, MD USA. Vet Affairs Long Beach Healthcare Syst, Hematol Oncol Sect, Long Beach, CA USA. Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA USA. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. Howard Univ, Dept Med, Washington, DC 20059 USA. Howard Univ, Ctr Sickle Cell Dis, Washington, DC USA. Howard Univ, Dept Med, Washington, DC USA. RP Acton, RT (reprint author), Univ Alabama, Dept Microbiol, 265 MCLM,1530 3rd Ave S, Birmingham, AL 35209 USA. EM acton@uab.edu FU NCRR NIH HHS [M01-RR00032, M01 RR000827, M01-RR10284]; NHLBI NIH HHS [N01-HC-05188, N01-HC-05186, N01-HC-05189, UH1-HL03679-05, N01-HC-05192, N01-HC-05191, N01-HC-05190, N01-HC-05185, HV48141] NR 69 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 2007 VL 71 IS 6 BP 518 EP 529 DI 10.1111/J.1399-0004.2007.00804.X PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 174CE UT WOS:000246918000005 PM 17539901 ER PT J AU Edelman, EA Girirajan, S Finucane, B Patel, PI Lupski, JR Smith, ACM Elsea, SH AF Edelman, E. A. Girirajan, S. Finucane, B. Patel, P. I. Lupski, J. R. Smith, A. C. M. Elsea, S. H. TI Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta-analysis of 105 cases SO CLINICAL GENETICS LA English DT Article DE 17p11.2 deletion; gender discrepancy; haploinsufficiency; mental retardation; myopia; overgrowth; RA/1; self-injury; Smith-Magenis syndrome ID METACARPOPHALANGEAL PATTERN PROFILE; CONTIGUOUS-GENE SYNDROME; INTERSTITIAL DELETION; EARLY-CHILDHOOD; 17P11.2 DELETIONS; OTITIS-MEDIA; BETA(1)-ADRENERGIC ANTAGONISTS; DEL (17)(P11.2P11.2); MALADAPTIVE BEHAVIOR; CIRCADIAN DISORDER AB Smith-Magenis syndrome (SMS) is a multisystem disorder characterized by developmental delay and mental retardation, a distinctive behavioral phenotype, and sleep disturbance. We undertook a comprehensive meta-analysis to identify genotype-phenotype relationships to further understand the clinical variability and genetic factors involved in SMS. Clinical and molecular information on 105 patients with SMS was obtained through research protocols and a review of the literature and analyzed using Fisher's exact test with two-tailed p values. Several differences in these groups of patients were identified based on genotype and gender. Patients with RAI1 mutation were more likely to exhibit overeating, obesity, polyembolokoilamania, self-hugging, muscle cramping, and dry skin and less likely to have short stature, hearing loss, frequent ear infections, and heart defects when compared with patients with deletion, while a subset of small deletion cases with deletions spanning from TNFRSF13B to MFAP4 was less likely to exhibit brachycephaly, dental anomalies, iris abnormalities, head-banging, and hyperactivity. Significant differences between genders were also identified, with females more likely to have myopia, eating/appetite problems, cold hands and feet, and frustration with communication when compared with males. These results confirm previous findings and identify new genotype-phenotype associations including differences in the frequency of short stature, hearing loss, ear infections, obesity, overeating, heart defects, self-injury, self-hugging, dry skin, seizures, and hyperactivity among others based on genotype. Additional studies are required to further explore the relationships between genotype and phenotype and any potential discrepancies in health care and parental attitudes toward males and females with SMS. C1 Virginia Commonwealth Univ, Dept Pediat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. Elwyn Inc, Genet Serv, Elwyn, PA USA. Baylor Coll Med, Dept Neurol, Houston, TX USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA. Baylor Coll Med, Dept Pediat, Houston, TX USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Georgetown Univ, Sch Med, Inst Mol & Human Genet, Dept Oncol, Washington, DC USA. Virginia Commonwealth Univ, Dept Pediat, Richmond, VA USA. RP Elsea, SH (reprint author), Virginia Commonwealth Univ, Dept Pediat, 12-018 Sanger Hall,1101 E Marshall St,POB 980441, Richmond, VA 23298 USA. EM selsea@vcu.edu RI Girirajan, Santhosh/A-5280-2010 FU NICHD NIH HHS [R01 HD38534] NR 80 TC 59 Z9 62 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 2007 VL 71 IS 6 BP 540 EP 550 DI 10.1111/j.1399-0004.2007.00815.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 174CE UT WOS:000246918000007 PM 17539903 ER PT J AU Theoret, MR Arlen, PM Pazdur, M Dahut, WL Schlom, J Gulley, JL AF Theoret, Marc R. Arlen, Philip M. Pazdur, Mary Dahut, William L. Schlom, Jeffrey Gulley, James L. TI Phase I trial of an enhanced prostate-specific antigen-based vaccine and Anti-CTLA-4 antibody in patients with metastatic androgen-independent prostate cancer SO CLINICAL GENITOURINARY CANCER LA English DT Article DE autoimmunity; co-stimulation; poxvirus; T cells ID COLONY-STIMULATING FACTOR; MITOXANTRONE PLUS PREDNISONE; T-CELL PROLIFERATION; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; SELF-ANTIGEN; PATIENTS PTS; ACTIVATION; VIRUS; CD28 AB Because of the clinical benefit associated with immune response seen with PSA-TRICOM-based vaccines and the knowledge that blocking CTLA-4 can further augment immune responses, the combination of this vaccine with anti-CTLA-4 is promising. Because of the nature of the autoimmune events associated with anti-CTLA-4 antibodies, a dose-escalation study will provide evidence of the maximum tolerated dose on which to base phase II combinations designed to answer questions about the efficacy of the combination. C1 NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Natl Inst Hlth, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Ctr Canc Res, Med Oncol Branch, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 33 TC 9 Z9 9 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2007 VL 5 IS 5 BP 347 EP 350 DI 10.3816/CGC.2007.n.017 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 194KU UT WOS:000248344100010 PM 17645835 ER PT J AU Akin, C Soto, D Brittain, E Chhabra, A Schwartz, LB Caughey, GH Metcalfe, DD AF Akin, Cem Soto, Darya Brittain, Erica Chhabra, Adhuna Schwartz, Lawrence B. Caughey, George H. Metcalfe, Dean D. TI Tryptase haplotype in mastocytosis: Relationship to disease variant and diagnostic utility of total tryptase levels SO CLINICAL IMMUNOLOGY LA English DT Article DE mastocytosis; tryptase; haplotype; genotype; allele; prothrombin time; partial thromboplastin time ID SYSTEMIC MASTOCYTOSIS; CHROMOSOME 16P13.3; MAST-CELLS; GENES; GAMMA; FORM AB Serum mast cell tryptase levels are used as a diagnostic criterion and surrogate marker of disease severity in mastocytosis. Approximately 29% of the healthy population lacks a tryptase genes; however, it is not known whether tack of a tryptase genes Leads to variability in tryptase levels or impacts on disease severity in mastocytosis. We have thus analyzed tryptase haplotype in patients with mastocytosis, computing correlations between haplotype and plasma total and mature tryptase levels; and disease category. We found: (1) the distribution of tryptase haplotype in patients with mastocytosis appeared consistent with Hardy-Weinberg equilibrium and the distribution in the general population; (2) the disease severity and plasma tryptase levels were not affected by the number of alpha or beta tryptase alleles in this study; and (3) information about the tryptase haplotype did not provide any prognostic value about the severity of disease. Total and mature tryptase levels positively correlated with disease severity, as well as prothrombin time and partial thromboplastin time, and negatively correlated with the hemoglobin concentration. (C) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Allergy & Infect Dis, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Natl Inst Allergy & Infect Dis, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23298 USA. RP Akin, C (reprint author), Univ Michigan, 5520-B,MSRB-1 Box 0600,1150 W Med Ctr, Ann Arbor, MI 48109 USA. EM cemakin@umich.edu OI Akin, Cem/0000-0001-6301-4520 FU Intramural NIH HHS [Z01 AI000249-26]; NHLBI NIH HHS [P01 HL024136-190014, HL024136, P01 HL024136]; NIAID NIH HHS [R37 AI020487, R01 AI020487, AI20487, R01 AI020487-19, R21 AI020487] NR 17 TC 15 Z9 15 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2007 VL 123 IS 3 BP 268 EP 271 DI 10.1016/j.clim.2007.02.007 PG 4 WC Immunology SC Immunology GA 176WO UT WOS:000247115800005 PM 17449330 ER PT J AU Hallett, M AF Hallett, Mark TI Volitional control of movement: The physiology of free will SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE volition; free will; movement-related cortical potential; Bereitschaftspotential; decision; transcranial magnetic stimulation; consciousness; movement; agency ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; EXTERNALLY TRIGGERED MOVEMENTS; SUPPLEMENTARY EYE FIELDS; ALIEN HAND SYNDROME; PREFRONTAL CORTEX; VOLUNTARY ACTION; CONSCIOUS-WILL; CORTICAL POTENTIALS; PERCEPTUAL DECISION AB This review deals with the physiology of the initiation of a voluntary movement and the appreciation of whether it is voluntary or not. I argue that free will is not a driving force for movement, but a conscious awareness concerning the nature of the movement. Movement initiation and the perception of willing the movement can be separately manipulated. Movement is generated subconsciously, and the conscious sense of volition comes later, but the exact time of this event is difficult to assess because of the potentially illusory nature of introspection. Neurological disorders of volition are also reviewed. The evidence suggests that movement is initiated in the frontal lobe, particularly the mesial areas, and the sense of volition arises as the result of a corollary discharge likely involving multiple areas with reciprocal connections including those in the parietal lobe and insular cortex. (C) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS [Z01 NS002669-23] NR 115 TC 96 Z9 99 U1 5 U2 46 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUN PY 2007 VL 118 IS 6 BP 1179 EP 1192 DI 10.1016/j.clinph.2007.03.019 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 177OL UT WOS:000247162300002 PM 17466580 ER PT J AU Huey, ED Probasco, JC Moll, J Stocking, J Ko, MH Grafman, J Wassermann, EM AF Huey, Edward D. Probasco, John C. Moll, Jorge Stocking, Jonathan Ko, Myoung-Hwan Grafman, Jordan Wassermann, Eric M. TI No effect of DC brain polarization on verbal fluency in patients with advanced frontotemporal dementia SO CLINICAL NEUROPHYSIOLOGY LA English DT Letter C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Chonbuk Natl Univ, Sch Med, Dept Phys Med & Rehabil, Jeonju, South Korea. NINDS, Brain Simulat Unit, NIH, Bethesda, MD 20892 USA. RP Huey, ED (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. EM hueye@ninds.nih.gov RI Moll, Jorge/B-2654-2013; OI Moll, Jorge/0000-0002-4297-591X; Grafman, Jordan H./0000-0001-8645-4457; Ko, Myoung-Hwan/0000-0002-0566-3677 FU Intramural NIH HHS [Z01 NS002977-09] NR 8 TC 15 Z9 15 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUN PY 2007 VL 118 IS 6 BP 1417 EP 1418 DI 10.1016/j.clinph.2007.02.026 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 177OL UT WOS:000247162300027 PM 17452012 ER PT J AU Reddy, UM Wapner, RJ AF Reddy, Uma M. Wapner, Ronald J. TI Comparison of first and second trimester aneuploidy risk assessment SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE Down syndrome; aneuploidy; nuchal translucency; quadruple screen ID DOWN-SYNDROME; NASAL BONE; 1ST-TRIMESTER; TRISOMY-21; ULTRASOUND; DIAGNOSIS AB Counseling regarding the options for aneuploidy risk assessment is complicated and requires thorough counseling with the patient. Second trimester serum risk assessment has been the gold standard because of widespread availability, low cost, and vast experience with counseling and performance. First trimester risk assessment is becoming more widely available and provides increased sensitivity for Down syndrome detection with a detection rate of approximately 87% (95% confidence interval: 84.0% to 89.4%), at a fixed false-positive rate of 5%. With the advent of first trimester techniques, controversy has arisen as there are advocates for the different recently available approaches. In this chapter, we outline the various options in a manner that will provide practical information for physicians offering such testing. Clearly, implementation of first trimester risk assessment requires special training and meticulous quality control standards for nuchal translucency and laboratory measurements, access to chorionic villus sampling, and also appropriate counseling regarding risk assessment options. C1 NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. RP Reddy, UM (reprint author), NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Rm 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 27 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2007 VL 50 IS 2 BP 442 EP 453 DI 10.1097/GRF.0b013e31804c9b99 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 172BW UT WOS:000246780100011 PM 17513930 ER PT J AU Weber, AM AF Weber, Anne M. TI Elective Cesarean delivery: The pelvic perspective SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE pelvic organ prolapse; urinary incontinence; fecal incontinence; elective cesarean delivery; vaginal delivery; childbirth ID RANDOMIZED CONTROLLED-TRIAL; TERM BREECH TRIAL; URINARY-INCONTINENCE; VAGINAL DELIVERY; ORGAN PROLAPSE; ANAL-SPHINCTER; FLOOR DISORDERS; UNITED-STATES; RISK-FACTORS; REPAIR AB Elective cesarean delivery, or cesarean delivery on maternal request, was the focus of a recent State-of-the-Science Conference sponsored by the National Institutes of Health. On the basis of the information from comprehensive literature review and expert speakers, the panelists determined that weak-quality evidence supported elective cesarean delivery over planned vaginal delivery for urinary incontinence, although the duration of effect is not clear. For other maternal outcomes related to pelvic floor function, including pelvic organ prolapse, fecal incontinence and other anorectal symptoms, and sexual function, weak-quality evidence did not favor either route of delivery. C1 NICHD, Pelv Floor Disorders Program, Contracept & Reprod Hlth Branch, Ctr Populat Res,NIH, Bethesda, MD USA. RP Weber, AM (reprint author), 399 Wickford Dr, Pittsburgh, PA 15238 USA. EM webera@mail.nih.gov NR 31 TC 15 Z9 16 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2007 VL 50 IS 2 BP 510 EP 517 DI 10.1097/GRF.0b013e31804c9cae PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 172BW UT WOS:000246780100017 PM 17513936 ER PT J AU Lertora, JJL Atkinson, AJ AF Lertora, J. J. L. Atkinson, A. J., Jr. TI Clinical pharmacology education and training at the national institutes of health SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB In 1965, the National Institute of General Medical Sciences (NIGMS) established the intramural Pharmacology Research Associate Training (PRAT) program with the primary goals of providing postdoctoral training in pharmacology for individuals with or without previous pharmacology graduate training, and allowing individuals with doctoral degrees in pharmacology to obtain advanced training in other areas of science at the National Institutes of Health (NIH). The program utilized research preceptors drawn from laboratories that were conducting pharmacology-related research at the NIH campus. Although primary emphasis was placed on training laboratory scientists, a number of PRAT fellows obtained training that enabled them to pursue successful careers in clinical pharmacology. A partial listing of these individuals is shown in Table 1. Eventually, a clinical pharmacology training option was formalized within the PRAT program by the appointment of a Clinical Pharmacology Program Director, but this was subsequently suspended when this individual left NIH for a position in the pharmaceutical industry. C1 NIH, Clin Pharmacol Program, Off Clin Res Training & Med Educ, Ctr Clin, Bethesda, MD 20892 USA. Northwestern Univ, Dept Mol Pharmacol & Biochem, Feinberg Med Sch Med, Chicago, IL 60611 USA. RP Lertora, JJL (reprint author), NIH, Clin Pharmacol Program, Off Clin Res Training & Med Educ, Ctr Clin, Bethesda, MD 20892 USA. EM lertoraj@cc.nih.gov NR 6 TC 5 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2007 VL 81 IS 6 BP 907 EP 909 DI 10.1038/sj.clpt.6100206 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 168QT UT WOS:000246539800022 PM 17429349 ER PT J AU Katsifis, GE Moutsopoulos, NM Wahl, SM AF Katsifis, Gikas E. Moutsopoulos, Niki M. Wahl, Sharon M. TI T lymphocytes in Sjogren's syndrome: Contributors to and regulators of pathophysiology SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY LA English DT Review DE autoimmune disease; Sjogren's syndrome; cytokines; Th1; Th2; Th17; regulatory T cells; TGF-beta; IFN; IL-17; BAFF ID GROWTH-FACTOR-BETA; LABIAL SALIVARY-GLANDS; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; IMMUNOLOGICAL SELF-TOLERANCE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; TRANSCRIPTION FACTOR FOXP3; CELL-ACTIVATING FACTOR AB Sjogren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and malfunction of the exocrine glands, resulting in dry mouth and eyes. This multigenic and multifunctional disease can present as primary Sjogren's syndrome or secondary to an underlying connective tissue disease. Immune activation subsequent to activation or apoptosis of glandular epithelial cells in genetically predisposed individuals may expose autoantigens, which engage self-perpetuating T cell dependent auto-immune sequelae. The cellular and molecular context of this immune response may drive proinflammatory (Th1 and Th17) and restrain inhibitory (Treg) pathways. Inability to suppress the immune response results in persistent tissue damage and compromised function of salivary and lacrimal glands. Defining the contributions of participating T cells may unravel strategies for therapeutic intervention. C1 NIDCR, NIH, Bethesda, MD 20892 USA. NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, NIH, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov NR 198 TC 47 Z9 52 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1080-0549 J9 CLIN REV ALLERG IMMU JI Clin. Rev. Allergy Immunol. PD JUN PY 2007 VL 32 IS 3 BP 252 EP 264 DI 10.1007/s12016-007-8011-8 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 234HF UT WOS:000251150600008 PM 17992592 ER PT J AU Xi, ZX Gardner, EL AF Xi, Zheng-Xiong Gardner, Eliot L. TI Pharmacological actions of NGB 2904, a selective dopamine D-3 receptor antagonist, in animal models of drug addiction SO CNS DRUG REVIEWS LA English DT Article DE antiaddiction drugs; cocaine; D-3 antagonists; D-3 receptors; dopamine; drug addiction; NGB 2904; SB-277011A ID DOPAMINE D-3 RECEPTOR; PROGRESSIVE-RATIO SCHEDULES; COCAINE-SEEKING BEHAVIOR; BRAIN-STIMULATION REWARD; D3 RECEPTOR; INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS; HIGH-AFFINITY; MEDICATION DEVELOPMENT; THERAPEUTIC AGENTS AB As a continuation of our work with SB-277011A, we have examined the effects of another highly elective dopamine (DA) D-3 receptor antagonist, N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904), in animal models of addiction. Our results indicate that by systemic administration, NGB 2904 inhibits intravenous cocaine self-administration maintained under a progressive-ratio (PR) reinforcement schedule, cocaine- or cocaine cue-induced reinstatement of cocaine-seeking behavior, and cocaine- or other addictive drug-enhanced brain stimulation reward (BSR). The action of NGB 2904 on PR cocaine self-administration was long-lasting (1-2 days) after a single injection, supporting its potential use in treatment of cocaine addiction. The effects of NGB 2904 in the BSR paradigm were dose-dependent for both NGB 2904 and cocaine; that is, only lower doses of NGB 2904 were effective, and their putative antiaddiction effect could be overcome by increasing the doses of cocaine or other addictive drugs. A dopamine-dependent mechanism is proposed to explain the effects of NGB 2904 on cocaine's actions in these animal models of drug addiction. The data reviewed in this paper suggest that NGB 2904 or other D-3-selective antagonists may have potential in controlling motivation for drug-taking behavior or relapse to drug-seeking behavior, but may have a limited role in antagonizing the acute rewarding effects produced by cocaine or other addictive drugs. In addition, NGB 2904 may also act as a useful tool to study the role of D-3 receptors in drug addiction. C1 NIDA, Neuropsychopharmacol Sect, Chem Biol Res Branch, Intramural Res Program, Baltimore, MD USA. RP Xi, ZX (reprint author), Bldg C,Room 394,5500 Nathan Stock Dr, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 78 TC 59 Z9 61 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1080-563X J9 CNS DRUG REV JI CNS Drug Rev. PD SUM PY 2007 VL 13 IS 2 BP 240 EP 259 PG 20 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 188MN UT WOS:000247924100006 PM 17627675 ER PT J AU Walsh, PJ Veauvy, CM McDonald, MD Pamenter, ME Buck, LT Wilkie, MP AF Walsh, Patrick J. Veauvy, Clemence M. McDonald, M. Danielle Pamenter, Matthew E. Buck, Leslie T. Wilkie, Michael P. TI Piscine insights into comparisons of anoxia tolerance, ammonia toxicity, stroke and hepatic encephalopathy SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Memorial Symposium held in Honor of Peter Lutz CY SEP 23, 2005 CL Florida Altantic Univ, Boca Raton, FL HO Florida Altantic Univ DE glutamate excitotoxicity; NMDA receptors; ammonia; glutamate neurotoxicity; fish models; anoxia; hyperammonemia ID PERIPHERAL BENZODIAZEPINE RECEPTOR; TURTLE TRACHEMYS-SCRIPTA; METHYL-D-ASPARTATE; GLUTAMATE TRANSPORTER; CRUCIAN CARP; ENERGY-METABOLISM; METHIONINE SULFOXIMINE; POECILIA-RETICULATA; NITROGEN-METABOLISM; HYPERAMMONEMIC RATS AB Although the number of fish species that have been studied for both hypoxia/anoxia tolerance and ammonia tolerance are few, there appears to be a correlation between the ability to survive these two insults. After establishing this correlation with examples from the literature, and after examining the role Peter Lutz played in catalyzing this convergent interest in two variables, this article explores potential mechanisms underpinning this correlation. We draw especially on the larger body of information for two human diseases with the same effected organ (brain), namely stroke and hepatic encephalopathy. While several dissimilarities exist between the responses of vertebrates to anoxia and hyperammonemia, one consistent observation in both conditions is an overactivation of NMDA receptors or glutamate neurotoxicity. We propose a glutamate excitotoxicity hypothesis to explain the correlation between ammonia and hypoxia resistance in fish. Furthermore, we suggest several experimental paths to test this hypothesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Ottawa, CAREG, Dept Biol, Ottawa, ON K1N 6N5, Canada. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr,Div Marine Bio, Miami, FL 33149 USA. Univ Toronto, Dept Zool, Toronto, ON M5S 3G5, Canada. Wilfrid Laurier Univ, Dept Biol, Waterloo, ON N2L 3C5, Canada. RP Walsh, PJ (reprint author), Univ Ottawa, CAREG, Dept Biol, 30 Marie Curie, Ottawa, ON K1N 6N5, Canada. EM pwalsh@uottawa.ca FU NIEHS NIH HHS [ES 05705, ES 11005, F32 ES005705, P30 ES005705, P30 ES005705-14, R01 ES011005, R01 ES011005-03] NR 86 TC 27 Z9 27 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JUN PY 2007 VL 147 IS 2 SI SI BP 332 EP 343 DI 10.1016/j.cbpa.2006.09.001 PG 12 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 172WJ UT WOS:000246834900008 PM 17046301 ER PT J AU Solomon, J Raymont, V Braun, A Butman, JA Grafman, J AF Solomon, Jeffrey Raymont, Vanessa Braun, Allen Butman, John A. Grafman, Jordan TI User-friendly software for the analysis of brain lesions (ABLe) SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE brain lesion; cytoarchitecture; Brodmann areas; computer software; prefrontal cortex ID IMAGE REGISTRATION; ATTENTION; INJURY AB We previously developed a software package called ABLe (analysis of brain lesions) which characterizes brain lesions in terms of lesion volume and intersection with cytoarchitecture (e.g. Brodmann areas). Since our previous publication, there have been significant improvements to this software package which utilize methods standard to the neuroimaging community. These features include spatial normalization to the MNI template brain (standard of the international consortium for brain mapping), and use of the volume occupancy Talairach labels (VOTL) and automated anatomical labeling (AAL) atlases for full brain quantification of structures impacted by the lesion. Methods for multi-subject studies including lesion-symptom mapping proposed by Bates et al. have been extended in ABLe to produce an exploratory analysis summarizing correlations between subjects with overlapping lesions and behavioral deficit. A subset of data from an ongoing traumatic head injury study correlating deficit with brain anatomy is used to demonstrate the power of this software package. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Med Numer Inc, Germantown, MD USA. Henry M Jackson Fdn, Vietnam Head Injury Study, Bethesda, MD USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NIDCD, Language Sect, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Solomon, J (reprint author), 20410 Observ Dr,Suite 210, Germantown, MD 20876 USA. EM jsolomon@cc.nih.gov RI Butman, John/A-2694-2008; OI Grafman, Jordan H./0000-0001-8645-4457; Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS [Z99 CL999999, 001-0512-948] NR 21 TC 65 Z9 65 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD JUN PY 2007 VL 86 IS 3 BP 245 EP 254 DI 10.1016/j.cmpb.2007.02.006 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 170KV UT WOS:000246663200006 PM 17408802 ER PT J AU Shah, M Holland, E Chan, CC AF Shah, Manan Holland, Edward Chan, Chi-Chao TI Resolution of autoimmune polyglandular syndrome-associated keratopathy with keratolimbal stem cell transplantation - Case report and historical literature review SO CORNEA LA English DT Review DE polyglandular; autoimmune; keratopathy; stem cell; keratitis; keratolimbal allograft; multiple endocrine deficiency ID OCULAR SURFACE DISEASE; CORNEAL DISEASES; REGULATOR GENE; DEFICIENCY; KERATITIS; HYPOPARATHYROIDISM; MANAGEMENT; PROTEIN; AIRE AB Purpose: To describe the presentation and treatment of a case of autoimmune polyglandular syndrome type 1 (APS1)-associated keratopathy and to review the associated literature. Methods: A 23-year-old man with decreased vision secondary to APS1-associated keratopathy was treated with systemic immunosuppression and keratolimbal allograft (KLAL) stem cell transplantation. Results: The patient maintains excellent vision 27 months after KLAL and systemic immunosuppression. Conclusions: An underlying etiology of APS1-associated keratopathy is stem cell deficiency, which can be treated effectively with KLAL and systemic immuno suppression. C1 Cincinnati Eye Inst, Edgewood, KY 41017 USA. NEI, Bethesda, MD 20892 USA. RP Holland, E (reprint author), Cincinnati Eye Inst, 580 S Loop Rd,Suite 200, Edgewood, KY 41017 USA. EM eholland@fuse.net FU Intramural NIH HHS [Z01 EY000222-22] NR 22 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2007 VL 26 IS 5 BP 632 EP 635 PG 4 WC Ophthalmology SC Ophthalmology GA 169QU UT WOS:000246607500026 PM 17525667 ER PT J AU Deans, KJ Minneci, PC Suffredini, AF Danner, RL Hoffman, WD Ciu, XZ Klein, HG Schechter, AN Banks, SM Eichacker, PQ Natanson, C AF Deans, Katherine J. Minneci, Peter C. Suffredini, Anthony F. Danner, Robert L. Hoffman, William D. Ciu, Xizhong Klein, Harvey G. Schechter, Alan N. Banks, Steven M. Eichacker, Peter Q. Natanson, Charles TI Randomization in clinical trials of titrated therapies: Unintended consequences of using fixed treatment protocols SO CRITICAL CARE MEDICINE LA English DT Article DE treatment dose; randomization; practice misalignment ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; ACUTE LUNG INJURY; TIDAL VOLUMES; MECHANICAL VENTILATION; COVARIATE INTERACTIONS; TRANSFUSION PRACTICES; BLOOD-TRANSFUSION; SEPTIC SHOCK; MANAGEMENT AB Objective: Clinical trial designs that randomize patients to fixed treatment regimens may disrupt preexisting relationships between illness severity and level of therapy. The practice misalignments created by such designs may have unintended effects on trial results and safety. Methods. To illustrate this problem, the Transfusion Requirements in Critical Care (TRICC) trial and the Acute Respiratory Distress Syndrome Network low tidal volume (ARMA) trial were analyzed. Results: Publications before TRICC indicated that clinicians used higher transfusion thresholds in patients with ischemic heart disease compared with younger, healthier patients (p = .001). The trial, however, randomized patients (n = 838) to liberal (10 g/dL hemoglobin) or restrictive (7 g/dL) transfusion thresholds. Thirty-day mortality was different and opposite in the liberal compared with the restrictive arm depending on presence (21 vs. 26%) or absence (25 vs. 16%) of ischemic heart disease (p = .03). At baseline in ARMA, consistent with prior publications, physicians set ventilator volumes lower in patients with high airway pressures and poor compliance (8.4-10.6 mL/kg interquartile range) than patients with less severe abnormalities (9.6-12 mL/kg) (p = .0001). In the trial, however, patients (n = 861) were randomized to low (6 mL/kg) or high (12 mL/kg) tidal volumes. In patients with low compliance (< 0.6 mL/kg), 28-day mortality was higher when tidal volumes were raised rather than lowered (42 vs. 29%), but this effect was reversed in patients with higher compliance (21 vs. 37%; p = .003). Conclusions: In TRICC and ARMA, randomization to fixed treatment regimens disrupted preexisting relationships between illness severity and therapy level. This created noncomparable subgroups in both study arms that received care different and opposite from titrated care, that is, practice misalignments. These subgroups reduced the interpretability and safety of each trial. Characterizing current practice, incorporating current practice controls, and using alternative trial designs to minimize practice misalignments should improve trial safety and interpretability. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. RP Eichacker, PQ (reprint author), NIH, Crit Care Med Dept, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 33 TC 88 Z9 91 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2007 VL 35 IS 6 BP 1509 EP 1516 DI 10.1097/01.CCM.0000266584.40715.A6 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 170QO UT WOS:000246679200008 PM 17440420 ER PT J AU Sherer, K Li, Y Cui, XZ Li, XM Subramanian, M Laird, MW Moayeri, M Leppla, SH Fitz, Y Su, JW Eichacker, PQ AF Sherer, Kevin Li, Yan Cui, Xizhong Li, Xuemei Subramanian, Mani Laird, Michael W. Moayeri, Mahtab Leppla, Stephen H. Fitz, Yvonne Su, Junwu Eichacker, Peter Q. TI Fluid support worsens outcome and negates the benefit of protective antigen-directed monoclonal antibody in a lethal toxin-infused rat Bacillus anthracis shock model SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 102nd International Conference of the American-Thoracic-Society CY MAY 19-24, 2006 CL San Diego, CA SP Amer Thorac Soc DE rodent; Bacillus anthracis; lethal toxin; sepsis; fluids; treatment ID INHALATIONAL ANTHRAX; SEPTIC SHOCK; SURVIVAL; SEPSIS; MAPKS; LIPOPOLYSACCHARIDE; RESUSCITATION; MANAGEMENT; COMPONENTS; CHALLENGE AB Objective: The aim of this study was to test the effects of normal saline treatment either alone or in combination with protective antigen-directed monoclonal antibody in a lethal toxin-infused rat model of anthrax sepsis. Design: Prospective controlled animal study. Setting: Animal research laboratory. Subjects: Sprague-Dawley rats (n = 539). Interventions: We initially tested the efficacy of three normal saline doses (5, 10, or 20 mL/kg/hr intravenously for 24 hrs) or none (controls) started when rats were treated with either lethal toxin (24-hr infusion) or, for comparison, lipopolysaccharide (24-hr infusion) or Escherichia coli (intravenous bolus). We then investigated delaying normal saline for 6 hrs or combining it with protective antigen-directed monoclonal antibody following lethal toxin challenge. Measurements and Main Results., Dose did not alter the effects of normal saline with any challenge (p not significant for all) or when combined with protective antigen-directed monoclonal antibody, so this variable was averaged in analysis. In initial studies, normal saline decreased mortality (mean hazards ratio of survival +/- SE) significantly with E. coli challenge (-0.66 +/- 0.25, p = .009 averaged over normal saline dose) but not lipopolysaccharide (-0.17 +/- 0.20). In contrast, normal saline increased mortality significantly with lethal toxin (0.69 +/- 0.20, p = .001) in a pattern different from E. coli and lipopolysaccharide (p <= .002 for each). In subsequent studies, normal saline alone once again increased mortality (0.8 +/- 0.3, p = .006), protective antigen-directed monoclonal antibody alone reduced it (-1.7 +/- 0.8, p = .03), and the combination had intermediate effects that were not significant (0.04 +/- 0.3). Conclusions. These findings raise the possibility that normal saline treatment may actually worsen outcome with anthrax lethal toxin. Furthermore, lethal toxin-directed therapies may not be as beneficial when used in combination with this type of fluid support. C1 NIH, Ctrit Care Med Dept, Clin Ctr, Bethesda, MD 20892 USA. NIAID, Crit Care Med Dept, Clin Ctr, NIH, Bethesda, MD 20892 USA. Human Genome Sci, Rockville, MD USA. Genentech Inc, San Francisco, CA USA. RP Eichacker, PQ (reprint author), NIH, Ctrit Care Med Dept, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU Intramural NIH HHS NR 38 TC 19 Z9 19 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2007 VL 35 IS 6 BP 1560 EP 1567 DI 10.1097/CCM.0000266535.95770.A2 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 170QO UT WOS:000246679200015 PM 17452924 ER PT J AU Suffredini, AF AF Suffredini, Anthony F. TI Systemic inflammation and sexual dimorphism: More than meets the eye SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE gender; innate immunity; vascular reactivity; lipopolysaccharide; inflammation; sepsis ID UNITED-STATES; GENDER; MORTALITY; RESPONSES; SEPSIS; EPIDEMIOLOGY; AUTOIMMUNITY; ENDOTOXIN; IMMUNITY; ESTROGEN C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Suffredini, AF (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 5 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2007 VL 35 IS 6 BP 1610 EP 1612 DI 10.1097/01.CCM.0000266793.09378.22 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 170QO UT WOS:000246679200022 PM 17522533 ER PT J AU Laine, C Horton, R DeAngelis, CD Drazen, JM Frizelle, FA Godlee, F Haug, C Hebert, PC Kotzin, S Marusic, A Sahni, P Schroeder, TV Sox, HC Van Der Weyden, MB Verheugt, FWA AF Laine, Christine Horton, Richard DeAngelis, Catherine D. Drazen, Jeffrey M. Frizelle, Frank A. Godlee, Fiona Haug, Charlotte Hebert, Paul C. Kotzin, Sheldon Marusic, Ana Sahni, Peush Schroeder, Torben V. Sox, Harold C. Van Der Weyden, Martin B. Verheugt, Freek W. A. TI Clinical trial registration: Looking back and moving ahead SO CROATIAN MEDICAL JOURNAL LA English DT Editorial Material C1 Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 5 TC 9 Z9 9 U1 0 U2 2 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD JUN PY 2007 VL 48 IS 3 BP 289 EP 291 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 189DW UT WOS:000247970600002 PM 17589970 ER PT J AU Matthews, CP Colburn, NH Young, MR AF Matthews, Connie P. Colburn, Nancy H. Young, Matthew R. TI AP-1 a target for cancer prevention SO CURRENT CANCER DRUG TARGETS LA English DT Review DE Fra-1; Jun; TAM67; tumor promotion; invasion; inflammation ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; GENE-EXPRESSION PROFILES; SKIN TUMOR-DEVELOPMENT; NEGATIVE C-JUN; PROSTATE-CANCER; BREAST-CANCER; TRANSCRIPTION FACTORS; COLORECTAL-CANCER AB The transcription factor activator protein 1 (AP-1) plays a pivotal role in tumorigenesis. AP-1 activity is increased in multiple human tumor types. Inhibitors of AP-1 have been shown to block tumor promotion, trans formation, progression and invasion. Chronic inflammation and tumor development are linked. AP-1 may act, in part, by perpetuating the inflammatory signal. AP-1 is a recognized molecular target of many antioxidant and anti-inflammatory chem,chemopreventive compounds. This review focuses on the AP-1 family proteins as targets for chemoprevention. C1 NCI, Lab Canc Prevent, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI, Lab Canc Prevent, Frederick, MD 21702 USA. EM youngm@ncifcrf.gov FU Intramural NIH HHS NR 86 TC 77 Z9 80 U1 0 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD JUN PY 2007 VL 7 IS 4 BP 317 EP 324 DI 10.2174/156800907780809723 PG 8 WC Oncology SC Oncology GA 173OX UT WOS:000246883500003 PM 17979626 ER PT J AU Schaffer, AA Salzer, U Hammarstrom, L Grimbacher, B AF Schaeffer, Alejandro A. Salzer, Ulrich Hammarstroem, Lennart Grimbacher, Bodo TI Deconstructing common variable immunodeficiency by genetic analysis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID HYPER-IGM SYNDROME; MEMORY B-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; X-LINKED AGAMMAGLOBULINEMIA; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; CLASS-SWITCH RECOMBINATION; AUTOSOMAL RECESSIVE FORM; HEAVY-CHAIN GENE; CLASS-III GENES; SOMATIC HYPERMUTATION AB Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. Patients have recurrent bacterial infections and an increased risk of developing autoimmune diseases, lung damage, and selected cancers. Since 2003, four genes have been shown to be mutated in CVID patients: ICOS, TNFRSF13B (encoding TACI), TNFRSF13C (encoding BAFF-R) and CD19. Heterozygous mutations in TNFRSF13B are also associated with CVID, whereas the other three genes are purely recessive. Recent genetic linkage studies have also identified possible loci for dominant CVID genes on chromosomes 4q 5p and 16q. These findings markedly improved the genetic diagnosis of CVID and point towards new strategies for future genetic studies. In addition, some CVID genes might be relevant to more common diseases such as asthma and stroke. C1 UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. Natl Lib Med, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, NIH, Bethesda, MD 20894 USA. Univ Freiburg, Med Ctr, Div Clin Immunol & Rheumatol, D-79106 Freiburg, Germany. Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Clin Immunol, SE-14186 Stockholm, Sweden. RP Grimbacher, B (reprint author), UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, Pond St, London NW3 2QG, England. EM b.grimbacher@medsch.ucl.ac.uk RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 95 TC 41 Z9 41 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2007 VL 17 IS 3 BP 201 EP 212 DI 10.1016/j.gde.2007.04.002 PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 183FA UT WOS:000247556900006 PM 17467261 ER PT J AU Arcos-Burgos, M Acosta, MT AF Arcos-Burgos, Mauricio Acosta, Maria Teresa TI Tuning major gene variants conditioning human behavior: the anachronism of ADHD SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; LATENT CLASS; GENOMEWIDE SCAN; SIB-PAIRS; DSM-IV; LINKAGE; LOCI; ASSOCIATION; PREVALENCE AB New findings suggest that attention deficit and hyperactivity disorder (ADHD) is the most common behavioral variant associated with a mental condition. ADHD prevalence reaches figures of 18% in populations worldwide. Furthermore, genetic variants conferring susceptibility to develop ADHD are not rare but very frequent and eventually totally fixed in some populations. These patterns of evolution can be associated with the fact that this behavioral trait had provided selective advantage. However, this behavioral trait is now under scrutiny because of new emerging social necessities. Recent molecular and clinical evidence supports Thom Hartmann's Hunter-Farmer theory, reaffirming that ADHD might be an anachronic behavioral trait. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Arcos-Burgos, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM marcosbu@mail.nih.gov NR 30 TC 13 Z9 13 U1 0 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 2007 VL 17 IS 3 BP 234 EP 238 DI 10.1016/j.gde.2007.04.011 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 183FA UT WOS:000247556900010 PM 17467976 ER PT J AU Davenport, MP Price, DA McMichael, AJ AF Davenport, Miles P. Price, David A. McMichael, Andrew J. TI The T cell repertoire in infection and vaccination: implications for control of persistent viruses SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; MURINE CYTOMEGALOVIRUS-INFECTION; SIMIAN IMMUNODEFICIENCY VIRUS; RECEPTOR RECOGNITION; HIV-1 INFECTION; CROSS-REACTIVITY; CLONAL SELECTION; VIRAL-INFECTION; RESPONSES; MEMORY AB Most currently available vaccines target acute infectious agents such as polio, smallpox and influenza virus. The development of vaccines to persistent infectious agents has proven much more difficult. Although it is possible to generate T cell responses to such viruses, these responses are currently unable to prevent the establishment of infection, and immune control may be lost during the chronic phase. Recent advances have increased our understanding of the interactions between persistent viruses and the available T cell repertoire, and will guide approaches to the generation and maintenance of an 'ideal' T cell response. C1 Univ New S Wales, Prince Wales Hosp, Dept Haematol, Kensington, NSW 2052, Australia. Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2052, Australia. Natl Inst Allergy & Infect Dis, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DS, England. RP McMichael, AJ (reprint author), Univ New S Wales, Prince Wales Hosp, Dept Haematol, Kensington, NSW 2052, Australia. EM andrew.mcmichael@ndm.ox.ac.uk RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963, MC_U137884177] NR 50 TC 47 Z9 47 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2007 VL 19 IS 3 BP 294 EP 300 DI 10.1016/j.coi.2007.04.001 PG 7 WC Immunology SC Immunology GA 173YH UT WOS:000246907900008 PM 17433874 ER PT J AU Bryceson, YT Ljunggren, HG AF Bryceson, Yenan T. Ljunggren, Hans-Gustaf TI Lymphocyte effector functions: armed for destruction? SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID NATURAL-KILLER-CELLS C1 Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. Natl Inst Allergy & Infect Dis, Lab Immunogenet, NIH, Rockville, MD 20852 USA. RP Bryceson, YT (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. EM ybryceson@nih.gov; hans-gustaf.ljunggren@ki.se OI Bryceson, Yenan/0000-0002-7783-9934 NR 5 TC 3 Z9 3 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2007 VL 19 IS 3 BP 337 EP 338 DI 10.1016/j.coi.2007.04.016 PG 2 WC Immunology SC Immunology GA 173YH UT WOS:000246907900014 PM 17442559 ER PT J AU Andrade, EC Krueger, DD Nairn, AC AF Andrade, Erika C. Krueger, Dilja D. Nairn, Angus C. TI Recent advances in neuroproteomics SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Review DE 2-DE; affinity chromatography; brain; DIGE; fractionation; gel electrophoresis; LC-MS/MS; organelle; phosphorylation; post-synaptic density; proteome ID TANDEM MASS-SPECTROMETRY; CODED AFFINITY TAGS; POSTSYNAPTIC DENSITY PREPARATIONS; ANTERIOR CINGULATE CORTEX; PLASMA-MEMBRANE PROTEINS; BRAIN PROTEOME PROJECT; RAT CEREBRAL-CORTEX; MOUSE-BRAIN; PHOSPHOPROTEOMIC ANALYSIS; NUCLEUS-ACCUMBENS AB The last few years have seen a rapid growth in the use of proteomic methods to study normal brain function. In addition, such methods have been used to analyze changes in protein expression associated with the onset and progression of neuronal disease. The field of neuroproteomics faces special challenges given the complex cellular and sub-cellular architecture of the central nervous system. This article presents a review of recent progress in studies of neuroproteomics, and highlights the strengths and limitations of current proteomic profiling technologies used in studies of neuronal protein expression. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA. Yale Univ, Sch Med, NIDA, Neuroproteom Ctr, New Haven, CT 06508 USA. RP Nairn, AC (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06508 USA. EM angus.nairn@yale.edu OI Krueger-Burg, Dilja/0000-0001-5597-6287; Nairn, Angus/0000-0002-7075-0195 FU NIDA NIH HHS [DA018343, DA10044, P01 DA010044, P30 DA018343] NR 104 TC 13 Z9 15 U1 0 U2 0 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 2007 VL 9 IS 3 BP 270 EP 281 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 201ZJ UT WOS:000248870900009 PM 17608026 ER PT J AU Xu, JH He, LM Wu, LG AF Xu, Jianhua He, Liming Wu, Ling-Gang TI Role of Ca2+ channels in short-term synaptic plasticity SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID PRESYNAPTIC CALCIUM CURRENT; PAIRED-PULSE FACILITATION; CALYX-TYPE SYNAPSE; RAT BRAIN-STEM; TRANSMITTER RELEASE; NEUROTRANSMITTER RELEASE; HELD SYNAPSE; POSTTETANIC POTENTIATION; NEUROMUSCULAR-JUNCTION; NERVE-TERMINALS AB Repetitive nerve activity induces various forms of short-term synaptic plasticity that have important computational roles in neuronal networks. Several forms of short-term plasticity are caused largely by changes in transmitter release, but the mechanisms that underlie these changes in the release process have been difficult to address. Recent studies of a giant synapse - the calyx of Held - have shed new light on this issue. Recordings of Ca2+ currents or Ca2+ concentrations at nerve terminals reveal that regulation of presynaptic Ca2+ channels has a significant role in three important forms of short-term plasticity: short-term depression, facilitation and post-tetanic potentiation. C1 Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856 FU Intramural NIH HHS NR 60 TC 53 Z9 58 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2007 VL 17 IS 3 BP 352 EP 359 DI 10.1016/j.conb.2007.04.005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 186JP UT WOS:000247775300012 PM 17466513 ER PT J AU Pelkey, KA McBain, CJ AF Pelkey, Kenneth A. McBain, Chris J. TI Differential regulation at functionally divergent release sites along a common axon SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID METABOTROPIC GLUTAMATE-RECEPTOR; DUAL INTRACELLULAR-RECORDINGS; FIBER-INTERNEURON SYNAPSES; TARGET-SPECIFIC EXPRESSION; PRESYNAPTIC ACTIVE ZONES; RAT HIPPOCAMPUS; TRANSMITTER RELEASE; NERVE-TERMINALS; PYRAMIDAL CELLS; FEEDFORWARD INHIBITION AB Information transfer within neuronal networks requires the precise coordination of distinct neuronal populations within a given circuit. Evidence from a variety of central pathways indicates that such coordination is mediated in part by the ability of neurons to differentially regulate release properties at functionally divergent presynaptic elements along their individual axons according to the identity of the postsynaptic cell being innervated. Recent findings have revealed the cellular mechanisms by which central afferents modify release properties at individual presynaptic sites independent of neighboring terminals. Such autonomy of presynaptic regulation enables target-cell-dependent short-term and long-term synaptic plasticity and ensures that distinct features of afferent activity are relayed to divergent target-cell populations. C1 NICHHD, NIH, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHHD, NIH, Lab Cellular & Synapt Neurophysiol, Bldg 35, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov FU Intramural NIH HHS NR 42 TC 29 Z9 29 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2007 VL 17 IS 3 BP 366 EP 373 DI 10.1016/j.conb.2007.04.008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 186JP UT WOS:000247775300014 PM 17493799 ER PT J AU Schmid, I Lambert, C Ambrozak, D Marti, GE Moss, DM Perfetto, SP AF Schmid, Ingrid Lambert, Claude Ambrozak, David Marti, Gerald E. Moss, Delynn M. Perfetto, Stephen P. TI International society for analytical cytology biosafety standard for sorting of unfixed cells SO CYTOMETRY PART A LA English DT Article DE flow cytometry; occupational health; bio-hazards; cell sorting; biosafety; aerosol containment ID HUMAN-IMMUNODEFICIENCY-VIRUS; FLOW-CYTOMETRY; POSTEXPOSURE PROPHYLAXIS; HEALTH-CARE; INFECTIONS; AEROSOL; CANCER; INACTIVATION; EXPOSURES; SURVIVAL AB Background: Cell sorting of viable biological specimens has become very prevalent in laboratories involved in basic and clinical research. As these samples can contain infectious agents, precautions to protect instrument operators and the environment from hazards arising from the use of sorters are paramount. To this end the International Society of Analytical Cytology (ISAC) took a lead in establishing biosafety guidelines for sorting of unfixed cells (Schmid et al., Cytometry 1997;28:99-117). During the time period these recommendations have been available, they have become recognized worldwide as the standard practices and safety precautions for laboratories performing viable cell sorting experiments. However, the field of cytometry has progressed since 1997, and the document requires an update. Methods: Initially, suggestions about the document format and content were discussed among members of the ISAC Biosafety Committee and were incorporated into a draft version that was sent to all committee members for review. Comments were collected, carefully considered, and incorporated as appropriate into a draft document that was posted on the ISAC web site to invite comments from the flow cytometry community at large. The revised document was then submitted to ISAC Council for review. Simultaneously, further comments were sought from newly-appointed ISAC Biosafety committee members. Results: This safety standard for performing viable cell sorting experiments was recently generated. The document contains background information on the biohazard potential of sorting and the hazard classification of infectious agents as well as recommendations on (1) sample handling, (2) operator training and personal protection, (3) laboratory design, (4) cell sorter set-up, maintenance, and decontamination, and (5) testing the instrument for the efficiency of aerosol containment. Conclusions: This standard constitutes an updated and expanded revision of the 1997 biosafety guideline document. It is intended to provide laboratories involved in cell sorting with safety practices that take into account the enhanced hazard potential of high-speed sorting. Most importantly; it states that droplet-based sorting of infectious or hazardous biological material requires a higher level of containment than the one recommended for the risk group classification of the pathogen. The document also provides information on safety features of novel instrumentation, new options for personal protective equipment, and recently developed methods for testing the efficiency of aerosol containment. Published 2007 Wdey-Liss, Inc(dagger). C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Hematol Oncol, Los Angeles, CA 90095 USA. Univ Hosp St Etienne, Immunol Lab, St Etienne, France. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, CBER FDA, Lab Med & Mol Genet, Flow & Image Cytometry Sect,Div Cell & Gene Thera, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Schmid, I (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Hematol Oncol, 12-236 Factor Bldg, Los Angeles, CA 90095 USA. EM schmid@mednet.ucla.edu FU NCI NIH HHS [CA-16042]; NIAID NIH HHS [AI-28697] NR 60 TC 26 Z9 27 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2007 VL 71A IS 6 BP 414 EP 437 DI 10.1002/cyto.a.20390 PG 24 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 171EQ UT WOS:000246718100010 PM 17385740 ER PT J AU Yamaguchi, TP Lewandoski, M Biris, KK Dunty, WC AF Yamaguchi, Terry P. Lewandoski, M. Biris, K. K. Dunty, W. C., Jr. TI Wnt3A/bcatenin signaling spatially positions segment boundaries by specifying presomitic mesoderm fates and posteriorly repressing boundary formation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, CDBL, NIH, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 6 BP 287 EP 288 DI 10.1016/j.ydbio.2007.03.047 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500026 ER PT J AU Zhu, JJ Nguyen, MT Nakamura, E AF Zhu, Jianjian Nguyen, Minh-Thanh Nakamura, Eiichiro TI Sonic Hedgehog control of pattern and growth can be uncoupled in the developing limb SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 28 BP 296 EP 296 DI 10.1016/j.ydbio.2007.03.072 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500048 ER PT J AU Weinstein, BM AF Weinstein, Brant M. TI Morphogenesis and patterning of the developing vasculature SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 31 BP 298 EP 298 DI 10.1016/j.ydbio.2007.03.076 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500051 ER PT J AU Rand, K Itoh, M Palardy, G Matsuda, M Yeo, SY Goswami, M Chitnis AF Rand, Kinneret Itoh, Motoyuki Palardy, Greg Matsuda, Miho Yeo, Sang-Yeob Goswami, Moloy Chitnis TI Cis-inhibition of Notch signaling in para-boundary cells in the zebrafish hindbrain SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NICHD, LMG, NIH, Bethesda, MD USA. Nagoya Univ, Grad Sch Sci, Nagoya, Aichi, Japan. Kyungpook Natl Univ, Coll Nat Sci, Taegu 702701, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 36 BP 301 EP 301 DI 10.1016/j.ydbio.2007.03.083 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500056 ER PT J AU Varela-Echavarria, A Houang, KM Tamariz, E Westphal, H Zhao, YN AF Varela-Echavarria, Alftedo Houang, Kimmi Tamariz, Elisa Westphal, Heiner Zhao, Yangu TI LIM homeodomain factor Lhx5 is required for normal development and migration of Cajal-Retzius cells SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Univ Nacl Autonoma Mexico, Inst Neurobiol, Queretaro 76230, Mexico. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 42 BP 303 EP 303 DI 10.1016/j.ydbio.2007.03.089 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500062 ER PT J AU Ueda, Y Lewandoski, M Plisov, S Wilson, C Sharma, N Elder, C Perantoni AF Ueda, Yutaka Lewandoski, M. Plisov, S. Wilson, C. Sharma, N. Elder, C. Perantoni TI Fgf8 is essential for development of the male reproductive tract SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 51 BP 306 EP 307 DI 10.1016/j.ydbio.2007.03.099 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500071 ER PT J AU Kelley, MW Montcouquiol, M Woods, C Jones, JE Jacques, BE Puligilla, C Dabdoub Driver, EC AF Kelley, Matthew W. Montcouquiol, Mireille Woods, Chad Jones, Jennifer E. Jacques, Bonnie E. Puligilla, Chandrakala Dabdoub Driver, Elizabeth C. TI Regulation of cell fate and patterning in the mammalian cochlea SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD USA. OI montcouquiol, mireille/0000-0001-8739-6519 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 65 BP 315 EP 316 DI 10.1016/j.ydbio.2007.03.119 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500085 ER PT J AU Lewandoski, M Yamaguchi, TP Duester, G Holder, N AF Lewandoski, Mark Yamaguchi, Terry P. Duester, Gregg Holder, Nakisha TI Genetic analysis of FGF signaling in axis extension and somitogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, NIH, Canc & Dev Biol Lab, Frederick, MD 21701 USA. Burnham Inst Med Res, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 109 BP 334 EP 334 DI 10.1016/j.ydbio.2007.03.167 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500129 ER PT J AU Matsuda, M Chitnis, A AF Matsuda, Miho Chitnis, Ajay TI Subcellular distribution of endogenous Delta protein in the zebrafish embryo reveals a potential role for Notch in determining Delta endocytosis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NICHD, NIH, Mol Genet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 117 BP 336 EP 337 DI 10.1016/j.ydbio.2007.03.175 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500137 ER PT J AU Underwood, S Mishina, Y Griesharnmer, U Martin, G Williams, T Lewamdoski, M AF Underwood, Sangeeta Mishina, Yuji Griesharnmer, Uta Martin, Gail Williams, Trevor Lewamdoski, Mark TI Genetic analysis of BMP-mediated cell survival in the limb bud mesenchyme SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, NIH, Canc & Dev Biol Lab, Frederick, MD 21701 USA. NIEHS, NIH, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Dept Anat, Program Dev Biol, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 132 BP 342 EP 342 DI 10.1016/j.ydbio.2007.03.191 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500151 ER PT J AU Westphal, H Tzchori, I Day, TF Carolan, PJ Zhao, Y Wassif, CA Lewandoski, M Gorivodsky, M AF Westphal, Heiner Tzchori, Itai Day, Timothy F. Carolan, Peter J. Zhao, Yangu Wassif, Christopher A. Lewandoski, M. Gorivodsky, Marat TI Ldb1, in conjunction with transcriptional regulators of the L1M-homeobox gene family, orchestrates limb patterning and outgrowth during mouse embryonic development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NICHD, LMGD, HHS, NIH, Bethesda, MD USA. NIGRI, GDRB, HHS, NIH, Bethesda, MD USA. NICHD, UMD, HDB, HHS,NIH, Bethesda, MD USA. NCI, LCDB, HHS, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 177 BP 357 EP 358 DI 10.1016/j.ydbio.2007.03.238 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500196 ER PT J AU Hsu, SN Yonekura, S Ting, CY Robertson, HM Lee, CH Chiba, A AF Hsu, Shu-Ning Yonekura, Shinichi Ting, Chun-Yuan Robertson, Hugh M. Lee, Chi-Hon Chiba, Akira TI Alternative splicing expands spatiotemporal expression complexity of arthropod N-Cadherin SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA. NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 235 BP 376 EP 376 DI 10.1016/j.ydbio.2007.03.551 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500251 ER PT J AU Sanchez, R Stewart, CL Escalante-Alcalde, D AF Sanchez, Roberto Stewart, Colin L. Escalante-Alcalde, Diana TI The role of LPP3 deficiency in neural development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. NCI, Ctr Canc Res, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 248 BP 381 EP 381 DI 10.1016/j.ydbio.2007.03.557 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500264 ER PT J AU Ogawa, K Shimosato, D Takahashi, K Yagi, R Toyooka, Y Masui, S Matoba, R Ko, MS AF Ogawa, Kazuya Shimosato, Daisuke Takahashi, Kadue Yagi, Rika Toyooka, Yayoi Masui, Shinji Matoba, R. Ko, Minoru S. TI Forced expression of Tbx3 promotes LIF-independent self-renewal of mouse ES cells SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP Soc Dev Biol, Soc Mexicana Biol Desarrollo, Latin Amer Soc Dev Biol C1 Riken Ctr Dev Biol, Lab Pluripotent Cell Studies, Kobe, Hyogo, Japan. NIA, NIH, Genet Lab, Dev Genom & Aging Sect, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 3 TC 2 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 275 BP 391 EP 392 DI 10.1016/j.ydbio.2007.03.575 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500291 ER PT J AU Holder, ND Wilson, C Elder, C Yamaguchi, TP Duester, G Lewandoski, M AF Holder, Nakisha D. Wilson, Catherine Elder, Cindy Yamaguchi, Terry P. Duester, Gregg Lewandoski, Mark TI Fgf4 and Fgf8 are required for maintenance of the primitive streak and somitic clock SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, NIH, Canc & Dev Biol Lab, Frederick, MD 21701 USA. Burnham Inst Med Res, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 301 BP 401 EP 401 DI 10.1016/j.ydbio.2007.03.602 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500317 ER PT J AU Tam, PP Lewis, SL Khoo, PL De Young, RA Westphal, H AF Tam, Patrick P. Lewis, Samara L. Khoo, Poh-Lynn De Young, R. Andrea Westphal, Heiner TI Dkk1 and Wnt3 interaction is critical for head morphogenesis in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NICHHD, NIH, Genet Mammalian Genes & Dev, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 302 BP 401 EP 401 DI 10.1016/j.ydbio.2007.03.603 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500318 ER PT J AU Feldman, B Brown, JL Noushmehr, H Kirby, M Elkahloun, AG AF Feldman, Benjamin Brown, Jamie L. Noushmehr, Houtan Kirby, Martha Elkahloun, Abdel G. TI FACS-assisted microdissection of early zebrafish embryos for transcriptional profiling and cell behavioral studies SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NIH, NHGRI, Bethesda, MD 20892 USA. RI Noushmehr, Houtan/C-9692-2013 OI Noushmehr, Houtan/0000-0003-4051-8114 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 330 BP 410 EP 410 DI 10.1016/j.ydbio.2007.03.631 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500345 ER PT J AU Perantom, A Wang, H Shanna, N AF Perantom, Alan Wang, Honghe Shanna, Nirmala TI beta-Catenin and MAPK/ERK signaling are both required for mesenchymal-epithelial transition (MET) in nephron formation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NCI, LCC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 372 BP 413 EP 414 DI 10.1016/j.ydbio.2007.03.284 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500354 ER PT J AU Cervantes, S Yamaguchi, TP Hebrok, M AF Cervantes, Sara Yamaguchi, Terry P. Hebrok, Matthias TI A non-canonical Wnt pathway mediated by Wnt5a is required for midgut elongation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 Univ Calif San Francisco, Ctr Diabet, Dept Med, San Francisco, CA 94143 USA. NCI, Ctr Canc Res, Canc & Dev Biol Lab, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 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 JUN 1 PY 2007 VL 306 IS 1 MA 359 BP 419 EP 420 DI 10.1016/j.ydbio.2007.03.651 PG 2 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500372 ER PT J AU Snir, M Feldman, B AF Snir, Mirit Feldman, Benjamin TI A putative role for dual specificity phosphatase 4 in endoderm development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 66th SDB Annual Meeting/8th SMBD Annual Meeting/3rd LASDB International Meeting CY JUN 16-20, 2007 CL Cancun, MEXICO SP SDB, SMBD, LASDB C1 NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 2007 VL 306 IS 1 MA 399 BP 433 EP 433 DI 10.1016/j.ydbio.2007.03.469 PG 1 WC Developmental Biology SC Developmental Biology GA 176YJ UT WOS:000247120500411 ER PT J AU Prag, G Watson, H Kim, YC Beach, BM Ghirlando, R Hummer, G Bonifacino, JS Hurley, JH AF Prag, Gali Watson, Hadiya Kim, Young C. Beach, Bridgette M. Ghirlando, Rodolfo Hummer, Gerhard Bonifacino, Juan S. Hurley, James H. TI The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent sorting SO DEVELOPMENTAL CELL LA English DT Article ID RECEPTOR DOWN-REGULATION; YEAST SACCHAROMYCES-CEREVISIAE; SRC HOMOLOGY-3 DOMAIN; CRYSTAL-STRUCTURE; BINDING DOMAINS; EARLY ENDOSOMES; GGA PROTEINS; MULTIVESICULAR ENDOSOMES; MEMBRANE-TRAFFICKING; MOLECULAR-MECHANISM AB The yeast Vps27/Hse1 complex and the homologous mammalian Hrs/STAM complex deliver ubiquitinated transmembrane proteins to the ESCRT endosomal-sorting pathway. The Vps27/Hse1 complex directly binds to ubiquitinated transmembrane proteins and recruits both ubiquitin ligases and deubiquitinating enzymes ' We have solved the crystal structure of the core responsible for the assembly of the Vps27/Hse1 complex at 3.0 angstrom resolution. The structure consists of two intertwined GAT domains, each consisting of two helices from one subunit and one from the other. The two GAT domains are connected by an antiparallel coiled coil, forming a 90 angstrom-long barbell-like structure. This structure places the domains of Vps27 and Hsel that recruit ubiquitinated cargo and deubiquitinating enzymes close to each other. Coarse-grained Monte Carlo simulations of the Vps27/Hse1 complex on a membrane show how the complex binds cooperatively to lipids and ubiquitinated membrane proteins and acts as a scaffold for ubiquitination reactions. C1 NIH, US Dept Hlth & Human Serv, Mol Biol Lab, NIDDKD, Bethesda, MD 20892 USA. NIH, US Dept Hlth & Human Serv, Phys Chem Lab, NIDDKD, Bethesda, MD 20892 USA. NIH, US Dept Hlth & Human Serv, Cell Biol & Metab Branch, NICHHD, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIH, US Dept Hlth & Human Serv, Mol Biol Lab, NIDDKD, Bethesda, MD 20892 USA. EM jh8e@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Hummer, Gerhard/A-2546-2013; OI Hummer, Gerhard/0000-0001-7768-746X; Bonifacino, Juan S./0000-0002-5673-6370 FU Intramural NIH HHS [Z01 DK036118-14, Z01 DK036126-01] NR 77 TC 46 Z9 49 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2007 VL 12 IS 6 BP 973 EP 986 DI 10.1016/j.devcel.2007.04.013 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 176YB UT WOS:000247119700016 PM 17543868 ER PT J AU Miura, S Mishina, Y AF Miura, Shigeto Mishina, Yuji TI The DVE changes distal epiblast fate from definitive endoderm to neurectoderm by antagonizing nodal signaling SO DEVELOPMENTAL DYNAMICS LA English DT Article DE DVE; AVE; ablation; embryo culture; distal epiblast; neuroectoderm; definitive endoderm ID ANTERIOR VISCERAL ENDODERM; WHOLE-EMBRYO CULTURE; MOUSE EMBRYO; PRIMITIVE ENDODERM; MAMMALIAN EMBRYO; EXTRAEMBRYONIC ECTODERM; TRANSCRIPTION FACTOR; AXIS FORMATION; NEURAL PLATE; STEM-CELLS AB To assess the function of the distal visceral endoderm (DVE) of embryonic day 5.5 (E5.5) embryos, we established a system to directly ablate the DVE and observe the consequences after culture. When the DVE was successfully ablated, such embryos (DVE-ablated embryos) showed deregulated expression of Nodal and Wnt3 and ectopically formed the primitive streak at the proximal portion of the embryo. The DVE and anterior visceral endoderm (AVE) are implicated in the development of neurectoderm. We found that the distal epiblast of E5.5 embryo rotates anteriorly by the beginning of gastrulation. These cells remained to be anteriorly located during gastrulation and contributed to the ectoderm in the anterior side of the embryo. This indicates that the distal epiblast of E5.5 embryo becomes neurectoderm in normal development. In DVE-ablated embryos, the distal epiblast did not show any movement during culture and was abnormally fated to early definitive endoderm lineage. The data suggest that down-regulation of Nodal signaling in the distal epiblast of E5.5 embryo may be an initial step of neural development. C1 Natl Inst Environm Hlth Sci, Mol Dev Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA. RP Miura, S (reprint author), Stowers Inst, 1000 E 50th St, Kansas City, MO 64110 USA. EM shi@stowers-institute.org FU Intramural NIH HHS NR 45 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2007 VL 236 IS 6 BP 1602 EP 1610 DI 10.1002/dvdy.21166 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 178MK UT WOS:000247224600022 PM 17471538 ER PT J AU Jia, M Li, MX Fields, RD Nelson, PG AF Jia, Min Li, Min-Xu Fields, R. Douglas Nelson, Phillip G. TI Extracellular ATP in activity-dependent remodeling of the neuromuscular junction SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE synapse elimination; ATP; purinergic signaling; activity-dependent plasticity; neuromuscular junction; development ID ACETYLCHOLINE-RECEPTORS; SKELETAL-MUSCLE; PROTEIN-KINASES; SCHWANN-CELLS; IN-VITRO; SYNAPSE; REINNERVATION; TRANSMISSION; ELIMINATION; MODULATION AB Electrical activity during early development affects the development and maintenance of synapses (Spitzer [2006]: Nature 4447:707-712), but the intercellular signals regulating maintenance of synapses are not well identified. At the neuromuscular junction, adenosine 5-triphosphate (ATP) is coreleased with acetylcholine at activated nerve terminals to modulate synaptic function. Here we use cocultured mouse motor neurons and muscle cells in a three-compartment cell culture chamber to test whether endogenously released ATP plays a role in activity-dependent maintenance of neuromuscular synapses. The results suggest that ATP release at the synapse counters the negative effect of electrical activity, thus stabilizing activated synapses. Confirming our previous work (Li et al. [2001]: Nat Neurosci 4:871-872), we found that in doubly innervated muscles, electrical stimulation induced heterosynaptic downregulation of the nonstimulated convergent input to the muscle fiber with no or little change of the stimulated inputs. However, in preparations that were stimulated in the presence of apyrase, an enzyme that degrades extracellular ATP, synapse downregulation of stimulated inputs was substantial and significant, and end plate potentials were reduced. Apyrase treatment for 20 h in the absence of stimulation did result in moderate diminution, but this was prevented by blocking spontaneous neural activity with tetrodotoxin. The P2 receptor blocker, suramin, also induced activity-dependent synapse diminution. The decrease in synaptic efficacy produced by prolonged stimulation in the presence of apyrase persisted for greater than 20 h, consistent with a developmental time-course and distinct from the rapid neuromodulatory actions of ATP that have been demonstrated by others. We conclude that extracellular ATP promotes stabilization of the neuromuscular junction and may play a role in activity-dependent synaptic modification during development. (c) 2007 Wiley Periodicals, Inc. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Nelson, PG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM nelsonp@mail.nih.gov NR 27 TC 4 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD JUN PY 2007 VL 67 IS 7 BP 924 EP 932 DI 10.1002/dneu.20402 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 183YW UT WOS:000247609300007 PM 17506503 ER PT J AU Sainz, E Cavenagh, MM LopezJimenez, ND Gutierrez, JC Battey, JF Northup, JK Sullivan, SL AF Sainz, Eduardo Cavenagh, Margaret M. LopezJimenez, Nelson D. Gutierrez, Joanne C. Battey, James F. Northup, John K. Sullivan, Susan L. TI The G-protein coupling properties of the human sweet and amino acid taste receptors SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE taste receptor; sweet; umami; signal transduction; G-proteins ID GTP-BINDING PROTEIN; UMAMI TASTE; ALPHA-GUSTDUCIN; TRANSMEMBRANE DOMAIN; SIGNALING PATHWAYS; PEPTIDE RECEPTOR; GLUTAMATE TASTE; MAMMALIAN SWEET; BITTER TASTE; TSH RECEPTOR AB The human T1R taste receptors are family C G-protein-coupled receptors (GPCRs) that act as heterodimers to mediate sweet (hT1R2 + hT1R3) and uniami (hT1R1 + hT1R3) taste modalities. Each T1R has a large extracellular ligand-binding domain linked to a seven transmembrane-spanning core domain (7TMD). We demonstrate that the 7TMDs of hT1R1 and hT1R2 display robust ligand-independent constitutive activity, efficiently catalyzing the exchange of GDP for GTP on G alpha subunits. In contrast, relative to the 7TMDs of hT1R1 and hT1R2, the 7TMD of hT1R3 couples poorly to G-proteins, suggesting that in vivo signaling may proceed primarily through hT1R1 and hT1R2. In addition, we provide direct evidence that the hT1Rs selectively signal through G alpha(i/o) pathways, coupling to multiple G alpha(i/o) subunits as well as the taste cell specific G beta(1 gamma 13) dimer. (c) 2007 Wiley Periodicals, Inc. C1 Natl Inst Deafness & Other Commun Disorders, Sect Mol Neurosci, NIH, Rockville, MD 20850 USA. NINDS, Sect G Protein Coupled Receptors, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Sect Signal Transduct, NIH, Rockville, MD 20850 USA. RP Sullivan, SL (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Mol Neurosci, NIH, 5 Res Court, Rockville, MD 20850 USA. EM sullivas@nided.nih.gov FU NIDCD NIH HHS [Z01 DC000034-08, Z01 DC000047-08, Z01 DC003004-02] NR 56 TC 15 Z9 17 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8451 EI 1932-846X J9 DEV NEUROBIOL JI Dev. Neurobiol. PD JUN PY 2007 VL 67 IS 7 BP 948 EP 959 DI 10.1002/dneu.20403 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 183YW UT WOS:000247609300009 PM 17506496 ER PT J AU Iyengar, SK Abboud, HE Goddard, KAB Saad, MF Adler, SG Arar, NH Bowden, DW Duggirala, R Elston, RC Hanson, RL Ipp, E Kao, WHL Kimmel, PL Klag, MJ Knowler, WC Meoni, LA Nelson, RG Nicholas, SB Pahl, MV Parekh, RS Quade, SRE Rich, SS Rotter, JI Scavini, M Schelling, JR Sedor, JR Sehgal, AR Shah, VO Smith, MW Taylor, KD Winkler, CA Zager, PG Freedman, BI AF Iyengar, Sudha K. Abboud, Hanna E. Goddard, Katrina A. B. Saad, Mohammed F. Adler, Sharon G. Arar, Nedal H. Bowden, Donald W. Duggirala, Ravi Elston, Robert C. Hanson, Robert L. Ipp, Eli Kao, W. H. Linda Kimmel, Paul L. Klag, Michael J. Knowler, William C. Meoni, Lucy A. Nelson, Robert G. Nicholas, Susanne B. Pahl, Madeleine V. Parekh, Rulan S. Quade, Shannon R. E. Rich, Stephen S. Rotter, Jerome I. Scavini, Marina Schelling, Jeffrey R. Sedor, John R. Sehgal, Ashwini R. Shah, Vallabh O. Smith, Michael W. Taylor, Kent D. Winkler, Cheryl A. Zager, Philip G. Freedman, Barry I. CA Family Invest Nephropathy TI Genome-wide scans for diabetic nephropathy and albuntinuria in multiethnic populations - The family investigation of nephropathy and diabetes (FIND) SO DIABETES LA English DT Article ID STAGE RENAL-DISEASE; CARNOSINASE GENE CNDP1; SUSCEPTIBILITY GENES; COMPLICATIONS TRIAL; AFRICAN-AMERICANS; VASCULAR-DISEASE; LINKAGE ANALYSIS; CANDIDATE GENES; LEUCINE REPEAT; PROTEINURIA AB The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, FIND Genet Anal & Data Coordinating Ctr, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIDDK, Phoenix, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. NIDDK, Program Off, Bethesda, MD USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, FIND Genet Anal & Data Coordinating Ctr, Wolstein Res Bldg,Room 1315,10900 Euclid Ave, Cleveland, OH 44106 USA. EM ski@case.edu RI Nelson, Robert/B-1470-2012; Smith, Michael/B-5341-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS; NCRR NIH HHS [M01-RR-000080, M01-RR-00425, M01-RR-00827-29, M01-RR-00997, M01-RR-01346, M01-RR-07122, RR03655]; NHGRI NIH HHS [N01-HG-65403]; NIDDK NIH HHS [U01DK57292-05] NR 33 TC 96 Z9 106 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1577 EP 1585 DI 10.2337/db06-1154 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000011 PM 17363742 ER PT J AU Fujimoto, WY Jablonski, KA Bray, GA Kriska, A Barrett-Connor, E Haffner, S Hanson, R Hill, JO Hubbard, V Stamm, E Pi-Sunyer, FX AF Fujimoto, Wilfred Y. Jablonski, Kathleen A. Bray, George A. Kriska, Andrea Barrett-Connor, Elizabeth Haffner, Steven Hanson, Robert Hill, James O. Hubbard, Van Stamm, E. Pi-Sunyer, F. Xavier CA Diabet Prevention Program Res Grp TI Body size and shape changes and the risk of diabetes in the diabetes prevention program SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; VISCERAL ADIPOSE-TISSUE; LIFE-STYLE INTERVENTION; FAT DISTRIBUTION; INSULIN SENSITIVITY; JAPANESE-AMERICANS; ABDOMINAL FAT; METABOLIC COMPLICATIONS; INTRAABDOMINAL FAT; WEIGHT-LOSS AB The researchers conducted this study to test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity. The Diabetes Prevention Program (DPP) recruited and randomized individuals with impaired glucose tolerance to treatment with placebo, metformin, or lifestyle modification. Height, weight, waist circumference, and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography were measured at baseline and at I year. Cox proportional hazards models assessed by sex the effect of change in these variables over the 1st year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants. Lifestyle reduced visceral fat at L2-L3 (men -24.3%, women -18.2%) and at L4-L5 (men -22.4%, women -17.8%), subcutaneous fat at L2-L3 (men -15.7%, women -11.4%) and at L4-L5 (men -16.7%, women -11.9%), weight (men -8.2%, women -7.8%), BMI (men -8.2%, women -7.8%), and waist circumference (men -7.5%, women -6.1%). Metformin reduced weight (-2.9%) and BMI (-2.9%) in men and subcutaneous fat (-3.6% at L2-L3 and -4.7% at L4-L5), weight (-3.3%), BMI (-3.3%), and waist circumference (-2.8%) in women. Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight, BMI, and central body fat distribution after adjustment for age and self-reported ethnicity. Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78285 USA. NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85016 USA. Univ Colorado, Sch Med, Ctr Human Nutr, Denver, CO 80202 USA. NIDDKD, Div Nutr Res, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80202 USA. St Lukes Roosevelt Hosp, Dept Med, New York, NY 10025 USA. RP Fujimoto, WY (reprint author), George Washington Univ, Ctr Biostat, 611 Execut Blvd,Suite 750,DPPOS, Rockville, MD 20852 USA. EM wilfuji@u.washington.edu RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Kriska, Andrea/0000-0002-3522-0869 FU NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 33 TC 55 Z9 56 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1680 EP 1685 DI 10.2337/db07-0009 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000024 PM 17363740 ER PT J AU Semple, RK Halberg, NH Burling, K Soos, MA Schraw, T Luan, JA Cochran, EK Dunger, DB Wareham, NJ Scherer, PE Gorden, P O'Rahilly, S AF Semple, Robert K. Halberg, Nils H. Burling, Keith Soos, Maria A. Schraw, Todd Luan, Jian'an Cochran, Elaine K. Dunger, David B. Wareham, Nicholas J. Scherer, Philipp E. Gorden, Phillip O'Rahilly, Stephen TI Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodies SO DIABETES LA English DT Article ID 3T3-L1 ADIPOCYTES; PLASMA ADIPONECTIN; OXIDATIVE STRESS; ADIPOSE-TISSUE; OBESITY; ACRP30; SECRETION; PATHWAY; HUMANS AB Total plasma adiponectin and high-molecular weight (HMW) polymeric adiponectin are strongly positively correlated with insulin sensitivity. However, we have recently reported paradoxical hyperadiponectinemia in patients with severe insulin resistance due to genetically defective insulin receptors. This implies either that the insulin receptor has a critical physiological role in controlling adiponectin production and/or clearance or that constitutive insulin receptor dysfunction influences adiponectin levels through developmental effects. The aim of the current study was to distinguish between these possibilities using a human model of reversible antibody-mediated insulin receptor dysfunction and to refine the previous observations by determining adiponectin complex distribution. Cross-sectional and longitudinal determination of fasting plasma adiponectin and adiponectin complex distribution was undertaken in patients with extreme insulin resistance due to insulin receptor mutations, anti-insulin receptor antibodies (type B insulin resistance), or an undefined cause. Despite extreme insulin resistance, patients with type B insulin resistance (all women; mean age 42 years [range 12-54]) had dramatically elevated total plasma adiponectin compared with the general population (mean 43.0 mg/l [range 31.3-54.2] vs. 8.9 mg/l [1.5-28.5 for BMI < 25 kg/m(2)]), which was accounted for largely by HMW polymers. Hyperadiponectinemia resolved in parallel with reduction of insulin receptor antibodies and clinical resolution of insulin resistance. Although the well-established inverse relationship between plasma insulin and adiponectin levels may, in part, reflect positive effects of adiponectin on insulin sensitivity, these data suggest that the magnitude of the effect of insulin action on adiponectin levels may have been underestimated. C1 Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QR, England. Albert Einstein Coll Med, Dept Cell Biol, Div Endocrinol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10467 USA. Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge CB2 2QQ, England. NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. Univ Cambridge, Elsie Widdowson Lab, MRC, Epidemiol Unit,Inst Publ Hlth, Cambridge, England. RP Semple, RK (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QR, England. EM rks16@cam.ac.uk OI Halberg, Nils/0000-0002-2943-3147; Dunger, Professor David/0000-0002-2566-9304; Semple, Robert/0000-0001-6539-3069 FU Medical Research Council [MC_U106179471]; Wellcome Trust [078986, , 080952] NR 24 TC 59 Z9 62 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1712 EP 1717 DI 10.2337/db06-1665 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000028 PM 17325257 ER PT J AU Ingelsson, E Sullivan, LM Murabito, JM Fox, CS Benjamin, EJ Polak, JF Meigs, JB Keyes, MJ O'Donnell, CJ Wang, TJ D'Agostino, RB Wolf, PA Vasan, RS AF Ingelsson, Erik Sullivan, Lisa M. Murabito, Joanne M. Fox, Caroline S. Benjamin, Emelia J. Polak, Joseph F. Meigs, James B. Keyes, Michelle J. O'Donnell, Christopher J. Wang, Thomas J. D'Agostino, Ralph B., Sr. Wolf, Philip A. Vasan, Ramachandran S. TI Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metabolism, Natl Heart, Lung & Blood Inst ID CORONARY-HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; RISK-FACTORS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; MEDIA THICKNESS; OLDER-ADULTS; ASSOCIATION; DIAGNOSIS; STROKE AB Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and uriary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than individuals without MetS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67-2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12-2.33]). Participants with MetS and subclinical. disease experienced increased risk of overt CVD (2.67 [1.62-4.41] compared with those without MetS, diabetes, or subclinical diseease), whereas the association of MetS with CVD risk was tenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87-2.90]). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition. C1 Natl Heart Lund & Blood Inst Framingham Study, Framingham, MA USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), FACC, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195, 1R01HL080124, 2K24HL04334] NR 43 TC 54 Z9 56 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2007 VL 56 IS 6 BP 1718 EP 1726 DI 10.2337/db07-0078 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 174GK UT WOS:000246930000029 PM 17369522 ER PT J AU Park, SW Goodpaster, BH Strotmeyer, ES Kuller, LH Broudeau, R Kammerer, C de Rekeneire, N Harris, TB Schwartz, AV Tylavsky, FA Cho, YW Newman, AB AF Park, Seok Won Goodpaster, Bret H. Strotmeyer, Elsa S. Kuller, Lewis H. Broudeau, Robert Kammerer, Candace de Rekeneire, Nathalie Harris, Tamara B. Schwartz, Ann V. Tylavsky, Frances A. Cho, Yong-wook Newman, Anne B. CA Hlth Aging Body Composition Study TI Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes - The Health, Aging, and Body Composition Study SO DIABETES CARE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc ID MASS; DISABILITY; QUALITY; PREVALENCE; NEUROPATHY; POLYNEUROPATHY; INDIVIDUALS; ASSOCIATION; PERFORMANCE; LIMITATIONS AB Objective - It has been shown that adults with either long-standing type I or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies, The aim of the study was to investigate longitudinal changes of muscle mass and strength in community-dwelling older adults with and without type 2 diabetes. Research Design and Methods - We examined leg and arm muscle mass and strength at baseline and 3 years later in 1,840 older adults aged 70-79 years in the Health, Aging, and Body Composition Study. Regional muscle mass was measured by dual energy X-ray absorptiometry, and muscle strength was measured using isokinetic and isometric dynamometers. Results - Older adults with type 2 diabetes (n = 305) showed greater declines in the leg muscle mass (-0.29 +/- 0.03 vs. -0,23 +/- 0.01 kg, P < 0.05) and strength (-16.5 +/- 1.2 vs. - 12.4 +/- 0.5 Nm, P = 0.001) compared with older adults without diabetes. Leg muscle quality, expressed as maximal strength per unit of muscle mass (Newton meters per kilogram), also declined more rapidly in older adults with diabetes (-1.6 +/- 0.2 vs. -1.2 +/- 0.1 Nm/kg, P < 0.05). Changes in arm muscle strength and quality were not different between those with and without diabetes. Rapid declines in leg muscle strength and quality were attenuated but remained significant after controlling for demographics, body composition, physical activity, combined chronic diseases, interleukin-6, and tumor necrosis factor-alpha. Conclusions - In older adults, type 2 diabetes is associated with accelerated loss of leg muscle strength and quality. C1 Pochon CHA Univ, Dept Internal Med, Pochon, South Korea. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Park, SW (reprint author), Pochon CHA Univ, Dept Internal Med, 351 Yatap Dong, Songnam 463712, South Korea. EM spark@cha.ac.kr RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 35 TC 179 Z9 180 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2007 VL 30 IS 6 BP 1507 EP 1512 DI 10.2337/dc06-2537 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175ES UT WOS:000246996400028 PM 17363749 ER PT J AU Koh, KK Quon, MJ Lee, SJ Han, SH Ahn, JY Kim, JA Chung, WJ Lee, Y Shin, EK AF Koh, Kwang Kon Quon, Michael J. Lee, Sang Jin Han, Seung Hwan Ahn, Jeong Yeal Kim, Jeong-A Chung, Wook-Jin Lee, Yonghee Shin, Eak Kyun TI Efonidipine simultaneously improves blood pressure, endothelial function, and metabolic parameters in nondiabetic patients with hypertension SO DIABETES CARE LA English DT Article ID THERAPEUTIC INTERVENTIONS; CARDIOVASCULAR-DISEASE; T-TYPE; ADIPONECTIN; CANDESARTAN; MECHANISMS; BLOCKER C1 Gachon Med Sch, Gil Heart Ctr, Dept Cardiol, Inchon 405760, South Korea. NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Gachon Med Sch, Lab Med, Dept Cardiol, Inchon 405760, South Korea. Ewha Womans Univ, Dept Stat, Seoul 120750, South Korea. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Dept Cardiol, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Chung, Wook-Jin/0000-0002-9767-7098; Quon , Michael /0000-0002-5289-3707 NR 19 TC 25 Z9 25 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2007 VL 30 IS 6 BP 1605 EP 1607 DI 10.2337/dc06-2267 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175ES UT WOS:000246996400051 PM 17351278 ER PT J AU Shim, JH Kim, SE Woo, DH Kim, SK Oh, CH McKay, R Kim, JH AF Shim, J. H. Kim, S. E. Woo, D. H. Kim, S. K. Oh, C. H. McKay, R. Kim, J. H. TI Directed differentiation of human embryonic stem cells towards a pancreatic cell fate SO DIABETOLOGIA LA English DT Article DE activin; differentiation; embryoid bodies; endoderm; human embryonic stem cells; hyperglycaemia; PDX1; retinoic acid; serum ID IN-VITRO DIFFERENTIATION; INSULIN-PRODUCING CELLS; RETINOIC ACID; DEFINITIVE ENDODERM; BETA-CELLS; NESTIN EXPRESSION; MOUSE PANCREAS; GENE; TRANSCRIPTION; PRECURSORS AB Aims/hypothesis The relative lack of successful pancreatic differentiation of human embryonic stem cells (hESCs) may suggest that directed differentiation of hESCs into definitive endoderm and subsequent commitment towards a pancreatic fate are not readily achieved. The aim of this study was to investigate whether sequential exposure of hESCs to epigenetic signals that mimic in vivo pancreatic development can efficiently generate pancreatic endodermal cells, and whether these cells can be further matured and reverse hyperglycaemia upon transplantation. Materials and methods The hESCs were sequentially treated with serum, activin and retinoic acid (RA) during embryoid body formation. The patterns of gene expression and protein production associated with embryonic germ layers and pancreatic endoderm were analysed by RT-PCR and immunostaining. The developmental competence and function of hESC-derived PDX1-positive cells were evaluated after in vivo transplantation. Results Sequential treatment with serum, activin and RA highly upregulated the expression of the genes encoding forkhead box protein A2 (FOXA2), SRY-box containing gene 17 (SOX17), pancreatic and duodenal homeobox 1 (PDX1) and homeobox HB9 (HLXB9). The population of pancreatic endodermal cells that produced PDX1 was significantly increased at the expense of ectodermal differentiation, and a subset of the PDX1-positive cells also produced FOXA2, caudal-type homeobox transcription factor 2 (CDX2), and nestin (NES). After transplantation, the PDX1-positive cells further differentiated into mature cell types producing insulin and glucagon, resulting in amelioration of hyperglycaemia and weight loss in streptozotocin-treated diabetic mice. Conclusions/interpretation Our strategy allows the progressive differentiation of hESCs into pancreatic endoderm capable of generating mature pancreatic cell types that function in vivo. These findings may establish the basis of further investigations for the purification of transplantable islet progenitors derived from hESCs. C1 Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Seoul 136713, South Korea. Korea Univ, Sch Med, Res Inst Med Imaging, Seoul 150050, South Korea. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, JH (reprint author), Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, W Bldg Room 304,Sci Campus,1,Anam Dong 5 Ga, Seoul 136713, South Korea. EM jhkim@korea.ac.kr RI Kim, Jong-Hoon/F-2504-2013; Kim, Jong-Hoon/H-1476-2015 NR 48 TC 134 Z9 142 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2007 VL 50 IS 6 BP 1228 EP 1238 DI 10.1007/s00125-007-0634-z PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 164YT UT WOS:000246271600015 PM 17457565 ER PT J AU Fetsch, PA Abati, A AF Fetsch, Patricia A. Abati, Andrea TI The effects of antibody clone and pretreatment method on the results of HER2 immunostaining in cytologic samples of metastatic breast cancer: A query and a review of the literature SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2005 CL San Antonio, TX SP US & Canadian Acad Pathol DE HER-2/neu; c-erbB-2; immunocytochemistry; heat-induced epitope retrieval; CB-11; TAB250; HercepTest; Herceptin; A0485 ID IN-SITU HYBRIDIZATION; HER-2/NEU PROTEIN EXPRESSION; SURGICAL ADJUVANT BREAST; ARCHIVAL TISSUE SAMPLES; MONOCLONAL-ANTIBODY; IMMUNOHISTOCHEMICAL EXPRESSION; IMMUNOCYTOCHEMICAL EVALUATION; GENE AMPLIFICATION; CLINICAL-ONCOLOGY; CARCINOMA AB The standardization and use of heat-induced epitope retrieval (HIER) is particularly important with immunohistochemical inarkers that direct the course of cancer treatment, such as Herceptin therapy. Increasingly many laboratories are performing immunohistochemical analysis using various antibodies and methodologies for HER2/neu. We attempted to determine the effects of antibody clone and pretreatment methods on the interpretation of HER-2/neu staining in cytologic samples. Cell block sections from 54 cases of metastatic breast cancer (24 FNAs, 30 effusions) were analyzed for HER2 expression using antibodies to CB-11. TAB250, and A0485. Antibodies were analyzed with and without HIER. One pathologist using the FDA-approved scoring system for the HercepTest reviewed all slides in a blinded fashion. Five of fifty-four cases (9%) using CB-11 showed a significant increase in HER2 immunoreactivity using HIER (i.e. from 0/1+ to 2-3+). However. in twenty-nine of fifty-four cases (54%), the cytoplasmic background was significantly higher after HIER. With the A0485 antibody. two of fifty four cases (4%) showed a significant increase in immunoreactivity using HIER, while seventeen of fifty-four cases (31%) exhibited only inore pronounced cytoplasmic staining. HIER pretreatment did not increase HER2 staining in any TAB250 stained sample, rather four of fifty-four cases (7%) showed a significant decrease in staining with HIER. We conclude that HIER may enhance membrane staining with the CB-11 and A0485 antibodies, but also increases cytoplasmic background. Loss of antigenicity is seen when HIER is used with TAB250. C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov NR 80 TC 7 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2007 VL 35 IS 6 BP 319 EP 328 DI 10.1002/dc.20638 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 171JV UT WOS:000246733000002 PM 17497656 ER PT J AU Horton, JK Stefanick, DF Kedar, PS Wilson, SH AF Horton, Julie K. Stefanick, Donna F. Kedar, Padmini S. Wilson, Samuel H. TI ATR signaling mediates an S-phase checkpoint after inhibition of poly(ADP-ribose) polymerase activity SO DNA REPAIR LA English DT Article DE PARP-1; PARP inhibitor; base excision repair; methyl methanesulfonate; cell cycle; cell signaling; Chk1; ATR; gamma H2AX ID HOMOLOGOUS RECOMBINATION REPAIR; EARLY EMBRYONIC LETHALITY; BASE EXCISION-REPAIR; OXIDATIVE DNA-DAMAGE; DOUBLE-STRAND BREAKS; CELL-CYCLE; RADIOSENSITIZING AGENT; REPLICATION FORKS; MAMMALIAN-CELLS; HISTONE H2AX AB Human fibroblasts, capable of expressing a kinase-dead form of ATR (ATRkd), can be sensitized to the cytotoxic effects of methyl methanesulfonate (MMS) by the PARP inhibitor 4-amino-1,8-naphthalimide (4-AN). The combination of MMS+4-AN results in accumulation of cells in S-phase of the cell cycle and activation of Chk1. Inhibition of ATR activity by expression of ATRkd suppresses the S-phase accumulation and partially reverses the Chk1 phosphorylation. The results confirm involvement of an ATR-mediated damage response pathway in the MMS + 4-AN-induced S-phase cell cycle checkpoint in human fibroblasts. Consistent with this hypothesis, the inhibitors caffeine and UCN-01 also abrogate the ATRand Chki-mediated delay in progression through S-phase. In the absence of ATR-mediated signaling, MMS + 4-AN exposure results in a G(2)/M arrest, rather than an S-phase checkpoint. Thus, whereas ATR mediates the S-phase response, it is not critical for arrest of cells in G(2)/M. (c) 2007 Elsevier B.V. All rights reserved. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050159-11] NR 37 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 1 PY 2007 VL 6 IS 6 BP 742 EP 750 DI 10.1016/j.dnarep.2006.12.015 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 180JI UT WOS:000247358700007 PM 17292679 ER PT J AU Tano, K Nakamura, J Asagoshi, K Arakawa, H Sonoda, E Braithwaite, EK Prasad, R Buerstedde, JM Takeda, S Watanabe, M Wilson, SH AF Tano, Keizo Nakamura, Jun Asagoshi, Kenjiro Arakawa, Hiroshi Sonoda, Eiichiro Braithwaite, Elena K. Prasad, Rajendra Buerstedde, Jean-Marie Takeda, Shunichi Watanabe, Masami Wilson, Samuel H. TI Interplay between DNA polymerases beta and lambda in repair of oxidation DNA damage in chicken DT40 cells SO DNA REPAIR LA English DT Article DE DNA polymerase lambda; DNA polymerase beta; oxidation DNA damage; DT40 ID BASE-EXCISION-REPAIR; HOMOLOGOUS RECOMBINATION; MOUSE FIBROBLASTS; LYASE ACTIVITY; PROTECTS AB DNA polymerase lambda (Pol lambda) is a DNA polymerase beta (Pol beta)-like enzyme with both DNA synthetic and 5'-deoxyribose-5'-phosphate lyase domains. Recent biochemical studies implicated Pol X as a backup enzyme to Pol beta in the mammalian base excision repair (BER) pathway. To examine the interrelationship between Pol lambda and Pol beta in BER of DNA damage in living cells, we disrupted the genes for both enzymes either singly or in combination in the chicken DT40 cell line and then characterized BER phenotypes. Disruption of the genes for both polymerases caused hypersensitivity to H2O2-induced cytotoxicity, whereas the effect of disruption of either polymerase alone was only modest. Similarly, BER capacity in cells after H2O2 exposure was lower in Pol beta(-/-) /Pol lambda(-/-) cells than in Pol beta(-/-), wild-type, and Pol lambda(-/-) cells, which were equivalent. These results suggest that these polymerases can complement for one another in counteracting oxidative DNA damage. Similar results were obtained in assays for in vitro BER capacity using cell extracts. With MMS-induced cytotoxicity, there was no significant effect on either survival or BER capacity from Pol X gene disruption. A strong hypersensitivity and reduction in BER capacity was observed for Pol beta(-/-)/Pol lambda(-/-) and Pol beta(-/-) cells, suggesting that Pol beta had a dominant role in counteracting alkylation DNA damage in this cell system. (c) 2007 Elsevier B.V. All rights reserved. C1 Kyoto Univ, Inst Res Reactor, Kumatori, Osaka, Japan. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. GSF, Natl Res Ctr Environm & Hlth, Inst Mol Radiobiol, Neuherberg Munich, Germany. Kyoto Univ, Grad Sch Med, Kyoto, Japan. RP Tano, K (reprint author), Kyoto Univ, Inst Res Reactor, Kumatori, Osaka, Japan. EM tano@rri.kyoto-u.ac.jp FU Intramural NIH HHS; NCI NIH HHS [P30-CA16086, P30 CA016086-259035, P30 CA016086-24, P30 CA016086]; NIEHS NIH HHS [P42 ES005948, P30-ES10126, ES11746, P30 ES010126, P30 ES010126-07, P42 ES005948-070001, P42 ES005948-15, P42-ES05948, R42 ES011746, R42 ES011746-05, R42 ES011746-05S1] NR 19 TC 37 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 1 PY 2007 VL 6 IS 6 BP 869 EP 875 DI 10.1016/j.dnarep.2007.01.011 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 180JI UT WOS:000247358700020 PM 17363341 ER PT J AU Taylor, KA AF Taylor, Katherine A. TI Building systems to support development of drugs for biodefense SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE drugs; biodefense; infectious diseases; research AB The mission of the National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID), is to support research and product development that addresses the control and prevention of infectious diseases. This mission includes the development of new drugs to mitigate illness, suffering, and death resulting from an expanding spectrum of naturally emerging diseases and potential biological weapons. DMID has established new resources and additional infrastructure to address these challenges. In addition, DMID plans to transition to a new paradigm for research and development approaches based on three concepts that comprise a broad spectrum approach: products with broad spectrum activity; broad spectrum technology that can be applied to improve specific drug characteristics (e.g., shelf life); and broad spectrum platforms that will reduce the time and cost to manufacture and evaluate products. (C) 2007 Wiley-Liss, Inc. C1 NIH, Dept Hlth & Human Serv, Off Biodef Res Affairs, Bethesda, MD 20892 USA. RP Taylor, KA (reprint author), NIH, NIAID, Dept Hlth & Human Serv, Div Microbiol & Infect Dis, Bldg 10, 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUN PY 2007 VL 68 IS 4 BP 183 EP 185 DI 10.1002/ddr.20180 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 230YL UT WOS:000250912200006 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. TI The role of electrophoresis in disease biomarker discovery SO ELECTROPHORESIS LA English DT Review DE biological fluids; biomarker discovery; CE-MS; SDS-PAGE-MS ID DIFFERENCE GEL-ELECTROPHORESIS; 2-DIMENSIONAL CAPILLARY-ELECTROPHORESIS; MICELLAR ELECTROKINETIC CHROMATOGRAPHY; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASES; HEPATOCELLULAR-CARCINOMA; PARKINSONS-DISEASE AB There has been increased activity in the last few years in the search for disease markers using fractionation of complex biological fluids combined with MS. While electrophoretic and chromatographic separations have played a major role in this endeavor, this manuscript is limited to a review of electrophoretic methods that have been established for disease biomarker discovery. These methods include 2-DE, difference gel electrophoresis (DIGE), and CE. We define what constitutes a biomarker, identify the steps required for establishing a biomarker, and describe the parameters needed in the design of an ideal diagnostic test. The application, advantages, and limitations of CE, DIGE, and 2-DE in meeting the goal of discovering novel biomarkers is discussed in detail, along with a few selected examples that illustrate the search for biomarkers for cancer and neurological diseases. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Proteom & Analyt Technologoies, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Lab Proteom & Analyt Technologoies, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 53 TC 42 Z9 45 U1 1 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2007 VL 28 IS 12 BP 1980 EP 1988 DI 10.1002/elps.200600834 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 188RC UT WOS:000247936000018 PM 17503404 ER PT J AU Race, BL Meade-White, KD Ward, A Jewellj, J Millert, MW Williams, ES Chesebro, B Race, RE AF Race, Brent L. Meade-White, Kimberly D. Ward, Anne Jewellj, Jean Millert, Michael W. Williams, Elizabeth S. Chesebro, Bruce Race, Richard E. TI Levels of abnormal prion protein in deer and elk with chronic wasting disease SO EMERGING INFECTIOUS DISEASES LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CERVUS-ELAPHUS-NELSONI; SUFFOLK SHEEP; MULE DEER; SPONGIFORM ENCEPHALOPATHY; ODOCOILEUS-HEMIONUS; LYMPHOID-TISSUES; TRANSGENIC MICE; SCRAPIE VIRUS; TRANSMISSION AB Chronic wasting disease (CWD) of deer and elk is a widespread health concern because its potential for cross-species transmission is undetermined. CWD prevalence in wild elk is much lower than its prevalence in wild deer, and whether CWD-infected deer and elk differ in ability to infect other species is unknown. Because lymphoid tissues are important in the pathogenesis of some transmissible spongiform encephalopathies such as sheep scrapie, we investigated whether CWD-affected elk and deer differ in distribution or quantity of disease-associated prion protein (PrPres) in lymphoid tissues. Immunoblot quantification of PrPres from tonsil and retropharyngeal lymph nodes showed much higher levels of PrPres in deer than in elk. This difference correlated with the natural prevalence of CWD in these species and suggested that CWD-infected deer may be more likely than elk to transmit the disease to other cervids and have a greater potential to transmit CWD to noncervids. C1 NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Univ Wyoming, Laramie, WY 82071 USA. Colorado Div Wildlife, Ft Collins, CO 80526 USA. RP Race, BL (reprint author), NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM rrace@niaid.nih.gov FU Intramural NIH HHS NR 38 TC 12 Z9 12 U1 1 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2007 VL 13 IS 6 BP 824 EP 830 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 173US UT WOS:000246898600002 PM 17553219 ER PT J AU Rimoin, AW Kisalu, N Kebela-Ilunga, B Mukaba, T Wright, LL Formenty, P Wolfe, ND Shongo, RL Tshioko, F Okitolonda, E Muyembe, JJ Ryder, RW Meyer, H AF Rimoin, Anne W. Kisalu, Neville Kebela-Ilunga, Benoit Mukaba, Thibaut Wright, Linda L. Formenty, Pierre Wolfe, Nathan D. Shongo, Robert Loshima Tshioko, Florimond Okitolonda, Emile Muyembe, Jean-Jacques Ryder, Robert W. Meyer, Hermann TI Endemic human monkeypox, democratic Republic of Congo, 2001-2004 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID VIRUS; ALIGNMENT AB By analyzing vesicle fluids and crusted scabs from 136 persons with suspected monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the hernagglutinin gene, and confirmed 94% of cases by virus culture. PCR demonstrated chickenpox in 61 patients. Coinfection with both viruses was found in 1 additional patient. C1 Bundeswehr Inst Microbiol, D-80937 Munich, Germany. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Inst Biomed Res, Kinshasa, Congo. Minist Hlth, Kinshasa, Congo. NIH, Bethesda, MD 20892 USA. WHO, CH-1211 Geneva, Switzerland. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. WHO, Kinshasa, Congo. Sch Publ Hlth, Kinshasa, Congo. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Meyer, H (reprint author), Bundeswehr Inst Microbiol, Neuherbergstr 11, D-80937 Munich, Germany. EM hermann1meyer@bundeswehr.org NR 15 TC 55 Z9 61 U1 0 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2007 VL 13 IS 6 BP 934 EP 937 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 173US UT WOS:000246898600025 PM 17553242 ER PT J AU Brouwers, FM Glaesker, S Nave, AF Vortmeyer, AO Lubensky, I Huang, S Abu-Asab, MS Eisenhofer, G Weil, RJ Park, DM Linehan, WM Pacak, K Zhuang, ZP AF Brouwers, Frederieke M. Glaesker, Sven Nave, Amanda F. Vortmeyer, Alexander O. Lubensky, Irina Huang, Steven Abu-Asab, Mones S. Eisenhofer, Graeme Weil, Robert J. Park, Deric M. Linehan, W. Marston Pacak, Karel Zhuang, Zhengping TI Proteomic profiling of von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 pheochromocytomas reveals different expression of chromogranin B SO ENDOCRINE-RELATED CANCER LA English DT Article ID SECRETOGRANIN-II; 2-ASSOCIATED PHEOCHROMOCYTOMAS; FAMILIAL PHEOCHROMOCYTOMA; DISEASE; NOREPINEPHRINE; ERYTHROPOIETIN; EPINEPHRINE; ANTIBODIES; PATHWAYS; RECEPTOR AB Pheochromocytomas are catecholamine-producing tumors that can occur in the context of von Hippel-Linclau syndrome (VHL) and multiple endocrine neoplasia type 2 (MEN2). Pheochromocytomas in these two syndromes differ in histopathological features, catecholamine metabolism, and clinical phenotype. To further investigate the nature of these differences, we compared the global protein expressions of 8 MEN2A-associated pheochromocytomas with 11 VHL-associated pheochromocytomas by two-dimensional gel electrophoresis proteomic profiling followed by sequencing and identification of differentially expressed proteins. Although both types of pheochromocytorna shared similarities in their protein expression patterns, the expression of several proteins was distinctly different between VHL- and MEN2A-associated pheochromocytomas. We identified several of these differentially expressed proteins. One of the proteins with higher expression in MEN2-associated tumors was chromogranin 13, of which the differential expression was confirmed by western blot analysis. Our results expand the evidence for proteomic differences between these two tumor entities, and suggest that VHL-associated pheochromocytomas may be deficient in fundamental machinery for catecholamine storage. In light of these new findings, as well as existing evidence for differences between both types of pheochromocytomas, we propose that these tumors may have different developmental origins. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NINCDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@mail.nih.gov RI Park, Deric/C-5675-2013; OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS NR 30 TC 8 Z9 8 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2007 VL 14 IS 2 BP 463 EP 471 DI 10.1677/ERC-06-0038 PG 9 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 199UI UT WOS:000248720300024 PM 17639059 ER PT J AU Saunier, B AF Saunier, Bertrand TI How low can maternal thyroxin go? SO ENDOCRINOLOGY LA English DT Editorial Material ID THYROID-HORMONE; BRAIN-DEVELOPMENT; EXPRESSION; RECEPTOR; ALTERS; FETAL C1 INSERM, F-75654 Paris 13, France. RP Saunier, B (reprint author), Natl Inst Allergy & Infect Dis, Lab Viral Dis, Mol Struct Sect, NIH, 4 Ctr Dr,Room 237, Bethesda, MD 20892 USA. EM bsaunier@niaid.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2007 VL 148 IS 6 BP 2591 EP 2592 DI 10.1210/en.2007-0320 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169DH UT WOS:000246572400003 PM 17507577 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Linear chromosomes in bacteria: no straight edge advantage? SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID COMPLETE GENOME SEQUENCE; CORYNEBACTERIUM-GLUTAMICUM; CLOSTRIDIUM-DIFFICILE; BETA-PROTEOBACTERIUM; EVOLUTION; REPLICATION; PLASTICITY; PLASMIDS; GENES; ENDS C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 40 TC 1 Z9 1 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD JUN PY 2007 VL 9 IS 6 BP 1357 EP 1362 DI 10.1111/j.1462-2920.2007.01328.x PG 6 WC Microbiology SC Microbiology GA 167LV UT WOS:000246454100001 PM 17504473 ER PT J AU Saydah, S Cowie, C Eberhardt, MS De Rekeneire, N Narayan, KMV AF Saydah, Sharon Cowie, Catherine Eberhardt, Mark S. De Rekeneire, Nathalie Narayan, K. M. Venkat TI Race and ethnic differences in glycemic control among adults with diagnosed diabetes in the United States SO ETHNICITY & DISEASE LA English DT Article DE race; ethnicity; diabetes; glycemic control ID BLOOD-PRESSURE; TYPE-2; CARE; HEALTH; RISK; COMPLICATIONS; DISPARITIES; MELLITUS; QUALITY AB Objective: Control of blood glucose levels reduces vascular complications among people with diabetes, but less than half of the adults with diabetes in the United States are achieving good glycemic control. This study examines 19992002 national data on the association between race/ethnicity and glycemic control among adults with previously diagnosed diabetes. Design: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, a cross-sectional survey of a nationally representative sample of the non-institutionalized civilian US population. Participants were non-pregnant adults, 20 years or older, with a previous diagnosis of diabetes, and who had participated in both the interview and examination in NHANES 1999-2002 (N=843). Glycemic control was determined by levels of glycosylated hemoglobin (A1C). We compared glycemic control by race/ethnicity and potential confounders including measures of socioeconomic status, obesity, healthcare access and diabetes treatment. Results: Overall, 44% of adults with previously diagnosed diabetes had good glycemic control (A1C levels < 7%). Mexican Americans and non-Hispanic Blacks were less likely to achieve good control (35.4% and 36.9%, respectively) compared with non-Hispanic Whites (48.6%). After multivariable adjustment for measures of socioeconomic status, obesity, healthcare access and utilization and diabetes treatment, differences in glycemic control by race/ethnicity remained. Conclusion: Glycemic control is low among all racial/ethnic groups, but is lower among non-Hispanic Blacks and Mexican Americans. These results provide guidance for public health workers and health professionals in targeting programs to improve glycemic control among adults with diagnosed diabetes in the United States. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIDDK, Bethesda, MD USA. Social & Sci Syst, Silver Spring, MD USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Saydah, S (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd, Hyattsville, MD 20782 USA. EM ssaydah@cdc.gov RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 22 TC 67 Z9 67 U1 2 U2 8 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2007 VL 17 IS 3 BP 529 EP 535 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 204TI UT WOS:000249066500018 PM 17985509 ER PT J AU Xu, XH Muller-Taubenberger, A Adley, KE Pawolleck, N Lee, VWY Wiedemann, C Sihra, TS Maniak, M Jin, T Williams, RSB AF Xu, Xuehua Mueller-Taubenberger, Annette Adley, Kathryn E. Pawolleck, Nadine Lee, Vivian W. Y. Wiedemann, Claudia Sihra, Talvinder S. Maniak, Markus Jin, Tian Williams, Robin S. B. TI Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid SO EUKARYOTIC CELL LA English DT Article ID DICTYOSTELIUM-DISCOIDEUM; HISTONE DEACETYLASE; IN-VIVO; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; NEUROTRANSMITTER RELEASE; NEUTROPHIL CHEMOTAXIS; STATUS EPILEPTICUS; NEURONAL GROWTH; MOOD STABILIZER; DISTINCT ROLES AB Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH(Crac) -green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP3 production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug. C1 Georgetown Univ, Sch Med, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Univ Munich, Inst Zellbiol, D-80336 Munich, Germany. UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. UCL, Dept Pharmacol, London WC1E 6BT, England. Univ Kassel, Abt Zellbiol, D-34132 Kassel, Germany. Roy Free & UCL, Sch Med, Ctr Mol Cell Biol, London NW3 2PF, England. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Williams, RSB (reprint author), Univ London, Royal Holloway & Bedford New Coll, Sch Biol Sci, Egham TW20 0EX, Surrey, England. EM robin.williams@rhul.ac.uk RI Sihra, Talvinder/A-4581-2009; Williams, Robin/G-6807-2011; OI Maniak, Markus/0000-0001-6442-5372 NR 65 TC 28 Z9 30 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUN PY 2007 VL 6 IS 6 BP 899 EP 906 DI 10.1128/EC.00104-06 PG 8 WC Microbiology; Mycology SC Microbiology; Mycology GA 181MB UT WOS:000247439700002 PM 17435006 ER PT J AU Koh, KK Quon, MJ Lee, Y Han, SH Ahn, JY Chung, WJ Kim, JA Shin, EK AF Koh, Kwang Kon Quon, Michael J. Lee, Yonghee Han, Seung Hwan Ahn, Jeong Yeal Chung, Wook-Jin Kim, Jeong-A Shin, Eak Kyun TI Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients SO EUROPEAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 55th Annual Scientific Session of the American-College-of-Cardiology CY MAR 11-14, 2006 CL Atlanta, GA SP Amer Coll Cardiol DE ACE-inhibitor; angiotensin II receptor; blocker; endotheliat function; insulin resistance; adipocytokines ID CONVERTING-ENZYME-INHIBITOR; II RECEPTOR BLOCKER; HIGH-RISK PATIENTS; HEART-FAILURE; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; RECIPROCAL RELATIONSHIPS; ENDOTHELIAL DYSFUNCTION; DIABETES-MELLITUS; FAT-CELLS AB Aims Ramipril and candesartan have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that combination therapy has additive beneficial effects to simultaneously improve endothetial dysfunction and adipocytokine profiles in patients with hypertension. Methods and results Thirty-four patients were given ramipril 10 mg and placebo, ramiprit 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebocontrolled cross-over trial with three treatment arms and two washout periods (each 2 months). Ramipril, candesartan, or combination therapy reduced blood pressure, improved flow-mediated dilation, and increased plasma adiponectin levels when compared with baseline values. However, combination therapy improved these outcome measures to a greater extent than either ramipril or candesartan alone (P < 0.001 and P = 0.016 for systolic and diastolic blood pressure, P < 0.001 and P = 0.048 for flow-mediated dilation and adiponectin Levels by ANOVA). In addition, combination therapy reduced plasma leptin Levels to a greater extent than either ramiprit or candesartan atone (P = 0.042 by ANOVA). There were correlations between percent changes in adiponectin levels and percent changes in insulin sensitivity (determined by QUICKI) (r=0.319, P=0.066) following ramipril. therapy, percent changes in QUICKI (r = 0. 374, P = 0.029) following combination therapy, and percent changes in QUICKI (r = 0.607, P < 0.001) following candesartan therapy. Conclusion Ramipril in combination with candesartan improves blood pressure, endothetial function, and adipocytokine profiles to a greater extent than monotherapy with either drug in hypertensive patients. C1 Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. Gachon Med Sch, Lab Med, Inchon 405760, South Korea. NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. Ewha Womans Univ, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Chung, Wook-Jin/0000-0002-9767-7098; Quon , Michael /0000-0002-5289-3707 NR 44 TC 28 Z9 29 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 JUN PY 2007 VL 28 IS 12 BP 1440 EP 1447 DI 10.1093/eurheartj/ehm101 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 192CX UT WOS:000248179500010 PM 17483542 ER PT J AU Dunn, BK Ford, LG AF Dunn, Barbara K. Ford, Leslie G. TI Hormonal interventions to prevent hormonal cancers: breast and prostate cancers SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Review DE cancer prevention; breast cancer; prostate cancer; hormonal intervention ID SURGICAL ADJUVANT BREAST; QUALITY-OF-LIFE; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; SERVICES-TASK-FORCE; BOWEL PROJECT P-1; ENDOMETRIAL CANCER; REPLACEMENT THERAPY; RECEIVING TAMOXIFEN AB In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo. European Journal of Cancer Prevention 16:232-242 (C) 2007 Lippincott Williams & Wilkins. C1 NCI, Div Canc Prevent, NIH, Deputy Directors Off, Bethesda, MD 20892 USA. NCI, Basic Prevent Sci Res Grp, Bethesda, MD 20892 USA. RP Ford, LG (reprint author), NCI, Div Canc Prevent, NIH, Deputy Directors Off, 6130 Execut Blvd,Execut Plaza N,Suite 2045, Bethesda, MD 20892 USA. EM lf50z@nih.gov NR 116 TC 9 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2007 VL 16 IS 3 BP 232 EP 242 DI 10.1097/CEJ.0b013e328011ed2d PG 11 WC Oncology SC Oncology GA 163UD UT WOS:000246187800010 PM 17415094 ER PT J AU Valent, P Akin, C Escribano, L Fodinger, M Hartmann, K Brockow, K Castells, M Sperr, WR Kluin-Nelemans, HC Hamdy, NAT Lortholary, O Robyn, J van Doormaal, J Sotlar, K Hauswirth, AW Arock, M Hermine, O Hellmann, A Triggiani, M Niedoszytko, M Schwartz, LB Orfao, A Horny, HP Metcalfe, DD AF Valent, P. Akin, C. Escribano, L. Foedinger, M. Hartmann, K. Brockow, K. Castells, M. Sperr, W. R. Kluin-Nelemans, H. C. Hamdy, N. A. T. Lortholary, O. Robyn, J. van Doormaal, J. Sotlar, K. Hauswirth, A. W. Arock, M. Hermine, O. Hellmann, A. Triggiani, M. Niedoszytko, M. Schwartz, L. B. Orfao, A. Horny, H.-P. Metcalfe, D. D. TI Standards and standardization in mastocytosis: Consensus statements on diagnostics, treatment recommendations and response criteria SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Proceedings Paper CT Standardization Conference 2005 CY NOV 03-06, 2005 CL Vienna, AUSTRIA DE criteria; mastocytosis; patient selection; standardization; targeted drugs ID MAST-CELL DISEASE; C-KIT MUTATION; ACUTE MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; AGGRESSIVE SYSTEMIC MASTOCYTOSIS; ORAL DISODIUM-CROMOGLYCATE; URINARY N-METHYLHISTAMINE; BONE-MARROW MASTOCYTOSIS; BLOOD MONONUCLEAR-CELLS; OF-THE-LITERATURE AB Although a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease-specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials. C1 Med Univ Vienna, Div Haematol & Haemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria. Univ Michigan, Div Allergy & Immunol, Dept Internal Med, Ann Arbor, MI 48109 USA. Hosp Ramon & Cajal, Unidad Mastocitosis, Hematol Serv, E-28034 Madrid, Spain. Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria. Tech Univ Munich, Dept Dermatol & Allergy Biederstein, D-8000 Munich, Germany. Univ Cologne, Clin Dermatol & Venerol, D-5000 Cologne 41, Germany. Univ Cologne, Polyclin Dermatol & Venerol, D-5000 Cologne 41, Germany. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Univ Groningen, Ctr Med, Dept Haematol, NL-9700 AB Groningen, Netherlands. Leiden Univ, Ctr Med, Dept Endocrinol & Metab Dis, NL-2300 RA Leiden, Netherlands. Univ Paris 05, Hop Necker Enfants Malades, Serv Maladies Infect, F-75270 Paris 06, France. NHLBI, Haematol Branch, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Inst Pathol, D-72074 Tubingen, Germany. Univ Hosp Groningen, Dept Allergol, Groningen, Netherlands. Ecole Normale Super, CNRS, UMR 8113, LBPA, Cachan, France. Univ Paris 05, Assistance Publ Hop Paris, Hop Necker Paris, Dept Adult Haematol, F-75005 Paris, France. Univ Paris 05, Assistance Publ Hop Paris, Hop Necker Paris, CNRS,UMR 8147, F-75005 Paris, France. Med Univ Gdansk, Dept Haematol, Gdansk, Poland. Univ Naples Federico 2, Fac Med & Chirurg, Cattedra Immunol Clin & Allergol, Naples, Italy. Med Univ Gdansk, Dept Allergol, Gdansk, Poland. Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23284 USA. Univ Salamanca, Serv Cent Citometria, Ctr Invest Canc, E-37008 Salamanca, Spain. Univ Salamanca, Dept Med, E-37008 Salamanca, Spain. Univ Schleswig Holstein, Inst Pathol, Lubeck, Germany. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Valent, P (reprint author), Med Univ Vienna, Div Haematol & Haemostaseol, Dept Internal Med 1, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM peter.valent@meduniwien.ac.at RI 2007, Secribsal/A-1556-2012; Hartmann, Karin/N-4865-2015 OI Hartmann, Karin/0000-0002-4595-8226 NR 133 TC 353 Z9 357 U1 1 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD JUN PY 2007 VL 37 IS 6 BP 435 EP 453 DI 10.1111/j.1365-2362.2007.01807.x PG 19 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 172GU UT WOS:000246792900001 PM 17537151 ER PT J AU Dubsky, P Saito, H Leogier, M Dantin, C Connolly, JE Banchereau, J Palucka, AK AF Dubsky, Peter Saito, Hiroaki Leogier, Marylene Dantin, Carole Connolly, John E. Banchereau, Jacques Palucka, A. Karolina TI IL-15-induced human DC efficiently prime melanoma-specific naive CD8(+) T cells to differentiate into CTL SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cancer; immunotherapy; tumor immunology; vaccines ID SKEWS MONOCYTE DIFFERENTIATION; NECROSIS-FACTOR-ALPHA; DENDRITIC CELLS; METASTATIC MELANOMA; IN-VITRO; IL-15; RESPONSES; INTERFERON; ACTIVATION; RECEPTOR AB Monocytes differentiate into dendritic cells (DC) in response to GM-CSF combined with other cytokines including IL-4 and IL-15. Here, we show that IL15-DC are efficient in priming naive CD8(+) T cells to differentiate into melanoma antigen-specific cytotoxic T lymphocytes (CTL). While both melanoma peptide-pulsed IL15-DC and IL4-DC expand high-precursor frequency MART-1-specific CD8(+) T cells after two stimulations i. n vitro, IL15-DC require much lower peptide concentration for priming. IL15-DC are more efficient in expanding gp100-specific CD8(+) T cells and can expand CD8(+) T cells specific for Tyrosinase and MAGE-3. CTL primed by ILI5-DC' are superior in their function as demonstrated by (i) higher IFN-gamma secretion, (ii) higher expression of Granzyme B and Perforin, and (iii) higher killing of allogeneic melanoma cell lines, most particularly the HLA-A*0201+ Sk-Mel-24 melanoma cells that are resistant to killing by CD8+ T cells primed with IL4-DC. Supernatants of the sonicated cells demonstrate unique expression of IL-1, IL-8 and IL-15. Therefore, membrane-bound IL-15 might contribute to enhanced priming by IL15-DC. Thus,, IL-15 induces myeloid DC that are efficient in priming and maturation of melanoma antigen-specific CTL. C1 Baylor Inst Immunol Res, NIAID, Cooperat Ctr Translat Res Human Immunol & Biodefe, Dallas, TX USA. Med Univ Vienna, Dept Surg, Vienna, Austria. RP Palucka, AK (reprint author), BIIR, 3434 Live Oak, Dallas, TX 75204 USA. EM karolinp@baylorhealth.edu RI Connolly, John/B-8099-2014 FU NCI NIH HHS [CA085540, CA78846, CA89440, P0-1 CA84512]; NIAID NIH HHS [U19 AI057234] NR 32 TC 95 Z9 101 U1 0 U2 8 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 JUN PY 2007 VL 37 IS 6 BP 1678 EP 1690 DI 10.1002/eji.200636329 PG 13 WC Immunology SC Immunology GA 179HF UT WOS:000247279600027 PM 17492620 ER PT J AU Yin, HH Park, BS Adermark, L Lovinger, DM AF Yin, Henry H. Park, Brian S. Adermark, Louise Lovinger, David M. TI Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE alcohol; basal ganglia; long-term depression; long-term potentiation; striatum; synaptic plasticity ID DORSAL STRIATUM; ENDOCANNABINOID RELEASE; BASAL GANGLIA; RECEPTOR FUNCTION; RAT NEOSTRIATUM; HABIT FORMATION; NMDA RECEPTOR; DEPRESSION; POTENTIATION; ACTIVATION AB The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is important to understand the effects of this drug on striatal function. In this study we examined the effects of ethanol on long-term synaptic plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a central role in the acquisition and selection of goal-directed actions. Ethanol was found to impair N-methyl-D-aspartic acid receptor (NMDAR)-dependent long-term potentiation (LTP) dose-dependently in the DMS, and to promote long-term depression (LTD) at the highest concentration (50 mM) used. These results suggest that ethanol, at a concentration usually associated with mild intoxication, could significantly change experience-dependent modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions. C1 NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Sect Synapt Pharmacol, NIH, 5625 Fishers Lane,TS-13, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov RI Adermark, Louise/D-2297-2014 OI Adermark, Louise/0000-0002-7165-9908 FU Intramural NIH HHS NR 47 TC 56 Z9 56 U1 0 U2 6 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 JUN PY 2007 VL 25 IS 11 BP 3226 EP 3232 DI 10.1111/j.1460-9568.2007.05606.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 176WL UT WOS:000247115500003 PM 17552991 ER PT J AU Papaleo, F Kieffer, BL Tabarin, A Contarino, A AF Papaleo, Francesco Kieffer, Brigitte L. Tabarin, Antoine Contarino, Angelo TI Decreased motivation to eat in mu-opioid receptor-deficient mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE food; liking; operant behaviour; opioid system; wanting ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; PROGRESSIVE RATIO; HIPPOCAMPAL-LESIONS; SUCROSE DRINKING; FOOD RESTRICTION; KNOCKOUT MICE; REWARD; NALTREXONE; NALOXONE AB Altered motivational processes might participate to the physiopathology of eating-related disorders. The endogenous opioid system is thought to mediate the hedonic properties of food intake. To assess the role for the mu-opioid receptor (MOR) pathway in the motivational properties of food intake, in the present study we tested wild-type and MOR-deficient mice (MOR-/-) in a nose-poke operant paradigm for chow or sucrose pellets. To avoid confounding factors linked to food restriction/deprivation experience, mice were always provided with food ad libitum. Although less MOR-/- than wild-type mice initiated operant behaviour, under a fixed ratio-1 (FR-1) reinforcement schedule the two genotypes showed similar patterns of food-driven nose-poking, indicating preserved cognitive abilities in MOR-deficient mice. However, during FR-3 and progressive ratio (PR) reinforcement experiments, MOR-/- mice showed lower levels of nose-poking for either chow or sucrose pellets than wild-type mice, indicating a crucial role for the MOR pathway in the motivational properties of food intake. Moreover, under the PR reinforcement schedule mice nose-poking for sucrose pellets showed higher genotype-independent breakpoint levels than mice working for chow pellets, indicating that the MOR pathway is not essential for hedonic processing of palatable food intake. Finally, MOR-/- mice did not differ from wild-type mice in the rate of operant responding extinction, further supporting the notion of unaltered cognitive abilities in the MOR-deficient mice. The present findings strongly indicate that the MOR pathway mediates the motivational properties of food intake, but it is not essential for hedonic processing of ingestive behaviour. C1 Univ Victor Segalen Bordeaux, Lab Homeostasie Allostasie Pathol, EA 3666, F-33076 Bordeaux, France. ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire,UMR 7104, Illkirch Graffenstaden, France. RP Contarino, A (reprint author), Natl Inst Mental Hlth, Clin Brain Disorders Branch, NIH, 10,Ctr Dr,Bldg 10,Room 4 N312, Bethesda, MD 20892 USA. EM angelo.contarino@nppda.u-bordeaux2.fr RI Contarino, Angelo/C-9429-2014; OI Papaleo, Francesco/0000-0002-6326-0657 FU PHS HHS [UO113481] NR 56 TC 43 Z9 43 U1 1 U2 3 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 JUN PY 2007 VL 25 IS 11 BP 3398 EP 3405 DI 10.1111/j.1460-9568.2007.05595.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 176WL UT WOS:000247115500020 PM 17553008 ER PT J AU Devan, BD Pistell, PJ Daffin, LW Nelson, CM Duffy, KB Bowker, JL Bharati, IS Sierra-Mercado, D Spangler, EL Ingram, DK AF Devan, Bryan D. Pistell, Paul J. Daffin, Lee W., Jr. Nelson, Christopher M. Duffy, Kara B. Bowker, Jonna L. Bharati, Ila S. Sierra-Mercado, Demetrio Spangler, Edward L. Ingram, Donald K. TI Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor N-omega-nitro-L-arginine methyl ester SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE phosphodiesterase inhibition; nitric oxide; cyclic GMP; aging; cognitive performance; stone maze ID OXIDE SYNTHASE INHIBITORS; CGMP SIGNAL-TRANSDUCTION; LONG-TERM POTENTIATION; AMYLOID-BETA PEPTIDE; ALZHEIMERS-DISEASE; COGNITIVE ENHANCEMENT; L-NAME; CHOLINERGIC HYPOTHESIS; PHOSPHODIESTERASE INHIBITION; SYNAPTIC PLASTICITY AB In a previous study, our laboratory reported that sildenafil citrate, a cyclic nucleotide phosphodiesterase type 5 inhibitor, reversed a learning impairment in rats induced by systemic inhibition of nitric oxide synthase (60 mg/kg, i.p., N-omega-nitro-L-arginine methyl ester; L-NAME). To limit the peripheral effects Of L-NAME and further localize the site of action of sildenafil, L-NAME (48 mu g, i.c.v.) was infused bilaterally into the lateral cerebral ventricles 30 min prior to maze training. Saline or sildenafil citrate (1.5 or 3.0 mg/kg, i.p.) was administered systemically 15 min before training. Drug injections occurred 24 h after pretraining rats to avoid foot shock on a one-way active avoidance straight runway. Following drug treatment, the rats received 15 training trials on a 14-unit T-maze task that requires learning a complex sequence of turns to avoid mild foot shock. This complex maze paradigm is sensitive to aging and blockade of cholinergic, N-methyl-D-aspartate and nitric oxide signaling systems. Behavioral measures of performance included deviations from the correct pathway (errors), runtime from start to goal (latency), shock frequency and shock duration. Statistical analysis revealed that central infusion of L-NAME impaired maze performance and that sildenafil (3.0 mg/kg) significantly attenuated the impairment. These results suggest that sildenafil citrate may serve as a cognitive enhancer by modulating central nitric oxide/cGMP signal transduction following N-methyl-D-aspartate receptor activation. This pathway has been implicated in age-related cognitive decline and may be a useful target for pharmacological intervention of neurodegenerative disease. (c) 2007 Elsevier B.V All rights reserved. C1 Towson Univ, Dept Psychol, Lab Comparat Neuropsychol, Towson, MD 21252 USA. NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH,Gerontol Res Ctr, Baltimore, MD 21204 USA. Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutrit Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. RP Devan, BD (reprint author), Towson Univ, Dept Psychol, Lab Comparat Neuropsychol, Towson, MD 21252 USA. EM bdevan@towson.edu FU Intramural NIH HHS NR 70 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 1 PY 2007 VL 563 IS 1-3 BP 134 EP 140 DI 10.1016/j.ejphar.2007.02.008 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169RC UT WOS:000246608300016 PM 17362916 ER PT J AU Wheaton, LA Mizelle, JC Forrester, LW Bai, O Shibasaki, H Macko, RF AF Wheaton, Lewis A. Mizelle, J. C. Forrester, Larry W. Bai, Ou Shibasaki, Hiroshi Macko, Richard F. TI How does the brain respond to unimodal and bimodal sensory demand in movement of the lower extremity? SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE motor planning; sensorimotor integration; motor control; multisensory integration; electroencephalography ID CONTINGENT NEGATIVE-VARIATION; SUPPLEMENTARY MOTOR AREA; FUNCTIONAL-ORGANIZATION; CORTICAL POTENTIALS; FINGER MOVEMENTS; ENHANCES RECOVERY; CORTEX; REORGANIZATION; INTRAPARIETAL; PREMOTOR AB Numerous electroencephalography (EEG) studies have shown that neurophysiological signals change in response to visual and sensory adaptations in upper extremity tasks. However, this has not been clearly studied in the lower extremity. In this study, we evaluated how sensory loading affects brain activations related to knee movement. Thirty-two channel EEG was recorded while ten subjects performed knee extension in four different conditions: no weight and no visual target (NWNT), weight affixed to the ankle and no visual target (WNT), no weight and a visual target (NWT), and both weight and target (WT). Surface electromyography (EMG) was recorded from the vastus medialis and vastus lateralis muscles to determine onset of the movement. EEG was epoched from -4.5 s before to 1 s after EMG onset. Epochs were averaged to acquire movement-related cortical potentials (MRCPs) of each task condition. MRCP amplitude during the pre-movement period from -2 s to EMG onset was evaluated at electrodes over motor, sensory, frontal, and parietal areas. The amplitude of the pre-movement potentials for the conditions was different across areas of interest. Over the motor area, NWNT had lower amplitude than any other condition and WT had higher amplitude than any other condition. There was no difference between unimodal NWT and WNT conditions. Mesial frontal and parietal areas showed larger MRCP to the bimodal condition than either unimodal or NWNT conditions. The parietal cortex was the only region that showed a difference between unimodal conditions with greater amplitude for NWT condition. Information concerning added sensory demand is processed by the motor cortex in a way that may be indifferent to the type of modality, but is influenced by the quantity of modalities at the level of the knee. Other brain structures such as parietal and premotor cortices respond based on the modality type to help plan appropriate strategies for motor control in response to sensory manipulations. This suggests that additional task demands in motor training may create a rich sensory environment that may be beneficial in promoting optimal neuromotor recovery. C1 Dept Vet Affairs, Baltimore, MD 21201 USA. Vet Affairs Med Ctr, Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Takeda Gen Hosp, Kyoto, Japan. RP Wheaton, LA (reprint author), Dept Vet Affairs, 10 N Greene St, Baltimore, MD 21201 USA. EM lwheaton@grecc.umaryland.edu RI Wheaton, Lewis /B-4482-2009 OI Wheaton, Lewis /0000-0003-0771-0294 NR 48 TC 11 Z9 11 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2007 VL 180 IS 2 BP 345 EP 354 DI 10.1007/s00221-007-0858-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 178EN UT WOS:000247204100013 PM 17256159 ER PT J AU Henriquez, VM Evinger, C AF Henriquez, Victor M. Evinger, Craig TI The three-neuron corneal reflex circuit and modulation of second-order corneal responsive neurons SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE blinking; cornea; corneal reflexes; trigeminal nuclei; blink adaptation ID SPINAL TRIGEMINAL NUCLEUS; EVOKED BLINK REFLEX; DORSAL-HORN NEURONS; MODEL SYSTEM; RAT; PROJECTIONS; LOCALIZATION; STIMULATION; MECHANISMS; PATHWAY AB Neurons located in the border region between the interpolaris and caudalis subdivisions of the spinal trigeminal nucleus (Vi/Vc) are second order neurons of the corneal reflex, receiving corneal afferents and projecting to the lid closing, orbicularis oculi (OO) motoneurons. Recordings of Vi/Vc neurons identified by antidromic activation from stimulation of the facial nucleus and non-identified Vi/Vc neurons reveal two neuron types, phasic and tonic. Corneal stimulation elicits A delta latency action potentials that occur early enough to initiate OO contraction and C-fiber latency action potentials that can modulate the end of the blink in phasic Vi/Vc neurons. Tonic Vi/Vc neurons exhibit a constant irregular, low frequency discharge as well as the cornea-evoked activity exhibited by phasic neurons. For both phasic and tonic neurons, blink amplitude increases with the total number of spikes evoked by the corneal stimulus. Peak firing frequency predicts peak orbicularis oculi EMG activity. Paradigms that suppress cornea-evoked blinks differentially affect Vi/Vc neurons. Microstimulation of the border region between the spinal trigeminal caudalis subdivision and the C1 spinal cord (Vc/C1) significantly reduces the number of spikes evoked by corneal stimulation and suppresses blink amplitude. In the paired stimulus paradigm, a blink evoked by a corneal stimulus 150 ms after an identical corneal stimulus is significantly smaller than the blink elicited by the first stimulus. Vi/Vc neuron discharge, however, is slightly larger for the second blink. Our data indicate that second-order Vi/Vc neurons do not determine the specific pattern of OO muscle activity; rather Vi/Vc neurons initiate OO motoneuron discharge and program the activity of another circuit that generates the late phase of the blink. The Vc/C1 suppression of Vi/Vc neurons suggests that the Vc/C1 region provides an "internal model" of the intended blink. C1 SUNY Stony Brook, Dept Neurobiol, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Behav & Ophthalmol, Stony Brook, NY 11794 USA. NINDS, Med Neurol Branch, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. RP Evinger, C (reprint author), SUNY Stony Brook, Dept Neurobiol, Stony Brook, NY 11794 USA. EM levinger@notes.cc.sunysb.edu FU NEI NIH HHS [EY07391, R01 EY007391] NR 36 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2007 VL 179 IS 4 BP 691 EP 702 DI 10.1007/s00221-006-0826-7 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 171QS UT WOS:000246751100015 PM 17216149 ER PT J AU Gordon, BC Revenis, AM Bonifacino, AC Sander, WE Metzger, ME Krouse, AE Usherson, TN Donahue, RE AF Gordon, Brent C. Revenis, Amy M. Bonifacino, Aylin C. Sander, William E. Metzger, Mark E. Krouse, Allen E. Usherson, Tatiana N. Donahue, Robert E. TI Paradoxical drop in circulating neutrophil count following granulocyte-colony stimulating factor and stem cell factor administration in rhesus macaques SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; BLOOD PROGENITOR CELLS; FACTOR G-CSF; IN-VIVO; GM-CSF; SURFACE EXPRESSION; KIT-LIGAND; ADHESION; MOBILIZATION; MOLECULES AB Objective. Granulocyte colony-stimulating factor (G-CSF) is frequently used therapeutically to treat chronic or transient neutropenia and to mobilize hematopoietic stem cells. Shortly following G-CSF administration, we observed a dramatic transient drop in circulating neutrophil number. This article characterizes this effect in a rhesus macaque animal model. Methods. Hematologic changes were monitored following subcutaneous (SQ) administration of G-CSE. G-CSF was administered as a single SQ dose at 10 mu g/kg or 50 mu g/kg. It was also administered (10 mu g/kg) in combination with stem cell factor (SCF; 200 mu g/kg) over 5 days. Flow cytometry was performed on serial blood samples to detect changes in cell surface adhesion protein expression. Results. Neutrophil count dramatically declined 30 minutes after G-CSF administration. This decline was observed whether 10 mu g/kg G-CSF was administered in combination with SCF over 5 days, or given as a single 10 mu g/kg dose. At a single 50 mu g/kg dose, the decline accelerated to 15 minutes. Neutrophil count returned to baseline after 120 minutes and rapidly increased thereafter. An increase in CD11a and CD49d expression coincided with the drop in neutrophil count. Conclusion. A transient paradoxical decline in neutrophil count was observed following administration of G-CSF either alone or in combination with SCE. This decline accelerated with the administration of a higher dose of G-CSF and was associated with an increase in CD11a and CD49d expression. It remains to be determined whether this decline in circulating neutrophils is associated with an increase in endothelial margination and/or entrance into extravascular compartments. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Natl Heart Lung & Blood Inst, Hematol Branch, NIH, Rockville, MD 20850 USA. RP Gordon, BC (reprint author), Natl Heart Lung & Blood Inst, Hematol Branch, NIH, 5 Res Court, Rockville, MD 20850 USA. EM donahuer@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 34 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2007 VL 35 IS 6 BP 872 EP 878 DI 10.1016/j.exphem.2007.03.011 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 179LQ UT WOS:000247291500005 PM 17533041 ER PT J AU Mankani, MH Kuznetsov, SA Robey, PG AF Mankani, Mahesh H. Kuznetsov, Sergei A. Robey, Pamela Gehron TI Formation of hematopoietic territories and bone by transplanted human bone marrow stromal cells requires a critical cell density SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID IN-VIVO; STEM-CELLS; OSTEOGENESIS; FIBROBLASTS; MOUSE; TISSUES; VITRO; MICE AB Objective. Bone marrow stromal cells (BMSCs) include multipotent cells with the ability to form mature bone organs upon in vivo transplantation. Hematopoiesis in these bone organs has been ascribed to the action of skeletal stem cells, which are capable of differentiating towards bone and hematopoiesis-supporting stroma. Yet, the creation of hematopoietic territories may be in part a natural consequence of the formation of a sufficiently mature and large bone microenvironment. Here, we describe, for the first time, a relationship between BMSC numbers and the extent of bone/hemtopoiesis formation in heterotopic transplants. Methods. Human BMCs were transplanted along with hydroxyapatite/tricalcium phosphate, utilizing a spectrum of dosages, into immunotolerant mice; the transplants were followed for up to 29 months. Results. The extent of bone and hematopoiesis formation increased with increasing BMSC numbers; however, the relationship was sigmoid in character, and a threshold number of BMCs was necessary for extensive bone formation or any hematopoiesis. Hematopoiesis only occurred in conjunction with extensive bone formation, and no hematopoiesis occurred where bone formation was poor. Consistent with our earlier studies of long-term BMSC transplantation, the transplants underwent a change in bone morphology but not bone content after 8 weeks. Conclusion. Our results have provided evidence that the formation of both hematopoiesis and a mature bone organ is as much a consequence of a sufficiently high local density of bone marrow stromal cells as it is the product of skeletal stem cell action. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, Div Plast Surg, San Francisco, CA 94143 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco Gen Hosp, Div Plast Surg, 1001 Potrero Ave,Box 0807, San Francisco, CA 94143 USA. EM mahesh.mankani@ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 22 TC 42 Z9 48 U1 0 U2 1 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 JUN PY 2007 VL 35 IS 6 BP 995 EP 1004 DI 10.1016/j.exphem.2007.01.051 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 179LQ UT WOS:000247291500018 PM 17960668 ER PT J AU Li, Y Sherer, K Cui, XZ Eichacker, PQ AF Li, Yan Sherer, Kevin Cui, Xizhong Eichacker, Peter Q. TI New insights into the pathogenesis and treatment of anthrax toxin-induced shock SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE anthrax; pathogenesis; toxin; treatment ID LETHAL FACTOR PROTEASE; CAPILLARY MORPHOGENESIS PROTEIN-2; T-LYMPHOCYTE ACTIVATION; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; MONOCLONAL-ANTIBODY; EDEMA FACTOR; CYCLIC-AMP; IN-VIVO; INHALATIONAL ANTHRAX AB Inhalational Bacillus anthracis infection is a leading bioterrorist health threat in the US today. Lethal (LeTx) and edema toxin production are key to the virulent effects of this lethal bacteria. Recent insights into the structure and function of these toxins have increased the understanding of both the pathogenesis and treatment of anthrax. These are binary type toxins comprised of protective antigen necessary for their cellular uptake and either lethal or edema factors, the toxigenic moieties. Primary cellular receptors for protective antigen have been identified and the processing of the completed toxins clarified. Consistent with the ability of lethal factor to cleave mitogen activated protein kinase kinases, the evidence indicates that an excessive inflammatory response does not contribute to shock with LeTx. Rather, the immunosuppressive effects of LeTx could promote infection; however, direct endothelial dysfunction may have an important role in shock due to LeTx. Recent studies show that edema factor, a potent adenyl cyclase, may have a major role in shock during anthrax and that it may also be immunosuppresive. Therapies under development which target several steps in the cellular uptake and function of these two toxins have been effective in both in vitro and in vivo systems. Understanding how best to apply these agents in combination with conventional treatments should be a goal of future research. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM peichacker@cc.nih.gov FU Intramural NIH HHS NR 112 TC 11 Z9 12 U1 0 U2 2 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 JUN PY 2007 VL 7 IS 6 BP 843 EP 854 DI 10.1517/14712598.7.6.843 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 182CY UT WOS:000247483900007 PM 17555370 ER PT J AU Blonder, J Veenstra, TD AF Blonder, Josip Veenstra, Timothy D. TI Computational prediction of proteotypic peptides SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE computational prediction; mass spectrometry; peptide identification; proteotypic peptide; quantitative proteomics ID QUANTITATIVE PROTEOMICS AB Mass spectrometry, the driving analytical force behind proteomics, is primarily used to identity and quantify as many proteins in a complex biological mixture as possible. While there are many ways to prepare samples, one aspect that is common to a vast majority of bottom-up proteomic studies is the digestion of proteins into tryptic peptides prior to their analysis by mass spectrometry. As correctly highlighted by Mallick and colleagues, only a few peptides are repeatedly and consistently identified for any given protein within a complex mixture. While the existence of these proteotypic peptides (to borrow the authors' terminology) is well known in the proteornics community, there has never been an empirical method to recognize which peptides may be proteotypic for a given protein. In this study, the investigators discovered over 16,000 proteotypic peptides from a collection of over 600,000 peptide identifications obtained from four different analytical platforms. The study examined a number of physicochemical parameters of these peptides to determine which properties were most relevant in defining a proteotypic peptide. These characteristic properties were then used to develop computational tools to predict proteotypic peptides for any given protein within an organism. C1 SAIC Frederick Inc, NCI, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, NCI, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM blonder@ncifcrf.gov; veenstra@ncifcrf.gov NR 5 TC 6 Z9 6 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JUN PY 2007 VL 4 IS 3 BP 351 EP 354 DI 10.1586/14789450.4.3.351 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 180QF UT WOS:000247379900013 PM 17552918 ER PT J AU Batkai, S Osei-Hyiaman, D Pan, H El-Assal, O Rajesh, M Mukhopadhyay, P Hong, F Harvey-White, J Jafri, A Hasko, G Huffman, JW Gao, B Kunos, G Pacher, P AF Batkai, Sandor Osei-Hyiaman, Douglas Pan, Hao El-Assal, Osama Rajesh, Mohanraj Mukhopadhyay, Partha Hong, Feng Harvey-White, Judith Jafri, Anjum Hasko, Gyorgy Huffman, John W. Gao, Bin Kunos, George Pacher, Pal TI Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury SO FASEB JOURNAL LA English DT Article DE endocannabinoids; anandamide; 2-arachidonoylglycerol; peroxynitrite; oxidative stress ID FOCAL CEREBRAL-ISCHEMIA; ACID AMIDE HYDROLASE; KNOCK-OUT MICE; CB2 RECEPTOR; ENDOCANNABINOID SYSTEM; REPERFUSION INJURY; LIVER-TRANSPLANTATION; N-ACYLETHANOLAMINES; HEMODYNAMIC PROFILE; MYOCARDIAL-ISCHEMIA AB Hepatic ischemia-reperfusion (I/R) injury continues to be a fatal complication that can follow liver surgery or transplantation. We have investigated the involvement of the endocannabinoid system in hepatic I/R injury using an in vivo mouse model. Here we report that I/R triggers several-fold increases in the hepatic levels of the endocannabinoids anandamide and 2-arachidonoylglycerol, which originate from hepatocytes, Kupffer, and endothelial cells. The I/R-induced increased tissue endocannabinoid levels positively correlate with the degree of hepatic damage and serum TNF- alpha, MIP- 1 alpha, and MIP- 2 levels. Furthermore, a brief exposure of hepatocytes to various oxidants (H2O2 and peroxynitrite) or inflammatory stimuli (endotoxin and TNF-alpha) also increases endocannabinoid levels. Activation of CB2 cannabinoid receptors by JWH133 protects against I/R damage by decreasing inflammatory cell infiltration, tissue and serum TNF-alpha, MIP-1 alpha and MIP- 2 levels, tissue lipid peroxidation, and expression of adhesion molecule ICAM- 1 in vivo. JWH133 also attenuates the TNF-alpha-induced ICAM-1 and VCAM- 1 expression in human liver sinusoidal endothelial cells (HLSECs) and the adhesion of human neutrophils to HLSECs in vitro. Consistent with the protective role of CB2 receptor activation, CB2-/- mice develop increased I/R-induced tissue damage and proinflammatory phenotype. These findings suggest that oxidative/nitrosative stress and inflammatory stimuli may trigger endocannabinoid production, and indicate that targeting CB2 cannabinoid receptors may represent a novel protective strategy against I/R injury. We also demonstrate that CB2-/- mice have a normal hemodynamic profile.-Batkai, S., Osei-Hyiaman, D., Pan, H., El-Assal, O., Rajesh, M., Mukhopadhyay, P., Hong, F., Harvey-White, J., Jafri, A., Hasko, G., Huffman, J. W., Gao, B., Kunos, G., Pacher, P. Cannabinoid-2 receptor mediates protection against hepatic ischemia/ reperfusion injury. C1 NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Dept Surg, New Jersey Med Sch, Newark, NJ 07103 USA. Clemson Univ, Howard L Hunter Chem Lab, Clemson, SC 29631 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z01 AA000375-02]; NIDA NIH HHS [DA03590, R01 DA003590] NR 67 TC 132 Z9 139 U1 1 U2 6 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 JUN PY 2007 VL 21 IS 8 BP 1788 EP 1800 DI 10.1096/fj.06-7451com PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 173IK UT WOS:000246866500021 PM 17327359 ER PT J AU Sredni, B Geffen-Aricha, R Duan, WZ Albeck, M Shalit, F Lander, HM Kinor, N Sagi, O Albeck, A Yosef, S Brodsky, M Sredni-Kenigsbuch, D Sonino, T Longo, DL Mattson, MP Yadid, G AF Sredni, Benjamin Geffen-Aricha, Revital Duan, Wenzhen Albeck, Michael Shalit, Frances Lander, Harry M. Kinor, Noa Sagi, Ortal Albeck, Amnon Yosef, Sigal Brodsky, Miri Sredni-Kenigsbuch, Dvora Sonino, Tali Longo, Dan L. Mattson, Mark P. Yadid, Gal TI Multifunctional tellurium molecule protects and restores dopaminergic neurons in Parkinson's disease models SO FASEB JOURNAL LA English DT Article DE 6neuroprotection; apoptosis; inflammation; cytokines; neurotrophic ID THIOL REDOX STATUS; IMMUNOMODULATOR AS101; NEUROTROPHIC FACTOR; APOPTOTIC DEATH; NIGROSTRIATAL SYSTEM; CELL-DEATH; TNF-ALPHA; NEURODEGENERATION; INTERLEUKIN-10; INHIBITION AB In Parkinson's disease ( PD) dopaminergic neurons in the substantia nigra ( SN) become dysfunctional and many ultimately die. We report that the tellurium immunomodulating compound ammonium trichloro(dioxoethylene-O, O'-) tellurate(AS101) protects dopaminergic neurons and improves motor function in animal models of PD. It is effective when administered systemically or by direct infusion into the brain. Multifunctional activities of AS101 were identified in this study. These were mainly due to the peculiar Tellur(IV)- thiol chemistry of the compound, which enabled the compound to interact with cysteine residues on both inflammatory and apoptotic caspases, resulting in their inactivation. Conversely, its interaction with a key cysteine residue on p21(ras), led to its activation, an obligatory activity for AS101-induced neuronal differentiation. Furthermore, AS101 inhibited IL-10, resulting in up-regulation of GDNF in the SN. This was associated with activation of the neuroprotective kinases Akt and mitogen-activated protein kinases, and up- regulation of the antiapoptotic protein Bcl-2. Inhibition of caspase-1 and caspase-3 activities were associated with decreased neuronal death and inhibition of IL-1 beta. We suggest that, because multiple mechanisms are involved in the dysfunction and death of neurons in PD, use of a multifunctional compound, exerting antiapoptotic, anti-inflammatory, and neurotrophic-inducing capabilities may be potentially efficacious for the treatment of PD.-Sredni B., Geffen R., Duan W., Albeck M., Shalit F., Lander H., Kinor N., Sagi O., Albeck A., Yosef S., Brodsky M., Sredni-Kenigsbuch D., Sonino T., Longo D., Mattson M., Yadid G. Multifunctional tellurium molecule protects and restores dopaminergic neurons in Parkinson's disease models. C1 Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, CAIR Inst, Ramat Gan, Israel. Bar Ilan Univ, Interdisiplinary Dept, Ramat Gan, Israel. Bar Ilan Univ, Dept Chem, Ramat Gan, Israel. Bar Ilan Univ, Multidisciplinary Brain Res Ctr, Ramat Gan, Israel. Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Lab Immunol, Baltimore, MD USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY USA. RP Sredni, B (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, CAIR Inst, Keren Hayessod St, Ramat Gan, Israel. EM srednib@mail.biu.ac.il RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 59 TC 33 Z9 34 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2007 VL 21 IS 8 BP 1870 EP 1883 DI 10.1096/fj.06-7500com PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 173IK UT WOS:000246866500028 PM 17314138 ER PT J AU Sinaii, N Cleary, SD Younes, N Ballweg, ML Stratton, P AF Sinaii, Ninet Cleary, Sean D. Younes, Naji Ballweg, Mary Lou Stratton, Pamela TI Treatment utilization for endometriosis symptoms: a cross-sectional survey study of lifetime experience SO FERTILITY AND STERILITY LA English DT Article DE endometriosis; endometriosis treatment; hormones; laparoscopy; laparotomy ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC PELVIC PAIN; REPRODUCTIVE HEALTH-CARE; IRRITABLE-BOWEL-SYNDROME; WOMEN; HYPNOSIS; PLACEBO AB Objective: To examine the lifetime utilization and perceived benefit of medical treatments and surgical procedures for endometriosis-related symptoms. Design: Cross-sectional study of self-reported survey data. Setting: Academic research setting. Patient(s): Self-reported surgically diagnosed endometriosis by 1,160 women responding to the 1998 Endometriosis Association survey. Intervention(s): None. Main Outcome Measure(s): Use, perceived helpfulness, and outcomes of medical treatments and surgical procedures. Result(s): Ninety-five percent of respondents reported pelvic pain, had endured symptoms on average of 16 years, and were young (mean: 36 years), white, and educated. Many women (46%) had tried three or more medical treatments, and almost 20% took them for 10+ years. Many reported medical treatments as helpful for symptoms (range, 36.4%-61.9%), but some reported stopping because of ineffectiveness (range, 15.6%-26.1%) or side effects (range, 10.0%-43.5%). Danazol or medroxyprogesterone acetate (MPA) was most commonly stopped because of side effects (range, 40.7%-43.5%). Surgical procedures were performed at least three times on 42%. Nearly 20% had a hysterectomy or oophorectomy; these procedures were reported as most successful in improving symptoms (45.9% and 37.8%, respectively). Conclusion(s): Despite reporting various treatments as helpful, women used many different types and endured symptoms for an average of almost two decades, indicating the profound effect of endometriosis on women's health. C1 Natl Inst Child & Human Dev, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. George Washington Univ, Biostat Ctr, Rockville, MD USA. Int Headquarters, Endometriosis Assoc, Milwaukee, WI USA. RP Sinaii, N (reprint author), 10 Ctr Dr,Bldg 10,CRC Rm 1-3140, Bethesda, MD 20892 USA. EM sinaiin@mail.nih.gov FU Intramural NIH HHS NR 18 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2007 VL 87 IS 6 BP 1277 EP 1286 DI 10.1016/j.fertnstert.2006.11.051 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 177JT UT WOS:000247150100006 PM 17296195 ER PT J AU Catherino, WH Malik, M AF Catherino, William H. Malik, Minnie TI Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med DE leiomyoma; all-trans retinoic acid; 9-cis retinoic acid; aldehyde dehydrogenase; alcohol dehydrogenase; CRBP; CRABP; CYP 26; microarray analysis; HPLC ID SMOOTH-MUSCLE CELLS; BREAST-CANCER; GENE-EXPRESSION; PROMYELOCYTIC LEUKEMIA; LUNG-CANCER; CHEMOPREVENTION; MYOMETRIUM; METABOLISM; THERAPY; PROLIFERATION AB Objective: To analyze expression of the retinoic acid signaling pathway genes that are involved in retinol metabolism, transport, transcriptional activation, and transcriptional products in spontaneous human leiomyomas, Design: Laboratory study of human leiomyoma and patient-matched myometrial tissue. Patient(s): Eight women undergoing hysterectomy for symptomatic leiomyomas. Intervention(s): Confirmation of an altered retinoic acid pathway analyzed by microarray, real time reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and high-performance liquid chromatography (HPLC). Main Outcome Measure(s): Gene and protein expression. Result(s): Regardless of patient demographics and leiomyoma location and size, we found decreased expression of the major genes involved in retinoic acid pathway including alcohol dehydrogenase-1 (-3.97- +/- 0.03-fold), aldehyde dehydrogenase-1 (-3.1- +/- 0.07-fold), cellular retinol binding protein-1 (-2.62- +/- 0.04-fold), and cellular retinoic acid binding protein-1 (-2.42- +/- 0.20-fold). Cytochrome P450 (CYP 26A1), which is responsible for retinoic acid metabolism, was highly up-regulated in leiomyomas (+5.4- +/- 0.53-fold). Nuclear receptors demonstrated a complex pattern of under-expression (RAR alpha, RAR beta, RXR alpha, RXR gamma) and overexpression (RAR gamma, RXR beta) at both the mRNA and protein level. Differences in protein amounts were confirmed by Western blot. Finally, a reduced amount of cellular ATRA and 9-cis retinoic acid was confirmed by HPLC in leiomyomas compared with myometrial tissues. Conclusion(s): Molecular alterations in the retinoic acid pathway of leiomyomata result in a decrease in retinoic acid exposure. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov OI Malik, Minnie/0000-0003-1129-6575 FU Intramural NIH HHS NR 54 TC 27 Z9 28 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 JUN PY 2007 VL 87 IS 6 BP 1388 EP 1398 DI 10.1016/j.fertnstert.2006.11.093 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 177JT UT WOS:000247150100023 PM 17276435 ER PT J AU Soule, BP Hyodo, F Matsumoto, K Simone, NL Cook, JA Krishna, MC Mitchell, JB AF Soule, Benjamin P. Hyodo, Fuminori Matsumoto, Ken-ichiro Simone, Nicole L. Cook, John A. Krishna, Murali C. Mitchell, James B. TI The chemistry and biology of nitroxide compounds SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE nitroxides; tempol; radiation; oxidative stress; magnetic resonance imaging; contrast agents; chemoprevention; hypertension; free radicals ID PERMEABLE RADICAL SCAVENGER; ELECTRON-PARAMAGNETIC-RESONANCE; SUPEROXIDE-DISMUTASE MIMICS; NUCLEAR MAGNETIC-RESONANCE; SENSITIVE CONTRAST AGENTS; LENS EPITHELIAL-CELLS; TUMOR REDOX STATUS; PARKINSONS-DISEASE; STABLE NITROXIDE; OXIDATIVE DAMAGE AB Cyclic nitroxides are a diverse group range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described, including their ability to degrade superoxide and peroxide, inhibit Fenton reactions, and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use, including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. Although much remains to be done, many applications have been well studied and some are currently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials. Published by Elsevier Inc. C1 NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Soule, BP (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM souleb@mail.nih.gov FU Intramural NIH HHS [Z01 SC006387-18] NR 99 TC 232 Z9 243 U1 4 U2 66 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN 1 PY 2007 VL 42 IS 11 BP 1632 EP 1650 DI 10.1016/j.freeradbiomed.2007.02.030 PG 19 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 165MK UT WOS:000246309400002 PM 17462532 ER PT J AU Thorburn, CM Prokunina-Olsson, L Sterba, KA Lum, RF Seldin, MF Alarcon-Riquelme, ME Criswell, LA AF Thorburn, C. M. Prokunina-Olsson, L. Sterba, K. A. Lum, R. F. Seldin, M. F. Alarcon-Riquelme, M. E. Criswell, L. A. TI Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort SO GENES AND IMMUNITY LA English DT Article DE systemic lupus erythematosus; PDCD1; family; based methods; haplotypes ID FAMILY-BASED ASSOCIATION; HAPLOTYPE RECONSTRUCTION; SUSCEPTIBILITY; POLYMORPHISM; POPULATIONS; STRATEGIES; ANTIBODIES; CRITERIA; LOCUS; PD-1 AB We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P = 0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P = 0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub-phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background. C1 Univ Calif San Francisco, Div Rheumatol, Rosalind Russell Med Res Ctr, Dept Med, San Francisco, CA 94143 USA. NHGRI, Genom Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Biochem & Mol Med, Rowe Program Human Genet, Davis, CA 95616 USA. Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. RP Criswell, LA (reprint author), Univ Calif San Francisco, Div Rheumatol, Rosalind Russell Med Res Ctr, Dept Med, 374 Parnassus Ave,Box 0500, San Francisco, CA 94143 USA. EM Lindsey.Criswell@ucsf.edu OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154 FU NCRR NIH HHS [5M01 RR 00079, M01 RR000079]; NIAMS NIH HHS [P60 AR053308, K24 AR 02175, K24 AR002175, P60 AR053308-01, R01 AR 44804]; NIDDK NIH HHS [T32 DK 07219, T32 DK007219]; NIEHS NIH HHS [ES 09911, R01 ES009911] NR 24 TC 63 Z9 64 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2007 VL 8 IS 4 BP 279 EP 287 DI 10.1038/sj.gene.6364383 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 176WP UT WOS:000247115900001 PM 17344889 ER PT J AU Rafiq, S Stevens, K Hurst, AJ Murray, A Henley, W Weedon, MN Bandinelli, S Corsi, AM Guralnik, JM Ferruci, L Melzer, D Frayling, TM AF Rafiq, S. Stevens, K. Hurst, A. J. Murray, A. Henley, W. Weedon, M. N. Bandinelli, S. Corsi, A. M. Guralnik, J. M. Ferruci, L. Melzer, D. Frayling, T. M. TI Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels SO GENES AND IMMUNITY LA English DT Article DE inflammation; genetics; aging ID NF-KAPPA-B; RECEPTOR ANTAGONIST; INFLAMMATORY MARKERS; INSULIN-RESISTANCE; APM1 GENE; FAT MASS; POLYMORPHISM; DISEASE; INCHIANTI; HAPLOTYPES AB Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range = 0.016-4.9 x 10(-5)). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r(2) = 0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r(2) = 0.91), may also be independently associated with IL-1RA levels (P = 0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1 beta (P = 0.03) level and may also be associated with interferon -gamma (P = 0.03), alpha-2 macroglobulin (P = 0.008) and adiponectin (P = 0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels. C1 Peninsula Coll Med & Dent, Exeter, Devon, England. Univ Plymouth, Sch Math & Stat, Plymouth PL4 8AA, Devon, England. ASF, Italian Natl Res Council Aging, Gariatr Rehabil Unit, Lab Clin Epidemiol, Florence, Italy. Tuscany Reg Hlth Agcy, IOT, Florence, Italy. Univ Florence, Dept Med & Surg Crit Care, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Frayling, TM (reprint author), Univ Exeter, Peninsula Med Sch, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM Tim.Frayling@pms.ac.uk OI Murray, Anna/0000-0002-2351-2522; Rafiq, Sajjad/0000-0003-4873-4540; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS; NIA NIH HHS [N01 AG 821336, N01 AG 916413, R01 AG 24233-01] NR 30 TC 57 Z9 58 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2007 VL 8 IS 4 BP 344 EP 351 DI 10.1038/sj.gene.6364393 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 176WP UT WOS:000247115900009 PM 17443229 ER PT J AU Costa, RM Gutierrez, R de Araujo, IE Coelho, MRP Kloth, AD Gainetdinov, RR Caron, MG Nicolelis, MAL Simon, SA AF Costa, R. M. Gutierrez, R. de Araujo, I. E. Coelho, M. R. P. Kloth, A. D. Gainetdinov, R. R. Caron, M. G. Nicolelis, M. A. L. Simon, S. A. TI Dopamine levels modulate the updating of tastant values SO GENES BRAIN AND BEHAVIOR LA English DT Article DE dopamine; learning; reinforcement; reward; taste ID BASOLATERAL AMYGDALA; NUCLEUS-ACCUMBENS; ORBITOFRONTAL CORTEX; LICKING BEHAVIOR; DEVALUATION TASK; MEMORY FORMATION; DORSAL STRIATUM; NMDA RECEPTORS; INSULAR CORTEX; DEFICIENT MICE AB To survive, animals must constantly update the internal value of stimuli they encounter; a process referred to as incentive learning. Although there have been many studies investigating whether dopamine is necessary for reward, or for the association between stimuli and actions with rewards, less is known about the role of dopamine in the updating of the internal value of stimuli per se. We used a single-bottle forced-choice task to investigate the role of dopamine in learning the value of tastants. We show that dopamine transporter knock-out mice (DAT-KO), which have constitutively elevated dopamine levels, develop a more positive bias towards a hedonically positive tastant (sucrose 400 mM) than their wild-type littermates. Furthermore, when compared to wild-type littermates, DAT-KO mice develop a less negative bias towards a hedonically negative tastant (quinine HCl 10 mM). Importantly, these effects develop with training, because at the onset of training DAT-KO and wild-type mice display similar biases towards sucrose and quinine. These data suggest that dopamine levels can modulate the updating of tastant values, a finding with implications for understanding sensory-specific motivation and reward seeking. C1 NIAAA, Sect In Vivo Neural Funct, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC USA. Duke Univ, Med Ctr, Ctr Neuroengn, Durham, NC USA. RP Costa, RM (reprint author), NIAAA, Sect In Vivo Neural Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room TS-20D,MS 9411, Rockville, MD 20852 USA. EM costarui@mail.nih.gov RI Gutierrez, Ranier/B-8130-2011; Gainetdinov, Raul/G-5875-2011; OI Gutierrez, Ranier/0000-0002-9688-0289; Costa, Rui/0000-0003-0495-8374; Gainetdinov, Raul/0000-0003-2951-6038 FU NIDCD NIH HHS [NIH-DC-01065] NR 61 TC 24 Z9 26 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUN PY 2007 VL 6 IS 4 BP 314 EP 320 DI 10.1111/j.1601-183X.2006.00257.x PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 170SI UT WOS:000246684000002 PM 16848782 ER PT J AU Kalueff, AV Fox, MA Gallagher, PS Murphy, DL AF Kalueff, A. V. Fox, M. A. Gallagher, P. S. Murphy, D. L. TI Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice SO GENES BRAIN AND BEHAVIOR LA English DT Article DE activity; anxiety; behavioral phenotype; knockout mice; serotonin syndrome-like behavior; serotonin transporter ID AUTISM SPECTRUM DISORDERS; 5-HT TRANSPORTER; DEFICIENT MICE; MUTANT MICE; OUT MICE; REUPTAKE TRANSPORTER; SOCIAL-INTERACTION; MONOAMINE-OXIDASE; TEST BATTERIES; ANIMAL-MODEL AB Although mice with a targeted disruption of the serotonin transporter (SERT) have been studied extensively using various tests, their complex behavioral phenotype is not yet fully understood. Here we assess in detail the behavior of adult female SERT wild type (+/+), heterozygous (+/-) and knockout (-/-) mice on an isogenic C57BL/6J background subjected to a battery of behavioral paradigms. Overall, there were no differences in the ability to find food or a novel object, nest-building, self-grooming and its sequencing, and horizontal rod balancing, indicating unimpaired sensory functions, motor co-ordination and behavioral sequencing. In contrast, there were striking reductions in exploration and activity in novelty-based tests (novel object, sticky label and open field tests), accompanied by pronounced thigmotaxis, suggesting that combined hypolocomotion and anxiety (rather than purely anxiety) influence the SERT -/- behavioral phenotype. Social interaction behaviors were also markedly reduced. In addition, SERT -/- mice tended to move close to the ground, frequently displayed spontaneous Straub tail, tics, tremor and backward gait - a phenotype generally consistent with 'serotonin syndrome'-like behavior. In line with replicated evidence of much enhanced serotonin availability in SERT -/- mice, this serotonin syndrome-like state may represent a third factor contributing to their behavioral profile. An understanding of the emerging complexity of SERT -/- mouse behavior is crucial for a detailed dissection of their phenotype and for developing further neurobehavioral models using these mice. C1 NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 85 TC 99 Z9 104 U1 3 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUN PY 2007 VL 6 IS 4 BP 389 EP 400 DI 10.1111/j.1601-183X.2006.00270.x PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 170SI UT WOS:000246684000010 PM 16939636 ER PT J AU Merlino, G Khanna, C AF Merlino, Glenn Khanna, Chand TI Fishing for the origins of cancer SO GENES & DEVELOPMENT LA English DT Article ID GENE-EXPRESSION SIGNATURES; MESENCHYMAL PROGENITOR CELLS; STEM-CELLS; RHABDOMYOSARCOMA DEVELOPMENT; EWINGS-SARCOMA; RAS GENES; K-RAS; ZEBRAFISH; MICE; TUMORS C1 NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov; khannac@mail.nih.gov NR 37 TC 16 Z9 17 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 2007 VL 21 IS 11 BP 1275 EP 1279 DI 10.1101/gad.1563707 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 174NH UT WOS:000246948500001 PM 17545462 ER PT J AU Piriyapongsa, J Marino-Ramirez, L Jordan, IK AF Piriyapongsa, Jittima Marino-Ramirez, Leonardo Jordan, I. King TI Origin and evolution of human microRNAs from transposable elements SO GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; HUMAN GENOME; REGULATORY SEQUENCES; NONCODING SEQUENCES; MAMMALIAN MICRORNAS; EPIGENETIC CONTROL; ANIMAL MICRORNAS; GENE ONTOLOGY; ALU ELEMENTS; SMALL RNAS AB We sought to evaluate the extent of the contribution of transposable elements (TEs) to human nuicroRNA (miRNA) genes along with the evolutionary dynamics of TE-derived human miRNAs. We found 55 experimentally characterized human miRNA genes that are derived from TEs, and these TE-derived miRNAs have the potential to regulate thousands of human genes. Sequence comparisons revealed that TE-derived human miRNAs are less conserved, on average, than non-TE-derived miRNAs. However, there are 18 TE-derived miRNAs that are relatively conserved, and 14 of these are related to the ancient L2 and MIR families. Comparison of miRNA vs. mRNA expression patterns for TE-derived miRNAs and their putative target genes showed numerous cases of anti-correlated expression that are consistent with regulation via mRNA degradation. In addition to the known human miRNAs that we show to be derived from TE sequences, we predict an additional 85 novel TE-derived miRNA genes. TE sequences are typically disregarded in genomic Surveys for miRNA genes and target sites; this is a mistake. Our results indicate that. TEs provide a natural mechanism for the origination miRNAs that can contribute to regulatory divergence between species as well as a rich Source for the discovery of as yet unknown miRNA genes. C1 Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, 310 Ferst Dr, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu RI Piriyapongsa, Jittima/F-7581-2012; Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural NIH HHS [Z99 LM999999] NR 79 TC 162 Z9 176 U1 2 U2 6 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2007 VL 176 IS 2 BP 1323 EP 1337 DI 10.1534/genetics.107.072553 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 187TF UT WOS:000247870700047 PM 17435244 ER PT J AU Margulies, EH Cooper, GM Asimenos, G Thomas, DJ Dewey, CN Siepel, A Birney, E Keefe, D Schwartz, AS Hou, MM Taylor, J Nikolaev, S Montoya-Burgos, JI Loytynoja, A Whelan, S Pardi, F Massingham, T Brown, JB Bickel, P Holmes, I Mullikin, JC Ureta-Vidal, A Paten, B Stone, EA Rosenbloom, KR Kent, WJ Antonarakis, SE Batzoglou, S Goldman, N Hardison, R Haussler, D Miller, W Pachter, L Green, ED Sidow, A AF Margulies, Elliott H. Cooper, Gregory M. Asimenos, George Thomas, Daryl J. Dewey, Colin N. Siepel, Adam Birney, Ewan Keefe, Damian Schwartz, Ariel S. Hou, Minmei Taylor, James Nikolaev, Sergey Montoya-Burgos, Juan I. Loytynoja, Ari Whelan, Simon Pardi, Fabio Massingham, Tim Brown, James B. Bickel, Peter Holmes, Ian Mullikin, James C. Ureta-Vidal, Abel Paten, Benedict Stone, Eric A. Rosenbloom, Kate R. Kent, W. James Antonarakis, Stylianos E. Batzoglou, Serafim Goldman, Nick Hardison, Ross Haussler, David Miller, Webb Pachter, Lior Green, Eric D. Sidow, Arend CA NISC Comparative Sequencing Progra Baylor Coll Med Human Genome Seque Washington Univ Genome Sequencing Broad Inst UCSC Genome Browser Team Brit Columbia Canc Agency Genome S TI Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome SO GENOME RESEARCH LA English DT Article ID CONSERVED NONCODING SEQUENCES; TRANSPOSABLE ELEMENTS; REGULATORY ELEMENTS; MAXIMUM-LIKELIHOOD; REGIONS; MOUSE; DNA; VERTEBRATE; EVOLUTION; INSIGHTS AB A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity ( sequence coverage), and specificity ( alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class ( with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. European Bioinformat Inst, Hinxton CB10 1SA, England. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. Univ Geneva, Fac Sci, Dept Zool & Anim Biol, CH-1211 Geneva, Switzerland. Univ Calif Berkeley, Dept Appl Sci & Engn, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. Natl Human Genome Res Inst, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. Penn State Univ, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. BC Canc Res Ctr, BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada. RP Margulies, EH (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM elliott@nhgri.nih.gov RI Hardison, Ross/G-1142-2010; Whelan, Simon/A-6638-2011; Cooper, Gregory/D-6914-2011; Nikolaev, Sergey/F-3148-2012; Taylor, James/F-1026-2011; Tang, Macy/B-9798-2014; Antonarakis, Stylianos/N-8866-2014; Brown, James/H-2971-2015; Marra, Marco/B-5987-2008; Stone, Eric/Q-7840-2016; OI Siepel, Adam/0000-0002-3557-7219; Hardison, Ross/0000-0003-4084-7516; Cooper, Gregory/0000-0001-5509-9923; Taylor, James/0000-0001-5079-840X; Antonarakis, Stylianos/0000-0001-8907-5823; Loytynoja, Ari/0000-0001-5389-6611; Goldman, Nick/0000-0001-8486-2211; Birney, Ewan/0000-0001-8314-8497; Hinrichs, Angie/0000-0002-1697-1130; Field, Matthew/0000-0003-0788-6513; Holmes, Ian/0000-0001-7639-5369 FU Intramural NIH HHS; NHGRI NIH HHS [P41 HG002371, R01 HG002238, R43 HG002632, U01 HG003150, U54 HG003273]; NIGMS NIH HHS [R01 GM076705] NR 72 TC 140 Z9 143 U1 2 U2 7 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 JUN PY 2007 VL 17 IS 6 BP 760 EP 774 DI 10.1101/gr.6034307 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 178NH UT WOS:000247226900009 PM 17567995 ER PT J AU Elnitski, L Shah, P Moreland, RT Umayam, L Wolfsberg, TG Baxevanis, AD AF Elnitski, Laura Shah, Prachi Moreland, R. Travis Umayam, Lowell Wolfsberg, Tyra G. Baxevanis, Andreas D. TI The ENCODEdb portal: Simplified access to ENCODE consortium data SO GENOME RESEARCH LA English DT Article ID ELEMENTS AB The Encyclopedia of DNA Elements ( ENCODE) project aims to identify and characterize all functional elements in a representative chromosomal sample comprising 1% of the human genome. Data generated by members of The ENCODE Project Consortium are housed in a number of public databases, such as the UCSC Genome Browser, NCBI's Gene Expression Omnibus ( GEO), and EBI's ArrayExpress. As such, it is often difficult for biologists to gather all of the ENCODE data from a particular genomic region of interest and integrate them with relevant information found in other public databases. The ENCODEdb portal was developed to address this problem. ENCODEdb provides a unified, single point-of-access to data generated by the ENCODE Consortium, as well as to data from other source databases that lie within ENCODE regions; this provides the user a complete view of all known data in a particular region of interest. ENCODEdb Genomic Context searches allow for the retrieval of information on functional elements annotated within ENCODE regions, including mRNA, EST, and STS sequences; single nucleotide polymorphisms, and UniGene clusters. Information is also retrieved from GEO, OMIM, and major genome sequence browsers. ENCODEdb Consortium Data searches allow users to perform compound queries on array-based ENCODE data available both from GEO and from the UCSC Genome Browser. Results are retrieved from a specific genomic area of interest and can be further manipulated in a variety of contexts, including the UCSC Genome Browser and the Galaxy large-scale genome analysis platform. The ENCODEdb portal is freely accessible at http://research.nhgri.nih.gov/ENCODEdb. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM andy@nhgri.nih.gov FU Intramural NIH HHS NR 10 TC 7 Z9 7 U1 1 U2 3 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 JUN PY 2007 VL 17 IS 6 BP 954 EP 959 DI 10.1101/gr.5582207 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 178NH UT WOS:000247226900027 PM 17568011 ER PT J AU Gerhold, D Bagchi, A Lu, MQ Figueroa, D Keenan, K Holder, D Wang, YH Jin, H Connolly, B Austin, C Alonso-Galicia, M AF Gerhold, David Bagchi, Ansuman Lu, Meiqing Figueroa, David Keenan, Kevin Holder, Dan Wang, Yuhong Jin, Hong Connolly, Brett Austin, Christopher Alonso-Galicia, Magdalena TI Androgens drive divergent responses to salt stress in male versus female rat kidneys SO GENOMICS LA English DT Article DE kidney; hypertension; rat; sex; gene expression; microarrays; angiotensin-vasopressin receptor; prolactin receptor; 5 alpha-reductase ID GROWTH-FACTOR-BETA; GENE-EXPRESSION; CRESCENTIC GLOMERULONEPHRITIS; ESSENTIAL-HYPERTENSION; RENAL INJURY; FACTOR-I; METABOLISM; GENDER; TISSUE; TUBULES AB Dahl-Iwai (DI) salt-sensitive rats were studied using microarrays to identify sex-specific differences in the kidney, both basal differences and differences in responses to a high-salt diet. In DI rat kidneys, gene expression profiles demonstrated inflammatory and fibrotic responses selectively in females. Gonadectomy of DI rats abrogated sex differences in gene expression. Gonadectomized female and gonadectornized male DI rats both responded to high salt with the same spectrum of gene expression changes as intact female DI rats. Androgens dominated' the sex-selective responses to salt. Several androgen-responsive genes with roles potentiating the differential responses to salt were identified, including increased male expression of angiotensin-vasopressin receptor and prolactin receptor, decreased 5 alpha-reductase, and mixed increases and decreases in expression of Cyp4a genes that can produce eicosanoid hormones. These sex differences potentiate sodium retention by males and increase kidney function during gestation in females. (c) 2007 Elsevier Inc. All rights reserved. C1 Merck Res Labs, Dept Safety Assessment, West Point, PA 19486 USA. Merck Res Labs, Dept Comp Sci & Appl Math, West Point, PA 19486 USA. Merck Res Labs, Dept Antiviral Res, West Point, PA 19486 USA. Merck Res Labs, Dept Biometr, West Point, PA 19486 USA. Merck Res Labs, Dept Imaging, West Point, PA 19486 USA. Merck Res Labs, Dept Cardiovasc Dis, West Point, PA 19486 USA. NIH, Chem Genom Ctr, Gaithersburg, MD 20892 USA. RP Gerhold, D (reprint author), Merck Res Labs, Dept Safety Assessment, West Point, PA 19486 USA. EM david_gerhold@merck.com NR 47 TC 11 Z9 12 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 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2007 VL 89 IS 6 BP 731 EP 744 DI 10.1016/j.ygeno.2007.01.009 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 171YC UT WOS:000246770300009 PM 17481853 ER PT J AU Dainty, LA Risinger, JI Morrison, C Chandramouli, GVR Bidus, MA Zahn, C Rose, GS Fowler, J Berchuck, A Maxwell, GL AF Dainty, Louis A. Risinger, John I. Morrison, Carl Chandramouli, G. V. R. Bidus, Michael A. Zahn, Chris Rose, G. Scott Fowler, Jeff Berchuck, Andrew Maxwell, G. Larry TI Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Gynecologic-Oncologists CY MAR 19-23, 2005 CL Miami Beach, FL SP Soc Gynecol Oncologists DE folate binding protein; papillary serous; gynecologic tumors ID GENE-EXPRESSION PROFILES; HUMAN OVARIAN-CARCINOMA; TISSUE MICROARRAY ANALYSIS; DIFFERENT HISTOLOGIC TYPES; ENDOMETRIAL CANCER; ANTITUMOR-ACTIVITY; IN-VITRO; RECEPTOR; ANTIGEN; ALPHA AB Purpose. Folate receptor alpha (FOLR1) is a membrane bound receptor involved in the transport of folate as well as other regulatory cellular processes. The purpose of this study was to examine the expression of FOLR1 in uterine cancers and to identify changes in gene expression that are associated with overexpression of FOLR1. Experimental design. Fifty-eight frozen uterine cancer specimens were stained for FOLR1 using immunohistochemistry and results were correlated with transcript expression noted on quantitative PCR. Total RNA from 16 cases of uterine serous carcinoma (USC) was analyzed for gene expression using the Affymetrix HG-U133A and HG-U133B GeneChip set. USCs overexpressing FOLR1 were compared to cancers with an absence of FOLR1 using binary comparison and template matching of data was used to identify genes that correlate with FOLR1 expression. Selected targets from this analysis were evaluated by quantitative PCR as well as in an independent set of USC represented in quadruplicate on a tissue microarray (TMA). Results. Overexpression of FOLR1 was observed in 11/16 (69%) of USC and 0/10 normal endometrium cases using frozen tissue specimens. Binary comparison between FOLR1 positive and negative cases identified 121 genes altered by 2-fold at p < 0.01 of which 45 are well correlated with FOLR1 expression pattern. Using quantitative PCR, both mesothelin (MSLN) and PTGS1 (COX1) were significantly increased in FOLR1 overexpressing tumors (p = 0.014 and p = 0.006 respectively). TMA confirmed that overexpression of FOLR1 and MSLN respectively occurred in 23/48 (48%) and 17/54 (32%) of pure USC. Conclusion. Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy. (c) 2007 Published by Elsevier Inc. C1 Walter Reed Army Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. Mem Hlth Univ, Med Ctr, Dept Lab Oncol Res, Curtis & Elizabeth Anderson Canc Inst, Savannah, GA 31404 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Div Gynecol Oncol, James Canc Ctr, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC 27110 USA. RP Maxwell, GL (reprint author), Walter Reed Army Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, 6900 Georgia Ave,NW, Washington, DC 20307 USA. EM george.maxwell@na.amedd.army.mil NR 36 TC 44 Z9 48 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2007 VL 105 IS 3 BP 563 EP 570 DI 10.1016/j.ygyno.2006.10.063 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 172PG UT WOS:000246815700002 PM 17400285 ER PT J AU Kuehl, M Brents, L Cultraro, C Demchenko, Y Dib, A Gabrea, A Zingone, A Staudt, L Barlogie, B Shaughnessy, J Bergsagel, PL AF Kuehl, M. Brents, L. Cultraro, C. Demchenko, Y. Dib, A. Gabrea, A. Zingone, A. Staudt, L. Barlogie, B. Shaughnessy, J. Bergsagel, P. L. TI Molecular lesions in multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE ID GENE C1 NCI, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Mayo Clin, Scottsdale, AZ USA. NR 10 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 IS 6 SU 2 BP 2 EP 3 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800003 ER PT J AU Hill, A Reid, SA Rother, RP Gladwin, MT Collinson, PO Gaze, DC Lowe, A Guthrie, A Sivananthan, MU Hillmen, P AF Hill, A. Reid, S. A. Rother, R. P. Gladwin, M. T. Collinson, P. O. Gaze, D. C. Lowe, A. Guthrie, A. Sivananthan, M. U. Hillmen, P. TI High definition contrast-enhanced MR imaging in paroxysmal nocturnal hemoglobinuria suggests a high frequency of subclinical thrombosis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Gen Infirm, Leeds LS1 3EX, W Yorkshire, England. NIH, Bethesda, MD 20892 USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. NR 0 TC 2 Z9 2 U1 0 U2 1 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 JUN PY 2007 VL 92 SU 1 MA 0066 BP 24 EP 25 PG 2 WC Hematology SC Hematology GA 177UB UT WOS:000247176900068 ER PT J AU Chng, WJ Kuehl, WM Bergsagel, PL AF Chng, W. J. Kuehl, W. M. Bergsagel, P. L. TI Synthesis of genetic and molecular prognostic models in myeloma (MM) SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Mayo Clin, Scottsdale, AZ USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 IS 6 SU 2 BP 110 EP 110 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800154 ER PT J AU Weichsel, R Dix, C Zezula, J Greiner, E Price, DA Einsele, H Seggewiss, R AF Weichsel, R. Dix, C. Zezula, J. Greiner, E. Price, D. A. Einsele, H. Seggewiss, R. TI Dasatinib inhibits T cell activation and proliferation in a dose-dependent manner SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Univ Wurzburg, Wurzburg, Germany. NIDDK, Med Chem Lab, Bethesda, MD 20892 USA. NIH, VRC, Human Immunol Sect, Bethesda, MD 20892 USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 SU 1 MA 0320 BP 115 EP 116 PG 2 WC Hematology SC Hematology GA 177UB UT WOS:000247176900322 ER PT J AU Janz, S Morse, HC AF Janz, S. Morse, H. C., III TI Plasma cell tumors in transgenic mice SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 NIAID, NIH, Immunopathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 IS 6 SU 2 BP 124 EP 124 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800201 ER PT J AU Schrezenmeier, H Luzzatto, L Rotoli, B Young, NS Schubert, J Urbano-Ispizua, A Coyle, L DeCastro, C Fu, CL Maciejewski, JP Kroon, HA Rother, RP Hillmen, P AF Schrezenmeier, H. Luzzatto, L. Rotoli, B. Young, N. S. Schubert, J. Urbano-Ispizua, A. Coyle, L. DeCastro, C. Fu, C. L. Maciejewski, J. P. Kroon, H. A. Rother, R. P. Hillmen, P. TI Safety and efficacy of theterminal complement inhibitor eculizumab in patients with paroxysmal nocturnal hemoglobinuria: Shepherd phase III clinical study results SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Univ Hosp Ulm, Ulm, Germany. Ist Toscano Tumori, Florence, Italy. Poloclin Napoli Federico II, Naples, Italy. NHLBI, Bethesda, MD 20892 USA. Univ Saarland, Sch Med, D-6650 Homburg, Germany. Hosp Clin Barcelona, Barcelona, Spain. Royal N Shore Hosp, St Leonards, NSW 2065, Australia. Duke Univ, Med Ctr, Durham, NC USA. Cleveland Clin, Weston, FL USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Alexion Pharmaceut Inc, Cheshire, CT USA. Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 SU 1 MA 0378 BP 137 EP 137 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900380 ER PT J AU Hillmen, P Muus, P Duhrsen, U Risitano, A Schubert, J Young, NS Schrezenmeier, H Szer, J Brodsky, RA Hill, A Socie, G Bessler, M Rollins, SA Rother, RP Bell, L Luzzatto, L AF Hillmen, P. Muus, P. Duehrsen, U. Risitano, A. Schubert, J. Young, N. S. Schrezenmeier, H. Szer, J. Brodsky, R. A. Hill, A. Socie, G. Bessler, M. Rollins, S. A. Rother, R. P. Bell, L. Luzzatto, L. TI Theterminal complement inhibitor eculizumab reduces thrombosis in patients with paroxysmal nocturnal hemoglobinuria SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 12th Congress of the European-Hematology-Association CY JUN 07-10, 2007 CL Vienna, AUSTRIA SP European Hematol Assoc C1 Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. Radbound Univ, Nijmegen, Netherlands. Univ Essen Gesamthsch, Essen, Germany. Med Federico II Univ, Naples, Italy. Univ Saarland, Sch Med, D-6650 Homburg, Germany. NHLBI, Bethesda, MD 20892 USA. Univ Hosp Ulm, Ulm, Germany. Royal Melbourne Hosp, Melbourne, Vic, Australia. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Hosp St Louis, INSERM, Paris, France. Washington Univ, Sch Med, St Louis, MO USA. Alexion Pharmaceut Inc, Cheshire, CT USA. Ist Toscano Tumori, Florence, Italy. RI Muus, P./L-4539-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 SU 1 MA 0380 BP 138 EP 138 PG 1 WC Hematology SC Hematology GA 177UB UT WOS:000247176900382 ER PT J AU Kiziltepe, T Hideshima, T Raje, N Ishitsuka, K Ocio, EM Catley, L Li, CQ Trudel, L Yasui, H Shirashi, N Tai, YT Chauhan, D Mitsiades, C Saavedra, JE Wong, GN Keefer, LK Shami, PJ Anderson, KC AF Kiziltepe, T. Hideshima, T. Raje, N. Ishitsuka, K. Ocio, E. M. Catley, L. Li, C. Q. Trudel, L. Yasui, H. Shirashi, N. Tai, Y. T. Chauhan, D. Mitsiades, C. Saavedra, J. E. Wong, G. N. Keefer, L. K. Shami, P. J. Anderson, K. C. TI The in vitro and in vivo anti-tumor effects of JS-K in MM SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, MIT, Biol Engn Div, Cambridge, MA 02139 USA. SAIC, Frederick, MD USA. NCI, NIH, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. Univ Utah, Dept Med Oncol, Salt Lake City, UT 84112 USA. Salt Lake City Vet Adm Med Ctr, Salt Lake City, UT USA. RI Catley, Laurence/E-5313-2013; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 IS 6 SU 2 BP 139 EP 140 PG 2 WC Hematology SC Hematology GA 181GS UT WOS:000247425800249 ER PT J AU Janz, S Potter, M AF Janz, S. Potter, M. TI Transgenic mouse models of macroglobulinemia waldenstrom SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 11th International Myeloma Workshop/4th International Workshop on Wladenestroms Macroglobulinemia CY JUN 25-30, 2007 CL Kos Isl, GREECE C1 NIH, NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2007 VL 92 IS 6 SU 2 BP 221 EP 221 PG 1 WC Hematology SC Hematology GA 181GS UT WOS:000247425800512 ER PT J AU Wragg, A Mellad, J San, H Mathur, A Boehm, M AF Wragg, A. Mellad, J. San, H. Mathur, A. Boehm, M. TI Genetic lineage tracking of haematopietic cells using the Cre/Lox system to investigate the role of endothelial progenitor cells in normal vascular development and after vascular injury in mice SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society CY JUN 04-07, 2007 CL Glasgow, SCOTLAND SP British Cardiovasc Soc C1 London Chest Hosp, London E2 9JX, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUN PY 2007 VL 93 SU 1 BP A98 EP A99 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171ND UT WOS:000246741800263 ER PT J AU Reddy, AB Maywood, ES Karp, NA King, VM Inoue, Y Gonzalez, FJ Lilley, KS Kyriacou, CP Hastings, MH AF Reddy, Akhilesh B. Maywood, Elizabeth S. Karp, Natasha A. King, Verdun M. Inoue, Yusuke Gonzalez, Frank J. Lilley, Kathryn S. Kyriacou, Charalambos P. Hastings, Michael H. TI Glucocorticoid signaling synchronizes the liver circadian transcriptome SO HEPATOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; GENE-EXPRESSION; PERIPHERAL-TISSUES; SUPRACHIASMATIC NUCLEUS; MICROARRAY ANALYSIS; MOUSE-LIVER; IN-VIVO; CLOCK; CELLS; OSCILLATORS AB Circadian control of physiology is mediated by local, tissue-based clocks, synchronized to each other and to solar time by signals from the suprachiasmatic nuclei (SCN), the master oscillator in the hypothalamus. These local clocks coordinate the transcription of key pathways to establish tissue-specific daily metabolic programs. How local transcriptomes are synchronized across the organism and their relative contribution to circadian output remain unclear. In the present study we showed that glucocorticoids alone are able to synchronize expression of about 60% of the circadian transcriptome. We propose that synchronization occurs directly by the action of glucocorticoids on a diverse range of downstream targets and indirectly by regulating the core clock genes mPer1, Bmal1, mCry1, and Dbp. We have identified the pivotal liver transcription factor, HNF4 alpha, as a mediator of circadian and glucocorticoid-regulated. transcription, showing that it is a key conduit for downstream targeting. Conclusion: We have demonstrated that by orchestrating transcriptional cascades, glucocorticoids are able to direct synchronization of a diverse range of functionally important circadian genes. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Cambridge Ctr Proteom, Cambridge, England. Univ Cambridge, Dept Anat, Cambridge, England. NCI, Bethesda, MD 20892 USA. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. RP Reddy, AB (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. EM areddy@cantab.net OI Karp, Natasha/0000-0002-8404-2907; Hastings, Michael Harvey/0000-0001-8576-6651 FU Biotechnology and Biological Sciences Research Council [BB/C006941/1]; Medical Research Council [MC_U105170643] NR 32 TC 110 Z9 115 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2007 VL 45 IS 6 BP 1478 EP 1488 DI 10.1002/hep.21571 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 175KC UT WOS:000247011500020 PM 17538967 ER PT J AU Jaeschke, H Liu, J AF Jaeschke, Hartmut Liu, Jie TI Neutrophil depletion protects against murine acetaminophen hepatotoxicity: Another perspective SO HEPATOLOGY LA English DT Letter ID LIVER C1 Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. NIEHS, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Jaeschke, H (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. NR 9 TC 33 Z9 34 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2007 VL 45 IS 6 BP 1588 EP 1589 DI 10.1002/hep.21549 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 175KC UT WOS:000247011500036 PM 17539019 ER PT J AU Date, T Miyamoto, M Kato, T Morikawa, K Murayama, A Akazawa, D Tanabe, J Sone, S Mizokami, M Wakita, T AF Date, Tomoko Miyamoto, Michiko Kato, Takanobu Morikawa, Kenichi Murayama, Asako Akazawa, Daisuke Tanabe, Junichi Sone, Saburo Mizokami, Masashi Wakita, Takaji TI An infectious and selectable full-length replicon system with hepatitis C virus JFH-1 strain SO HEPATOLOGY RESEARCH LA English DT Article DE hepatitis C virus; infectious virus; replicon; RNA replication ID NON-B-HEPATITIS; CELL-CULTURE; RNA REPLICATION; EFFICIENT REPLICATION; SUBGENOMIC REPLICON; NON-A; SEQUENCE-ANALYSIS; CDNA-CLONE; GENOME; MUTATIONS AB Aim: The hepatitis C virus (HCV) strain JFH-1 was cloned from a patient with fulminant hepatitis. A JFH-1 subgenomic replicon and full-length JFH-1 RNA efficiently replicate in cultured cells. In this study, an infectious, selectable HCV replicon containing full-length JFH-1 cDNA was constructed. Methods: The full-genome replicon was constructed using the neomycin-resistant gene, EMCV IRES and wild-type JFH-1 cDNA. Huh7 cells were transfected with RNA synthesized in vitro, and then cultured with G418. Independent colonies were cloned to establish cell lines that replicate the full-length HCV replicon. Results: HCV RNA replication was detected in each isolated cell line. HCV proteins and HCV RNA were secreted into culture medium, and exhibited identical density profiles. Interestingly, culture supernatants of the replicon cells were infectious for naive Huh7 cells. Long-term culture did not affect replication of replicon RNA in the replicon cells, but it reduced core protein secretion and infectivity of culture supernatant. Culture supernatant obtained after serial passage of replicon virus was infectious for Huh7 cells. Conclusion: Selectable infection was established using HCV replicon containing full-length genotype 2a JFH-1 cDNA. This system might be useful for HCV research. C1 Tokyo Metropolitan Inst Neurosci, Dept Microbiol, Tokyo, Japan. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi, Japan. Toray Industries Ltd, Pharmaceut Res Lab, Kanagawa, Japan. NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RP Wakita, T (reprint author), Natl Inst Infect Dis, Dept Virol 2, 1-23-1 Toyama, Tokyo 1628640, Japan. EM wakita@nih.go.jp NR 31 TC 17 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD JUN PY 2007 VL 37 IS 6 BP 433 EP 443 DI 10.1111/j.1872-034X.2007.00056.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172GY UT WOS:000246793400007 PM 17437527 ER PT J AU Stratakis, CA Bornstein, SR AF Stratakis, C. A. Bornstein, S. R. TI Symposium on cortisol secretion abnormalities honoring Dr. George P. Chrousos SO HORMONE AND METABOLIC RESEARCH LA English DT Editorial Material DE cushing syndrome; cortisol resistance; hypothalamic-pituitaryadrenal axis; congenital adrenal hyperplasia; adrenal tumors; depression; corticotrophin-feleasing hormone (CRH) ID FAMILIAL GLUCOCORTICOID RESISTANCE; CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL AXIS; CUSHINGS-SYNDROME; MOLECULAR-MECHANISMS; STIMULATION TEST; CARNEY COMPLEX; INFLAMMATION; DEPRESSION; DIAGNOSIS C1 NICHD, DEB, Pediat Endocrinol Interinst Training Program, Hertiable Disorders Branch, Bethesda, MD 20892 USA. Tech Univ Dresden, Dept Internal Med, Dresden, Germany. RP Stratakis, CA (reprint author), NICHD, DEB, Pediat Endocrinol Interinst Training Program, Hertiable Disorders Branch, Bethesda, MD 20892 USA. EM stratakc@ccl.nichd.nih.gov NR 30 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2007 VL 39 IS 6 BP 401 EP 403 DI 10.1055/s-2007-980199 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 185SP UT WOS:000247731000001 PM 17578755 ER PT J AU Butts, CL Shukair, SA Duncan, KM Harris, CW Belyavskaya, E Sternberg, EM AF Butts, C. L. Shukair, S. A. Duncan, K. M. Harris, C. W. Belyavskaya, E. Sternberg, E. M. TI Effects of dexamethasone on rat dendritic cell function SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Cortisol Secretion Abnormalities CY JUN, 2006 CL Bethesda, MD SP NICHD DE steroid hormones; immune cell modulation; antigen presenting/processing ID STRESS HORMONES; NEUROENDOCRINE REGULATION; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSE; TNF-ALPHA; IL-12; GLUCOCORTICOIDS; INDUCTION; INCREASES; CYTOKINES AB Glucocorticoids have been reported to affect immunity at varying concentrations. While glucocorticoids have shown profound effects on innate immunity, their effects on rat dendritic cells have not been fully examined. In this study, we evaluated the effects of the synthetic glucocorticoid dexamethasone on cultured rat dendritic cells (DCs) from spleen and derived from bone marrow cells to determine whether responsiveness to dexamethasone varies between DCs from different organ sites. Cells were analyzed for expression of glucocorticoid receptor (GR), the primary receptor through which clexamethasone exerts its effects and was found to be primarily located in the cytoplasm of immature DCs. Bone marrow-derived DCs showed more sensitivity to dexamethasone treatment compared to splenic DCs. Dexamethasone treatment of LPS-matured DCs had profound dose-dependent effects on cytokine production. Dexamethasone treatment also led to a dose-dependent downregulation of expression of costimulatory molecules by mature DCs. Dexamethasone modified immature DC uptake of antigen (FITC-Dextran), with slightly higher numbers of splenic DCs taking up antigen compared to bone marrow-derived DCs. These data suggest that dexamethasone is able to similarly affect both bone marrowderived and splenic DC function at the immature and mature DC states and could contribute to exacerbation of infection by hindering DC-mediated immune responses. C1 Natl Inst Mental, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), Natl Inst Mental, Sect Neuroendocrine Immunol & Behav, NIH, 5626 Fishers Lane Room 4N15, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov NR 40 TC 8 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2007 VL 39 IS 6 BP 404 EP 412 DI 10.1055/s-2007-980195 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 185SP UT WOS:000247731000002 PM 17578756 ER PT J AU Kino, T AF Kino, T. TI Tissue glucocorticoid sensitivity: Beyond stochastic regulation on the diverse actions of glucocorticoids SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Cortisol Secretion Abnormalities CY JUN, 2006 CL Bethesda, MD SP NICHD DE tissue glucocorticoid sensitivity; glucocorticoid receptor; cyclin-dependent kinase 5 ID CYCLIN-DEPENDENT KINASE-5; PITUITARY-ADRENAL AXIS; RECEPTOR; PHOSPHORYLATION; RESISTANCE; CDK5; P25; P35; TARGET; NEUROFILAMENT AB Glucocorticoids have a broad array of life-sustaining functions, such as for the maintenance of the basal- and stress-related organ homeostasis. They are also frequently used as therapeutic compounds for many pathologic conditions. Thus, changes of tissue sensitivity to glucocorticoids play important roles in the physiologic conditions and are associated with and influence the course of numerous pathologic states. Changes in tissue glucocorticoid sensitivity may present on either side of an optimal range, respectively as glucocorticoid resistance or hypersensitivity, and may be generalized or tissue-specific. Recent insights into the mechanisms of the glucocorticoid receptor (GR) action indicated that the glu-cocorticoid signaling system is highly stochastic. Indeed, numerous factors contribute to the hormonal action at each step of the GR signaling cascade, such as ligand availability, receptor isoform expression, intracellular circulation, promoter association, attraction of cofactors, and finally clearance of the receptor from the target genes. Importantly, these regulatory mechanisms appear to be functional in tissue-, gene- and cellular biologic state-specific fashions. As an example of such phase-specific factors, we discussed influence of the cyclin-dependent kinase 5 to the GR transcriptional activity, which specifically functions in the central nervous system and may thus play an important role in the regulation of glucocorticoid action in this organ. C1 Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, Pediat Endocrinol Sect, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, Pediat Endocrinol Sect, NIH, Bldg 10 Clin Res Ctr,Rm 1-3140 10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Intramural NIH HHS NR 43 TC 32 Z9 32 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2007 VL 39 IS 6 BP 420 EP 424 DI 10.1055/s-2007-980193 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 185SP UT WOS:000247731000004 PM 17578758 ER PT J AU Charmandari, E Kino, T AF Charmandari, E. Kino, T. TI Novel causes of generalized glucocorticoid resistance SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Cortisol Secretion Abnormalities CY JUN, 2006 CL Bethesda, MD SP NICHD DE glucocorticoid receptor (GR); glucocorticoid resistance; mutations human glucocorticoid receptor (hGR) gene ID LIGAND-BINDING DOMAIN; PRIMARY CORTISOL RESISTANCE; RESISTANCE/HYPERSENSITIVITY SYNDROMES; CLINICAL PHENOTYPE; POINT MUTATION; RECEPTOR GENE; GR; DISEASE AB Glucocorticoid resistance is a rare condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. Compensatory elevations in circulating adrenocorticotropic hormone (ACTH) concentrations lead to increased secretion of cortisol and adrenal steroids with mineralocorticoid and/or androgenic activity, but no clinical evidence of hypercortisolism. The clinical spectrum of the condition is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue and/or mineralocorticoid excess. The molecular basis of glucocorticoid resistance has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction, thereby altering tissue sensitivity to glucocorticoids. The study of functional defects of natural hGR mutants enhances our understanding of the molecular mechanisms of hGR action and highlights the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology. C1 Natl Inst Child Hlth & Human Dev, Reprod Biol & Med Branch, Sect Pediat Endocrinol, NIH, Bethesda, MD USA. RP Charmandari, E (reprint author), Leeds Gen Infirm, Level B,Room 134 Claredon Wing Belgrove Grove, Leeds LS2 9NS, W Yorkshire, England. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS NR 22 TC 11 Z9 11 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2007 VL 39 IS 6 BP 445 EP 450 DI 10.1055/s-2007-980196 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 185SP UT WOS:000247731000008 PM 17578762 ER PT J AU Stratakis, CA AF Stratakis, C. A. TI Adrenocortical tumors, primary pigmented adrenocortical disease (PPNAD)/Carney complex, and other bilateral hyperplasias: the NIH studies SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Cortisol Secretion Abnormalities CY JUN, 2006 CL Bethesda, MD SP NICHD DE adrenal cortex genetics; tumor; primary pigmented adreno cortical disease (PPNAD); carney complex; hyperplasias ID PSAMMOMATOUS MELANOTIC SCHWANNOMA; FAMILIAL ADENOMATOUS POLYPOSIS; BECKWITH-WIEDEMANN SYNDROME; ADRENAL-CORTICAL CARCINOMA; SPOTTY SKIN PIGMENTATION; INCLUDING CARDIAC MYXOMA; LINE P53 MUTATIONS; CARNEY-COMPLEX; ENDOCRINE OVERACTIVITY; CUSHINGS-SYNDROME AB It has been estimated that up to 1 in 10 adults has at least one adrenocortical nodule up to 1 cm on autopsy; these benign tumors may contribute to metabolic syndrome, hypertension, obesity and abnormalities of the hypothalamic-pituitary adrenal (HPA) axis that can be linked to other serious disorders such as osteoporosis, depression and late-onset diabetes mellitus. In addition, up to 1 in 1500 of these adrenal "incidentalomas" may hide a carcinoma, which, if diagnosed late or left untreated, is associated with significant morbidity and mortality. Consistent with the theme of this symposium, in the present report, we review the efforts undertaken at the National Institutes of Health (NIH) in the last quarter century to unravel the complex clinical genetics and molecular mechanisms involved in adrenal tumorigenesis. We first proposed that adrenocortical tumors form in a molecular sequence of events similar to that in other organs: as the pathology of the tumor increases towards malignancy, genetic changes accumulate. For example, known genetic associations, like TP53 gene changes, occur during the latest stages of adrenocortical tumorigenesis. At the NIH, significant progress has been made in the understanding of the genetics of primary pigmented adrenocortical disease (PPNAD) and other forms of bilateral adrenocortical hyperplasias. This recently led to the identification of phosphodiesterase 11 A (PDE11A) mutations as a low-penetrance predisposing factor to adrenocortical hyperplasias of both the pigmented and non-pigmented variants. C1 Natl Inst Child Hlth & Human Dev, Program Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Natl Inst Child Hlth & Human Dev, Program Genet & Endocrinol, NIH, Bldg 10 CRC Room 1 East 3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS NR 96 TC 38 Z9 39 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2007 VL 39 IS 6 BP 467 EP 473 DI 10.1055/s-2007-981477 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 185SP UT WOS:000247731000012 PM 17578766 ER PT J AU Giedd, JN Schmitt, JE Neale, MC AF Giedd, Jay N. Schmitt, James Eric Neale, Michael C. TI Structural brain magnetic resonance imaging of pediatric twins SO HUMAN BRAIN MAPPING LA English DT Review DE child development; adolescent development; heredity; neuroanatomy; cerebellum ID MRI DATA; EVOLUTION AB To explore the relative impact of genetic and nongenetics factors on human brain anatomy during childhood and adolescence development, a collaborative team from the Child Psychiatry Branch of the National Institute of Mental Health and Virginia Commonwealth University is applying structural equation modeling to brain morphometric data acquired via magnetic resonance imaging from a large sample of monozygotic and dizygotic pediatric subjects. In this report, we discuss methodologic issues related to pediatric neuroimaging twin studies and synthesize results to date from the project. Current sample size from the ongoing longitudinal study is approximately 150 twin pairs. Consistent themes are: (1) heritability is high and shared environmental effects low for most brain morphometric measures; (2) the cerebellum has a distinct heritability profile; (3) genetic and environmental factors contribute to the development of the cortex in a regional and age specific manner; and (4) shared genetic effects account for more of the variance than structure specific effects. Understanding of influences on trajectories of brain development may shed light on the emergence of psychopathology during childhood and adolescence and ultimately may guide therapeutic interventions. C1 NIMH, Brain Imaging Unit, Child Psychiat Branch, NIH,Dept Hltlh & Human Serv, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA 23298 USA. RP Giedd, JN (reprint author), NIMH, Brain Imaging Unit, Child Psychiat Branch, NIH,Dept Hltlh & Human Serv, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Neale, Michael/B-1418-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 27 TC 38 Z9 38 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2007 VL 28 IS 6 BP 474 EP 481 DI 10.1002/hbm.20403 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 169YV UT WOS:000246628900003 PM 17437295 ER PT J AU Nieman, BJ Lerch, JP Bock, NA Chen, XJ Sled, JG Henkelman, RM AF Nieman, Brian J. Lerch, Jason P. Bock, Nicholas A. Chen, X. Josette Sled, John G. Henkelman, R. Mark TI Mouse behavioral mutants have neuroimaging abnormalities SO HUMAN BRAIN MAPPING LA English DT Article DE neuroanatomy; diagnostic imaging; magnetic resonance imaging; imaging; three-dimensional; phenotype; mice; mice, mutant strains; mice, transgenic ID FALSE DISCOVERY RATE; DEFICIT-HYPERACTIVITY DISORDER; AUTOMATED IMAGE REGISTRATION; HUNTINGTONS-DISEASE; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; CORPUS-CALLOSUM; BRAIN; MRI; VALIDATION AB Impaired cognitive, memory, or motor performance is a distinguishing characteristic of neurological diseases. Although these symptoms are frequently the most evident in human patients, additional markers of disease are critical for proper diagnosis and staging. Noninvasive neuroimaging methods have become essential in this capacity and provide means of evaluating disease and tracking progression. These imaging methods are also becoming available to scientists in the research laboratory for assessment of animal models of neurological disease. Imaging in mouse models of neurological disease is of particular interest, owing to the availability of inbred strains and genetic manipulation tools that permit detailed investigation of the roles of various genes and gene products in disease pathogenesis. However, the relative prevalence of neuroimaging abnormalities in mice exhibiting neurological symptoms has not been reported. This prevalence has both theoretical and practical value because it is influenced by both the sensitivity of macroscopic anatomical measures to underlying genetic and disease processes and by the efficiency of neuroimaging in detecting and characterizing these effects. In this paper, we describe a meta-analysis of studies involving behavioral mouse mutants at our laboratory. In summary, we have evaluated 15 different mutant genotypes, of which 13 showed abnormal neuroimaging findings. This indicates a surprisingly high prevalence of neuroimaging abnormalities (87%) and suggests that disease processes affecting behavior generally alter neuroanatomy as well. As a consequence, neuroimaging provides a highly sensitive marker of neurological disease in mice exhibiting abnormal behavior. C1 Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M4X 1K9, Canada. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10012 USA. NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Henkelman, RM (reprint author), Hosp Sick Children, Mouse Imaging Ctr, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM mhenkel@phenogenomics.ca RI Sled, John/D-8268-2012; Henkelman, Mark/F-3662-2011 OI Sled, John/0000-0002-4461-283X; NR 43 TC 25 Z9 25 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2007 VL 28 IS 6 BP 567 EP 575 DI 10.1002/hbm.20408 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 169YV UT WOS:000246628900011 PM 17437292 ER PT J AU Li, HL Romieu, I Wu, H Sienra-Monge, JJ Ramirez-Aguilar, M del Rio-Navarro, BE del Lara-Sanchez, IC Kistner, EO Gjessing, HK London, SJ AF Li, Huiling Romieu, Isabelle Wu, Hao Sienra-Monge, Juan-Jose Ramirez-Aguilar, Matiana del Rio-Navarro, Blanca Estela del Lara-Sanchez, Irma Carmen Kistner, Emily O. Gjessing, Hakon K. London, Stephanie J. TI Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy SO HUMAN GENETICS LA English DT Article DE TGFB1; asthma; allergy; polymorphism; genetic; SNP ID CASE-PARENT TRIADS; SINGLE-NUCLEOTIDE POLYMORPHISMS; SMOOTH-MUSCLE-CELLS; LINKAGE DISEQUILIBRIUM; TGF-BETA-1 GENE; GROWTH-FACTOR-BETA-1 GENE; BRONCHIAL-ASTHMA; LUNG-DISEASE; ASSOCIATION; FIBROSIS AB Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR) = 1.42, 95% confidence interval (CI) = 1.08-1.87 for one copy; RR (95%CI) = 1.95 (1.36-2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09-1.98) for one and 2.00 (1.38-2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR = 1.48, 95% CI = 1.11-1.95 for one copy; RR = 1.77, 95% CI = 1.22-2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders. C1 NIEHS, Epidemiol Branch, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Norwegian Inst Publ Hlth, Oslo, Norway. RP Li, HL (reprint author), NIEHS, Epidemiol Branch, Div Intramural Res, NIH, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Gjessing, Hakon/A-5871-2012; OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES049019, Z01 ES049019-10] NR 64 TC 32 Z9 41 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 2007 VL 121 IS 5 BP 529 EP 538 DI 10.1007/s00439-007-0337-z PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 164ZB UT WOS:000246272400001 PM 17333284 ER PT J AU Reiner, AP Carlson, CS Ziv, E Iribarren, C Jaquish, CE Nickerson, DA AF Reiner, Alexander P. Carlson, Christopher S. Ziv, Elad Iribarren, Carlos Jaquish, Cashell E. Nickerson, Deborah A. TI Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study SO HUMAN GENETICS LA English DT Article ID MULTILOCUS GENOTYPE DATA; RISK-FACTORS; ADMIXTURE PROPORTIONS; ALLELIC ASSOCIATION; INSULIN-RESISTANCE; RACIAL-DIFFERENCES; COMPLEX TRAITS; STRATIFICATION; LOCI; ATHEROSCLEROSIS AB African-American populations are genetically admixed. Studies performed among unrelated individuals from ethnically admixed populations may be both vulnerable to confounding by population stratification, but offer an opportunity for efficiently mapping complex traits through admixture linkage disequilibrium. By typing 42 ancestry-informative markers and estimating genetic ancestry, we assessed genetic admixture and heterogeneity among African-American participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We also assessed associations between individual genetic ancestry and several quantitative and binary traits related to cardiovascular risk. We found evidence of population sub-structure and excess inter-marker linkage disequilibrium, consistent with recent admixture. The estimated group admixture proportions were 78.1% African and 22.9% European, but differed according to geographic region. In multiple regression models, African ancestry was significantly associated with decreased total cholesterol, decreased LDL-cholesterol, and decreased triglycerides, and also with increased risk of insulin resistance. These observed associations between African ancestry and several lipid traits are consistent with the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification. These results demonstrate the potential for confounding of genetic associations with some cardiovascular disease-related traits in large studies involving US African-Americans. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Washington, Dept Genome Sci & Bioengn, Seattle, WA 98195 USA. Kaiser Permanente Div Res, Oakland, CA USA. NHLBI, Bethesda, MD 20892 USA. RP Reiner, AP (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. EM apreiner@u.washington.edu RI Ziv, Elad/L-5396-2014 FU NHLBI NIH HHS [N01-HC-45134, HL066642, HL066682, HL071017, N01-HC-05187, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 53 TC 58 Z9 58 U1 1 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 JUN PY 2007 VL 121 IS 5 BP 565 EP 575 DI 10.1007/s00439-007-0350-2 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 164ZB UT WOS:000246272400005 PM 17356887 ER PT J AU Gu, CC Hunt, SC Kardia, S Turner, ST Chakravarti, A Schork, N Olshen, R Curb, D Jaquish, C Boerwinkle, E Rao, DC AF Gu, C. Charles Hunt, Steven C. Kardia, Sharon Turner, Stephen T. Chakravarti, Aravinda Schork, Nicholas Olshen, Richard Curb, David Jaquish, Cashell Boerwinkle, Eric Rao, D. C. TI An investigation of genome-wide associations of hypertension with microsatellite markers in the Family Blood Pressure Program (FBPP) SO HUMAN GENETICS LA English DT Article ID BODY-MASS INDEX; QUANTITATIVE TRAIT LOCUS; TRANSFER-RNA SYNTHETASE; LINKAGE ANALYSIS; CHOREA-ACANTHOCYTOSIS; SUSCEPTIBILITY LOCUS; AFRICAN-AMERICANS; TOURETTE-SYNDROME; CROHNS-DISEASE; NATIONAL-HEART AB The Family Blood Pressure Program (FBPP) has data on 387 microsatellite markers in 13,524 subjects from four major ethnic groups. We investigated genetic association with hypertension of the linkage markers. Family-based methods were used to test association of the 387 loci with resting blood pressures (BPs) [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and the hypertension status (HT). We applied a vote-counting approach to pool results across the three correlated traits, network samples, and ethnic groups to refine the selection of susceptibility loci. The association analyses captured signals missed by previous linkage scans. We found 71 loci associated with at least one of the three traits in at least one of the four ethnic groups at the significance level of 0.01. After validation across multiple samples and related traits, we identified by vote-counting 21 candidate loci for hypertension. Two loci, D3S2459 and D10S1412 confirmed findings in Network-specific linkage scans (GENOA and SAPPHIRe). Many of the candidate loci were reported by others in linkage to BPs, body weight, heart disease, and diabetes. We also observed frequent presence of quantitative trait loci (QTLs) involved in autoimmune and neurological disorders (e.g., NOD2). The vote-counting method of pooling results recognizes the potential that a gene may be involved in varying ways among different samples, which we believe is responsible for identifying genes in the less explored inflammatory pathways to hypertension. C1 Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet & Psychiat, St Louis, MO USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Mayo Clin, Coll Med, Rochester, MN USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. Univ Calif San Diego, Dept Psychiat, Polymorphism Res Lab, San Diego, CA 92103 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Pacific Hlth Res Inst, Honolulu, HI USA. NHLBI, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. RP Gu, CC (reprint author), Washington Univ, Sch Med, Div Biostat, 660 S Euclid Ave,Campus Box 8067, St Louis, MO 63110 USA. EM gc@wubios.wustl.edu RI Gu, Charles/A-7934-2010 OI Gu, Charles/0000-0002-8527-8145 NR 79 TC 12 Z9 15 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 JUN PY 2007 VL 121 IS 5 BP 577 EP 590 DI 10.1007/s00439-007-0349-8 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 164ZB UT WOS:000246272400006 PM 17372766 ER PT J AU Fyr, CLW Kanaya, AM Cummings, SR Reich, D Hsueh, WC Reiner, AP Harris, TB Moffett, S Li, RL Ding, JZ Miljkovic-Gacic, I Ziv, E AF Fyr, Christina L. Wassel Kanaya, Alka M. Cummings, Steve R. Reich, David Hsueh, Wen-Chi Reiner, Alexander P. Harris, Tamara B. Moffett, Susan Li, Rongling Ding, Jingzhong Miljkovic-Gacic, Iva Ziv, Elad CA HABC Study TI Genetic admixture, adipocytokines, and adiposity in black Americans: The health, aging, and body composition study SO HUMAN GENETICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; C-REACTIVE PROTEIN; INSULIN-RESISTANCE ATHEROSCLEROSIS; CORONARY-HEART-DISEASE; AFRICAN-AMERICAN; ADIPONECTIN LEVELS; DIABETES-MELLITUS; CARDIOVASCULAR HEALTH; LEPTIN CONCENTRATIONS AB Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3 +/- 15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin. C1 Univ Minnesota, Dept Epidemiol, Minneapolis, MN 55454 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Calif Pacific Med Ctr, San Francisco, CA USA. Harvard Univ, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RP Fyr, CLW (reprint author), Univ Minnesota, Dept Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM Christina.Wassel-Fyr@ucsf.edu RI Ziv, Elad/L-5396-2014; OI Miljkovic, Iva/0000-0002-3155-9777 NR 45 TC 17 Z9 18 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 JUN PY 2007 VL 121 IS 5 BP 615 EP 624 DI 10.1007/s00439-007-0353-z PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 164ZB UT WOS:000246272400010 ER PT J AU Camp, NJ Cannon-Albright, LA Farnham, JM Baffoe-Bonnie, AB George, A Powell, I Bailey-Wilson, JE Carpten, JD Giles, GG Hopper, JL Severi, G English, DR Foulkes, WD Maehle, L Moller, P Eeles, R Easton, D Badzioch, MD Whittemore, AS Oakley-Girvan, I Hsieh, CL Dimitrov, L Xu, JF Stanford, JL Johanneson, B Deutsch, K Mcintosh, L Ostrander, EA Wiley, KE Isaacs, SD Walsh, PC Thibodeau, SN McDonnell, SK Hebbring, S Schaid, DJ Lange, EM Cooney, KA Tammela, TLJ Schleutker, J Paiss, T Maier, C Gronberg, H Wiklund, F Emanuelsson, M Isaacs, WB AF Camp, Nicola J. Cannon-Albright, Lisa A. Farnham, James M. Baffoe-Bonnie, Agnes B. George, Asha Powell, Isaac Bailey-Wilson, Joan E. Carpten, John D. Giles, Graham G. Hopper, John L. Severi, Gianluca English, Dallas R. Foulkes, William D. Maehle, Lovise Moller, Pal Eeles, Ros Easton, Douglas Badzioch, Michael D. Whittemore, Alice S. Oakley-Girvan, Ingrid Hsieh, Chih-Lin Dimitrov, Latchezar Xu, Jianfeng Stanford, Janet L. Johanneson, Bo Deutsch, Kerry Mcintosh, Laura Ostrander, Elaine A. Wiley, Kathleen E. Isaacs, Sarah D. Walsh, Patrick C. Thibodeau, Stephen N. McDonnell, Shannon K. Hebbring, Scott Schaid, Daniel J. Lange, Ethan M. Cooney, Kathleen A. Tammela, Teuvo L. J. Schleutker, Johanna Paiss, Thomas Maier, Christiane Gronberg, Henrik Wiklund, Fredrik Emanuelsson, Monica Isaacs, William B. CA Int Consortium Prostate Canc Genet TI Compelling evidence for a prostate cancer gene at 22q12.3 by the International Consortium for Prostate Cancer Genetics SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE SCAN; SUSCEPTIBILITY GENES; LINKAGE ANALYSIS; FAMILIES; SCREEN; LOCI; PEDIGREES; DISEASE; SEARCH AB Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants) contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in 54 pedigrees selected to be informative for recombinant mapping from nine member groups of the International Consortium for Prostate Cancer Genetics (ICPCG). These 54 pedigrees included the 14 extended pedigrees from Utah and 40 pedigrees from eight other ICPCG member groups. The additional 40 pedigrees were selected from a total pool of 1213 such that each pedigree was required to contain both at least four prostate cancer (PRCA) cases and exhibit evidence for linkage to the chromosome 22q region. The recombinant events in these 40 independent pedigrees confirmed the previously proposed region. Further, when all 54 pedigrees were considered, the three-recombinant consensus region was narrowed down by more than a megabase to 2.2 Mb at chromosome 22q12.3 flanked by D22S281 and D22S683. This narrower region eliminated 20 annotated genes from that previously proposed, leaving only 11 genes. This region at 22q12.3 is the most consistently identified and smallest linkage region for PRCA. This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases. C1 Univ Utah, Sch Med, ICPCG Grp, Salt Lake City, UT 84108 USA. Univ Utah, Sch Med, Div Genet Epidemiol, Salt Lake City, UT 84108 USA. African Amer Hereditary Prostate Canc ICPCG Grp, Philadelphia, PA USA. Fox Chase Canc Ctr, Philadelphia, PA USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Translat Genom Res Inst, Genet Basis Human Dis Res Div, Phoenix, AZ USA. Canc Council Victoria, ACTANE Consortium ICPCG Grp, Melbourne, Vic, Australia. Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3002, Australia. McGill Univ, Dept Oncol, Montreal, PQ H3A 2T5, Canada. Norwegian Radium Hosp, Oslo 3, Norway. Royal Marsden NHS Fdn, Canc Res Inst, Surrey, England. Canc Res UK Genet Epidemiol Unit, Cambridge, England. Univ Washington, Med Ctr, Div Med Genet, Seattle, WA 98195 USA. Stanford Univ, Sch Med, BC CA HI ICPCG Grp, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Stanford Comlprehens Canc Ctr, Stanford, CA 94305 USA. Univ So Calif, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Wake Forest Univ, Sch Med, Data Coordinating Ctr ICPCG, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Ctr Human Genet, Winston Salem, NC 27109 USA. Fred Hutchinson Canc Res Ctr, FHCRC ICPCG Grp, Div Publ Hlth Sci, Seattle, WA 98104 USA. NIH, Canc Genet Branch, Bethesda, MD 20892 USA. Inst Syst Biol, Seattle, WA USA. Johns Hopkins Univ, ICPCG Grp, Baltimore, MD 21218 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Mayo Clin, ICPCG Grp, Rochester, MN USA. Univ Michigan, ICPCG Grp, Ann Arbor, MI 48109 USA. Univ Tampere, ICPCG Grp, FIN-33101 Tampere, Finland. Univ Tampere, Tampere Univ Hosp, FIN-33101 Tampere, Finland. Univ Ulm, ICPCG Grp, D-89069 Ulm, Germany. Univ Ulm, Dept Urol, D-89069 Ulm, Germany. Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany. Umea Univ, ICPCG Grp, S-90187 Umea, Sweden. Umea Univ, Oncol Ctr, S-90187 Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. RP Camp, NJ (reprint author), Univ Utah, Sch Med, ICPCG Grp, 391 Chipeta Way,Suite D, Salt Lake City, UT 84108 USA. EM nicola.camp@utah.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920; Eeles, Rosalind/0000-0002-3698-6241; Farnham, James/0000-0002-8213-949X; albright, lisa/0000-0003-2602-3668; foulkes, william/0000-0001-7427-4651; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188; Ostrander, Elaine/0000-0001-6075-9738 FU Cancer Research UK [10118]; Intramural NIH HHS [Z01 HG200331-03]; Medical Research Council [G0501019]; NCI NIH HHS [CA-06927, CA079596, CA106523, CA72818, CA78836, CA80122, CA90752, CA95052, CA98364, K07 CA098364, K07 CA098364-01A1, N01-CP-35141, N01PC35141, P30 CA006927, R01 CA067044, R01 CA072818, R01 CA072818-03, R01 CA078836, R01 CA078836-01, R01 CA079596, R01 CA079596-01A1, R01 CA080122, R01 CA080122-01, R01 CA090752, R01 CA095052, R01 CA095052-01A2, R01 CA106523, R01 CA106523-01A1, U01 CA067044, U01 CA089600, U01 CA089600-01A2, U01 CA89600]; NCRR NIH HHS [G12 RR003048, M01 RR000064, M01-RR00064, RR03048]; NHGRI NIH HHS [1-HG75418, N01HG65403, N01HG75418] NR 19 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2007 VL 16 IS 11 BP 1271 EP 1278 DI 10.1093/hmg/ddm075 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 190IU UT WOS:000248053300001 PM 17478474 ER PT J AU Giardine, B Riemer, C Hefferon, T Thomas, D Hsu, F Zielenski, J Sang, YH Elnitski, L Cutting, G Trumbower, H Kern, A Kuhn, R Patrinos, GP Hughes, J Higgs, D Chui, D Scriver, C Phommarinh, M Patnaik, SK Blumenfeld, O Gottlieb, B Vihinen, M Valiaho, J Kent, J Miller, W Hardison, RC AF Giardine, Belinda Riemer, Cathy Hefferon, Tim Thomas, Daryl Hsu, Fan Zielenski, Julian Sang, Yunhua Elnitski, Laura Cutting, Garry Trumbower, Heather Kern, Andrew Kuhn, Robert Patrinos, George P. Hughes, Jim Higgs, Doug Chui, David Scriver, Charles Phommarinh, Manyphong Patnaik, Santosh K. Blumenfeld, Olga Gottlieb, Bruce Vihinen, Mauno Valiaho, Jouni Kent, Jim Miller, Webb Hardison, Ross C. TI PhenCode: Connecting ENCODE data with mutations and phenotype SO HUMAN MUTATION LA English DT Article DE ENCODE; mutations; phenotype; UCSC Genome Browser ID HUMAN HEMOGLOBIN-VARIANTS; BETA-GLOBIN GENE; THALASSEMIA MUTATIONS; SEQUENCE VARIATION; LOCUS; KNOWLEDGEBASE; ELEMENTS; CLUSTER; SERVER; SITES AB PhenCode (Phenotypes for ENCODE; www.bx.psu.edu/phencode) is a collaborative, exploratory project to help understand phenotypes of human mutations in the context of sequence and functional data from genome projects. Currently, it connects human phenotype and clinical data in various locus,specific databases (LSDBs) with data on genome sequences, evolutionary history, and function from the ENCODE project and other resources in the UCSC Genome Browser. Initially, we focused on a few selected LSDBs covering genes encoding alpha- and beta-globins (HBA, HBB), phenylalanine hydroxylase (PAH), blood group antigens (various genes), androgen receptor (AR), cystic fibrosis transmembrane conductance regulator (CFTR), and Bruton's tyrosine kinase (BTK), but we plan to include additional loci of clinical importance, ultimately genomewide. We have also imported variant data and associated OMIM links from Swiss-Prot. Users can find interesting mutations in the UCSC Genome Browser (in a new Locus Variants track) and follow links back to the LSDBs for more detailed information. Alternatively, they can start with queries on mutations or phenotypes at an LSDB and then display the results at the Genome Browser to view complementary information such as functional data (e.g., chromatin modifications and protein binding from the ENCODE consortium), evolutionary constraint, regulatory potential, and/or any other tracks they choose. We present several examples illustrating the power of these connections for exploring phenotypes associated with functional elements, and for identifying genomic data that could help to explain clinical phenotypes. C1 Penn State Univ, Wartik Lab 304, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. NHGRI, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Erasmus MC, Fac Med, Dept Cell Biol & Genet, Rotterdam, Netherlands. Weatherall Inst Mol Med, Oxford, England. Boston Univ, Dept Med, Boston, MA 02215 USA. Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada. Albert Einstein Coll Med, Dept Chem, Bronx, NY 10467 USA. Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Hardison, RC (reprint author), Penn State Univ, Wartik Lab 304, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. EM rch8@psu.edu RI Hardison, Ross/G-1142-2010; Giardine, Belinda/A-1599-2010; Vihinen, Mauno/A-8452-2012 OI Hardison, Ross/0000-0003-4084-7516; Vihinen, Mauno/0000-0002-9614-7976 FU Intramural NIH HHS; Medical Research Council [MC_U137961144]; NHGRI NIH HHS [1P41HG02371, HG002238]; NIDDK NIH HHS [DK65806] NR 31 TC 50 Z9 57 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2007 VL 28 IS 6 BP 554 EP 562 DI 10.1002/humu.20484 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 164DH UT WOS:000246212800003 PM 17326095 ER PT J AU Petitjean, A Mathe, E Kato, S Ishioka, C Tavtigian, SV Hainaut, P Olivier, M AF Petitjean, Audrey Mathe, Ewy Kato, Shunsuke Ishioka, Chikashi Tavtigian, Sean V. Hainaut, Pierre Olivier, Magali TI Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database SO HUMAN MUTATION LA English DT Article DE TP53; p53; missense mutation; transactivation; functional assay ID LI-FRAUMENI-SYNDROME; BREAST-CANCER; GAIN; GENE; HETEROZYGOSITY AB The tumor suppressor gene TP53 is frequently mutated in human cancers. More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays. The International Agency for Research on Cancer (IARC) TP53 database (www-p53.iarc.fr) compiles all genetic variations that have been reported in TP53. Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors. This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns. These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest. C1 WHO, Int Agcy Res Canc, Grp Mol Carcinogenesis & Biomakers, F-69372 Lyon 08, France. WHO, Int Agcy Res Canc, Genet Susceptibil Grp, F-69372 Lyon 08, France. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Inst Dev Aging & CAnc, Dept Clin Oncol, Aoba Ku, Sendai, Miyagi, Japan. RP Hainaut, P (reprint author), WHO, Int Agcy Res Canc, Grp Mol Carcinogenesis & Biomakers, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM Hainaut@iarc.fr RI Olivier, Magali/G-3728-2010; Hainaut, Pierre /B-6018-2012; Kato, Shunsuke/F-7607-2014 OI Olivier, Magali/0000-0002-8202-342X; Hainaut, Pierre /0000-0002-1303-1610; NR 23 TC 854 Z9 878 U1 7 U2 40 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2007 VL 28 IS 6 BP 622 EP 629 DI 10.1002/humu.20495 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 164DH UT WOS:000246212800010 PM 17311302 ER PT J AU Mitchell, GF Dunlap, ME Warnica, W Ducharme, A Arnold, JMO Tardif, JC Solomon, SD Domanski, MJ Jablonski, KA Rice, MM Pfeffer, MA AF Mitchell, Gary F. Dunlap, Mark E. Warnica, Wayne Ducharme, Anique Arnold, J. Malcolm O. Tardif, Jean-Claude Solomon, Scott D. Domanski, Michael J. Jablonski, Kathleen A. Rice, Madeline M. Pfeffer, Marc A. CA Prevention Events Angiotensin Conv TI Long-term trandolapril treatment is associated with reduced aortic stiffness - The Prevention of Events with Angiotensin-Converting Enzyme inhibition hemodynamic substudy SO HYPERTENSION LA English DT Article DE angiotensin-converting enzyme; coronary artery disease; randomized clinical trial; arterial stiffness; pulse wave velocity ID PULSE-WAVE VELOCITY; CHRONIC HEART-FAILURE; AGE-RELATED-CHANGES; ARTERIAL STIFFNESS; GENE POLYMORPHISM; SYSTOLIC HYPERTENSION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR MORTALITY; INDEPENDENT PREDICTOR; EJECTION FRACTIONS AB The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus placebo added to conventional therapy in patients with stable coronary disease and preserved left ventricular function. The PEACE hemodynamic substudy evaluated effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were performed in 300 participants from 5 PEACE centers a median of 52 months (range, 25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg per day or placebo. Central pulsatile hemodynamics and carotid-femoral pulse wave velocity were assessed by using echocardiography, tonometry of the carotid and femoral arteries, and body surface transit distances. Patients randomly assigned to trandolapril tended to be older (mean +/- SD: 64.2 +/- 7.9 versus 62.9 +/- 7.7 years; P = 0.14), with a higher body mass index (28.5 +/- 4.0 versus 27.8 +/- 3.9 kg/m(2); P = 0.09) and lower ejection fraction (57.1 +/- 8.1% versus 58.7 +/- 8.4%; P < 0.01). At the time of the hemodynamic substudy, the trandolapril group had lower mean arterial pressure (93.1 +/- 10.2 versus 96.3 +/- 11.3 mm Hg; P < 0.01) and lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s]; P = 0.02). The difference in carotid-femoral pulse wave velocity persisted (P < 0.01) in an analysis that adjusted for baseline characteristics and follow-up mean pressure. In contrast, there was no difference in aortic compliance, characteristic impedance, augmentation index, or total arterial compliance. Angiotensin-converting enzyme inhibition with trandolapril produced a modest reduction in carotid-femoral pulse wave velocity, a measure of aortic wall stiffness, beyond what would be expected from blood pressure lowering or differences in baseline characteristics alone. C1 Cardiovasc Engn Inc, Waltham, MA 02453 USA. Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. London Hlth Sci Ctr, London, ON, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM GaryFMitchell@mindspring.com RI Solomon, Scott/I-5789-2013 FU NHLBI NIH HHS [N01 HC065149, N01 HC065149-15, N01HC065149] NR 41 TC 57 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2007 VL 49 IS 6 BP 1271 EP 1277 DI 10.1161/HYPERTENSIONAHA.106.085738 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171FN UT WOS:000246720800019 PM 17452505 ER PT J AU Mitchell, GF Guo, CY Kathiresan, S Vasan, RS Larson, MG Vita, JA Keyes, MJ Vyas, M Newton-Cheh, C Musone, SL Camargo, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ AF Mitchell, Gary F. Guo, Chao-Yu Kathiresan, Sekar Vasan, Ramachandran S. Larson, Martin G. Vita, Joseph A. Keyes, Michelle J. Vyas, Mitul Newton-Cheh, Christopher Musone, Stacy L. Camargo, Amy L. Drake, Jared A. Levy, Daniel O'Donnell, Christopher J. Hirschhorn, Joel N. Benjamin, Emelia J. TI Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus - The Framingham Heart Study SO HYPERTENSION LA English DT Article DE single nucleotide polymorphism; nitric oxide synthase; pulse pressure; medical genetics; epidemiology ID BLOOD-PRESSURE; ARTERIAL STIFFNESS; ESSENTIAL-HYPERTENSION; AORTIC STIFFNESS; WAVE REFLECTION; IN-VIVO; POLYMORPHISM; DISTENSIBILITY; CLEAVAGE; GLU(298) AB Arterial stiffness is a moderately heritable trait that is affected by alterations in the bioavailability of NO. Previous studies have found associations between variants in the gene for endothelial NO synthase (NOS3) and arterial properties. We previously identified a linkage peak for forward pressure wave amplitude in the immediate vicinity of NOS3. Therefore, we evaluated relations between arterial stiffness measures and common genetic variants at this locus. Eighteen single nucleotide polymorphisms capturing approximate to 90% of underlying common variation in NOS3 were genotyped in unrelated Framingham Heart Study participants (N = 1157; 52.2% women; mean age: 62 years) with routinely ascertained tonometry data that provided 5 arterial phenotypes (forward and reflected pressure wave amplitude, central pulse pressure, carotid - femoral pulse wave velocity, and mean arterial pressure). In women but not men, the genotype for the common NOS3 missense mutation (Glu298Asp, rs1799983) was related to central pulse pressure (women: GG = 53 +/- 0.9, GT = 54 +/- 0.9, and TT = 47 +/- 2.0 mm Hg, P = 0.0047; men: GG = 50 +/- 1.0, GT = 49 +/- 0.9, and TT = 47 +/- 1.8 mm Hg, P = 0.30) and forward wave amplitude (women: GG = 41 +/- 0.7, GT = 42 +/- 0.7, and TT = 38 +/- 1.6 mm Hg, P = 0.029; men: GG = 42 +/- 0.9, GT = 41 +/- 0.8, and TT = 39 +/- 1.5 mm Hg, P = 0.47). The only other nominally significant sex-specific association in men but not women was between an intronic polymorphism (rs1800781) and reflected wave amplitude (women: AA = 10.4 +/- 0.4, AG = 11.1 +/- 0.6, and GG = 8.9 +/- 2.2 mm Hg, P = 0.50; men: AA = 6.1 +/- 0.3, AG = 7.3 +/- 0.5, and GG = 11.3 +/- 2.3 mm Hg, P = 0.014). After adjusting for multiple testing (18 polymorphisms and 5 phenotypes), these nominal associations were no longer significant. The present study was suggestive of modest relations between common genetic variants at the NOS3 locus and arterial stiffness. C1 Cardiovasc Engn Inc, Waltham, MA 02453 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. MIT, Program Med & Populat Genet, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM GaryFMitchell@mindspring.com OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL60040, HL66582, HL70100, HL71039, K24-HL-04334, N01-HC-25195, N01-HV28178] NR 25 TC 20 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2007 VL 49 IS 6 BP 1285 EP 1290 DI 10.1161/HYPERTENSIONAHA.106.085266 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171FN UT WOS:000246720800021 PM 17404185 ER PT J AU Rodriguez, M Liow, JS Thada, S Sibomana, M Chelikani, S Mulnix, T Johnson, CA Michel, C Barker, WC Carson, RE AF Rodriguez, Mario Liow, Jeih-San Thada, Shanthalaxmi Sibomana, Merence Chelikani, Sudhakar Mulnix, Tim Johnson, Calvin A. Michel, Christian Barker, W. Craig Carson, Richard E. TI Count-rate dependent component-based normalization for the HRRT SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE component-based normalization; HRRT; MOLAR; pile-up effect ID RESOLUTION RESEARCH TOMOGRAPH; LIST-MODE LIKELIHOOD; 3D PET; IMAGE-RECONSTRUCTION; PILEUP-PREVENTION; 3-D PET; DETECTOR; ALGORITHM; DESIGN AB Component-based normalization is an important technique for PET scanners with a high number of lines of response (LOR), e.g., 4.5 x 10(9) for the HRRT. It reduces the problem of measuring the sensitivity of each LOR to that of estimating the individual crystal efficiencies (E), e.g., 119808 for the HRRT. We propose a component-based method to compute e for the HRRT. In addition, the block design of the HRRT produces pulse pile-up which causes apparent changes in e with count rate. These effects occur within the block and between the front (LSO) and back (LYSO) crystal layers. We use a rotating source to measure the E values and a decaying uniform phantom to account for E variations with count rate. The computation of efficiencies is achieved with similar to 1% statistical noise with an acquisition of similar to 1 h. Count rate dependency of E is implemented as a linear model in terms of block singles rate. Four approaches to modify e with count rate were compared. Among them, an independent parameter for each crystal produced the best results, both visually and quantitatively. Failure to account for the count rate dependency in E leads to high resolution artifacts in the reconstructed images, most visible in the transverse plane, in the center of the field-of-view. C1 Yale Univ, Sch Med, PET Ctr, New Haven, CT 06536 USA. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, PET Dept, NIH, Bethesda, MD 20892 USA. Siemens Med Solut, Mol Imaging Div, Knoxville, TN 37932 USA. Ctr Informat Technol, Div Computat Biosci, NIH, Bethesda, MD 20892 USA. RP Rodriguez, M (reprint author), Yale Univ, Sch Med, PET Ctr, 333 Cedar St, New Haven, CT 06536 USA. EM richard.e.carson@yale.edu RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 37 TC 15 Z9 15 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 2007 VL 54 IS 3 BP 486 EP 495 DI 10.1109/TNS.2007.897824 PN 1 PG 10 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 180UI UT WOS:000247391200012 ER PT J AU Freedman, NMT Moreno, RM Le Meunier, L Bacharach, SL AF Freedman, Nanette M. T. Moreno, Roberto Maass Le Meunier, Ludovic Bacharach, Stephen L. TI Identification of contrast media in PET/CT using dual energy CT SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE attenuation correction; contrast media; dual energy CT; PET/CT ID ATTENUATION CORRECTION; ORAL CONTRAST; INTRAVENOUS CONTRAST; ARTIFACTS; IMAGES; TOMOGRAPHY; EMISSION; IMPLANTS; SCANNER; PHANTOM AB Iodine-containing contrast media facilitate interpretation of CT images. In PET/CT such CT images are often converted to 511 keV attenuation maps to correct the PET images for tissue attenuation. Current conversion methods based on single-energy CT do not account for contrast media, and may therefore generate artifacts in the PET images. A method is presented in which fractional differences of CT images at two energies (DECT) are interpreted, using well-known properties of dual-energy x-ray imaging, to identify regions of contrast media. The identified regions can then be assigned soft-tissue attenuation values to minimize effects of contrast media on the PET,attenuation-corrected images.. Method: Two cylinder phantoms, including a bone insert and inserts containing iodine-based contrast, were imaged in a PET/CT scanner at 140, 120, 100 and 80 kVp. DECT fractional difference images were created for 120, 100 and 80 kVp relative to 140kVp. Results: Fractional differences ((HU80-HU140)/HU140) were close to 6.9 for contrast, regardless of concentration, and 0.47 for bone. This is due to steeper decrease in CT attenuation with increasing energy for iodine, compared to bone, and potentially allows automatic detection of contrast-containing tissue. Results were corroborated with theoretical calculations. Conclusion: DECT permits reliable separation of contrast from soft tissue and bone on CT. This identification of contrast could be used to avoid contrast errors in PET/CT attenuation correction by preventing erroneous automatic conversion of contrast containing regions to inaccurate 511 keV attenuation coefficients. C1 Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Med Biophys & Nucl Med, IL-91120 Jerusalem, Israel. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 90000 USA. RP Freedman, NMT (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Med Biophys & Nucl Med, IL-91120 Jerusalem, Israel. EM freedman@hadassah.org.il; rmaass@nih.gov; l_le_meunier@yahoo.com; steve.bacharach@radiology.ucsf.edu NR 30 TC 1 Z9 1 U1 2 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 2007 VL 54 IS 3 BP 523 EP 527 DI 10.1109/TNS.2007.896210 PN 1 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 180UI UT WOS:000247391200016 ER PT J AU Swindle, EJ Metcalfe, DD AF Swindle, Emily J. Metcalfe, Dean D. TI The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes SO IMMUNOLOGICAL REVIEWS LA English DT Review DE mast cell; reactive oxygen species; nitric oxide; inflammation ID ISCHEMIA-REPERFUSION INJURY; FC-EPSILON-RI; INDUCED MICROVASCULAR DYSFUNCTION; MOUSE SKELETAL-MUSCLE; HISTAMINE-RELEASE; NADPH OXIDASE; AIRWAY INFLAMMATION; SUPEROXIDE GENERATION; INTESTINAL ISCHEMIA; IN-VIVO AB Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), including nitric oxide, are produced in cells by a variety of enzymatic and non-enzymatic mechanisms. At high levels, both types of oxidants are used to kill ingested organisms within phagocytes. At low levels, RNOS may diffuse outside cells where they impact the vasculature and nervous system. Recent evidence suggests that low levels of ROS produced within cells are involved in cell signaling. Along with these physiological roles, many pathological conditions exist where detrimental high-level ROS and RNOS are produced. Many situations in which ROS/RNOS are associated also involve mast cell activation. In innate immunity, such mast cells are involved in the immune response toward pathogens. In acquired immunity, activation of mast cells by cross-linking of receptor-bound immunoglobulin E causes the release of mediators involved in the allergic inflammatory response. In this review, we describe the principle pathways for ROS and RNOS generation by cells and discuss the existence of such pathways in mast cells. In addition, we examine the evidence for a functional role for ROS and RNOS in mast cell secretory responses and discuss evidence for a direct relationship between ROS, RNOS, and mast cells in mast cell-dependent inflammatory conditions. C1 NIAID, Allerg Dis Lab, NIH, Bethesda, MD 20892 USA. RP Swindle, EJ (reprint author), NIAID, Allerg Dis Lab, NIH, Bldg 10,Room 11C 209,10 Ctr Dr, Bethesda, MD 20892 USA. EM ejswindle@niaid.nih.gov FU Intramural NIH HHS NR 158 TC 105 Z9 108 U1 1 U2 19 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2007 VL 217 BP 186 EP 205 DI 10.1111/j.1600-065X.2007.00513.x PG 20 WC Immunology SC Immunology GA 165PH UT WOS:000246317100014 PM 17498060 ER PT J AU Rivera, J Olivera, A AF Rivera, Juan Olivera, Ana TI Src family kinases and lipid mediators in control of allergic inflammation SO IMMUNOLOGICAL REVIEWS LA English DT Review DE Fc epsilon RI; Lyn; Fyn; IgE; mast cell; PTEN; degranulation; sphingosine kinase ID FC-EPSILON-RI; NF-KAPPA-B; MAST-CELL ACTIVATION; AFFINITY IGE RECEPTOR; DETERGENT-RESISTANT MEMBRANES; PHOSPHOLIPASE-D; IMMUNOGLOBULIN-E; PHOSPHOINOSITIDE 3-KINASE; CYTOKINE PRODUCTION; SPHINGOSINE KINASE AB The Src family kinases Fyn and Lyn are important modulators of the molecular events initiated by engagement of the high-affinity IgE receptor (Fc epsilon RI). These kinases control many of the early signaling events and initiate the production of several lipid metabolites that have an important role in regulating mast cell responses. The intracellular level of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which is produced by phosphatidylinositol 3-OH kinase, plays an important role in determining the extent of a mast cells response to a stimulus. Enhanced levels lead to a hyperdegranulating phenotype (as seen in SHIP-1(-/-) and Lyn(-/-) mast cells), whereas decreased levels cause hypodegranulation (as seen in Fyn(-/-) mast cells). Downregulation of mast cell phosphatase and tensin homologue deleted on chromosone 10 expression, a phosphatase that reduces cellular levels of PIP3, caused constitutive cytokine production, demonstrating that this response is particularly sensitive to PIP3 levels. Lyn and Fyn are also intimately linked to other lipid kinases, like sphingosine kinases (SphK). By producing sphingosine-1-phosphate (S1P), SphKs contribute to mast cell chemotaxis and degranulation. In vivo studies now reveal that circulating S1P as well as that found within the mast cell is important in determining mast cell responsiveness. These studies demonstrate the connection between Src protein tyrosine kinases and lipid second messengers that control mast cell function and allergic responses. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov FU Intramural NIH HHS NR 120 TC 45 Z9 47 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2007 VL 217 BP 255 EP 268 DI 10.1111/j.1600-065X.2007.00505.x PG 14 WC Immunology SC Immunology GA 165PH UT WOS:000246317100018 PM 17498064 ER PT J AU Jin, Z Romero-Steiner, S Carlone, GM Robbins, JB Schneerson, R AF Jin, Zhigang Romero-Steiner, Sandra Carlone, George M. Robbins, John B. Schneerson, Rachel TI Haemophilus influenzae type a infection and its prevention SO INFECTION AND IMMUNITY LA English DT Review ID HEMOPHILUS-INFLUENZAE; INVASIVE DISEASE; CAPSULAR TRANSFORMANTS; VIRULENCE; POLYSACCHARIDE; MENINGITIS; SEROTYPE; EPIDEMIOLOGY; IMMUNIZATION; VACCINATION C1 NICHHD, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Bacterial Dis, Atlanta, GA 30333 USA. RP Robbins, JB (reprint author), NICHHD, NIH, Bldg 31,Room 2A29, Bethesda, MD 20892 USA. EM robbinsjo@mail.nih.gov OI Romero-Steiner, Sandra/0000-0003-4128-7768 NR 46 TC 20 Z9 21 U1 1 U2 4 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 JUN PY 2007 VL 75 IS 6 BP 2650 EP 2654 DI 10.1128/IAI.01774-06 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 172SN UT WOS:000246824500001 PM 17353280 ER PT J AU Yu, SQ Gu, XX AF Yu, Shengqing Gu, Xin-Xing TI Biological and immunological characteristics of lipooligosaccharide-based conjugate vaccines for serotype C Moraxella catarrhalis SO INFECTION AND IMMUNITY LA English DT Article ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; OUTER-MEMBRANE PROTEINS; BRANHAMELLA-CATARRHALIS; OTITIS-MEDIA; DETOXIFIED LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDE ANTIGENS; PULMONARY CLEARANCE; ANTIBODY-RESPONSE; IMMUNE-RESPONSE; PATHOGEN AB Moraxella catarrhalis is an important bacterial cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS), a major surface antigen of this bacterium, is a potential vaccine component against the organism. There are three major LOS serotypes (serotypes A, B, and C in clinical isolates of M. catarrhalis. Our previous studies demonstrated that serotype A and B LOS-based conjugates were immunogenic in animals and elicited bactericidal antibodies. In this study, LOS from serotype C strain 26404 was isolated, detoxified, and conjugated to tetanus toxoid (TT) or the cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT, dLOS-CRM-1, and dLOS-CRM-2 vaccine candidates. The molar ratios (dLOS/protein) of the resulting conjugates were 47:1, 19:1, and 32:1, respectively, while the weight ratios were 0.94, 0.84 and 1.44, respectively. All conjugates were highly immunogenic in both mouse and rabbit models. Three subcutaneous injections of each conjugate formulated with the Ribi adjuvant elicited >700-fold increases in serum anti-LOS immunoglobulin G levels in mice (5 mu g of dLOS) and >2,000-fold increases in rabbits (50 mu g of dLOS). The resulting mouse and rabbit antisera showed complement-mediated bactericidal activity against the homologous strain. In addition, a representative rabbit antiserum showed bactericidal activity against 14 of 18 testable strains, and this bactericidal activity could be 100% inhibited by the serotype C or A LOS but only 30% inhibited by the serotype B LOS. These results indicate that the serotype C LOS-based conjugates can be used as vaccine components for further investigation in humans. C1 Natl Inst Deafness & Commun Disorders, Vaccine Res Sect, Rockville, MD 20850 USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov FU Intramural NIH HHS NR 43 TC 19 Z9 20 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2007 VL 75 IS 6 BP 2974 EP 2980 DI 10.1128/IAI.01915-06 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 172SN UT WOS:000246824500037 PM 17371852 ER PT J AU Gordin, FM Schultz, ME Huber, R Zubairi, S Stock, F Kariyil, J AF Gordin, Fred M. Schultz, Maureen E. Huber, Ruth Zubairi, Sabiha Stock, Frida Kariyil, Joseph TI A cluster of hemodialysis-related bacteremia linked to artificial fingernails SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; PSEUDOMONAS-AERUGINOSA; OUTBREAK; INFECTIONS AB We examined a cluster of 5 hemodialysis patients who contracted gram-negative bacteremia. A nurse who used an artificial fingernail to open a vial of heparin that was mixed to make a flush solution had a culture of an artificial fingernail specimen positive for Serratia marcescens. The typing of the S. marcescens strains isolated from the 5 patients and the nurse showed them to be identical. This finding provides strong support for policies prohibiting artificial nails for healthcare workers in all hemodialysis units. C1 George Washington Univ, Vet Affairs Med Ctr, Washington, DC 20052 USA. George Washington Univ, Dept Med, Washington, DC 20052 USA. NIH, Ctr Clin, Dept Lab Med, Washington, DC USA. RP Gordin, FM (reprint author), Vet Adm Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM fred.gordin@va.gov NR 10 TC 8 Z9 8 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2007 VL 28 IS 6 BP 743 EP 744 DI 10.1086/517977 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205NQ UT WOS:000249121300021 PM 17520554 ER PT J AU Powers, JH AF Powers, John H. TI Diagnosis and treatment of acute otitis media: Evaluating the evidence SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID NET ANTIBIOTIC PRESCRIPTION; DOUBLE-BLIND; CONTROLLED TRIAL; CLINICAL-TRIALS; EARLY-CHILDHOOD; END-POINTS; CHILDREN; PLACEBO; AMOXICILLIN; METAANALYSIS AB Acute otitis media (AOM) is one of the most common illnesses for which children in the United States receive an antimicrobial agent. Of the six recommendations offered in recent guidelines for treatment of AOM, only one, the assessment and treatment of pain with analgesics, is based on strong evidence. This article reviews the diagnosis of AOM and the accuracy of various signs and symptoms in indicating a bacterial origin, the data on the effect of antimicrobial agents compared with placebo in the treatment of AOM, and the gaps in knowledge that should be addressed by future research and clinical trials. C1 NIAID, Sci Applicat Int Corp, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Washington, DC USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Powers, JH (reprint author), 6700B Rockledge Dr,Room 1123, Bethesda, MD 20892 USA. EM powersjohn@mail.nih.gov NR 71 TC 8 Z9 8 U1 1 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2007 VL 21 IS 2 BP 409 EP + DI 10.1016/j.idc.2007.03.013 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189AQ UT WOS:000247961100007 PM 17561076 ER PT J AU Koenig, MA Jamil, K Streatfield, PK Saha, T Al-Sabir, A El Arifeen, S Hill, K Haque, Y AF Koenig, Michael A. Jamil, Kanta Streatfield, Peter K. Saha, Tulshi Al-Sabir, Ahmed El Arifeen, Shams Hill, Ken Haque, Yasmin TI Maternal health and care-seeking behavior in Bangladesh: Findings from a national survey SO INTERNATIONAL FAMILY PLANNING PERSPECTIVES LA English DT Article ID RURAL BANGLADESH; OBSTETRIC COMPLICATIONS; MORTALITY; DISTRICT; RECALL; COST AB CONTEXT: Although the reduction of maternal mortality levels is a key Millennium Development Goal, community-based evidence on obstetric complications and maternal care-seeking behavior remains limited in low-resource countries. METHODS: This study presents an overview of key findings from the 2007 Bangladesh Maternal Health Services and Maternal Mortality Survey of ever-married women aged 13-49. The survey collected data on the prevalence of obstetric complications, women's knowledge of life-threatening complications, treatment-seeking behavior and reasons for delay in seeking medical care. RESULTS: Bangladeshi women report low but increasing use of antenatal core, as well as low rates of delivery in a health facility or with the assistance of a skilled provider. Although almost half of women reported having one or more complications during pregnancy that they perceived as life threatening, only one in three sought treatment from a qualified provider. More than three-fourths of women with the time-sensitive complications of convulsions or excessive bleeding either failed to seek any treatment or sought treatment from an unqualified provider. The principal reason cited for failing to seek care for life-threatening complications was concern over medical costs, and pronounced socioeconomic disparities were found for maternal care-seeking behavior in both urban and rural Bangladesh. CONCLUSIONS: Despite these gaps in access to skilled delivery and effective emergency obstetric care, some progress has been made in reducing maternal mortality levels. Improved obstetric care and declining levels of fertility and unwanted pregnancy may have played critical roles in addressing the maternal health care needs of Bangladeshi women. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. US Agcy Int Dev, Dhaka, Bangladesh. Int Ctr Diarrhoeal Dis Res, Hlth & Demog Surveillance Unit, Dhaka 1000, Bangladesh. Int Ctr Diarrhoeal Dis Res, Child Hlth Unit, Dhaka 1000, Bangladesh. NIAAA, Bethesda, MD USA. Natl Inst Populat Res & Training, Dhaka, Bangladesh. Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. UNICEF, Colombo, Sri Lanka. RP Koenig, MA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. EM mkoenig@jhsph.edu RI Sandall, Jane/D-4146-2009 OI Sandall, Jane/0000-0003-2000-743X NR 31 TC 39 Z9 39 U1 1 U2 6 PU ALAN GUTTMACHER INST PI NEW YORK PA 125 MAIDEN LANE, 7TH FLOOR, NEW YORK, NY 10038 USA SN 0190-3187 J9 INT FAM PLAN PERSPEC JI Int. Fam. Plan. Perspect. PD JUN PY 2007 VL 33 IS 2 BP 75 EP 82 DI 10.1363/3307507 PG 8 WC Demography; Family Studies; Social Sciences, Biomedical SC Demography; Family Studies; Biomedical Social Sciences GA 186BF UT WOS:000247753400004 PM 17588851 ER PT J AU Hong, KM Yang, SH Chowdhuri, SR Player, A Hames, M Fukuoka, J Meerzaman, D Dracheva, T Sun, ZF Yang, P Jen, J AF Hong, Kyeong-Man Yang, Sei-Hoon Chowdhuri, Sinchita Roy Player, Audrey Hames, Megan Fukuoka, Junya Meerzaman, Daoud Dracheva, Tatiana Sun, Zhifu Yang, Ping Jen, Jin TI Inactivation of LLC1 gene in nonsmall cell lung cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE nonsmall cell lung cancer; serial analysis of geneexpression; promoter methylation; LLC1 ID MESSENGER-RNA EXPRESSION; SQUAMOUS-CELL; SERIAL ANALYSIS; BREAST-CANCER; CPG ISLANDS; METHYLATION; ADENOCARCINOMA; IDENTIFICATION; CARCINOMAS; MARKER AB Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis. (c) 2007 Wiley-Liss, Inc. C1 NCI, Ctr Canc Res, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Goyang, South Korea. Mayo Clin Canc Ctr, Rochester, MN USA. RP Jen, J (reprint author), NCI, Ctr Canc Res, Lab Populat Genet, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM jenj@mail.nih.gov OI Sun, Zhifu/0000-0001-8461-7523 FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010165-05, Z01 CP010162-05, Z01 CP010164-05]; PHS HHS [0510370, R0184354, R01 80127] NR 33 TC 8 Z9 8 U1 0 U2 1 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 JUN 1 PY 2007 VL 120 IS 11 BP 2353 EP 2358 DI 10.1002/ijc.22577 PG 6 WC Oncology SC Oncology GA 156XV UT WOS:000245684100010 PM 17304513 ER PT J AU Moore, LE Malats, N Rothmans, N Real, FX Kogevinas, M Karami, S Garcia-Closas, R Silverman, D Chanock, S Welch, R Tardon, A Serra, C Carrato, A Dosemeci, M Garcia-Closas, M AF Moore, Lee E. Malats, Nuria Rothmans, Nathaniel Real, Francisco X. Kogevinas, Manolis Karami, Sara Garcia-Closas, Reina Silverman, Debra Chanock, Stephen Welch, Robert Tardon, Adonina Serra, Consol Carrato, Alfredo Dosemeci, Mustafa Garcia-Closas, Montserrat TI Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder cancer; folate metabolism; one-carbon metabolism; GSTM1; CTH; genetic susceptibility ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; COMMON MUTATION; RISK-FACTOR; FOLATE; CARCINOGENESIS; METAANALYSIS; VEGETABLES; DISEASE; FRUITS; COHORT AB We have previously reported significant inverse associations between bladder cancer risk and dietary intake of vitamins B2, B6, B12, folate and protein in a hospital-based bladder cancer case-control study conducted in Spain (1,150 cases;1,149 controls). Because these dietary factors are involved in the one-carbon metabolism pathway, we evaluated associations between bladder cancer risk and 33 single nucleotide polymorphisms (SNPs) in 8 genes (CBS, CTH, MTHFR, MTR, MTRR, SHMT1, SLC19A1 and TYMS) and interactions with dietary variables involved in this pathway. Two SNPs in the CTH gene were significantly associated with bladder cancer risk. OR (95% CI) for heterozygous and the homozygous variants compared to homozygous wild-type individuals were: 1.37 (1.04-1.80) IVS3-66 A > C and 1.22 (1.02-1.45) IVS10-430 C > T. Because the CTH gene is important for glutathione synthesis, we examined interactions with the GSTM1 gene, which codes for glutathione S-transferase mu u. Increased risk for individuals with the IVS10-430 CT or TT genotype was limited to those with the GSTM1 null genotype (p-interaction = 0.02). No other SNPs were associated with risk of bladder cancer. These findings suggest that common genetic variants in the one-carbon pathway may not play an important role in the etiology of bladder cancer. However, our results provide some evidence that variation in glutathione synthesis may contribute to risk, particularly among individuals who carry a deletion in GSTM1. Additional work is needed to comprehensively evaluate genomic variation in CTH and related genes in the trans-sulfuration pathway and bladder cancer risk. (c) 2007 Wiley-Liss, Inc. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. IMIM, Barcelona, Spain. Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain. Hosp Univ Canarias, Dept Prevent Med, San Cristobal la Laguna, Spain. Natl Canc Inst, Core Genotyping Facil Adv Technol Ctr, Dept Hlth & Human Serv, Rockville, MD USA. Univ Oviedo, Dept Prevent Med & Publ Hlth, Oviedo, Spain. Univ Pompeu Fabra, Dept Expt & Hlth Sci, Unit Res Occupat Hlth, Barcelona, Spain. Corp Parc Tauli, Sabadell, Spain. Hosp Gen Elche, Dept Med Oncol, Elche, Spain. RP Moore, LE (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. EM moorele@mail.nih.gov RI Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; 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; Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784 NR 32 TC 43 Z9 45 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2007 VL 120 IS 11 BP 2452 EP 2458 DI 10.1002/ijc.22565 PG 7 WC Oncology SC Oncology GA 156XV UT WOS:000245684100023 PM 17311259 ER PT J AU Mitrou, PN Albanes, D Weinstein, SJ Pietinen, P Taylor, PR Virtamo, J Leitzmann, MF AF Mitrou, Panagiota N. Albanes, Demetrius Weinstein, Stephanie J. Pietinen, Pirjo Taylor, Philip R. Virtamo, Jarmo Leitzmann, Michael F. TI A prospective study of dietary calcium, dairy products and prostate cancer risk (Finland) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE dietary calcium; dairy products; prostate cancer ID VITAMIN-D SUPPLEMENTATION; UNITED-STATES; PROSPECTIVE COHORT; COLORECTAL-CANCER; ANIMAL PRODUCTS; BETA-CAROTENE; REDUCED RISK; MEN; PHOSPHORUS; EPIDEMIOLOGY AB High dietary intakes of calcium and dairy products have been hypothesized to enhance prostate cancer risk, but available prospective data regarding these associations are inconsistent. We examined dietary intakes of calcium and dairy products in relation to risk of prostate cancer in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study, a cohort of 29,133 male smokers aged 5069 years at study entry. Dietary intake was assessed at baseline using a validated 276-item food use questionnaire. Cox proportional hazards regression was used to adjust for known or suspected risk factors for prostate cancer. During 17 years of follow-up, we ascertained 1,267 incident cases of prostate cancer. High versus low intake of dietary calcium was associated with a marked increase in prostate cancer risk. The multivariate relative risk (RR) of prostate cancer for >= 2,000 mg/day compared to <1,000 mg/day of calcium intake was 1.63 (95% confidence interval (CI), 1.27-2.10; p trend < 0.0001). Total dairy intake was also positively associated with risk of prostate cancer. The multivariate RR of prostate cancer comparing extreme quintiles of intake was 1.26 (95% CI, 1.04-1.51; p trend = 0.03). However, no association with total dairy intake remained after we adjusted for calcium (p trend = 0.17). Findings were similar by stage and grade of prostate cancer. The results from this large prospective study suggest that intake of calcium or some related component contained in dairy foods is associated with increased prostate cancer risk. (c) 2007 Wiley-Liss, Inc. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Mitrou, PN (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Execut Plaza S, Rockville, MD 20852 USA. EM mitroup@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01 RC37004, N01 RC45035]; NCI NIH HHS [N01 CN45165] NR 64 TC 47 Z9 47 U1 8 U2 18 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 JUN 1 PY 2007 VL 120 IS 11 BP 2466 EP 2473 DI 10.1002/ijc.22553 PG 8 WC Oncology SC Oncology GA 156XV UT WOS:000245684100025 PM 17278090 ER PT J AU Farma, JM Puhlmann, M Soriano, PA Cox, D Paciotti, GF Tamarkin, L Alexander, HR AF Farma, Jeffrey M. Puhlmann, Markus Soriano, Perry A. Cox, Derrick Paciotti, Giulio F. Tamarkin, Lawrence Alexander, H. Richard TI Direct evidence for rapid and selective induction of tumor neovascular permeability by tumor necrosis factor and a novel derivative, colloidal gold bound tumor necrosis factor SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE TNF; vascular targeting; tumor neovasculature; permeability; in-vivo videomicroscopy ID ISOLATED LIMB PERFUSION; ISOLATED HEPATIC PERFUSION; LIPOSOMAL DOXORUBICIN DOXIL(R); HUMAN ADENOCARCINOMA LS174T; FACTOR-ALPHA; TNF-ALPHA; ANTITUMOR-ACTIVITY; BEARING RATS; SCID MICE; MELPHALAN AB Tumor necrosis factor (TNF) causes regression of advanced cancers when used in isolation perfusion with melphalan; evidence suggests these effects are mediated via selective yet uncharacterized actions on tumor neovasculature. A novel derivative, colloidal gold bound TNF (cAu-TNF) has been shown to have similar antitumor effects as native TNF with less systemic toxicity in mice. These studies were done to determine their effects on tumor neovasculature, using in vivo video microscopy. Female C57BL/6 mice bearing 20 mm(2) MC38 or LLC tumors that are TNF sensitive and resistant tumors, respectively, had dorsal skinfold chambers implanted. The rate of interstitial accumulation of Texas red fluorescently labeled albumin in tumor and normal vasculature was measured after intravenous TNF, cAu-TNF or PBS. Changes in interstitial fluorescent intensity over time were quantified as a reflection of alterations in vascular permeability. MC38 bearing mice treated with TNF or cAu-TNF demonstrated a rapid, selective and significant increase in tracer accumulation in areas of neovasculature compared to those of normal vasculature. Experiments in LLC tumor bearing mice showed similar results. Monoclonal antibody against tissue factor partially abrogated the effects of TNF on MC38 neovasculature. These data provide direct evidence that TNF and cAu-TNF selectively and rapidly alter permeability in tumor neovasculature; a phenomenon that may be exploited to enhance selective delivery of chemotherapeutics to tumor. (c) 2007 Wiley-Liss,Inc. C1 Univ Maryland, Med Ctr, Dept Surg, Baltimore, MD 21201 USA. CytImmune Sci Inc, Rockville, MD USA. NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Alexander, HR (reprint author), Univ Maryland, Med Ctr, Dept Surg, 22 S Greene St,S4B05A, Baltimore, MD 21201 USA. EM hralexander@gmail.umaryland.edu NR 38 TC 44 Z9 47 U1 2 U2 11 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 JUN 1 PY 2007 VL 120 IS 11 BP 2474 EP 2480 DI 10.1002/ijc.22270 PG 7 WC Oncology SC Oncology GA 156XV UT WOS:000245684100026 PM 17330231 ER PT J AU Lissowska, J Brinton, LA Garcia-Closas, M AF Lissowska, Jolanta Brinton, Louise A. Garcia-Closas, Montserrat TI Re: More data regarding the effects of passive smoking on breast cancer risk among younger women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter C1 Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lissowska, J (reprint author), Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. EM lissowsj@goi.waw.pl RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2007 VL 120 IS 11 BP 2517 EP 2518 DI 10.1002/ijc.22610 PG 2 WC Oncology SC Oncology GA 156XV UT WOS:000245684100032 PM 17290385 ER PT J AU Banovac, F Abeledo, H Campos-Nanez, E Wood, BJ Popa, T Cheng, P Cleary, K AF Banovac, Filip Abeledo, Hernan Campos-Nanez, Enrique Wood, Bradford J. Popa, Teo Cheng, Patrick Cleary, Kevin TI An image-guided system for optimized volumetric treatment planning and execution for radiofrequency ablation of liver tumors SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Radiofrequency ablation; Liver tumors; Image guidance; Optimization; Planning AB Radiofrequency ablation of liver tumors is becoming an increasingly popular option for the treatment of cancer. However, the procedure has several technical challenges, mostly associated with precision targeting of the tumor and ensuring complete ablation coverage. In this paper we describe an image-guided system that we are developing for improved visualization and probe placement during these procedures. The system will include a pre-procedure optimization module and an intra-procedure guidance component. The system concept is explained and some preliminary results are given. While this system is designed for radiofrequency ablation of liver tumors, the methods are applicable to other organs and treatment methods. C1 [Banovac, Filip; Popa, Teo; Cheng, Patrick; Cleary, Kevin] Georgetown Univ, Med Ctr, Imaging Sci & Informat Syst ISIS Ctr, Washington, DC 20007 USA. [Abeledo, Hernan; Campos-Nanez, Enrique] George Washington Univ, Dept Engn Management & Syst Engn, Washington, DC USA. [Wood, Bradford J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Banovac, F (reprint author), Georgetown Univ, Med Ctr, Imaging Sci & Informat Syst ISIS Ctr, Washington, DC 20007 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S146 EP S147 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200077 ER PT J AU Krucker, J Xu, S Glossop, N Neeman, Z Locklin, J Wood, BJ AF Kruecker, J. Xu, S. Glossop, N. Neeman, Z. Locklin, J. Wood, B. J. TI Electromagnetic needle tracking and multi-modality imaging for biopsy and ablation guidance SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Electromagnetic tracking; Needle tracking; Radiofrequency ablation; Multi-modality imaging; Registration AB Purpose: To evaluate accuracy and demonstrate utility of electromagnetic (EM) tracking for guidance during soft-tissue ablation and biopsy procedures. Methods A prototype interventional navigation system using EM tracking for localization of needles and ultrasound probes was used to assist ultrasound and CT guidance of radiofrequency ablations and biopsies in 16 patients. The system allows simultaneous display of up to two prior 3D images in combination with realtime ultrasound and tracked needle visualization. All procedures were carried out on a 16 slice CT scanner. The accuracy of needle tracking was evaluated by comparing the needle position predicted by the tracking system with needle positions confirmed in CT scans. Two different registration methods were compared, and setup time for the navigation system was recorded. In addition, the error in aiming a needle at a target from the skin entry point with and without the assistance of the tracking system was compared in 5 patients. Results The average additional, tracking-related setup and initialization time was 12 min. The average tracking accuracy was 3.8 mm when using only external skin fiducials for registration, and improved to 2.9 mm when including one internal tracked needle position for registration. The accuracy of needle aiming was improved from over 10 mm for ultrasound/CT guidance to 2 mm when using tracking. Using target information from prior PET and MR scans via registration with the pre-procedural CT scan in two patients was successful. This research was supported in part by the Intramural Research Program of the NIH, Clinical Center. C1 [Kruecker, J.; Xu, S.] Philips Res North Amer, Briarcliff Manor, NY 10510 USA. [Glossop, N.] Traxtal Inc, Toronto, ON, Canada. [Neeman, Z.; Locklin, J.; Wood, B. J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Krucker, J (reprint author), Philips Res North Amer, Briarcliff Manor, NY 10510 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S147 EP S150 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200078 ER PT J AU Backlund, E Rowe, G Lynch, J Wolfson, MC Kaplan, GA Sorlie, PD AF Backlund, Eric Rowe, Geoff Lynch, John Wolfson, Michael C. Kaplan, George A. Sorlie, Paul D. TI Income inequality and mortality: a multilevel prospective study of 521248 individuals in 50 US states SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE income distribution; differential mortality; socioeconomic factors; multilevel models ID UNITED-STATES; PSYCHOSOCIAL ENVIRONMENT; POPULATION HEALTH; ASSOCIATION; CITIES; RACE AB Background Some of the most consistent evidence in favour of an association between income inequality and health has been among US states. However, in multilevel studies of mortality, only two out of five studies have reported a positive relationship with income inequality after adjustment for the compositional characteristics of the state's inhabitants. in this study, we attempt to clarify these mixed results by analysing the relationship within age-sex groups and by applying a previously unused analytical method to a database that contains more deaths than any multilevel study to date. Methods The US National Longitudinal Mortality Study (NLMS) was used to model the relationship between income inequality in US states and mortality using both a novel and previously used methodologies that fall into the general framework of multilevel regression. We adjust age-sex specific models for nine socioeconomic and demographic variables at the individual level and percentage black and region at the state level. Results The preponderance of evidence from this study suggests that 1990 state-level income inequality is associated with a 40% differential in state level mortality rates (95% CI=26-56%) for men 25-64 years and a 14% (95% CI=3-27%) differential for women 25-64 years after adjustment for compositional factors. No such relationship was found for men or women over 65. Conlcusions The relationship between income inequality and mortality is only robust to adjustment for compositional factors in men and women under 65. This explains why income inequality is not a major driver of mortality trends in the United States because most deaths occur at ages 65 and over. This analysis does suggest, however, the certain causes of death that occur primarily in the population under 65 may be associated with income inequality. Comparison of analytical techniques also suggests coefficients for income inequality in previous multilevel mortality studies may be biased, but further research is needed to provide a definitive answer. C1 US Bur Census, Washington, DC 20233 USA. STAT Canada, Ottawa, ON K1A OT6, Canada. McGill Univ, Dept Epidemiol & Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. NHLBI, Natl Inst Hlth, Bethesda, MD USA. RP Backlund, E (reprint author), US Bur Census, Data Integrat Div, Washington, DC 20233 USA. EM eric.lars.backlund@census.gov RI Lynch, John/A-4797-2008 OI Lynch, John/0000-0003-2781-7902 FU NICHD NIH HHS [R24 HD047861, R24 HD047861-01] NR 36 TC 49 Z9 49 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2007 VL 36 IS 3 BP 590 EP 596 DI 10.1093/ije/dym012 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 205FD UT WOS:000249098500025 PM 17363395 ER PT J AU Simonsen, L AF Simonsen, Lone TI Commentary: Observational studies and the art of accurately measuring influenza vaccine benefits SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID MORTALITY; EFFICACY; SENIORS C1 NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Simonsen, L (reprint author), NIAID, NIH, 6700B Rockledge Dr,1107, Bethesda, MD 20892 USA. EM lsimonsen@niaid.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 10 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2007 VL 36 IS 3 BP 631 EP 632 DI 10.1093/ije/dym084 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 205FD UT WOS:000249098500032 PM 17586538 ER PT J AU Voon, V Fox, S Butler, TR Lang, AE AF Voon, Valerie Fox, Susan Butler, Tracy R. Lang, Anthony E. TI Antidepressants and psychosis in Parkinson disease: a case series SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID VISUAL HALLUCINATIONS; DEPRESSION C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Voon, V (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 10 Ctr Dr,MSC 1428,Blsg 10,Rm 5S213, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov OI Butler, Tracy/0000-0002-3849-7951 NR 5 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2007 VL 22 IS 6 BP 601 EP 604 DI 10.1002/gps.1764 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 181OO UT WOS:000247446200014 PM 17450623 ER PT J AU Stetler-Stevenson, M AF Stetler-Stevenson, Maryalice TI 2006 Bethesda International Consensus Conference on flow cytometric immunophenotyping of hematolymphoid neoplasia SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Pathol Lab, Flow Cytometry Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1751-5521 J9 INT J LAB HEMATOL JI Int. J. Lab. Hematol. PD JUN PY 2007 VL 29 SU 1 MA 31 BP 26 EP 27 PG 2 WC Hematology SC Hematology GA 170JR UT WOS:000246660200033 ER PT J AU Hudziak, JJ Achenbach, TM Althoff, RR Pine, DS AF Hudziak, James J. Achenbach, Thomas M. Althoff, Robert R. Pine, Daniel S. TI A dimensional approach to developmental psychopathology SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dimensional Approaches to Psychiatric Classification CY JUL, 2006 CL Bethesda, MD SP Amer Psychiat Assoc DE dimensional approaches; conduct disorder; DSM ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; BIPOLAR DISORDER; HUMAN BRAIN; CHILDREN; BEHAVIOR; ADOLESCENTS; PREVALENCE; SCALE; ADHD; COMORBIDITY AB The expression psychopathology in general and child psychopathology in particular, is affected by multiple sources of variance. Some of these sources include gender differences, informant differences, and age-related differences. In this paper, we discuss how these sources of variance complicate both research and clinical management. We argue that the current diagnostic system would be aided by the inclusion of a quantitative axis that can take these sources of variance into account. We reason that the fields of genomics and neuroscience are prepared to move the field of developmental psychopathology forward, but need a diagnostic system that allows for these sources of variance to be controlled. We demonstrate how in Conduct Disorder, inclusion of dimensional information would allow the clinician or researcher to demonstrate not only the presence or absence of pathology, but also the degree to which the disorder is manifested in a particular individual. Because dimensional approaches are already used widely as an alternative measure of psychopathology, we argue that there is reason to consider dimensionalizing some aspects of the DSM. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Univ Vermont, Burlington, VT 05401 USA. Vrije Univ Amsterdam, Inst Earth Sci, NL-1081 HV Amsterdam, Netherlands. NIMH, Bethesda, MD 20892 USA. RP Hudziak, JJ (reprint author), Univ Vermont, Box 364SJ3,FAHC,1 S Prospect, Burlington, VT 05401 USA. EM james.hudziak@uvm.edu RI Achenbach, Thomas/E-8254-2010; OI Hudziak, James/0000-0001-9653-758X NR 33 TC 79 Z9 81 U1 1 U2 23 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD JUN PY 2007 VL 16 SU 1 BP S16 EP S23 DI 10.1002/mpr.217 PG 8 WC Psychiatry SC Psychiatry GA 187WT UT WOS:000247880500004 PM 17623391 ER PT J AU Lopez, MF Compton, WM Grant, BF Breiling, JP AF Lopez, Marsha F. Compton, Wilson M. Grant, Bridget F. Breiling, James P. TI Dimensional approaches in diagnostic classification: a critical appraisal SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Editorial Material C1 NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. NIMH, Bethesda, MD USA. RP Lopez, MF (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, NIH, 6001 Execut Blvd,Rm 5156,MSC 9589, Bethesda, MD 20892 USA. EM lopezmar@nida.nih.gov NR 3 TC 12 Z9 13 U1 0 U2 5 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD JUN PY 2007 VL 16 SU 1 BP S6 EP S7 DI 10.1002/mpr.213 PG 2 WC Psychiatry SC Psychiatry GA 187WT UT WOS:000247880500002 PM 17623396 ER PT J AU Mabley, JG Wallace, R Pacher, P Murphy, K Szabo, C AF Mabley, Jon G. Wallace, Rebecca Pacher, Pal Murphy, Kanneganti Szabo, Csaba TI Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE keratinocytes; oxidative stress; poly(adenosine diphosphate-ribose) polymerase; 1 alpha,25-dihydroxyvitamin D3; 7-dehydrocholesterol ID 1-ALPHA,25-DIHYDROXYVITAMIN D-3 CALCITRIOL; KERATINOCYTE LINE HACAT; UVB-INDUCED CONVERSION; ADP-RIBOSE POLYMERASE; HUMAN-SKIN; ENDOTHELIAL DYSFUNCTION; POTENT INHIBITOR; IL-12 PRODUCTION; IN-VITRO; ACTIVATION AB Vitamin D is well characterized for its role in mineral homeostasis and maintenance of normal skeletal architecture. Vitamin D has been demonstrated to exert anti-inflammatory effects in a variety of disease states including diabetes, arthritis and inflammatory bowel disease. In these diseases poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitors have also proved effective as anti-inflammatory agents. Here we present data demonstrating that the active metabolite of vitamin D, 1 alpha,25-dihydroxyvitamin D3, is a PARP inhibitor. UV irradiation-mediated PARP activation in human keratinocytes can be inhibited by treatment with vitamin D, 7-dehydrocholesterol or 1 alpha,25-dihydrox, vitamin D3. Inhibition of cytochrome P450 reversed the PARP inhibitory action of vitamin D and 7-dehydrocholesterol, indicating that conversion to 1 alpha,25-dihydroxyvitamin D3 mediates their PARP inhibitory action. Vitamin E, may protect keratinocytes against over-activation of PARP resulting from exposure to sunlight. PARP inhibition may contribute to the pharmacological and anti-inflammatory effects of vitamin D. C1 Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England. Inotek Pharmaceut Corp, Beverly, MA USA. NIAAA, NIH, Lab Physiol Studies, Rockville, MD 20852 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Mabley, JG (reprint author), Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England. EM j.g.mabley@brighton.ac.uk RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 41 TC 23 Z9 23 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JUN PY 2007 VL 19 IS 6 BP 947 EP 952 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 172CF UT WOS:000246781000012 PM 17487428 ER PT J AU Lissner, L Troiano, RP Midthune, D Heitmann, BL Kipnis, V Subar, AF Potischman, N AF Lissner, L. Troiano, R. P. Midthune, D. Heitmann, B. L. Kipnis, V. Subar, A. F. Potischman, N. TI OPEN about obesity: recovery biomarkers, dietary reporting errors and BMI SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE biomarkers; diet; energy intake; protein intake; under-reporting ID VALIDATION; ADULTS; BIAS AB Objective: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using energy and protein recovery biomarkers as reference measures. Population and methods: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. Results: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender differences in obesity-related bias were noted. Among women, the DLW-based energy requirement was 378 kcal greater in obese than in non-obese groups; the FFQ was able to detect a statistically significant portion of this extra energy, while the 24HR was not. Among men, the DLW-based energy requirement was 485 kcal greater in the obese group; however, neither FFQ nor 24HR detected this difference in energy requirement. Combining protein and energy estimates, obese men significantly over-reported the proportion of energy from protein using the 24HR, but not with the FFQ. In obese women, no significant reporting error for energy percent protein was observed by either method. At the individual level, correlations between energy expenditure and reported energy intake tended to be weaker in obese than non-obese groups, particularly with the 24HR. Correlations between true and reported protein density were consistently higher than for protein or energy alone, and did not vary significantly with obesity. Conclusion: This work adds to existing evidence that neither of these commonly used dietary reporting methods adequately measures energy or protein intake in obese groups. The 24HR, while capturing more realistic energy distributions for usual intake, may be particularly problematic in the obese. C1 Univ Gothenburg, Sahlgrenska Acad, Dept Community Med & Publ Hlth, SE-40530 Gothenburg, Sweden. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Copenhagen Univ Hosp, Res Unit Dietary Studies, Inst Prevent Med, Copenhagen, Denmark. RP Lissner, L (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Community Med & Publ Hlth, Box 454, SE-40530 Gothenburg, Sweden. EM Lauren.lissner@medfak.gu.se OI Troiano, Richard/0000-0002-6807-989X NR 20 TC 59 Z9 59 U1 0 U2 4 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 JUN PY 2007 VL 31 IS 6 BP 956 EP 961 DI 10.1038/sj.ijo.0803527 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 173XU UT WOS:000246906600013 PM 17299385 ER PT J AU Huber, J Loffler, M Bilban, M Reimers, M Kadl, A Todoric, J Zeyda, M Geyeregger, R Schreiner, M Weichhart, T Leitinger, N Waldhausl, W Stulnig, TM AF Huber, J. Loeffler, M. Bilban, M. Reimers, M. Kadl, A. Todoric, J. Zeyda, M. Geyeregger, R. Schreiner, M. Weichhart, T. Leitinger, N. Waldhaeusl, W. Stulnig, T. M. TI Prevention of high-fat diet-induced adipose tissue remodeling in obese diabetic mice by n-3 polyunsaturated fatty acids SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE polyunsaturated fatty acids; matrix remodeling; high-fat diet; white adipose tissue ID MATRIX-METALLOPROTEINASE INHIBITION; INSULIN-RESISTANCE; GENE-EXPRESSION; CATHEPSIN-S; ADIPOCYTE DIFFERENTIATION; EXTRACELLULAR-MATRIX; EMERGING ROLES; FISH INTAKE; RISK; ADIPONECTIN AB Objective: Obesity is associated with reduced insulin sensitivity and extensive reorganization of adipose tissue. As polyunsaturated fatty acids ( PUFA) appear to inhibit diabetes development, we investigated PUFA effects on markers of matrix remodeling in white adipose tissue. Methods and procedure: Male obese diabetic (db/db) mice were treated with either a low-fat standard diet ( LF), or high-fat diets rich in saturated and monounsaturated fatty acids (HF/S), n-6 PUFA (HF/6) or the latter including marine n-3 PUFA (HF/3). White adipose tissue was analyzed for gene expression, fatty acid composition and by immunofluorescence. Results: HF/S treatment increased adipose tissue expression of a number of genes involved in matrix degradation including matrix metalloproteinase (MMP)-12, -14 and cathepsin K, L and S compared with LF. MMP-12 gene was expressed in macrophages and adipocytes, and MMP-12 protein colocalized with both cell types. In addition, mean adipocyte area increased by 1.6-fold in HF/S-treated mice. Genes essential for collagen production, such as procollagen I, III, VI, tenascin C and biglycan were upregulated in HF/S-treated animals as well. N-3 PUFA supplementation resulted in enrichment of these fatty acids in adipose tissue. Moreover, n-3 PUFA inhibited the HF/S-induced upregulation of genes involved in matrix degradation and production I restored mean adipocyte area and prevented MMP-12 expression in macrophages and adipocytes. Conclusion: N-3 PUFA prevent high-fat diet-induced matrix remodeling and adipocyte enlargement in adipose tissue of obese diabetic mice. Such changes could contribute to diabetes prevention by n-3 PUFA in obese patients. C1 Med Univ Vienna, Clin Div Endocrinol & Metab, Dept Internal Med 3, A-1090 Vienna, Austria. Med Univ Vienna, Dept Med & Chem Lab Diagnost, A-1090 Vienna, Austria. Ludwig Boltzmann Inst Clin & Expt Oncol, Vienna, Austria. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Pharmacol, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. Boku Univ Nat Resources & Appl Life Sci, Dept Food Sci & Technol, Div Food Chem, Vienna, Austria. Med Univ Vienna, Dept Internal Med 3, Clin Div Nephrol & Dial, Vienna, Austria. RP Stulnig, TM (reprint author), Med Univ Vienna, Clin Div Endocrinol & Metab, Dept Internal Med 3, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM thomas.stulnig@meduniwien.ac.at RI Loffler, Michael/F-1748-2013; Weichhart, Thomas/J-3531-2014; OI Loffler, Michael/0000-0002-6529-9723; Weichhart, Thomas/0000-0002-4349-0797; Stulnig, Thomas/0000-0003-3300-6161; Zeyda, Maximilian/0000-0001-5000-1974 NR 69 TC 60 Z9 61 U1 0 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 JUN PY 2007 VL 31 IS 6 BP 1004 EP 1013 DI 10.1038/sj.ijo.0803511 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 173XU UT WOS:000246906600019 PM 17130847 ER PT J AU Gaffney, DK Du Bois, A Narayan, K Reed, N Toita, T Pignata, S Blake, P Portelance, L Sadoyze, A Potter, R Colombo, A Randall, M Mirza, MR Trimble, EL AF Gaffney, David K. Du Bois, Andreas Narayan, Kailash Reed, Nick Toita, Takafumi Pignata, Sandro Blake, Peter Portelance, Lorraine Sadoyze, Azmat Potter, Richard Colombo, Alessandro Randall, Marcus Mirza, Mansoor R. Trimble, Edward L. TI Practice patterns of radiotherapy in cervical cancer among member groups of the Gynecologic Cancer Intergroup (GCIG) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE cervix; chemoradiation; cooperative group ID SQUAMOUS-CELL CANCER; CONCURRENT CHEMOTHERAPY; RADIATION-THERAPY; UTERINE CERVIX; PELVIC RADIATION; ONCOLOGY-GROUP; CARCINOMA; CARE; CISPLATIN; RISK AB Purpose: The aim of this study was to describe radiotherapeutic practice of the treatment of cervical cancer in member groups of the Gynecologic Cancer Intergroup (GCIG). Methods and Materials: A survey was developed and distributed to the members of the GCIG focusing on details of radiotherapy practice. Different scenarios were queried including advanced cervical cancer, postoperative patients, and para-aortic-positive lymph node cases. Items focused on indications for radiation therapy, radiation fields, dose, use of chemotherapy, brachytherapy and others. The cooperative groups from North America were compared with the other groups to evaluate potential differences in radiotherapy doses. Results: A total of 39 surveys were returned from 13 different cooperative groups. For the treatment of advanced cervical cancer, external beam pelvic doses and total doses to point A were 47 + 3.5 Gy (mean + SD) and 79.1 + 7.9 Gy, respectively. Point A doses were not different between the North American cooperative groups compared with the others (p = 0.103). All groups used concomitant chemotherapy, with 30 of 36 respondents using weekly cisplatin. Of 33 respondents, 31 intervened for a low hemoglobin level. For a para-aortic field, the upper border was most commonly (15 of 24) at the T12-L1 interspace. Maintenance chemotherapy (after radiotherapy) was not performed by 68% of respondents. For vaginal brachytherapy after hysterectomy, 23 groups performed HDR brachytherapy and four groups used LDR brachytherapy. In the use of brachytherapy, there was no uniformity in dose prescription. Conclusions: Radiotherapy practices among member groups of the GCIG are similar in terms of both doses and use of chemotherapy. (C) 2007 Elsevier Inc. C1 Radiat Therapy Oncol Grp, Salt Lake City, UT USA. Arbeitsgemeinschaft Gynaekol Onkol Studiengrp Ova, Wiesbaden, Germany. Australia & New Zealand Gynecol Oncol Grp, Melbourne, Vic, Australia. European Org Res Treatment Canc, Glasgow, Lanark, Scotland. Japanese Gynecol Oncol Grp, Okinawa, Japan. Multictr Italian Trials Ovarian Canc, Naples, Italy. Royal Marsden Hosp, London SW3 6JJ, England. Natl Canc Inst Canada, Montreal, PQ, Canada. Scottish Gynaecol Canc Trials Grp, Glasgow, Lanark, Scotland. Arbeitsgemeinschaft Gynaekol Onkol Austria, Vienna, Austria. Mario Negri Gynecol Oncol Grp, Lecce, Italy. Gynecol Oncol Grp, Lexington, KY USA. Nord Soc Gynecol Oncol, Odense, Denmark. Natl Canc Inst, Baltimore, MD USA. RP Gaffney, DK (reprint author), Huntsman Canc Hosp, Dept Radiat Oncol, 1950 Circle Hope,Rm 1570, Salt Lake City, UT 84112 USA. EM david.gaffney@hci.utah.edu NR 23 TC 18 Z9 19 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2007 VL 68 IS 2 BP 485 EP 490 DI 10.1016/j.ijrobp.2006.12.013 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 171IS UT WOS:000246730000024 PM 17336465 ER PT J AU Kim, MK Na, JR Cho, DH Soung, NK Yang, DC AF Kim, Myung Kyum Na, Ju-Ryun Cho, Dong Ha Soung, Nak-Kyun Yang, Deok-Chun TI Parapedobacter koreensis gen. nov., sp nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COMB-NOV; SPHINGOBACTERIUM-SPIRITIVORUM; FLAVOBACTERIUM-YABUUCHIAE; EMENDED DESCRIPTION; SOUTH-KOREA; PEDOBACTER; BACTERIUM; SOIL; PROPOSAL AB Strain Jip14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from dried rice straw and characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain Jip14(T) belongs to the family Sphingobacteriaceae, and the highest degree of sequence similarity was determined to be to Pedobacter saltans DSM 12145(T) (88.5%), Pedobacter africanus DSM 12126(T) (8 7.6%), Pedobacter heparinus DSM 2366(T) (87.1%) and Pedobacter caeni LMG 22862(T) (86.9%). Chemotaxonomic data revealed that strain Jip14(T) possesses menaquinone MK-7 and the predominant fatty acids C-15 : 0 iso, C-16 : 0, C-16 : 0 10-methyl, C-17 : 0 iso 3-OH and summed feature 3 (C-15 : 0 iso 2-OH/C-16: 1 omega 7c). The results of physiological and biochemical tests clearly demonstrated that strain Jip14(T) represents a distinct species. Based on these data, Jip14(T) should be classified within a novel genus and species, for which the name Parapedobacter koreensis gen. nov., sp. nov. is proposed. The type strain of Parapedobacter koreensis is Jip14(T) (= KCTC 12643(T) = LMG 23493(T)). C1 Kyung Hee Univ, Coll Life Sci, Dept Oriental Med Mat & Proc, Kyunggido 449701, South Korea. Kangwon Natl Univ, Sch Biosci & Biotechnol, Chunchon 200701, South Korea. Canc Res Ctr, Natl Canc Inst, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Coll Life Sci, Dept Oriental Med Mat & Proc, 1 Seocheon-dong, Kyunggido 449701, South Korea. EM deokchunyang@yahoo.co.kr NR 31 TC 14 Z9 14 U1 0 U2 0 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 JUN PY 2007 VL 57 BP 1336 EP 1341 DI 10.1099/ijs.0.64677-0 PN 6 PG 6 WC Microbiology SC Microbiology GA 185YK UT WOS:000247746100032 PM 17551054 ER PT J AU Portnoy, B Miller, J Brown-Huamani, K DeVoto, E AF Portnoy, Barry Miller, Jennifer Brown-Huamani, Kathryn DeVoto, Emily TI Impact of the National Institutes of Health Consensus Development program on stimulating National Institutes of Health-Funded Research, 1998 to 2001 SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE Consensus development; impact evaluation; diffusion of innovation ID BREAST-CONSERVING SURGERY; CONFERENCES AB Objectives: The National Institutes of Health (NIH) Consensus Development Conference (CDC) was instituted to provide evidence-based guidance on controversial medical issues to researchers, health practitioners, and the public; however, the degree of impact this activity has on stimulating relevant research is unclear. This study examines the impact of CDC statements on the initiation of related NIH-funded research projects. Methods: Six CDCs from 1998 to 2001 were examined. Research initiatives related to the Conferences' topics were collected through two discrete methods: (i) the overall number of relevant pre- and postconference research activities was compiled using NIH's Information for Management, Planning, Analysis, and Coordination 11 (IMPAC 11) and the Department of Health and Human Services' (DHHS) Computer Retrieval of Information on Scientific Projects (CRISP) grant application and award databases; (ii) for each CDC, the sponsoring institute's conference coordinator and other identified Program Directors were queried for their knowledge of new conference-specific research initiatives sponsored by their institute. The main outcome measure was the total number of requests for applications, requests for proposals, program announcements, broad agency announcements, notices, and funded investigator-initiated research program grants (RO1s) for a given Consensus topic in the 3 years before (baseline measure) and following (measure of impact) a CDC. Results: As identified through NIH's IMPAC 11 and DHHS' CRISP grants and announcements databases, the total number of relevant postconference research initiatives increased for five of six CDCs when compared with baseline activity levels; research activities remained constant for the sixth. When inclusion criteria were restricted to institute-identified research initiatives, two of six CDC topics had overall increases in relevant research activity in the postconference period. Conclusions: CDCs appear to have a positive impact on the stimulation of related NIH-funded research initiatives. Future outcomes evaluations using prospective data collection methods and more robust participation by sponsoring and cosponsoring institutes should strengthen the reliability of the association between new research initiatives on a given topic and their causal relationship to a given CDC. C1 NIH, Off Med Applicat Res, Off Director, Off Dis Prevent, Bethesda, MD 20892 USA. Sci Consulting Grp Inc, Gaithersburg, MD 20878 USA. RP Portnoy, B (reprint author), NIH, Off Med Applicat Res, Off Director, Off Dis Prevent, 6100 Execut Blvd,Room 2B03, Bethesda, MD 20892 USA. EM portnoyb@od.nih.gov; khuamani@scgcorp.com; emily.devoto@gmail.com FU NIH HHS [EB 03-122 OD-ODP] NR 16 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SUM PY 2007 VL 23 IS 3 BP 343 EP 348 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 187KF UT WOS:000247845800007 PM 17579937 ER PT J AU Shan, XY Tian, J Ying, HS Quaia, C Optican, LM Walker, MF Famargo, RJ Zee, DS AF Shan, Xiaoyan Tian, Jing Ying, Howard S. Quaia, Christian Optican, Lance M. Walker, Mark F. Famargo, Rafael J. Zee, David S. TI Acute superior oblique palsy in monkeys: I. Changes in static eye alignment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HEAD-TILT TEST; TROCHLEAR NERVE PALSY; OTOLITH-OCULAR REFLEX; EXTRAOCULAR-MUSCLES; VISUAL LOCALIZATION; CONGENITAL ABSENCE; FUNCTIONAL-ANATOMY; PHORIA ADAPTATION; SACCADIC SYSTEM; RHESUS-MONKEY AB PURPOSE. To investigate immediate and long-term changes in static ocular alignment with acute acquired superior oblique palsy (SOP) in monkeys. METHODS. The trochlear nerve was severed intracranially in two rhesus monkeys. After the surgery, the paretic eye was patched for 6 to 9, days, and then binocular viewing was allowed. Three-axis eye movements (horizontal, vertical, and torsional) were measured with binocular, dual search coils. Eye movements were recorded over a +/- 20 degrees horizontal and vertical range of fixations before the lesion and then, beginning the first day after surgery. Changes in alignment with +/- 30 degrees head tilt were also studied. RESULTS. The main findings were (1) misalignment (10-12 degrees vertical in adduction, down; 10-12 degrees torsional in abduction down); (2) changes in vertical deviation (VD) with head tilt ( 2-6 degrees with left versus right 30 degrees tilt); and (3) changes in comitance and VD over time. During the early postlesion period, before binocular viewing was allowed, VD decreased and comitance improved. Once binocular viewing was allowed, VD increased and comitance worsened. CONCLUSIONS. Rhesus monkeys with induced SOP show a characteristic pattern of misalignment that helps define the ocular motor signature of acute denervation of the superior oblique muscle. The animals also showed striking changes over time in the amount and comitance of the vertical misalignment that depended on whether viewing was monocular or binocular, suggesting a role for proprioception in adaptation to misalignment with habitual monocular viewing. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Zee, DS (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Path 2-210,600 N Wolfe St, Baltimore, MD 21287 USA. EM dzee@jhmi.edu FU NEI NIH HHS [K12EY015025, K23 EY00400, R01-EY001849] NR 59 TC 21 Z9 21 U1 0 U2 2 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 JUN PY 2007 VL 48 IS 6 BP 2602 EP 2611 DI 10.1167/iovs.06-1316 PG 10 WC Ophthalmology SC Ophthalmology GA 174UA UT WOS:000246967100019 PM 17525190 ER PT J AU Shan, XY Ying, HS Tian, J Quaia, C Walker, MF Optican, LM Tamargo, RJ Zee, DS AF Shan, Xiaoyan Ying, Howard S. Tian, Jing Quaia, Christian Walker, Mark F. Optican, Lance M. Tamargo, Rafael J. Zee, David S. TI Acute superior oblique palsy in monkeys: II. Changes in dynamic properties during vertical saccades SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OCULAR ALIGNMENT; VELOCITY; SYSTEM AB PURPOSE. To investigate vertical and torsional eye motion during and immediately after vertical saccades with acute acquit superior oblique palsy (SOP) in monkeys. METHODS. The trochlear nerve was severed intracranially in two rhesus monkeys. After surgery, the paretic eye was patched for 6 to 9 days, and then binocular viewing was allowed. Three-axis eye movements (horizontal, vertical, and torsion) were measured with binocular, dual search coils. Eye movements were recorded before surgery and then beginning 2 to 3 days after surgery during 20 degrees vertical saccades over a +/- 20 degrees horizontal and vertical range. RESULTS. The main findings were: (1) Saccade amplitude in the paretic eye (PE) was smaller than that of the normal eye (NE), especially for downward saccades with the PE in adduction; (2) vertical drift was backward after upward saccades with the PE in adduction or abduction, onward after downward saccades with the PE in adduction, but backward for downward saccades with the PE in abduction, drift time constants averaged 35 ms; (3) peak dynamic blip intrasaccadic torsion increased (relative extorsion), the most for upward saccades with the PE in abduction; (4) postsaccadic torsional drift increased (relative intorsion), the most for downward saccades with the PE in adduction; and (5) the peak velocity-amplitude relationship in vertical saccades was little affected, but the ratio between the peak velocity of the two eyes was a consistent indicator of the palsy. CONCLUSIONS. Rhesus monkeys with acute acquired SOP show characteristic changes in vertical and torsional movements during and immediately after vertical saccades that help define the ocular motor signature of denervation of the SO muscle. These dynamic changes were largely unrelated to the changes in static alignment over time, suggesting that static and dynamic disturbances in SOP are influenced by separate central mechanisms. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Zee, DS (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Path 2-210,600 N Wolfe St, Baltimore, MD 21287 USA. EM dzee@jhmi.edu FU NEI NIH HHS [K12EY015025, K23 EY00400, R01-EY001849] NR 19 TC 9 Z9 9 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2007 VL 48 IS 6 BP 2612 EP 2620 DI 10.1167/iovs.06-1318 PG 9 WC Ophthalmology SC Ophthalmology GA 174UA UT WOS:000246967100020 PM 17525191 ER PT J AU Tian, J Shan, XY Zee, DS Ying, H Tamargo, RJ Quaia, C Optican, LM Walker, MF AF Tian, Jing Shan, Xiaoyan Zee, David S. Ying, Howard Tamargo, Rafael J. Quaia, Christian Optican, Lance M. Walker, Mark F. TI Acute superior oblique palsy in monkeys: III. Relationship to listing's law SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PRIMARY POSITION; EYE POSITION; NERVE PALSY; SACCADES; SYSTEM AB PURPOSE. To investigate the three-dimensional orientation of the eye and its relationship to Listing's Law in monkeys with acute acquired superior oblique palsy (SOP). METHODS. The trochlear nerve was severed intracranially in two rhesus monkeys. Three-axis eye movements (horizontal, vertical, and torsion) were measured with binocular, dual search coils during fixation of targets in a 40 degrees x 40 degrees grid. Rotation vectors were calculated, and Listing's plane (LP) was determined by a least-squares planar fit of eye torsion as a function of horizontal and vertical position. RESULTS. The main findings were: (1) In the paretic eye, there was an immediate and sustained rotation of the orientation plane by approximately 25 degrees in the temporal direction; (2) the thickness of LP, defined as the torsional standard deviation (SD), increased little (by 0.13 degrees in M1 and 0.08 degrees in M2) after SOP, and (3) the SD of intrasaccadic torsion was slightly greater than that during fixation, but there was no change after SOP. CONCLUSIONS. Acute SOP in rhesus monkeys leads to a temporal rotation of LP. This is consistent with a relatively increased extorsion in down gaze due to a loss of normal intorsion by the superior oblique muscle. The SD of torsion increased by only a small amount, implying that the validity of Listing's Law is not affected much by complete SOP, despite the large change in the orientation of LP. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Zee, DS (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM dzee@jhmi.edu FU NEI NIH HHS [K12EY015025, R01-EY001849] NR 16 TC 6 Z9 6 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2007 VL 48 IS 6 BP 2621 EP 2625 DI 10.1167/iovs.06-1319 PG 5 WC Ophthalmology SC Ophthalmology GA 174UA UT WOS:000246967100021 PM 17525192 ER PT J AU Compton, P Ling, W Chiang, CN Moody, DE Huber, A Ling, D Charuvastra, C AF Compton, Peggy Ling, Walter Chiang, C. Nora Moody, David E. Huber, Alice Ling, Debbie Charuvastra, Charles TI Pharmacokinetics of buprenorphine: A comparison of sublingual tablet versus liquid after chronic dosing SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE buprenorphine; pharmacokinetics; bioavailability ID RELATIVE BIOAVAILABILITY; CLINICAL-PHARMACOLOGY; CYTOCHROME-P450 3A4; OPIATE DEPENDENCE; N-DEALKYLATION; METHADONE; NORBUPRENORPHINE; NALOXONE; FORMULATIONS; EFFICACY AB Although briprenorphine is approved for use in the outpatient treatment of opioid addiction in 2 tablet formulations, a monoproduct containing buprenorphine only (Subutex) and a buprenorphine/naloxone combination product (Suboxone), much of the clinical data that support the approval by the U.S. Food and Drug Administration were generated by using a sublingual liquid. To interpret the literature in prescribing parameters for tablet buprenorphine, this study was designed to determine steady state buprenorphine plasma levels for the 2 formulations and to assess the relative bioavailability of each. A randomized, double-blind, crossover study with dose increases was conducted during a 12-week period at an outpatient treatment clinic. Of the 184 subjects initially randomized to treatment, 133 (72.3%) were evaluated for the steady-state trough plasma concentration, 16 (8.7%) for relative bioavailability, and 31 (16.8%) for dose proportionality. At steady state, differences in the trough plasma concentrations of buprenorphine between the 2 formulations were found across all the dose levels. Average plasma concentration (C-avg) of the tablet at twice the milligram dose of the liquid was twice that of the liquid; intersubject variability was greater for the tablet. At double the dose of tablet, there is no difference in steady state plasma concentrations. The bioavailability seems equivalent for the 2 formulations across all the dose levels. C1 [Compton, Peggy] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Ling, Walter; Ling, Debbie; Charuvastra, Charles] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA. [Chiang, C. Nora] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. [Moody, David E.] Univ Utah, Ctr Human Toxicol, Salt Lake City, UT USA. [Huber, Alice] Univ Washington, Drug & Alcohol Inst, Seattle, WA 98195 USA. RP Compton, P (reprint author), Univ Calif Los Angeles, Sch Nursing, Factor Bldg 4-246,Box 956918, Los Angeles, CA 90095 USA. EM peompton@sonnet.ucla.edu NR 29 TC 3 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JUN PY 2007 VL 1 IS 2 BP 88 EP 95 DI 10.1097/ADM.0b013e31806dcc3e PG 8 WC Substance Abuse SC Substance Abuse GA 305GK UT WOS:000256165700006 PM 21768940 ER PT J AU Bell, SG Newcomer, SF Bachrach, C Borawski, E Jemmott, JB Morrison, D Stanton, B Tortolero, S Zimmerman, R AF Bell, Stephanie G. Newcomer, Susan F. Bachrach, Christine Borawski, Elaine Jemmott, John B., III Morrison, Diane Stanton, Bonita Tortolero, Susan Zimmerman, Richard TI Challenges in replicating interventions SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; interventions; sexual behavior; HIV risk ID PREVENTION PROGRAMS; SAFER CHOICES; SUBSTANCE USE; HIV; HEALTH; IMPACT; ADOLESCENTS; CURRICULUM; PREGNANCY; FIDELITY AB Purpose: To describe and reflect on an effort to document, through a set of 6 interventions, the process of adapting effective youth risk behavior interventions for new settings, and to provide insights into how this might best be accomplished. Methods: Six studies were funded by the NIH, starting in 1999. The studies were funded in response to a Request for Applications (RFA) to replicate HIV prevention interventions for youth. Researchers were to select an HIV risk reduction intervention program shown to be effective in one adolescent population and to replicate it in a new community or different adolescent population. This was to be done while systematically documenting those processes and aspects of the intervention hypothesized to be critical to the development of community-based, culturally sensitive programs. The replication was to assess the variations necessary to gain cooperation, implement a locally feasible and meaningful intervention, and evaluate the outcomes in the new setting. The rationale for this initiative and description of the goals and approaches to adaptation of the funded researchers are described. Results: Issues relevant to all interventions are discussed, in addition to those unique to replication. The processes and the consequences of the adaptations are then discussed. The further challenges in taking a successful intervention "to scale" are not discussed. Conclusions: Replications of effective interventions face all of the challenges of implementation design, plus additional challenges of balancing fidelity to the original intervention and sensitivity to the needs of new populations. (c) 2007 Society for Adolescent Medicine. All rights reserved. C1 NICHD, NIH, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Case Western Reserve, Cleveland, OH USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Seattle, WA 98195 USA. Wayne State Univ, Detroit, MI USA. Univ Texas, Med Ctr Houston, Houston, TX USA. Univ Kentucky, Lexington, KY USA. RP Newcomer, SF (reprint author), NICHD, NIH, Bldg 61E,Room 8B7G, Bethesda, MD 20892 USA. EM newcomes@mail.nih.gov FU NICHD NIH HHS [R01 HD039109, R01 HD038420, R01 HD038420-05S1, R01 HD038456, R01 HD038456-03, R01 HD038457, R01 HD038457-05, R01 HD039109-05, R01-HD038420, R01-HD038456, R01-HD038457, R01-HD039109]; NIMH NIH HHS [R01 MH061187, R01 MH061187-05, R01 MH061761, R01 MH061761-06, R01 MH069229, R01-MH061187, R01-MH061761] NR 38 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JUN PY 2007 VL 40 IS 6 BP 514 EP 520 DI 10.1016/j.jadohealth.2006.09.005 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 174FA UT WOS:000246925900005 PM 17531757 ER PT J AU Rosenberg, HF Phipps, S Foster, PS AF Rosenberg, Helene F. Phipps, Simon Foster, Paul S. TI Eosinophil trafficking in allergy and asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE inflammation; ILs; cytokines; hematopoiesis ID COLONY-STIMULATING FACTOR; SMALL-MOLECULE; HYGIENE HYPOTHESIS; BONE-MARROW; ANTI-INTERLEUKIN-5 ANTIBODY; HYPEREOSINOPHILIC-SYNDROMES; PULMONARY EOSINOPHILIA; MEPOLIZUMAB THERAPY; LUNG INFLAMMATION; ATOPIC-DERMATITIS AB Blood eosinophilia and tissue eosinophilia are characteristic features of allergic inflammation and asthma, conditions associated with prominent production of TH2 cytokines IL-4, IL-5, and IL-13. In this review, we will consider recent advances in our understanding of the molecular mechanisms that promote expansion and differentiation of eosinophil progenitors in bone marrow, eosinophil recruitment in response to chemokine receptor 3 agonists eosinophil transit mediated by specific ligand-receptor interactions, and prolonged survival of eosinophils in peripheral tissues. Novel rational therapies including antiselectin and antichemokine receptor modalities designed to block eosinophil development and trafficking are discussed, together with the implications of recent clinical studies that have evaluated the efficacy of humanized anti-IL-5 mAb therapy. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Newcastle, Ctr Asthma & Resp Dis, Sch Biomed Sci, Newcastle, NSW 2308, Australia. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov RI Phipps, Simon/F-9170-2010; Foster, Paul/G-5057-2013 OI Phipps, Simon/0000-0002-7388-3612; NR 110 TC 188 Z9 194 U1 1 U2 9 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 JUN PY 2007 VL 119 IS 6 BP 1303 EP 1310 DI 10.1016/j.jaci.2007.03.048 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 178PO UT WOS:000247232800002 PM 17481712 ER PT J AU Pahwa, S Muresan, P Sleasman, J Fenton, T Moye, J Deveikis, A Wara, D Van Dyke, R AF Pahwa, Savita Muresan, Petronella Sleasman, John Fenton, Terry Moye, John Deveikis, Audra Wara, Diane Van Dyke, Russ CA AIDS Trials Study TI Phase I/II trial of intermittent subcutaneous IL-2 administration in pediatric patients with moderate immune suppression: Results of Pediatric AIDS Clinical Trials Study 402 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTES; INTERLEUKIN-2; INFECTION; INDUCTION; THERAPY C1 Univ Miami, Miller Sch Med, Miami, FL 33152 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Childrens Hosp, St Petersburg, FL USA. Univ S Florida, Tampa, FL USA. NICHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. Long Beach Mem Med Ctr, Long Beach, CA USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Tulane Univ Hosp, New Orleans, LA USA. RP Pahwa, S (reprint author), Univ Miami, Miller Sch Med, Miami, FL 33152 USA. EM spahwa@med.miami.edu OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [U01 AI41089]; NICHD NIH HHS [N01 HD 33162, N01 HD 33345] NR 9 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2007 VL 119 IS 6 BP 1538 EP 1541 DI 10.1016/j.jaci.2006.12.674 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 178PO UT WOS:000247232800034 PM 17418382 ER PT J AU Carter, MC Robyn, JA Bressler, PB Walker, JC Shapiro, GG Metcalfe, DD AF Carter, Melody C. Robyn, Jamie A. Bressler, Peter B. Walker, John C. Shapiro, Gail G. Metcalfe, Dean D. TI Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. Carolina Allergy & Asthma, Chapel Hill, NC USA. Univ Washington, Childrens Hosp, NW Allery & Asthma Ctr, Richland, WA USA. Reg Med Ctr, Richland, WA USA. Univ Washington, Sch Med, NW Allergy & Asthma Ctr, Seattle, WA 98195 USA. RP Carter, MC (reprint author), NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. EM mcarter@niaid.nih.gov FU Intramural NIH HHS NR 4 TC 77 Z9 77 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2007 VL 119 IS 6 BP 1550 EP 1551 DI 10.1016/j.jaci.2007.03.032 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 178PO UT WOS:000247232800039 PM 17481708 ER PT J AU Smith, ML Vorce, SP Holler, JM Shimomura, E Magluilo, J Jacobs, AJ Huestis, MA AF Smith, Michael L. Vorce, Shawn P. Holler, Justin M. Shimomura, Eric Magluilo, Joe Jacobs, Aaron J. Huestis, Marilyn A. TI Modern instrumental methods in forensic toxicology SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Review ID TANDEM MASS-SPECTROMETRY; PRESSURE CHEMICAL-IONIZATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; 2-DIMENSIONAL GAS-CHROMATOGRAPHY; TIME-OF-FLIGHT; SOLID-PHASE EXTRACTION; LC-MS-MS; SULFATED-GAMMA-CYCLODEXTRIN; CONTROLLED ORAL CODEINE; GC-EI-MS C1 Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Rockville, MD 20850 USA. USA, Med Dept Board, Ft Sam Houston, TX 78234 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Smith, ML (reprint author), Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, 1413 Res Blvd,Bldg 102, Rockville, MD 20850 USA. EM smithml@afip.osd.mil FU Intramural NIH HHS [Z01 DA000414-10, Z01 DA000412-10] NR 189 TC 18 Z9 18 U1 2 U2 17 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUN PY 2007 VL 31 IS 5 BP 237 EP 253 PG 17 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 179MY UT WOS:000247295200001 PM 17579968 ER PT J AU Choo, RE Jansson, LM Scheidweiler, K Huestis, MA AF Choo, Robin E. Jansson, Lauren M. Scheidweiler, Karl Huestis, Marilyn A. TI A validated liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric method for the quantification of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and 2-ethyl-5-methyl-3,3-diphenylpyroline (EMDP) in human breast milk SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID METABOLITES; DRUGS; MAINTENANCE; COCAINE C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Pittsburgh, Titusville, PA USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000433-08]; NIDA NIH HHS [K08 DA000495, K08 DA00495] NR 18 TC 19 Z9 19 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUN PY 2007 VL 31 IS 5 BP 265 EP 269 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 179MY UT WOS:000247295200003 PM 17579970 ER PT J AU Walsh, S Metter, EJ Ferrucci, L Roth, SM AF Walsh, Sean Metter, E. Jeffrey Ferrucci, Luigi Roth, Stephen M. TI Activin-type II receptor B (ACVR2B) and follistatin haplotype associations with muscle mass and strength in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE genetics; skeletal muscle; sex ID MYOSTATIN PATHWAY GENES; FAT-FREE MASS; SKELETAL-MUSCLE; BONE-DENSITY; HUMAN GENOME; MEN; AGE; POLYMORPHISM; EXPRESSION; SARCOPENIA AB Genetic variation in myostatin, a negative regulator of skeletal muscle, in cattle has shown remarkable influence on skeletal muscle, resulting in a double-muscled phenotype in certain breeds; however, DNA sequence variation within this gene in humans has not been consistently associated with skeletal muscle mass or strength. Follistatin and activin-type II receptor B (ACVR2B) are two myostatin-related genes involved in the regulation and signaling of myostatin. We sought to identify associations between genetic variation and haplotype structure in both follistatin and ACVR2B with skeletal muscle-related phenotypes. Three hundred fifteen men and 278 women aged 19-90 yr from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings (Hap Groups) based on HapMap data. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Quadriceps peak torque (strength) was measured using an isokinetic dynamometer. Women carriers of ACVR2B Hap Group 1 exhibited significantly less quadriceps muscle strength (shortening phase) than women homozygous for Hap Group 2 (109.2 +/- 1.9 vs. 118.6 +/- 4.1 N-m, 30 degrees/s, respectively, P = 0.036). No significant association was observed in men. Male carriers of follistatin Hap Group 3 exhibited significantly less total leg fat-free mass than noricarriers (16.6 +/- 0.3 vs. 17.5 +/- 0.2 kg, respectively, P = 0.012). No significant associations between these haplotype groups were observed in women. These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships. C1 Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD USA. RP Roth, SM (reprint author), Univ Maryland, Dept Kinesiol, 2134 HHP Bldg, College Pk, MD 20742 USA. EM sroth1@umd.edu OI Roth, Stephen/0000-0002-7841-3695 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [L30 AG024705, AG-021500, AG-022791, K01 AG022791, K01 AG022791-05, L30 AG024705-03, R01 AG021500, R01 AG021500-03] NR 40 TC 27 Z9 28 U1 1 U2 7 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 JUN PY 2007 VL 102 IS 6 BP 2142 EP 2148 DI 10.1152/japplphysiol.01322.2006 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KJ UT WOS:000248410800011 PM 17347381 ER PT J AU Spouge, JL AF Spouge, John L. TI Markov additive processes and repeats in sequences SO JOURNAL OF APPLIED PROBABILITY LA English DT Article DE Markov additive process; biological sequence analysis; repeats ID COMPARATIVE STATISTICS; PROTEIN SEQUENCES; ACID-SEQUENCES; PARTIAL-SUMS; DNA; DISTRIBUTIONS; DATABASES; CHAINS AB Computer analysis of biological sequences often detects deviations from a random model. In the usual model, sequence letters are chosen independently, according to some fixed distribution over the relevant alphabet. Real biological sequences often contain simple repeats, however, which can be broadly characterized as multiple contiguous copies (usually inexact) of a specific word. This paper quantifies inexact simple repeats as local sums in a Markov additive process (MAP). The maximum of the local sums has an asymptotic distribution with two parameters (lambda and k), which are given by general MAP formulas. The general MAP formulas are usually computationally intractable, but an essential simplification in the case of repeats permits. and k to be computed from matrices whose dimension equals the size of the relevant alphabet. The simplification applies to some MAPs where the summand distributions do not depend on consecutive pairs of Markov states as usual, but on pairs with a fixed time-lag larger than one. C1 Natl Lib Med, Natl Ctr Biotechnol, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov NR 23 TC 2 Z9 2 U1 0 U2 2 PU APPLIED PROBABILITY TRUST PI SHEFFIELD PA THE UNIVERSITY, SCHOOL MATHEMATICS STATISTICS, SHEFFIELD S3 7RH, ENGLAND SN 0021-9002 J9 J APPL PROBAB JI J. Appl. Probab. PD JUN PY 2007 VL 44 IS 2 BP 514 EP 527 DI 10.1239/jap/1183667418 PG 14 WC Statistics & Probability SC Mathematics GA 196UP UT WOS:000248508000018 ER PT J AU Hook-Barnard, IG Brickman, TJ McIntosh, MA AF Hook-Barnard, India G. Brickman, Timothy J. McIntosh, Mark A. TI Identification of an AU-rich translational enhancer within the Escherichia coli fepB leader RNA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RIBOSOMAL-PROTEIN S1; MESSENGER-RNA; BINDING-SITES; SEQUENCE; GENE; INITIATION; PROMOTER; SUBUNIT; ELEMENT; TRANSPORT AB The fepB gene encodes a periplasmic binding protein that is essential for the uptake of ferric enterobactin by Escherichia coli. Its transcription is regulated in response to iron levels by the Fur repressor. The fepB transcript includes a 217-nucleotide leader sequence with several features suggestive of posttranscriptional regulation. To investigate the fepB leader for its contribution to fepB expression, defined deletions and substitution mutations in the leader were characterized using fepB-phoA translational fusions. The fepB leader was found to be necessary for maximal fepB expression, primarily due to the influence of an AU-rich translational enhancer (TE) located 5' to the Shine-Dalgarno sequence. Deletions or substitutions within the TE sequence decreased fepB-phoA expression fivefold. RNase protection and in vitro transcription-translation assays demonstrated that the TE augmented translational efficiency, as well as RNA levels. Moreover, primer extension inhibition assays showed that the TE increases ribosome binding. In contrast to the enhancing effect of the TE, the natural fepB GUG start codon decreased ribosome binding and reduced jebB expression 2.5-fold compared with the results obtained with leaders bearing an AUG initiation codon. Thus, the TE-GUG organization in fepB results in an intermediate level of expression compared to the level with AUG, with or without the TE. Furthermore, we found that the TE-GUG sequence is conserved among the eight gram-negative strains examined that have fepB genes, suggesting that this organization may provide a selective advantage. C1 Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. RP Hook-Barnard, IG (reprint author), Natl Inst Hlth, Bldg 8,Room 2A-24, Bethesda, MD 20892 USA. EM indiah@intra.niddk.nih.gov FU NIAID NIH HHS [T32 AI007276, 5 T32 AI07276]; NIGMS NIH HHS [GM54243] NR 55 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2007 VL 189 IS 11 BP 4028 EP 4037 DI 10.1128/JB.01924-06 PG 10 WC Microbiology SC Microbiology GA 179JN UT WOS:000247285900011 PM 17400738 ER PT J AU Phadtare, S Kazakov, T Bubunenko, M Court, DL Pestova, T Severinov, K AF Phadtare, Sangita Kazakov, Teymur Bubunenko, Mikhail Court, Donald L. Pestova, Tatyana Severinov, Konstantin TI Transcription antitermination by translation initiation factor IF1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLD-SHOCK PROTEIN; SOLUTION NMR STRUCTURE; ACID MELTING ACTIVITY; ESCHERICHIA-COLI; RNA-BINDING; CSPA-FAMILY; BACILLUS-SUBTILIS; CRYSTAL-STRUCTURE; CELL VIABILITY; DOMAIN AB Bacterial translation initiation factor IF1 is an S1 domain protein that belongs to the oligomer binding (OB) fold proteins. Cold shock domain (CSD)-containing proteins such as CspA (the major cold shock protein of Escherichia coli) and its homologues also belong to the OB fold protein family. The striking structural similarity between IF1 and CspA homologues suggests a functional overlap between these proteins. Certain members of the CspA family of cold shock proteins act as nucleic acid chaperones: they melt secondary structures in nucleic acids and act as transcription antiterminators. This activity may help the cell to acclimatize to low temperatures, since cold-induced stabilization of secondary structures in nascent RNA can impede transcription elongation. Here we show that the E. coli translation initiation factor, IF1, also has RNA chaperone activity and acts as a transcription antiterminator in vivo and in vitro. We further show that the RNA chaperone activity of IF1, although critical for transcription antitermination, is not essential for its role in supporting cell growth, which presumably functions in translation. The results thus indicate that IF1 may participate in transcription regulation and that cross talk and/or functional overlap may exist between the Csp family proteins, known to be involved in transcription regulation at cold shock, and S1 domain proteins, known to function in translation. C1 Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Biochem & Mol Biol, Waksman Inst, Piscataway, NJ 08854 USA. Natl Canc Inst Frederick, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. SUNY Downstate Med Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. RP Phadtare, S (reprint author), Robert Wood Johnson Med Sch, Dept Biochem, 675 Hoes Lane,Rm 615, Piscataway, NJ 08854 USA. EM phadtasa@umdnj.edu RI Severinov, Konstantin/C-8545-2016 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [GM59295, R01 GM059295] NR 46 TC 15 Z9 15 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2007 VL 189 IS 11 BP 4087 EP 4093 DI 10.1128/JB.00188-07 PG 7 WC Microbiology SC Microbiology GA 179JN UT WOS:000247285900018 PM 17384193 ER PT J AU Thompson, KM Rhodius, VA Gottesman, S AF Thompson, Karl M. Rhodius, Virgil A. Gottesman, Susan TI sigma(E) regulates and is regulated by a small RNA in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ENVELOPE-STRESS-RESPONSE; OMPC PORIN OVEREXPRESSION; OUTER-MEMBRANE PROTEINS; EXTRACYTOPLASMIC STRESS; STATIONARY-PHASE; MESSENGER-RNA; POSTTRANSCRIPTIONAL REGULATION; TRANSCRIPTIONAL ACTIVATOR; TRANSLATIONAL CONTROL; COMPARATIVE GENOMICS AB RybB is a small, Hfq-binding noncoding RNA originally identified in a screen of conserved intergenic regions in Escherichia coli. Fusions of the rybB promoter to lacZ were used to screen plasmid genomic libraries and genomic transposon mutants for regulators of rybB expression. A number of plasmids, including some carrying rybB, negatively regulated the fusion. An insertion in the rep helicase and one upstream of dnaK decreased expression of the fusion. Multicopy suppressors of these insertions led to identification of two plasmids that stimulated the fusion. One contained the gene for the response regulator OmpR; the second contained mipA, encoding a murein hydrolase. The involvement of MipA and OmpR in cell surface synthesis suggested that the rybB promoter might be dependent on sigma(E). The sequence upstream of the +1 of rybB contains a consensus sigma(E) promoter. The activity of rybB-lacZ was increased in cells lacking the RseA anti-sigma factor and when sigma(E) was overproduced from a heterologous promoter. The activity of rybB-1acZ and the detection of RybB were totally abolished in an rpoE-null strain. In vitro, sigma(E) efficiently transcribes from this promoter. Both a rybB mutation and an hfq mutation significantly increased expression of both rybB-1acZ and rpoE-lacZ fusions, consistent with negative regulation of the alpha(E) response by RybB and other small RNAs. Based on the plasmid screens, NsrR, a repressor sensitive to nitric oxide, was also found to negatively regulate sigma(E)-dependent promoters in an RseA-independent fashion. C1 NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. RP Gottesman, S (reprint author), NCI, Lab Mol Biol, NIH, Bldg 37,Rm 5132, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU Intramural NIH HHS NR 66 TC 79 Z9 79 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2007 VL 189 IS 11 BP 4243 EP 4256 DI 10.1128/JB.00020-07 PG 14 WC Microbiology SC Microbiology GA 179JN UT WOS:000247285900035 PM 17416652 ER PT J AU Ma, WZ Sung, HJ Park, JY Matoba, S Hwang, PM AF Ma, Wenzhe Sung, Ho Joong Park, Joon Y. Matoba, Satoaki Hwang, Paul M. TI A pivotal role for p53: balancing aerobic respiration and glycolysis SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE synthesis of cytochrome c oxidase 2; cytochrome c oxidase; tumor protein p53 ID TUMOR-SUPPRESSOR P53; CYTOCHROME-C-OXIDASE; CANCER-CELLS; RAT HEPATOMA; MITOCHONDRIAL; EXPRESSION; GENES; HEXOKINASE; METABOLISM; PATHWAYS AB The genetic basis of increased glycolytic activity observed in cancer cells is likely to be the result of complex interactions of multiple regulatory pathways. Here we review the recent evidence of a simple genetic mechanism by which tumor suppressor p53 regulates mitochondrial respiration with secondary changes in glycolysis that are reminiscent of the Warburg effect. The biological significance of this regulation of the two major pathways of energy generation by p53 remains to be seen. C1 NIH, NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. Kyoto Prefectural Univ Med, Dept Cardiovasc Med, Kyoto 6028566, Japan. RP Hwang, PM (reprint author), NIH, NHLBI, Cardiol Branch, 10-CRC 5-5330, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS NR 27 TC 72 Z9 82 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 2007 VL 39 IS 3 BP 243 EP 246 DI 10.1007/s10863-007-9083-0 PG 4 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 222MY UT WOS:000250302800005 PM 17551815 ER PT J AU Medvedev, AE Piao, W Shoenfelt, J Rhee, SH Chen, HY Basu, S Wahl, LM Fenton, MJ Vogel, SN AF Medvedev, Andrei E. Piao, Wenji Shoenfelt, Joanna Rhee, Sang Hoon Chen, Haiyan Basu, Subhendu Wahl, Larry M. Fenton, Matthew J. Vogel, Stefanie N. TI Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; RECEPTOR-ASSOCIATED KINASE; TOLL-LIKE RECEPTORS; DOUBLE-STRANDED-RNA; CONFERS LIPOPOLYSACCHARIDE RESPONSIVENESS; PATTERN-RECOGNITION RECEPTOR; BRUTONS TYROSINE KINASE; HUMAN NK CELLS; ADAPTER MOLECULE; INNATE IMMUNITY AB In this study, we examined whether tyrosine phosphorylation of the Toll-IL-1 resistance (TIR) domain of Toll-like receptor (TLR) 4 is required for signaling and blocked in endotoxin tolerance. Introduction of the P712H mutation, responsible for lipopolysaccharide (LPS) unresponsiveness of C3H/HeJ mice, into the TIR domain of constitutively active mouse Delta TLR4 and mutation of the homologous P714 in human CD4-TLR4 rendered them signaling-incompetent and blocked TLR4 tyrosine phosphorylation. Mutations of tyrosine residues Y674A and Y680A within the TIR domains of CD4-TLR4 impaired its ability to elicit phosphorylation of p38 and JNK mitogen-activated protein kinases, I kappa B-alpha degradation, and activation of NF-kappa B and RANTES reporters. Likewise, full-length human TLR4 expressing Y674A or Y680A mutations showed suppressed capacities to mediate LPS-inducible cell activation. Signaling deficiencies of the Y674A and Y680A TLR4s correlated with altered MyD88-TLR4 interactions, increased associations with a short IRAK-1 isoform, and decreased amounts of activated IRAK-1 in complex with TLR4. Pretreatment of human embryonic kidney (HEK) 293/TLR4/MD-2 cells with protein tyrosine kinase or Src kinase inhibitors suppressed LPS-driven TLR4 tyrosine phosphorylation, p38 and NF-kappa B activation. TLR2 and TLR4 agonists induced TLR tyrosine phosphorylation in HEK293 cells overexpressing CD14, MD-2, and TLR4 or TLR2. Induction of endotoxin tolerance in HEK293/TLR4/MD-2 transfectants and in human monocytes markedly suppressed LPS-mediated TLR4 tyrosine phosphorylation and recruitment of Lyn kinase to TLR4, but did not affect TLR4-MD-2 interactions. Thus, our data demonstrate that TLR4 tyrosine phosphorylation is important for signaling and is impaired in endotoxin-tolerant cells, and suggest involvement of Lyn kinase in these processes. C1 Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Medvedev, AE (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. EM amedvedev@som.umaryland.edu FU NIAID NIH HHS [AI-059524, AI-44936, R01 AI044936, AI-057490, R01 AI044936-06, R01 AI057490, R01 AI057490-04, R01 AI059524, R01 AI059524-04] NR 89 TC 113 Z9 118 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2007 VL 282 IS 22 BP 16042 EP 16053 DI 10.1074/jbc.M606781200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172HH UT WOS:000246794300012 PM 17392283 ER PT J AU Kim, HS Kim, MS Hancock, AL Harper, JCP Park, JY Poy, G Perantoni, AO Cam, M Malik, K Lee, SB AF Kim, Ho-Shik Kim, Myoung Shin Hancock, Anne L. Harper, James C. P. Park, Jik Young Poy, George Perantoni, Alan O. Cam, Margaret Malik, Karim Lee, Sean Bong TI Identification of novel Wilms' tumor suppressor gene target genes implicated in kidney development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; TRANSCRIPTIONAL REGULATION; WT1 GENE; BINDING-SITES; EGF RECEPTOR; EXPRESSION; APOPTOSIS; INDUCTION; MOUSE; SLUG AB The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor that is vital during development of several organs including metanephric kidneys. Despite the critical regulatory role of WT1, the pathways and mechanisms by which WT1 orchestrates development remain elusive. To identify WT1 target genes, we performed a genome-wide expression profiling analysis in cells expressing inducible WT1. We identified a number of direct WT1 target genes, including the epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine CX3CL1, and the transcription factors SLUG and JUNB. The target genes were validated using quantitative reverse transcriptase-polymerase chain reaction, small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number of the WT1 target genes had overlapping expression patterns with the highly restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic kidney culture assay, we found that the addition of recombinant epiregulin, amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud branching morphogenesis. Our genome-wide screen implicates WT1 in the transcriptional regulation of the EGF-family of growth factors as well as the CX3CL1 chemokine during nephrogenesis. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. Univ Bristol, Canc & Leukaemia Childhood Sargent Unit, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England. RP Lee, SB (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,9D11, Bethesda, MD 20892 USA. EM seanL@intra.niddk.nih.gov FU Intramural NIH HHS NR 66 TC 36 Z9 38 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2007 VL 282 IS 22 BP 16278 EP 16287 DI 10.1074/jbc.M700215200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172HH UT WOS:000246794300035 PM 17430890 ER PT J AU Gau, SSF Shang, CY Merikangas, KR Chiu, YN Soong, WT Cheng, ATA AF Gau, Susan Shur-Fen Shang, Chi-Yung Merikangas, Kathleen R. Chiu, Yen-Nan Soong, Wei-Tsuen Cheng, Andrew Tai-Ann TI Association between morningness-eveningness and behavioral/emotional problems among adolescents SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE morningness-eveningness; evening type; behavioral/emotional problems; suicidality; substance use; adolescents ID SLEEP-WAKE PATTERNS; CIGARETTE-SMOKING; MENTAL-DISORDERS; SUBSTANCE USE; CHILDREN; TAIWAN; PHASE; PREFERENCE; BEHAVIOR; RHYTHM AB Adolescent eveningness is associated with age, parental monitoring, daytime sleepiness, sleep problems, moodiness, and the use of coffee. This study investigated the association between adolescent morningness-eveningness and psychopathology, substance use, and suicidality in 1332 students ages 12 to 13. Each student-participant completed the Chinese version of the Child Morningness/Eveningness Scale (CMES), the Pubertal Development Scale, and a questionnaire about their sleep schedule, trouble sleeping, habitual substance use, and suicidality. Their mothers completed the Child Behavioral Checklist and Chinese Health Questionnaire. The morning (n = 412), intermediate (n = 740), and evening (n = 180) groups were operationally defined by the CMES t scores. The mixed model was used for data analysis. The evening group had shorter weekday sleep time, longer weekend sleep time, more daytime napping, and greater sleep compensation on weekends and was more likely than the other 2 groups to have behavioral/emotional problems, suicidality, and habitual substance use. Internalizing and externalizing problems partially explained the association between eveningness, substance use, and suicidality. The findings suggest that eveningness may be an indicator for adolescents with behavioral/emotional problems and risky behaviors and suggest an investigation for possible intervention. C1 Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 10002, Taiwan. Natl Taiwan Univ, Coll Med, Dept Psychiat, Taipei, Taiwan. Natl Taiwan Univ Hosp, Yun Lin Branch, Dept Psychiat, Yunlin, Taiwan. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. RP Gau, SSF (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan S Rd, Taipei 10002, Taiwan. EM gaushufe@ntu.edu.tw RI Jelinek, Milan/C-8515-2011; OI Gau, Susan Shur-Fen/0000-0002-2718-8221; Shang, Chi-Yung/0000-0001-6658-7359 NR 27 TC 120 Z9 124 U1 3 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD JUN PY 2007 VL 22 IS 3 BP 268 EP 274 DI 10.1177/0748730406298447 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 171VO UT WOS:000246763700008 PM 17517916 ER PT J AU Lin, DC Dimitriadis, EK Horkay, F AF Lin, David C. Dimitriadis, Emilios K. Horkay, Ferenc TI Robust strategies for automated AFM force curve analysis - I. Non-adhesive indentation of soft, inhomogeneous materials SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE atomic force microscopy; contact mechanics; elasticity; indentation ID THIN POLYMER-FILMS; ELASTIC PROPERTIES; LIVING CELLS; SINGLE BIOMOLECULES; ARTICULAR-CARTILAGE; POISSON RATIO; MICROSCOPY; CALIBRATION; ADHESION; SAMPLES AB The atomic force microscope (AFM) has,found wide applicability as a nanoindentation Bethesda, MID 20892 tool to measure local elastic properties of soft materials. An automated approach to the processing of AFM indentation data, namely, the extraction of Young's modulus, is essential to realizing the high-throughput potential of the instrument as an elasticity probe for typical soft materials that exhibit inhomogeneity at microscopic scales. This paper focuses on Hertzian analysis techniques, which are applicable to linear elastic indentation. We compiled a series of synergistic strategies into an algorithm that overcomes many of the complications that have previously impeded efforts to automate the fitting of contact mechanics models to indentation data. AFM raster data sets containing up to 1024 individual force-displacement curves and macroscopic compression data were obtained from testing polyvinyl alcohol gels of known composition. Local elastic properties of tissue-engineered cartilage were also measured by the AFM. All AFM data sets were processed using customized software based on the algorithm, and the extracted values of Young's modulus were compared to those obtained by macroscopic testing. Accuracy of the technique was verified by the good agreement between values of Young's modulus obtained by AFM and by direct compression of the synthetic gels. Validation of robustness was achieved by successfully fitting the vastly different types of force curves generated from the indentation of tissue-engineered cartilage. For AFM indentation data that are amenable to Hertzian analysis, the method presented here minimizes subjectivity in preprocessing and allows for improved consistency and minimized user intervention. Automated, large-scale analysis of indentation data holds tremendous potential in bioengineering applications, such as high-resolution elasticity mapping of natural and artificial tissues. C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NIH, Lab Integrat & Med Biophys, 9 Mem Dr,Bldg 9 Rm 1E118, Bethesda, MD 20892 USA. EM lindavid@mail.nih.gov; dimitria@helix.nih.gov; horkay@helix.nih.gov FU Intramural NIH HHS NR 53 TC 123 Z9 125 U1 8 U2 71 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JUN PY 2007 VL 129 IS 3 BP 430 EP 440 DI 10.1115/1.2720924 PG 11 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 178KL UT WOS:000247219500016 PM 17536911 ER PT J AU Brazhnik, O Jones, JF AF Brazhnik, Olga Jones, John F. TI Anatomy of data integration SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE informational value of data; clinical data integration; database architecture; data processing; conceptual modeling ID HOSPITAL INFORMATION-SYSTEM; KNOWLEDGE-BASED SYSTEMS; HEALTH-CARE; CLINICAL INFORMATION; DATA MODELS; DATABASES; DISCOVERY; ONTOLOGY; DESIGN; SCHEMA AB Producing reliable information is the ultimate goal of data processing. The ocean of data created with the advances of science and technologies calls for integration of data coming from heterogeneous sources that are diverse in their purposes, business rules, underlying models and enabling technologies. Reference models, Semantic Web, standards, ontology, and other technologies enable fast and efficient merging of heterogeneous data, while the reliability of produced information is largely defined by how well the data represent the reality. In this paper, we initiate a framework for assessing the informational value of data that includes data dimensions; aligning data quality with business practices; identifying authoritative sources and integration keys; merging models; uniting updates of varying frequency and overlapping or gapped data sets. Published by Elsevier Inc. C1 NIH, Ctr Informat Technol, Bethesda, MD 20817 USA. RP Brazhnik, O (reprint author), NIH, Ctr Informat Technol, 10401 Fernwood Rd,Room 3NW03, Bethesda, MD 20817 USA. EM brazhnik@nih.gov RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X FU Intramural NIH HHS [Z99 RR999999] NR 70 TC 27 Z9 28 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2007 VL 40 IS 3 BP 252 EP 269 DI 10.1016/j.jbi.2006.09.001 PG 18 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 188XZ UT WOS:000247953900004 PM 17071142 ER PT J AU Tolstorukov, MY Zhurkin, VB Olson, WK AF Tolstorukov, Michael Y. Zhurkin, Victor B. Olson, Wilma K. TI Structural properties of GC-rich sequences may hinder nucleosome positioning in CpG islands SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 V Karazin Kharkov Natl Univ, NIH, UA-61024 Kharkov, Ukraine. NCI, Bethesda, MD 20892 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. EM tolstorukov@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 25 BP 624 EP 625 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600036 ER PT J AU Cui, F Zhurkin, VB AF Cui, Feng Zhurkin, Victor B. TI Chicken and yeast nucleosomal DNA sequences differ at the ends: A possible relation to the linker histone binding SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract ID CHROMATIN C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. EM cuif@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 26 BP 626 EP 627 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600037 ER PT J AU Wang, D Cui, F Zhurkin, VB AF Wang, Difei Cui, Feng Zhurkin, Victor B. TI The 'Kink-and-slide' folding of DNA in nucleosome is facilitated by asymmetric interactions of the histone arginines in the minor groove SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. EM wangdi@mail.nih.gov RI Wang, Difei/E-7066-2010 NR 4 TC 2 Z9 2 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 27 BP 627 EP 627 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600038 ER PT J AU Ma, B Levine, AJ AF Ma, Buyong Levine, Arnold J. TI Deducing the multiple binding modes of p53 tetramer - DNA interaction based on full-site palindrome of p53 response elements: Convergence of sequence and geometry based recognitions SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Inc, Canc Res Ctr, Frederick, MD 21702 USA. Inst Adv Study, Princeton, NJ 08540 USA. EM mab@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 46 BP 638 EP 638 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600057 ER PT J AU Pan, YP Nussinov, R AF Pan, Yongping Nussinov, Ruth TI Sequence dependence of DNA bending upon p53 binding: A molecular dynamics simulation SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, Frederick, MD 21702 USA. EM pany@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 51 BP 641 EP 642 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600062 ER PT J AU Cui, F Sirotin, M Zhurkin, VB AF Cui, Feng Sirotin, Michael Zhurkin, Victor B. TI The p53-DNA binding in the chromatin context: p53-induced activation of the apoptotic and cell cycle arrest genes SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract ID DNA C1 NIH, NCI, Cell Biol Lab, Bethesda, MD 20892 USA. EM zhurkin@nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 56 BP 644 EP 645 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600067 ER PT J AU Moreno, A Knee, J Hawkins, M Mukerji, I AF Moreno, A. Knee, J. Hawkins, M. Mukerji, I. TI Spectroscopic investigations of DNA dynamics and relationship to HU DNA interactions SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 NCI, Dept Chem, Bethesda, MD 20892 USA. Wesleyan Univ, Mol Biophys Program, Middletown, CT 06459 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. EM amoreno@wesleyan.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 84 BP 668 EP 669 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600095 ER PT J AU Parker, SCJ Hansen, L Bishop, E Landsman, D Margulies, EH Tullius, TD AF Parker, Stephen C. J. Hansen, Loren Bishop, Eric Landsman, David Margulies, Elliott H. Tullius, Thomas D. CA NISC Comparat Sequencing Program TI Widespread DNA structural constraint in the human genome SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 Boston Univ, Program Bioinformat, Boston, MA USA. NIH, NHGRI, Bethesda, MD 20892 USA. Boston Univ, Dept Chem, Boston, MA 02215 USA. EM parker@bu.edu RI Landsman, David/C-5923-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 160 BP 716 EP 716 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600171 ER PT J AU Vuyisich, M Gnanakaran, G Lovchik, JA Lyons, CR DeBord, KL Gupta, G AF Vuyisich, Momochilo Gnanakaran, Gnana Lovchik, Julie A. Lyons, C. Rick DeBord, Kristin L. Gupta, Goutam TI Novel therapy for anthrax SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract ID RECEPTOR; TOXIN C1 Biosci Div, Los Alamos Natl Lab, Grp B 1, Los Alamos, NM 87545 USA. Div Theory, Los Alamos Natl Lab, Grp T 10, Los Alamos, NM 87545 USA. Univ New Mexico, Hlth Sci Ctr, Ctr Infect Dis & Immun, Albuquerque, NM 87131 USA. NIAID, Div Microbiol & Infect Dis, Off Bio Defense Res Affairs, Bethesda, MD 20892 USA. EM gxg@lanl.gov NR 6 TC 0 Z9 0 U1 0 U2 3 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 171 BP 727 EP 728 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600182 ER PT J AU Stan, G Thirumalai, D Lorimer, GH Brooks, BR AF Stan, George Thirumalai, D. Lorimer, George H. Brooks, Bernard R. TI Computational models of chaperonin-mediated protein folding SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Meeting Abstract C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. Univ Maryland, Inst Phys Sci & Technol, Dept Chem, Biophys Program, College Pk, MD 20742 USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 2007 VL 24 IS 6 MA 209 BP 757 EP 757 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179KY UT WOS:000247289600220 ER PT J AU Geller, JL Khosravi, A Kelly, MH Riminucci, M Adams, JS Collins, MT AF Geller, Jordan L. Khosravi, Azarmindokht Kelly, Marilyn H. Riminucci, Mara Adams, John S. Collins, Michael T. TI Cinacalcet in the management of tumor-induced osteomalacia SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE hypophosphatemia; fibroblast growth factor-23; phosphatonin; hypoparathyroidism; phosphate; oncogenic osteomalacia ID HYPOPHOSPHATEMIC RICKETS; ONCOGENIC OSTEOMALACIA; PHOSPHORUS HOMEOSTASIS; PHOSPHATE HOMEOSTASIS; PARATHYROID-HORMONE; DIETARY PHOSPHATE; HEALTHY-MEN; VITAMIN-D; FGF-23; FIBROBLAST-GROWTH-FACTOR-23 AB Both FGF-23 and PTH inhibit renal phosphate reabsorption. We treated two patients with TIO and FGF-23-mediated hypophosphatemia with cinacalcet to test the hypothesis that medicinally induced hypoparathyroidism would decrease renal phosphate wasting. Cinacalcet treatment resulted in increased renal phosphate reabsorption, allowed for a decrease in phosphate supplementation, and showed evidence of bone healing in one of the two patients. Introduction: Tumor-induced osteomalacia (TIO) is a rare, acquired disease of renal phosphate wasting, which results in hypophosphatemia and osteomalacia. It is caused by mesenchymal tumors that produce the phosphate and vitamin D-regulating hormone, fibroblast growth factor (FGF)-23. Removal of the tumor is curative, but the tumors are often difficult to locate. Medical treatment involves high doses of oral phosphate and calcitriol, but the phosphate is often poorly tolerated and leads to diarrhea. Because PTH also promotes phosphaturia, and patients with hypoparathyroidism are hyperphosphatemic in the setting of elevated serum FGF-23, we postulated that the calcium-sensing receptor agonist, cinacalcet, which can induce hypoparathyroidism, would be an effective adjuvant in the treatment of TIO. Materials and Methods: Two subjects with presumed TIO in whom the tumor was not located after extensive testing and who did not tolerate medical therapy with phosphorus and calcitriol were treated with cinacalcet. Results: Neither treatment with phosphorus nor combined treatment with phosphorus and calcitriol had an effect on serum FGF-23 levels. Treatment with cinacalcet resulted in increased renal phosphate reabsorption and serum phosphorus and allowed for a decrease in phosphate supplementation to a dose that was tolerated. On this regimen, one patient showed significant bone healing as shown by resolution of activity on bone scan and lack of osteomalacia as assessed by histomorphometry. Conclusions: These data show that medically induced hypoparathyroidism with cinacalcet is a therapeutic option for disorders of FGF-23-mediated hypophosphatemia and that, in the absence of PTH, the phosphaturic effect of FGF-23 is decreased. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Clin Res Inst, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90048 USA. Dept Hlth & Human Serv, Bethesda, MD USA. Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00185 Rome, Italy. Univ Aquila, Dept Expt Med, Div Pathol, I-67100 Laquila, Italy. RP Collins, MT (reprint author), NIH, Craniofacial & Skin Dis Branch, Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv,Skeletal Clin Studies Unit, Bldg 30,Room 228,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov RI Adams, John/I-3365-2013 OI Adams, John/0000-0001-9607-5020 FU Intramural NIH HHS NR 27 TC 50 Z9 50 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2007 VL 22 IS 6 BP 931 EP 937 DI 10.1359/JBMR.070304 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170QF UT WOS:000246678300018 PM 17352646 ER PT J AU Rutten, LJF Squiers, L Hesse, B AF Rutten, Lila J. Finney Squiers, Linda Hesse, Bradford TI Cancer-related information sought by the general public: Evidence from the National Cancer Institute's Cancer Information Service, 2002-2003 SO JOURNAL OF CANCER EDUCATION LA English DT Article ID IMPACT; KNOWLEDGE; PREVENTION; SEEKING; RISK AB Background. We examined the main topics of inquiry (Subjects of Interaction-SOI) of calls made by the general public to the National Cancer Institute's Cancer Information Service's (CIS) 1-800-4-CANCER telephone information service. Methods. We analyzed data from 37,620 callers to the CIS between September 2002 and August 2003. We conducted frequencies, chi-squares, and logistic regressions to ascertain sample characteristics and sociodemographic correlates of each SOL Results. We found differences in discussion of the 7 main SOI by age, sex, ethnicity, race, and education. Conclusions. Findings inform the CIS' and other organizations' efforts to develop and disseminate cancer information. C1 NCI, SAIC Frederick Inc, Hlth Commun & Informat Res Branch, Behav Res Program,Div Canc Ontrol & Populat Sci, Frederick, MD 21701 USA. NCI, Off Canc Informat Serv, Off Commun, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Rutten, LJF (reprint author), 6130 Execut Blvd,Room 4051A,MSC 7365, Bethesda, MD 20892 USA. EM finneyl@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 26 TC 7 Z9 7 U1 3 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SUM PY 2007 VL 22 IS 2 BP 91 EP 98 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 186TK UT WOS:000247800900005 ER PT J AU Okunji, C Komarnytsky, S Fear, G Poulev, A Ribnicky, DM Awachie, PI Ito, Y Raskin, I AF Okunji, Christopher Komarnytsky, Slavko Fear, Georgie Poulev, Alexander Ribnicky, David M. Awachie, Peter I. Ito, Yoichiro Raskin, Ilya TI Preparative isolation and identification of tyrosinase inhibitors from the seeds of Garcinia kola by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE Garcinia kola; tyrosinase; biflavanones; high-speed counter-current chromatography (HSCCC) ID BIFLAVANONES; BIFLAVONOIDS; ACID AB In continuation of our search for bioactive natural products that can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation, 50 extracts/fractions from 21 families of medicinal plants from West and Central Africa were evaluated for inhibitory activity against tyrosinase (E:C:1.14.18.1), the rate-limiting enzyme in melanin synthesis. Four extracts including the methanol extract of Garcinia kola seeds at 100 mu g/ml displayed >60% inhibition of tyrosinase activity. Preparative high-speed counter-current chromatography with solvent system composed of n-hexane-ethyl acetate-methanol-water (3:5:3:5) successfully separated the most active extract from G. kola seed. By stepwise increase of the flow-rate of the mobile phase, five major biflavanones including GB-I-glucoside (1) GB-la (2), GB-1 (3), GB-2 (4), kolaflavonone (5) were successfully isolated in 6 h. Compound (4) was the most potent (IC50 582 mu M) and compared favorably with a reference tyrosinase inhibitor (kojic acid, IC50 130 mu M). (C) 2007 Elsevier B.V. All rights reserved. C1 Rutgers State Univ, Cook Coll, Biotech Ctr, New Brunswick, NJ 08901 USA. Int Ctr Ethnomed & Drug Dev, Nsukka, Nigeria. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Rutgers State Univ, Cook Coll, Biotech Ctr, 59 Dudley Rd, New Brunswick, NJ 08901 USA. EM itoy2@mail.nih.gov RI Komarnytsky, Slavko/A-9575-2009 OI Komarnytsky, Slavko/0000-0003-4665-4993 NR 21 TC 23 Z9 23 U1 1 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 1 PY 2007 VL 1151 IS 1-2 BP 45 EP 50 DI 10.1016/j.chroma.2007.02.085 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400008 PM 17367799 ER PT J AU Yanagida, A Yamakawa, Y Noji, R Oda, A Shindo, H Ito, Y Shibusawa, Y AF Yanagida, Akio Yamakawa, Yutaka Noji, Ryoko Oda, Ako Shindo, Heisaburo Ito, Yoichiro Shibusawa, Yoichi TI Comprehensive separation of secondary metabolites in natural products by high-speed counter-current chromatography using a three-phase solvent system SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE three-phase solvent system; high-speed counter-current chromatography; comprehensive separation; secondary metabolite; crude natural drug; tea ID CCC AB High-speed counter-current chromatography (HSCCC) using the three-phase solvent system n-hexane-methyl acetate-acetonitrile-water at a volume ratio of 4:4:3:4 was applied to the comprehensive separation of secondary metabolites in several natural product extracts. A wide variety of secondary metabolites in each natural product was effectively extracted with the three-phase solvent system, and the filtered extract was directly submitted to the HSCCC separation using the same three-phase system. In the HSCCC profiles of crude natural drugs listed in the Japanese Pharmacopoeia, several physiologically active compounds were clearly separated from other components in the extracts. The HSCCC profiles of several tea products, each manufactured by a different process, clearly showed their compositional difference in main compounds such as catechins, caffeine, and pigments. These HSCCC profiles also provide useful information about hydrophobic diversity of whole components present in each natural product. (C) 2007 Elsevier B.V. All rights reserved. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Struct Biol & Analyt Sci, Hachioji, Tokyo 1920392, Japan. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Yanagida, A (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Struct Biol & Analyt Sci, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. EM yanagida@ps.toyaku.ac.jp NR 9 TC 21 Z9 23 U1 5 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 1 PY 2007 VL 1151 IS 1-2 BP 74 EP 81 DI 10.1016/j.chroma.2007.03.071 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400012 PM 17399729 ER PT J AU Weisz, A Idina, A Ben-Ari, J Karni, M Mandelbaum, A Ito, Y AF Weisz, Adrian Idina, Ana Ben-Ari, Julius Karni, Miriam Mandelbaum, Asher Ito, Yoichiro TI Preparative separation of isomeric and stereoisomeric dicarboxylic acids by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE pH-zone-refining counter-current chromatography; dicarboxylic acids; separation of stereoisomers; dimerization energies; pK(a); mechanism ID LIQUID PARTITION CHROMATOGRAPHY; SOLID SUPPORT; DISSOCIATION; EQUILIBRIA; COMPONENTS AB This work involves the preparative separation of some isomeric dicarboxylic acids using pH-zone-refining counter-current chromatography (CCC), a relatively new preparative technique for the separation of ionizable compounds. The paper concentrates especially on the separation of a synthetic mixture of closely related cis and trans pairs of 1-methyl- and 1,3-dimethyl-1,3-cyclohexanedicarboxylic acids. The elution sequence of the isomers is discussed in terms of their relative acidities (pK(a) values) in solution and gas phase, hydrophobicities, and steric configuration. Two possible explanations are suggested for the mechanism of separation. They both involve the amount of retainer acid used, as it affects the separation and plays a role in the chemohydrodynamic equilibrium of the dicarboxylic acids in the column. (C) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel. Technion Israel Inst Technol, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-32000 Haifa, Israel. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 29 TC 18 Z9 18 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUN 1 PY 2007 VL 1151 IS 1-2 BP 82 EP 90 DI 10.1016/j.chroma.2007.03.085 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400013 PM 17433339 ER EF