FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Markey, SP AF Markey, Sanford P. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Methods of Analysis of Drugs and Drug Metabolites SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FLUORESCENCE POLARIZATION IMMUNOASSAY; TANDEM MASS-SPECTROMETRY; ENZYME-MULTIPLIED IMMUNOASSAY; HEART-TRANSPLANT PATIENTS; BLOOD CYCLOSPORINE-A; WHOLE-BLOOD; CROSS-REACTIVITY; ASSAY-METHODS; LIVER C1 NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. NR 36 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 163 EP 178 DI 10.1016/B978-012369417-1/50052-3 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900014 ER PT J AU Preusch, PC AF Preusch, Peter C. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Equilibrative and Concentrative Transport Mechanisms SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID BLOOD-BRAIN-BARRIER; P-GLYCOPROTEIN GENE; AMINOMETHYL)-1-CYCLOHEXANE ACETIC-ACID; RESISTANCE-ASSOCIATED PROTEIN; ORGANIC CATION TRANSPORTERS; MEDIATED DRUG TRANSPORT; RETRACTED ARTICLE. SEE; MULTIDRUG-RESISTANCE; IN-VIVO; ESCHERICHIA-COLI C1 NIGMS, NIH, Pharmacol Physiol & Biol Chem Div, Bethesda, MD 20892 USA. RP Preusch, PC (reprint author), NIGMS, NIH, Pharmacol Physiol & Biol Chem Div, Bethesda, MD 20892 USA. NR 179 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 197 EP 227 DI 10.1016/B978-012369417-1/50054-7 PG 31 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900016 ER PT J AU Robertson, S Penzak, S AF Robertson, Sarah Penzak, Scott BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Drug Interactions SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID ST-JOHNS-WORT; ORAL-CONTRACEPTIVE STEROIDS; COA REDUCTASE INHIBITORS; TORSADES-DE-POINTES; P-GLYCOPROTEIN; GRAPEFRUIT JUICE; CLINICAL-IMPLICATIONS; HYPERICUM-PERFORATUM; HEALTHY-VOLUNTEERS; FASTING CONDITIONS C1 [Robertson, Sarah; Penzak, Scott] NIH, Ctr Clin, Clin Pharmacokinet Res Lab, Dept Pharm, Bethesda, MD 20892 USA. RP Robertson, S (reprint author), NIH, Ctr Clin, Clin Pharmacokinet Res Lab, Dept Pharm, Bethesda, MD 20892 USA. NR 109 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 229 EP 247 DI 10.1016/B978-012369417-1/50055-9 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900017 ER PT J AU Atkinson, AJ Markey, SP AF Atkinson, Arthur J., Jr. Markey, Sanford P. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Biochemical Mechanisms of Drug Toxicity SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID ACETAMINOPHEN-INDUCED HEPATOTOXICITY; THERAPY-RELATED MYELODYSPLASIA; PROCAINAMIDE-INDUCED LUPUS; ACUTE MYELOID-LEUKEMIA; FETAL HYDANTOIN SYNDROME; INDUCED HEPATIC-INJURY; N-ACETYLPROCAINAMIDE; TIENILIC ACID; HALOTHANE HEPATITIS; COVALENT BINDING C1 [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Markey, Sanford P.] NIMH, NIH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 249 EP 271 DI 10.1016/B978-012369417-1/50056-0 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900018 ER PT B AU Atkinson, AJ Rolan, P AF Atkinson, Arthur J., Jr. Rolan, Paul BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Physiological and Laboratory Markers of Drug Effect SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; SURROGATE END-POINTS; PRIMARY VENTRICULAR-FIBRILLATION; PROPHYLACTIC LIDOCAINE; CLINICAL-TRIALS; BLOOD-PRESSURE; BIOMARKER DISCOVERY; PLASMA-LIPIDS C1 [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Rolan, Paul] ICON Medeval Clin Pharmacol, Manchester, Lancs, England. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 70 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2; 978-0-12-369417-1 PY 2007 BP 275 EP 287 DI 10.1016/B978-012369417-1/50057-2 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900019 ER PT J AU Lowe, ES Balis, FM AF Lowe, Elizabeth S. Balis, Frank M. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Dose-Effect and Concentration-Effect Analysis SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID PHASE-I; TRIAL; THEOPHYLLINE; MODELS C1 [Lowe, Elizabeth S.] AstraZeneca, Wilmington, DE 19850 USA. [Balis, Frank M.] NCI, Pediat Oncol Branch, NIH, Pharmacol & Expt Therapeut Sect, Bethesda, MD 20892 USA. RP Lowe, ES (reprint author), AstraZeneca, Wilmington, DE 19850 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 289 EP 300 DI 10.1016/B978-012369417-1/50058-4 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900020 ER PT J AU Holford, NHG Atkinson, AJ AF Holford, Nicholas H. G. Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Time Course of Drug Response SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID EPSILON-AMINOCAPROIC ACID; PHARMACODYNAMIC MODELS; N-ACETYLPROCAINAMIDE; RECEPTOR-BINDING; ACUTE TOLERANCE; KINETICS; HUMANS; PHARMACOKINETICS; COCAINE; BENZODIAZEPINES C1 [Holford, Nicholas H. G.] Univ Auckland, Sch Med, Dept Pharmacol & Clin Pharmacol, Auckland, New Zealand. [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Holford, NHG (reprint author), Univ Auckland, Sch Med, Dept Pharmacol & Clin Pharmacol, Auckland, New Zealand. OI Holford, Nick/0000-0002-4031-2514 NR 39 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 301 EP 311 DI 10.1016/B978-012369417-1/50059-6 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900021 ER PT J AU Fox, E Balis, FM AF Fox, Elizabeth Balis, Frank M. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Drug Therapy in Neonates and Pediatric Patients SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; THEOPHYLLINE METABOLISM; DEVELOPMENTAL ASPECTS; PREMATURE-INFANTS; HUMAN LIVER; 1ST YEAR; INTRATHECAL METHOTREXATE; CLINICAL-PHARMACOLOGY; CYTOCHROME-P450 3A; DOSAGE REGIMEN C1 [Fox, Elizabeth] NCI, NIH, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Fox, E (reprint author), NCI, NIH, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 55 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 359 EP 373 DI 10.1016/B978-012369417-1/50063-8 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900025 ER PT B AU Abernethy, DR AF Abernethy, Darrell R. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Drug Therapy in the Elderly SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONGESTIVE-HEART-FAILURE; OLDER CANCER-PATIENTS; TARDIVE-DYSKINESIA; RENAL-FUNCTION; BREAST-CANCER; RISK-FACTORS; SYSTEMIC HYPERTENSION; CREATININE CLEARANCE; INDUCED HYPONATREMIA C1 NIA, Geriatr Res Ctr, Clin Invest Lab, Baltimore, MD 21224 USA. RP Abernethy, DR (reprint author), NIA, Geriatr Res Ctr, Clin Invest Lab, Baltimore, MD 21224 USA. NR 102 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2; 978-0-12-369417-1 PY 2007 BP 375 EP 388 DI 10.1016/B978-012369417-1/50064-X PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900026 ER PT J AU Calis, KA Sidawy, EN Young, LR AF Calis, Karim Anton Sidawy, Emil N. Young, Linda R. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Clinical Analysis of Adverse Drug Reactions SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID HOSPITALIZED-PATIENTS; CAUSALITY ASSESSMENT; RISK-FACTOR; EVENTS; METABOLISM; COSTS; SURVEILLANCE; MORTALITY; ADMISSION; DISEASE C1 [Calis, Karim Anton] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Calis, Karim Anton] NIH, Mark O Hatfield Clin Res Ctr, Ctr Clin, Bethesda, MD 20892 USA. [Sidawy, Emil N.] Shady Grove Adventist Hosp, Rockville, MD USA. [Young, Linda R.] Caril Med Ctr, Dept Pharm Serv, Roanoke, VA USA. RP Calis, KA (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. NR 68 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 389 EP 402 DI 10.1016/B978-012369417-1/50065-1 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900027 ER PT J AU Dedrick, RL Atkinson, AJ AF Dedrick, Robert L. Atkinson, Arthur J., Jr. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Animal Scale-Up SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID IN-VIVO CORRELATION; PHARMACOKINETIC PARAMETERS; DRUG-METABOLISM; OVARIAN-CANCER; CLEARANCE; HUMANS; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; DEAMINATION; RATIONALE; MONKEY C1 [Dedrick, Robert L.] NIH, Off Res Serv, OD, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Atkinson, Arthur J., Jr.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Dedrick, RL (reprint author), NIH, Off Res Serv, OD, Div Bioengn & Phys Sci, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 463 EP 471 DI 10.1016/B978-012369417-1/50070-5 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900032 ER PT J AU Collins, JM AF Collins, Jerry M. BA Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP BF Atkinson, AJ Abernethy, DR Daniels, CE Dedrick, RL Markey, SP TI Phase I Clinical Studies SO PRINCIPLES OF CLINICAL PHARMACOLOGY, 2ND EDITION LA English DT Article; Book Chapter ID DRUG DEVELOPMENT; TRIALS; PHARMACOLOGY; PHARMACOKINETICS; METABOLISM C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Collins, JM (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046642-2 PY 2007 BP 473 EP 478 DI 10.1016/B978-012369417-1/50071-7 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCR24 UT WOS:000311079900033 ER PT J AU Robey, PG Bianco, P AF Robey, Pamela Gehron Bianco, Paolo BE Lanza, R Langer, R Vacanti, J TI Postnatal Stem Cells SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID MARROW STROMAL CELLS; IN-VITRO; EPIDERMOLYSIS-BULLOSA; REGENERATIVE BIOLOGY; PROGENITOR CELLS; CARDIAC REPAIR; HEART-DISEASE; SPINAL-CORD; BONE; PLASTICITY C1 [Robey, Pamela Gehron] NIDCR, NIH, Bethesda, MD 20817 USA. [Bianco, Paolo] Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy. RP Robey, PG (reprint author), NIDCR, NIH, Bethesda, MD 20817 USA. NR 78 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 459 EP 468 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100037 ER PT J AU Chen, FH Song, L Mauck, RL Li, WJ Tuan, RS AF Chen, Faye H. Song, Lin Mauck, Robert L. Li, Wan-Ju Tuan, Rocky S. BE Lanza, R Langer, R Vacanti, J TI Mesenchymal Stem Cells SO PRINCIPLES OF TISSUE ENGINEERING, 3RD EDITION LA English DT Article; Book Chapter ID HUMAN-BONE-MARROW; SUPPRESSES OSTEOGENIC DIFFERENTIATION; 3-DIMENSIONAL NANOFIBROUS SCAFFOLD; TISSUE-ENGINEERED CARTILAGE; IN-VITRO DIFFERENTIATION; HUMAN TRABECULAR BONE; STROMAL CELLS; EXTRACELLULAR-MATRIX; ARTICULAR-CARTILAGE; CHONDROGENIC DIFFERENTIATION C1 [Chen, Faye H.; Song, Lin; Li, Wan-Ju; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. [Song, Lin] Stryker Orthopaed, Mahwah, NJ 07430 USA. [Mauck, Robert L.] Univ Penn, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. RP Chen, FH (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. NR 144 TC 8 Z9 9 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054884-5 PY 2007 BP 823 EP 843 DI 10.1016/B978-012370615-7/50059-7 PG 21 WC Cell & Tissue Engineering SC Cell Biology GA BCN48 UT WOS:000310773100059 ER PT J AU Musgrove, P AF Musgrove, Philip BE Preker, AS Scheffler, RM Bassett, MC TI Economics of Private Voluntary Health Insurance Revisited SO PRIVATE VOLUNTARY HEALTH INSURANCE IN DEVELOPMENT: FRIEND OR FOE LA English DT Article; Book Chapter C1 [Musgrove, Philip] Natl Inst Hlth, Dis Control Prior Project, Fogarty Int Ctr, Bethesda, MD USA. [Musgrove, Philip] World Bank, Washington, DC USA. [Musgrove, Philip] WHO, Geneva, Switzerland. [Musgrove, Philip] Brookings Inst, Washington, DC 20036 USA. [Musgrove, Philip] Johns Hopkins Univ, Sch Adv Int Studies, Baltimore, MD 21218 USA. [Musgrove, Philip] American Univ, Washington, DC 20016 USA. [Musgrove, Philip] George Washington Univ, Washington, DC 20052 USA. [Musgrove, Philip] Univ Florida, Gainesville, FL 32611 USA. RP Musgrove, P (reprint author), Natl Inst Hlth, Dis Control Prior Project, Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6620-2 PY 2007 BP 169 EP 178 D2 10.1596/978-0-8213-6619-6 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BZY65 UT WOS:000303391200008 ER PT B AU Lin, DC Dimitriadis, EK Horkay, F AF Lin, David C. Dimitriadis, Emillos K. Horkay, Ferenc GP ASME TI Elasticity of cartilage measured by large strain, non-Hertzian AFM nanoindentation SO PROCEEDING OF THE ASME SUMMER BIOENGINEERING CONFERENCE - 2007 LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 24-28, 2007 CL Keystone, CO SP ASME, Bioengn Div C1 [Lin, David C.; Horkay, Ferenc] NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NIH, Lab Integrat & Med Biophys, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4798-5 PY 2007 BP 945 EP 946 PG 2 WC Engineering, Biomedical SC Engineering GA BHB85 UT WOS:000252105700473 ER PT B AU Tohara, T Katayarna, M Takajyo, A Inoue, K Shirakawa, S Kitado, M Takahashi, T Nishimura, Y AF Tohara, T. Katayarna, M. Takajyo, A. Inoue, K. Shirakawa, S. Kitado, M. Takahashi, T. Nishimura, Y. GP IEEE TI Time frequency analysis of biological signals during sleep SO PROCEEDINGS OF SICE ANNUAL CONFERENCE, VOLS 1-8 LA English DT Proceedings Paper CT Annual Conference on the Society-of-Instrument-and-Control-Engineers CY SEP 17-20, 2007 CL Kagawa Univ, Takamatsu, JAPAN SP IEEE Ind Electron Soc, IEEE Robot & Automat Soc, IEEE Control Syst Soc, IEEE Syst, Man & Cybernet Soc, Instrumentat, Syst & Automat Soc, Inst Control, Robot, & Syst, China Instrument & Control Soc, Chinese Assoc Automat, Chinese Automat Control Soc, Int Measurement Confederat, IEEE Japan Council, IFAC NMO, Inst Elect Engn Japan HO Kagawa Univ DE wavelet analysis; sleep stage; impulse response; signal of pressure sensor; feature extraction AB We have developed a relevance between sleep stage (Stage MT, W, 1, 2, 3, 4, REM) and rhythm of autonomic nerve activity computed by frequency analysis of heartbeat interval. Heartbeat during sleep was changed by sleep state. Extraction of relationships between sleep stage and heartbeat interval from signal of pressure sensor located in bed is goal. Then, we tried to apply continuous wavelet analysis to ECG in order to extract more precise information for the relationships. Moreover, we applied wavelet transform of impulse as mother wavelet that is impulse response of signal of pressure sensor on one heartbeat. In this paper we had six all-night sleep experiments, and compared result each subjects. As a result, we were able to estimate sleep state freely from sensor of pressure signal. C1 [Tohara, T.; Katayarna, M.; Takajyo, A.; Inoue, K.] Kyushu Inst Technol, Kitakyushu, Fukuoka 804, Japan. [Shirakawa, S.] NIMH, Bethesda, MD USA. [Kitado, M.; Takahashi, T.; Nishimura, Y.] Matsushita Elect Works Ltd, Tokyo, Japan. RP Tohara, T (reprint author), Kyushu Inst Technol, Kitakyushu, Fukuoka 804, Japan. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-4-907764-28-9 PY 2007 BP 1920 EP + PG 2 WC Automation & Control Systems; Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Engineering, Electrical & Electronic; Robotics SC Automation & Control Systems; Computer Science; Engineering; Robotics GA BHR23 UT WOS:000255608502073 ER PT B AU Lonser, RR AF Lonser, R. R. GP Medimond TI Image-guided convection-enhanced drug delivery SO PROCEEDINGS OF THE 13TH EUROPEAN CONGRESS OF NEUROSURGERY LA English DT Proceedings Paper CT 13th European Congress of Neurosurgery CY SEP 02-07, 2007 CL Glasgow, SCOTLAND ID BRAIN-STEM; REAL-TIME; PERFUSION AB Direct perfusion of specific regions of the central nervous system (CNS) by convection-enhanced delivery (CED) is rapidly becoming more widely used for the delivery of compounds in the research and treatment of various neural disorders. Two patients with progressive intrinsic brainstern pathology (Type 2 Gaucher disease and diffuse pontine glioma) were treated by CED of putative therapeutic agents mixed with gadolinium-DTPA. Using intraoperative MR-scanning, real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with drug and gadolinium-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term toxicity. CED may be used to safely perfuse targeted diseased regions of the CNS, including the brainstem, with therapeutic agents. Co-infused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstern and other CNS disorders may benefit from a similar treatment paradigm. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-385-1 PY 2007 BP 49 EP 55 PG 7 WC Surgery SC Surgery GA BGZ56 UT WOS:000251574500009 ER PT B AU Olden, K AF Olden, Kenneth BE Chen, H Hong, Q Ding, JY Wang, XY TI Gene-environment interactions in the development of complex phenotypes SO PROCEEDINGS OF THE 4TH INTERNATIONAL ACADEMIC CONFERENCE ON ENVIRONMENTAL AND OCCUPATIONAL MEDICINE LA English DT Proceedings Paper CT 4th International Academic Conference on Environmental and Occupational Medicine CY OCT 16-19, 2006 CL Kunming, PEOPLES R CHINA SP Journal Environm & Occupat Med, Editorial Off, Shanghai Ctr Dis Control & Prevent, EHIB, Dept Hlth Serv, Kunming Med Coll, Sch Public Hlth, Shanghai Prevent Med Assoc, Int Soc Environm Epidemiol, Environm Hlth Perspect, Shanghai Inst Prevent Med, WHO Collaborating Ctr Occupat Hlth, Fudan Univ, Sch Public Hlth, Shanghai Environm Mutagen Soc ID HUMAN GENOME; POLYMORPHISMS; HEALTH; DISEASE AB The lack of knowledge that we have about the earliest events in disease development is largely due to the multi-factorial nature of disease risk. This information gap is primarily the consequence of the lack of appreciation of the fact that most diseases arise from the complex interactions between genes and the environment as a function of the age or stage of development of the individual. The relationship between genes and the environment is best captured by the quotation: "genetics loads the gun, but the environment pulls the trigger." A loaded gun by itself causes no harm. It is only when the trigger is pulled that the potential for harm is released or initiated. Likewise, one can inherit a predisposition for a devastating disease, yet never develop the disease unless exposed to the environmental trigger(s). That is, diseases result from an unfavorable combination of genetic variations and environmental exposures. Whether an environmental exposure causes illness or not is dependent on the efficiency of the so-called "environmental response machinery" (i.e., the complex of metabolic pathways that can modulate response to environmental perturbations) that one has inherited. Thus, elucidating the causes of most chronic diseases will require an understanding of both the genetic and environmental contribution to their etiology. Unfortunately, the exploration of the relationship between genes and the environment has been hampered in the past by the limited knowledge of the human genome, and by the inclination of scientists to study disease development using exposure to a single environmental agent. Rarely in the past were interactions between multiple genes or between genes and environmental agents considered in studies on the causes of human illness. C1 Natl Inst Environm Hlth Sci, Cell Adhes & Metastasis Sect, Mol Carcinogenesis Lab, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Olden, K (reprint author), Natl Inst Environm Hlth Sci, Cell Adhes & Metastasis Sect, Mol Carcinogenesis Lab, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL ENVIRONMENTAL & OCCUPATION MEDICINE-JEOM PI SHANGHAI PA 1380 ZHONGSHAN ROAD W, SHANGHAI, 200336, PEOPLES R CHINA PY 2007 BP 1 EP 3 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BGV71 UT WOS:000250819100001 ER PT B AU Shah, J AF Shah, J. BE Park, C TI Uncovering the biochemical milieu of myofascial trigger points: Implications in the management of chronic soft tissue pain syndromes SO PROCEEDINGS OF THE 4TH WORLD CONGRESS OF THE INTERNATIONAL SOCIETY OF PHYSICAL AND REHABILITATION MEDICINE LA English DT Proceedings Paper CT 4th World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine CY JUN 10-14, 2007 CL Seoul, SOUTH KOREA ID MUSCLE; RAT AB Myofascial pain is a very common component of chronic soft tissue pain syndromes. It has been characterized by a physical finding (i.e., hyperirritable nodules in taut bands of skeletal muscle) and symptom cluster without demonstrable pathology. Although data demonstrate a role for endogenous substances in muscle pain, the pathogenesis of myofascial pain remains elusive. The impact of our studies using a novel microdialysis technology is four-fold: 1) elucidation of the pathophysiology of myofascial pain through quantitative measures of cytokines, neuropeptides, catecholamines and others; 2) development of technologies to assay tissue in-vivo for extremely small molecules in minute quantities; 3) application of a heuristic method to identify biochemical targets for musculoskeletal pain disorders and assessment of quantitative outcome measures of efficacy at the biomolecular level; 4) development of unique in situ delivery systems for the amelioration of musculoskeletal pain disorders. C1 [Shah, J.] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 1 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-344-8 PY 2007 BP 255 EP 260 PG 6 WC Medicine, Research & Experimental; Rehabilitation SC Research & Experimental Medicine; Rehabilitation GA BGZ72 UT WOS:000251612100048 ER PT B AU Hallett, M AF Hallett, M. BE Park, C TI Contribution of the contralesional hemisphere in stroke recovery SO PROCEEDINGS OF THE 4TH WORLD CONGRESS OF THE INTERNATIONAL SOCIETY OF PHYSICAL AND REHABILITATION MEDICINE LA English DT Proceedings Paper CT 4th World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine CY JUN 10-14, 2007 CL Seoul, SOUTH KOREA ID FUNCTIONAL REORGANIZATION; MOTOR CORTEX; STIMULATION; HAND; BRAIN; ARM AB The contralesional hemisphere can contribute to recovery of motor function when the lesioned hemisphere itself is unable to regain control. Its contribution is usually small and with poor quality except in the situation of midline muscles. C1 [Hallett, M.] NINDS, NIH, Human Motor Control Sect, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-344-8 PY 2007 BP 401 EP 403 PG 3 WC Medicine, Research & Experimental; Rehabilitation SC Research & Experimental Medicine; Rehabilitation GA BGZ72 UT WOS:000251612100075 ER PT B AU Yang, MQ Elnitski, LL AF Yang, Mary Qu Elnitski, Laura L. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI IEEE 7(th) BIBE Keynote: Promoter studies in the human genome: one perspective on an unfinished story SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc ID IDENTIFICATION; HELIX C1 [Yang, Mary Qu; Elnitski, Laura L.] NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD 20852 USA. RP Yang, MQ (reprint author), NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD 20852 USA. EM yangma@mail.nih.gov; elnitski@mail.nih.gov; yangma@mail.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 4 EP 6 PG 3 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200004 ER PT B AU Yang, MQ Yang, JY AF Yang, Mary Qu Yang, Jack Y. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI An investigation into the feasibility of detecting microscopic disease using machine learning SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc AB The prognosis for many cancers could be improved dramatically if they could be detected while still at the microscopic disease stage. We are investigating the possibility of detecting microscopic disease using machine learning approaches based on features derived from gene expression levels and metabolic profiles. We use immunochemistry and QRT-PCR to measure the gene expression profiles from a number of antigens such as cyclin E, P27(KIP1), FHIT, Ki-67, PCNA, Bax, Bcl-2. P53, Fas, FasL and hTERT in several particular types of neuroendocrine tumors such as pheochromocytomas, paragangliomas; and the adrenocortical carcinomas (ACC), adenomas (ACA), and hyperplasia (ACH) in Cushing's syndrome. We provide statistical evidence that, higher expression levels of hTERT, PCNA and Ki67 etc. are associated with a,higher risk that the tumors are malignant or borderline, as opposed to benign. We also investigated whether higher expression levels of the P27(KIP1) and FHIT etc. are associated with a decreased risk of adrenomedullary tumors. While no significant difference was found between cell-arrest antigens such as P27(KIP1) for malignant, borderline, and benign tumors, there was a significant difference between expression levels of such antigens in normal adrenal medulla samples and in adrenomedullary tumors. C1 [Yang, Mary Qu] NHGRI, Natl Inst Hlth, US Dept HHS, Rockville, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Yang, Mary Qu] US DOE, Oak Ridge, TN USA. RP Yang, MQ (reprint author), NHGRI, Natl Inst Hlth, US Dept HHS, Rockville, MD 20852 USA. EM yangma@mail.NIH.gov; yang@hadron.mgh.Harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 9 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200007 ER PT B AU Molnar, LK AF Molnar, Linda K. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI IEEE 7(th) BIBE invited workshop keynote: Nanobioinformatics: The enabling technology of personalized medicine SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man, Cybermet Soc AB Medical practice is changing at a rapid pace due to the influx of biological information from novel technologies. The management and analysis of this information is critical to the development of personalized medicine. For example, informatics can be applied to the identification of single nucleotide polymorphisms that may correlate with disease, disease susceptibility, or adverse drug or stress reactions. In addition, many important medical conditions and risk factors are multigenic or, as a further complication, depend on interactions between gene products and the patterns of their expression and posttranslational modification and, therefore, can also benefit from informatics tools. More recently, nanotechnologies are predicted to have a radical impact on how we study, diagnose and treat disease. Researchers develop and apply nanotechnology to all aspects of drug development and patient care from streamlining the drug development process through miniaturization, increased sensitivity, high-throughput analysis and automation for target identification and validation; developing quantum dots for in vivo imaging; utilizing contrast and optical imaging agents and ultrasensitive biomarker detection for early detection and diagnosis; to developing a plethora of multifunctional, targeted drug delivery vehicles for treatment and, eventually, real-time therapeutic monitoring. For instance, there are already examples of multifunctional nanoparticles that target vascular peptides, growth factor receptors, and transmembrane proteins such as ion channels that are utilized for both cancer and cardiovascular disease recognition. Because of the incredible sensitivity, flexibility and throughput that nanotechnologies offer combined with the modularity of nanoparticle-based therapeutics, nanotechnology is poised to play a key role in personalized medicine. In order for this to occur, an informatics infrastructure for nanotechnology must be built. The foundation of this infrastructure is the development of ontologies and databases of the description and physical characterization of the nanoparticle-based diagnostics and therapeutics. Systematically identifying and analyzing essential information pertaining to physical, chemical, structural, mechanical, biological and other parameters is critical to understanding structure-function relationships and resultant medical applications and to making this information accessible to the clinical community. The realization of personalized medicine depends on bioinformatics to unravel patterns in complex data sets, precise technology for understanding and diagnosis, and interventions designed at the nanoscale to be specific as well as effective-it depends, in short, on the integration of biotechnology, nanotechnology and informatics. Bioinformaties and nanobioinformatics are the cohesive forces that will bind these technologies together. Just as bioinformatics played a transformative role in the explosive growth of modern biology, nanobioinformatics has the potential to enable the application of nanotechnology-based diagnostics and therapeutics for personalized medicine. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Molnar, LK (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 11 EP 11 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200008 ER PT B AU Chen, YH Zhang, XQ Yang, MQ Yang, JY AF Chen, Yuehui Zhang, Xueqin Yang, Mary Qu Yang, Jack Y. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Ensemble of probabilistic neural networks for protein fold recognition SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc ID PREDICTION AB Protein data contain discriminative patterns that can be used in many beneficial applications if they are defined correctly. Protein classification in terms of fold recognition plays an important role in computational protein analysis, since it can contribute to the determination of the function of a protein whose structure is unknown. In this paper, a Probabilistic Neural Network Ensemble (PNNE) model is proposed for multi-class protein folds recognition problem. For training and evaluating the proposed method we use two datasets containing 27 SCOP folds. Experimental results show that the proposed method can improve the prediction accuracy and outperform other related approaches. C1 [Chen, Yuehui; Zhang, Xueqin] Univ Jinan, Sch Informat Sci & Engn, Jiwei Rd 106, Jinan 250022, Peoples R China. [Yang, Mary Qu] US Dept Hlth & Human Serv, NIH, Natl Human Genome Res Inst, Bethesda, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. RP Chen, YH (reprint author), Univ Jinan, Sch Informat Sci & Engn, Jiwei Rd 106, Jinan 250022, Peoples R China. EM yhchen@ujn.edu.cn; yangma@mail.NIH.gov; yang@hadron.mgh.Harvard.edu FU National Science Foundation of China [60573065]; Key Subject Research Foundation of Shandong Province FX This research is supported by the National Science Foundation of China under grant No. 60573065 and the Key Subject Research Foundation of Shandong Province. NR 18 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 66 EP + PG 3 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200018 ER PT B AU Pirooznia, M Rawat, A Gong, P Yang, JY Perkins, EJ Yang, MQ Deng, Y AF Pirooznia, Mehdi Rawat, Arun Gong, Ping Yang, Jack Y. Perkins, Edward J. Yang, Mary Qu Deng, Youping BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI An effective interwoven loop design application for two-channel microarray experiments SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE microarray; interwoven loop design; experiment design ID GENE-EXPRESSION AB Microarray technology is widely applied to address complex scientific questions. However, there remain fundamental issues of how to design experiments to ensure that the resulting data enables robust statistical analysis. Interwoven loop design has several advantages over other designs. However it suffers in the complexity of design. We have implemented an online web application which allows users to find optimal loop designs for two-color microarray experiments. Given a number of conditions (such as treatments or time points) and replicates, the application will rind the best possible design of the experiment and output experimental parameters. It is freely available from http://mcbc.usm.edu/iloop. C1 [Pirooznia, Mehdi; Rawat, Arun; Deng, Youping] Univ Southern Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Gong, Ping] SpecPro Inc, Vicksburg, MS 39180 USA. [Perkins, Edward J.] US Army, Engn Res Dev Ctr, Environm Lab, Vicksburg, MS 39180 USA. [Yang, Jack Y.] Harvard Univ, Harvard Med Sci, Cambridge, MA 02138 USA. [Yang, Mary Qu] Natl Inst Hlth, Natl Human Genome Rese Inst, Bethesda, MD 20852 USA. RP Deng, Y (reprint author), Univ Southern Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. FU Mississippi Computational Biology Consortium [NSF EPS-0556308]; Army Environmental Quality Program of the US Army Corps of Engineers [W912HZ-05-P-0145]; Mississippi Functional Genomics Network [2P20RRO16476-04] FX This work was supported by the Mississippi Computational Biology Consortium (NSF EPS-0556308), Army Environmental Quality Program of the US Army Corps of Engineers (under contract #W912HZ-05-P-0145) and the Mississippi Functional Genomics Network (DHHS/NIH/NCRR Grant# 2P20RRO16476-04). Permission to publish this information was granted by the Chief of Engineers. NR 20 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 187 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200035 ER PT B AU Yang, JY Yang, MQ Niemierko, A Deng, YP AF Yang, Jack Y. Yang, Mary Qu Niemierko, Andrzej Deng, Youping BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Non-monotonic radio-sensitivity over tumor volumes on adjuvant radio therapy SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE radiotherapy; microscopic tumor tissue; Poisson statistics; radio-sensitivity and cell killing; Niemierko's EUD; equivalent radio-sensitivity model AB Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics have been used extensively to validate clinical data. We found that Poisson statistics on RT is actually derived from bacterial cells despite of many validations from clinical data. However cancerous cells do have abnormal cellular communications and use chemical messengers to signal both surrounding normal and cancerous cells to develop new blood vessels and to invade, to metastasis and to overcome intercellular spatial confinements in general. We therefore investigated the cell killing effects on adjuvant RT and found that radio-sensitivity is actually not a monotonic function of volume as it was believed before. We present detailed analysis and explanation to justify above statement. Based on Niemierko's EUD, we present an equivalent radio-sensitivity model. We conclude that radio sensitivity is a sophisticated function over tumor volumes, since tumor responses upon radio therapy also depend on cellular communications. C1 [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Niemierko, Andrzej] Massachusetts Gen Hosp, Div Biomath & Biostat, Boston, MA 02114 USA. [Yang, Mary Qu] NIH, Natl Human Genome Res Inst, US Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Deng, Youping] Univ Southern Mississippi, Dept Biol Sci, Bioinformat & Canc Bio Lab, Hattiesburg, MS 39406 USA. RP Yang, JY (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM yang@hadron.mgh.Harvard.edu; yangma@mail.NIH.gov FU NIHWNCI [RO1 CA50628] FX The research was partially supported by NIHWNCI RO1 CA50628 NR 17 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 524 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200083 ER PT B AU Li, GZ Meng, HH Yang, MQ Yang, JY AF Li, Guo-Zheng Meng, Hao-Hua Yang, Mary Qu Yang, Jack Y. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Support vector regression with feature selection for the multivariate calibration of spectrofluorimetric determination of aromatic amino acids SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc AB Several artificial intelligent methods, including Support Vector Regression (SVR), Artificial Neural Networks (ANNs), and Partial Least Square (PLS) are used for the multivariate calibration in the determination of the three aromatic amino acids (phenylalanine, tyrosine and tryptophan) in their mixtures by fluorescence spectroscopy. The results of the leave-one-out method show that SVR perform better than other methods, and appear to be good methods for this task. Furthermore, feature selection is performed for SVR to remove redundant features and a novel algorithm named PRITER (Prediction RIsk based FEature selection for support vector Regression) is proposed. Results on the above multivariate calibration data set show that PRIFER is a powerful tool for solving the multivariate calibration problems. C1 [Li, Guo-Zheng] Nanjing Univ, State Key Lab Novel Software Technol, Nanjing 210093, Peoples R China. Shanghai Univ, Sch Comp Sci & Engn, Shanghai 200072, Peoples R China. [Yang, Mary Qu] NIH, NHGRI, US Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. RP Li, GZ (reprint author), Nanjing Univ, State Key Lab Novel Software Technol, Nanjing 210093, Peoples R China. EM gzli@shu.edu.cn; yangma@mail.NIH.GOV; jyang@hadron.mgh.Harvard.edu FU Nature Science Foundation of China [20503015]; Nature Science Project of Shanghai Municipal Education Committee [05AZ67]; Institute of Systems Biology of Shanghai University FX Thanks to the late professor Nian-Yi Chen for his advices to this paper. This work was supported in part by the Nature Science Foundation of China under grant no. 20503015, Nature Science Project of Shanghai Municipal Education Committee under grant no. 05AZ67 and open funding by Institute of Systems Biology of Shanghai University NR 28 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 842 EP + PG 3 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200130 ER PT B AU Bu, HL Li, GZ Zeng, XQ Yang, JY Yang, MQ AF Bu, Hua-Long Li, Guo-Zheng Zeng, Xue-Qiang Yang, Jack Y. Yang, Mary Qu BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Feature selection and partial least squares based dimension reduction for tumor classification SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE feature selection; Partial Least Squares; microarray analysis ID EXPRESSION; CANCER AB Partial Least Squares (PLS) is one of the widely used dimension reduction methods for analysis of gene expression microarray data, it represents the data in a low dimensional space through linear transformation, the size of the reduced space by PLS is critical to generalization performance of classifiers. The previous works always determined the top fixed number of components or the top several components by cross-validation. Here we demonstrate the usage of feature selection for PLS based dimension reduction. As a case study, PLS is combined with two feature selection methods (Genetic Algorithm and Sequential Backward Floating Selection) to get more robust and efficient dimensional space, and then the constructed data from the selected components is used as input for the Support Vector Machine (SVM) classifier. We use the method for tumor classification on gene microarray data, experimental results illustrate that our proposed framework is effective both to reduce classification error rates and get compact dimensional space. C1 [Bu, Hua-Long; Li, Guo-Zheng; Zeng, Xue-Qiang] Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. [Yang, Mary Qu] NIH, Dept Hlth & Human Serv Bethesda, Rockville, MD 20852 USA. RP Bu, HL (reprint author), Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. FU Nature Science Foundation of China [20503015]; Nature Science Project of Shanghai Municipal Education Committee [05AZ67]; Institute of Systems Biology of Shanghai University, China FX This work was supported in part by the Nature Science Foundation of China under grant no.20503015, Nature Science Project of Shanghai Municipal Education Committee under grant no.05AZ67 and open funding by Institute of Systems Biology of Shanghai University, China. NR 25 TC 2 Z9 2 U1 3 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 967 EP + PG 3 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200147 ER PT B AU Li, GZ Zeng, XQ Yang, JY Yang, MQ AF Li, Guo-Zheng Zeng, Xue-Qiang Yang, Jack Y. Yang, Mary Qu BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Partial least squares based dimension reduction with gene selection for tumor classification SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc DE partial least squares; dimension reduction; gene selection ID EXPRESSION DATA; CANCER; REGRESSION; PREDICTION; PATTERNS AB Analyzing gene expression data from DNA microarrays by commonly used classifiers is a hard task, be-cause there are only a few observations but with thou-sands of measured genes in the data set. Partial least squares based dimension reduction (PLSDR) is superior to handling such high dimensional problem, but irrelevant features will introduce errors into the dimension reduction process and reduce the classification accuracy of learning machines. Here feature selection is applied to filter the data and an algorithm named PLS DRg is described by integrating PLSDR with gene selection, which can effectively improve classification accuracy of learning machines. Feature selection is performed by the indication of t-statistics scores on standardized probes. Experimental results on seven microarray data sets show that the proposed method PLS DRg is effective and reliable to improve the generalization performance of classifiers. C1 [Li, Guo-Zheng; Zeng, Xue-Qiang] Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. [Yang, Mary Qu] NIH, Natl Human Genome Res Inst, US Dept Hlth & Human serv, Bethesda, MD 20852 USA. RP Li, GZ (reprint author), Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. EM stamina_gzli@shu.edu.cn; zeng@shu.edu.cn; jyang@hadron.mgh.Harvard.edu; yangma@mail.NIH.GOV FU Nature Science Foundation of China [20503015]; Nature Science Project of Shanghai Municipal Education Committee [05AZ67]; open funding by Institute of Systems Biology of Shanghai University and Scientific Research Fund of Jiangxi Provincial Education Departments [2007-57] FX This work was supported in part by the Nature Science Foundation of China under grant no. 20503015, Nature Science Project of Shanghai Municipal Education Committee under grant no. 05AZ67, open funding by Institute of Systems Biology of Shanghai University and Scientific Research Fund of Jiangxi Provincial Education Departments under grant no. 2007-57. NR 24 TC 12 Z9 13 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 1439 EP + PG 2 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200235 ER PT B AU Yang, MQ Elnitski, LL AF Yang, Mary Qu Elnitski, Laura L. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI An overview of bidirectional promoters SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man, Cybermet Soc AB A promoter is a region of DNA to which RNA polymerase binds in the presence of transcription factors; the RNA polymerase then transcribes the DNA in the 5' to 3' direction. Two genes that are transcribed in opposite directions, and for which their 5' ends are within 1000 base pairs of each other are said to be in a head-to-head configuration. The significance of this configuration is that since the promoter region lies upstream of the 5' end of the corresponding gene, it is likely that the promoter regions for the two genes lie in the region between the 5' ends; such a region is called a bidirectional promoter region. Bidirectional promoters are interesting because they aid in localizing promoter regions, and also suggest the possibility of co- regulation of the genes that bound the bidirectional promoter. In this talk we discuss the history of bidirectional promoter research, and broad scope of current research in this area, including recent work that suggests that certain cancer genes are enriched in bidirectional promoters, and also discuss a method for feature-based classification of human bidirectional promoters. C1 [Yang, Mary Qu; Elnitski, Laura L.] US Dept HHS, Genom Funct Anal Sect, NHGRI, NIH, Rockville, MD 20852 USA. RP Yang, MQ (reprint author), US Dept HHS, Genom Funct Anal Sect, NHGRI, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 1447 EP 1447 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200238 ER PT B AU Baxevanis, AD AF Baxevanis, Andreas D. BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Transforming medicine: Genomics, bioinformatics, and human health SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man, Cybermet Soc AB The completion of human genome sequencing in April 2003 marked the beginning of a new era for modern biology. Since that time, the impact of having the human sequence in hand has been nothing short of tremendous. The attainment of this goal, which many have compared to landing a man on the moon, will obviously have a profound effect on how biological and biomedical research will be conducted in the future. The intelligent use of sequence data from humans and other organisms, along with recent technological innovation fostered by the Human Genome Project, has already led to important advances in our understanding of diseases that have a genetic basis. More importantly, the advent of the genomic era will have a profound effect on how health care is delivered from this point forward. This lecture will provide an overview of current research themes in genomics and bioinformatics, all of which are aimed at understanding the genetic factors influencing risk for complex diseases. These efforts include whole-genome association approaches to common disease, large-scale clinical genotyping projects, the comprehensive identification of the structural and functional components in the human genome (the ENCODE Project), the Cancer Genome Atlas, and new advances in the area of chemical genomics. These research efforts, all of which rely on cutting-edge genomic and bioinformatics approaches, have already begun to yield important insight into genetic pathways that make us more susceptible to genetic disorders. These findings, in turn, are establishing an important groundwork for the discovery of new molecular targets for diagnosis, treatment, and prevention of human disease. C1 US Dept HHS, NHGRI, NIH, Bethesda, MD USA. RP Baxevanis, AD (reprint author), US Dept HHS, NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 1449 EP 1449 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200240 ER PT B AU Jakobsson, E Wang, MD Molnar, L AF Jakobsson, Eric Wang, May D. Molnar, Linda BA Yang, JY BF Yang, JY BE Yang, MQ Zhu, MM Zhang, Y Arabnia, HR Deng, Y Bourbakis, N TI Bio-nano-info integration for personalized medicine SO PROCEEDINGS OF THE 7TH IEEE INTERNATIONAL SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, VOLS I AND II LA English DT Proceedings Paper CT 7th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 14-17, 2007 CL Boston, MA SP IEEE, IEEE Comp Soc, IEEE Engn Med Biol, NSF, Int Soc Intelligent Biol Med, Syst, Man & Cybernet Soc AB Every disease has genetic and molecular basis. For example, in 2005, cancer became the number one killer in the USA for people under the age of 85. It is estimated that 1.3 million people will be diagnosed with cancer and more than 560,000 people will die each year. The underlying reasons for these statistics include the biological complexity of cancer as a disease which we are just now beginning to understand. The Human Genome Project and other advanced technologies such as bionanotechnologies bring new hope to patient care because they can potentially address the disease on the molecular level. These new technologies, when linked to an individual patient's molecular profile, can provide personalized and predictive early detection, diagnosis, prognosis tracking, and novel targeted therapies. In concert with development of these advanced technologies we must develop ways to validate the novel biotechnologies; methods to analyze the high volume of data coming from genomics, molecular imaging, and bionanotechnologies; and methods to interpret these data and make relevant predictions for patient care. This workshop keynote lecture will focus on how linking molecular biology, with advances in nanotechnology and information technology, to speed up the discovery and development process and clinical translation that leads to the advances in patient care. Specifically, the workshop keynote lecture will cover topics in ontology, data mining, data management, and image analysis that enable biomarker-based diagnosis, molecular imaging probe design, and therapeutic development. C1 [Jakobsson, Eric] Univ Illinois, Natl Ctr Supercomp Applicat, Beckman Inst Adv Sci & Technol, Natl Ctr Biomimet Nanoconductors, Urbana, IL 61801 USA. [Wang, May D.] Georgia Tech Emory Univ, Emory GT Ctr Canc Nanotechnol Excellence, Atlanta, GA USA. [Molnar, Linda] NIH, Natl Canc Ctr, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Jakobsson, E (reprint author), Univ Illinois, Natl Ctr Supercomp Applicat, Beckman Inst Adv Sci & Technol, Natl Ctr Biomimet Nanoconductors, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1509-0 PY 2007 BP 1452 EP 1452 PG 1 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHG41 UT WOS:000252958200242 ER PT B AU Liu, HC Wu, DB Yih, JM Liu, SW AF Liu, Hsiang-Chuan Wu, Der-Bang Yih, Jeng-Ming Liu, Shin-Wu BE Revetria, R Cecchi, A Schenone, M Mladenov, V Zemliak, A TI Fuzzy possibility C-mean based on mahalanobis distance and separable criterion SO PROCEEDINGS OF THE 7TH WSEAS INTERNATIONAL CONFERENCE ON APPLIED COMPUTER SCIENCE: COMPUTER SCIENCE CHALLENGES SE Electrical and Computer Engineering Series LA English DT Proceedings Paper CT 7th WSEAS International Conference on Applied Computer Science (ACS 07) CY NOV 21-23, 2007 CL Venice, ITALY SP WSEAS DE FPCM-MS; FPCM-M; FCM-M; GK algorithms; GG algorithms; Mahalanobis distance AB The well known fuzzy partition clustering algorithms are most based on Euclidean distance function, which can only be used to detect spherical structural clusters. Gustafson-Kessel (GK) clustering algorithm and Gath-Geva (GG) clustering algorithm, were developed to detect non-spherical structural clusters, but both of them based on semi-supervised Mahalanobis distance needed additional prior information. An improved Fuzzy C-Mean algorithm based on unsupervised Mahalanobis distance, FCM-M, was proposed by our previous work, but it didn't consider the relationships between cluster centers in the objective fimction. In this paper, we proposed an improved Fuzzy C-Mean algorithm, FPCM-MS, which is not only based on unsupervised Mahalanobis distance,. but also considering the relationships between cluster centers, and the relationships between the center of all points and the cluster centers in the objective function, the singular and the initial values problems were also solved. A real data set was applied to prove that the performance of the FPCM-MS algorithm gave more accurate clustering results than the FCM and FCM-M methods, and the ratio method which is proposed by us is the better of the two methods for selecting the initial values. C1 [Liu, Hsiang-Chuan] Univ E Asia, Dept Bioinformat, 500 Lioufeng Rd, Wufeng 41354, Taichung Cty, Taiwan. [Wu, Der-Bang; Yih, Jeng-Ming] Taichung Univ, Dept Math Educ, Taichung, Taiwan. [Wu, Der-Bang; Yih, Jeng-Ming] Taichung Univ, Grad Inst Educ Measurement, Taichung, Taiwan. [Liu, Shin-Wu] NIH, Natl Inst Allergy & Infectious Diseases, Bethesda, MD USA. RP Liu, HC (reprint author), Univ E Asia, Dept Bioinformat, 500 Lioufeng Rd, Wufeng 41354, Taichung Cty, Taiwan. EM lhc@asia.edu.tw; wudb@hotmail.com; yih@mail.nteu.edu.tw; fpan0366@yahoo.com.tw NR 8 TC 0 Z9 0 U1 0 U2 2 PU WORLD SCIENTIFIC AND ENGINEERING ACAD AND SOC PI ATHENS PA AG LOANNOU THEOLOGOU 17-23, 15773 ZOGRAPHOU, ATHENS, GREECE BN 978-960-6766-15-2 J9 ELE COM ENG PY 2007 BP 105 EP + PG 2 WC Computer Science, Interdisciplinary Applications SC Computer Science GA BHL49 UT WOS:000254075400017 ER PT B AU Gorbach, AM Wang, H Marsh, D Holstein-Rathlou, N AF Gorbach, A. M. Wang, H. Marsh, D. Holstein-Rathlou, N. BE Lombard, JH TI Assessment of rat renal perfusion using infrared imaging SO PROCEEDINGS OF THE 8TH WORLD CONGRESS FOR MICROCIRCULATION LA English DT Proceedings Paper CT 8th World Congress for Microcirculation CY AUG 15-19, 2007 CL Milwaukee, WI ID AUTOREGULATION AB An adapted infrared (IR) camera was used along with image processing software to assess microcirculatory fluctuations in localized renal blood flow, including the extent of regions containing nephrons exhibiting spontaneous oscillations in their individual blood flow. The IR camera was able to assess changes in rat renal perfusion during baseline conditions, during Occlusion of the main renal artery, and during administration of either saline, papaverin or angiotensin II. Concurrent recordings were made of tubular pressure in superficial nephrons. The IR and tubular pressure measurements each revealed the presence of oscillation peaks at 0.02-0.05 Hz and similar to 0.01 Hz. The highest local synchrony of the 0.02-0.05 Hz oscillations was confined to the immediate vicinities of the warmest areas of the kidney visible by IR after reperfusion. Propagated phenomena for the similar to 0.01 Hz frequency were observed between several areas of the renal cortical surface. C1 [Gorbach, A. M.] NIH, Bethesda, MD 20892 USA. RP Gorbach, AM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-373-8 PY 2007 BP 239 EP 246 PG 8 WC Cardiac & Cardiovascular Systems; Mathematical & Computational Biology; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Mathematical & Computational Biology; Physiology GA BGZ13 UT WOS:000251442300038 ER PT B AU Memarzadeh, F Jiang, J Manning, A AF Memarzadeh, Farhad Jiang, Jane Manning, Andy GP ASME TI Numerical investigation on ventilation strategy for laboratories: An approach to control thermal comfort and air quality using active chilled beams SO PROCEEDINGS OF THE ENERGY SUSTAINABILITY CONFERENCE 2007 LA English DT Proceedings Paper CT ASME Energy Sustainability Conference CY JUN 27-30, 2007 CL Long Beach, CA SP ASME, Adv Energy Syst, ASME, Solar Energy Div ID FLOW AB Laboratories are usually equipment intensive. The supply now rates required to cool these laboratories are generally higher than in a less equipment intensive zone of the building. The thermal comfort of occupants in laboratories can be controlled by the choice of ventilation strategy. This study employs Computational Fluid Dynamics (CFD) simulation to assess the performance of active chilled beams in a general laboratory layout with some equipment intensive areas and the removal effectiveness of such a system. The chilled beam performance is also compared with at of ceiling diffusers. The results from this study show that the chilled beams improve thermal comfort, and they can be operated at as low as 4 ACH while maintaining very satisfactory average PPD (around 10%) in the occupied zones. The chilled beam system also improves removal effectiveness because of the inherent higher total supply flow rate that results in a better mixing in the room than ceiling diffusers. The chilled beams in the cases studied are seen to have an insignificant effect on the hood containment. As satisfactory thermal comfort and air quality can be achieved at a lower flow rate in comparison with all-air ceiling diffusers, a 14% saving is estimated in annual energy cost for cooling and ventilating a typical lab in the Washington DC area. C1 [Memarzadeh, Farhad] NIH, Bethesda, MD 20892 USA. RP Memarzadeh, F (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 1 U1 0 U2 4 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4797-8 PY 2007 BP 409 EP 416 PG 8 WC Construction & Building Technology; Energy & Fuels; Engineering, Mechanical SC Construction & Building Technology; Energy & Fuels; Engineering GA BHM58 UT WOS:000254287400046 ER PT J AU Emmett, P Steer, C Hibbeln, J Davis, J Golding, J AF Emmett, P. Steer, C. Hibbeln, J. Davis, J. Golding, J. TI Fish eating in pregnancy in relation to depression during and after pregnancy SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Meeting Abstract C1 [Emmett, P.] Univ Bristol, Dept Social Med, Bristol BS8 1TQ, Avon, England. [Steer, C.; Golding, J.] Univ Bristol, Dept Commun Based Med, Bristol BS8 1TQ, Avon, England. [Hibbeln, J.] NIH, Bethesda, MD 20892 USA. [Davis, J.] Univ Illinois, Chicago, IL 60680 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PY 2007 VL 66 SI SI BP 64A EP 64A PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 254MG UT WOS:000252590100121 ER PT S AU Phuboon-Ob, J Auepanwiriyakul, R AF Phuboon-ob, Jiratta Auepanwiriyakul, Raweewan BE Ardil, C TI Two-Phase Optimization for Selecting Materialized Views in a Data Warehouse SO PROCEEDINGS OF WORLD ACADEMY OF SCIENCE, ENGINEERING AND TECHNOLOGY, VOL 19 SE Proceedings of World Academy of Science Engineering and Technology LA English DT Proceedings Paper CT Conference of the World-Academy-of-Science-Engineering-and-Technology CY JAN 29-31, 2007 CL Bangkok, THAILAND DE Data warehouse; materialized views; view selection problem; two-phase optimization AB A data warehouse (DW) is a system which has value and role for decision-making by querying. Queries to DW are critical regarding to their complexity and length. They often access millions of tuples, and involve joins between relations and aggregations. Materialized views are able to provide the better performance for DW queries. However, these views have maintenance cost, so materialization of all views is not possible. An important challenge of DW environment is materialized view selection because we have to realize the trade-off between performance and view maintenance. Therefore, in this paper, we introduce a new approach aimed to solve this challenge based on Two-Phase Optimization (2PO), which is a combination of Simulated Annealing (SA) and Iterative Improvement (11), with the use of Multiple View Processing Plan (MVPP). Our experiments show that 2PO outperform the original algorithms in terms of query processing cost and view maintenance cost. C1 [Phuboon-ob, Jiratta; Auepanwiriyakul, Raweewan] NIDA, Sch Appl Stat, Bangkok, Thailand. RP Phuboon-Ob, J (reprint author), NIDA, Sch Appl Stat, Bangkok, Thailand. NR 11 TC 1 Z9 1 U1 0 U2 0 PU WORLD ACAD SCI, ENG & TECH-WASET PI CANAKKALE PA PO BOX 125, CANAKKALE, 17100, TURKEY SN 1307-6884 J9 PROC WRLD ACAD SCI E PY 2007 VL 19 BP 277 EP 281 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA BIK70 UT WOS:000260422800051 ER PT S AU Phuboon-Ob, J Auepanwiriyakul, R AF Phuboon-Ob, Jiratta Auepanwiriyakul, Raweewan BE Ardil, C TI Selecting Materialized Views Using Two-Phase Optimization with Multiple View Processing Plan SO PROCEEDINGS OF WORLD ACADEMY OF SCIENCE, ENGINEERING AND TECHNOLOGY, VOL 21 SE Proceedings of World Academy of Science Engineering and Technology LA English DT Proceedings Paper CT Conference of the World-Academy-of-Science-Engineering-and-Technology CY MAY 25-27, 2007 CL Vienna, AUSTRIA DE Data warehouse; materialized views; view selection problem; two-phase optimization AB A data warehouse (DW) is a system which has value and role for decision-making by querying. Queries to DW are critical regarding to their complexity and length. They often access millions of tuples, and involve joins between relations and aggregations. Materialized views are able to provide the better performance for DW queries. However, these views have maintenance cost, so materialization of all views is not possible. An important challenge of DW environment is materialized view selection because we have to realize the trade-off between performance and view maintenance cost. Therefore, in this paper, we introduce a new approach aimed at solve this challenge based on Two-Phase Optimization (2PO), which is a combination of Simulated Annealing (SA) and Iterative Improvement (II), with the use of Multiple View Processing Plan (MVPP). Our experiments show that our method provides a further improvement in term of query processing cost and view maintenance cost. C1 [Phuboon-Ob, Jiratta; Auepanwiriyakul, Raweewan] NIDA, Sch Appl Stat, Bangkok, Thailand. RP Phuboon-Ob, J (reprint author), NIDA, Sch Appl Stat, Bangkok, Thailand. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WORLD ACAD SCI, ENG & TECH-WASET PI CANAKKALE PA PO BOX 125, CANAKKALE, 17100, TURKEY SN 1307-6884 J9 PROC WRLD ACAD SCI E PY 2007 VL 21 BP 166 EP 171 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Multidisciplinary SC Computer Science; Engineering GA BIK71 UT WOS:000260423500030 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Project Management Process SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 1 EP 13 D2 10.1007/978-0-387-73683-9_1 PG 13 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100004 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Project Management for Healthcare Informatics Foreword SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Editorial Material; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP V EP VI D2 10.1007/978-0-387-73683-9_1 PG 2 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100001 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Project Management for Healthcare Informatics Preface SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Editorial Material; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP VII EP VII D2 10.1007/978-0-387-73683-9_1 PG 1 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100002 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Project Management for Healthcare Informatics Preface SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Editorial Material; Book Chapter ID SYSTEMS C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP IX EP + D2 10.1007/978-0-387-73683-9_1 PG 6 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100003 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Initiation Phase SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 15 EP 20 D2 10.1007/978-0-387-73683-9_1 PG 6 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100005 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Planning Phase SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 21 EP 33 D2 10.1007/978-0-387-73683-9_1 PG 13 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100006 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Execution Phase SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 35 EP 49 D2 10.1007/978-0-387-73683-9_1 PG 15 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100007 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Control Phase SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 51 EP 61 D2 10.1007/978-0-387-73683-9_1 PG 11 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100008 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Closing Phase SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 63 EP 68 D2 10.1007/978-0-387-73683-9_1 PG 6 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100009 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Applying the Project Management Process in Healthcare Informatics SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 69 EP 77 D2 10.1007/978-0-387-73683-9_1 PG 9 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100010 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Applying the Project Management Process in Healthcare Management SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Article; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 79 EP 90 D2 10.1007/978-0-387-73683-9_1 PG 12 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100011 ER PT S AU Romano, CA AF Romano, Carol A. BA Houston, SM Bove, LA BF Houston, SM Bove, LA TI Project Management for Healthcare Informatics Summary SO PROJECT MANAGEMENT FOR HEALTHCARE INFORMATICS SE Health Informatics Series LA English DT Editorial Material; Book Chapter C1 [Romano, Carol A.] NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-1917 BN 978-0-387-73683-9 J9 HEALTH INFORM SER PY 2007 BP 91 EP 93 D2 10.1007/978-0-387-73683-9_1 PG 3 WC Health Care Sciences & Services; Medical Informatics; Nursing SC Health Care Sciences & Services; Medical Informatics; Nursing GA BNJ86 UT WOS:000274766100012 ER PT J AU Seubert, JM Zeldin, DC Nithipatikom, K Gross, GJ AF Seubert, John M. Zeldin, Darryl C. Nithipatikom, Kasem Gross, Garrett J. TI Role of epoxyeicosatrienoic acids in protecting the myocardium following ischemia/reperfusion injury SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE arachidonic acid; cytochrome P450; eicosanoids; ischemia reperfusion injury; cardioprotection ID MITOCHONDRIAL PERMEABILITY TRANSITION; CA2+-ACTIVATED K+ CHANNELS; SOLUBLE EPOXIDE HYDROLASE; DEPENDENT POTASSIUM CHANNELS; ACTIVATED PROTEIN-KINASE; ARACHIDONIC-ACID; ISCHEMIA-REPERFUSION; SIGNALING PATHWAYS; MOLECULAR-CLONING; CYCLOSPORINE-A AB Cardiomyocyte injury following ischemia-reperfusion can lead to cell death and result in cardiac dysfunction. A wide range of cardioprotective factors have been studied to date, but only recently has the cardioprotective role of fatty acids, specifically arachidonic acid (AA), been investigated. This fatty acid can be found in the membranes of cells in an inactive state and can be released by phospholipases in response to several stimuli, such as ischemia. The metabolism of AA involves the cycloxygenase (COX) and lipoxygenase (LOX) pathways, as well as the less well characterized cytochrome P450 (CYP) monooxygenase pathway. Current research suggests important differences with respect to the cardiovascular actions of specific CYP mediated arachidonic acid metabolites. For example, CYP mediated hydroxylation of AA produces 20-hydroxyeicosatetraenoic acid (20-HETE) which has detrimental effects in the heart during ischemia, pro-inflammatory effects during reperfusion and potent vasoconstrictor effects in the coronary circulation. Conversely, epoxidation of AA by CYP enzymes generates 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) that have been shown to reduce ischemia-reperfusion injury, have potent anti-inflammatory effects within the vasculature, and are potent vasodilators in the coronary circulation. This review aims to provide an overview of current data on the role of these CYP pathways in the heart with an emphasis on their involvement as mediators of ischemia-reperfusion injury. A better understanding of these relationships will facilitate identification of novel targets for the prevention and/or treatment of ischemic heart disease, a major worldwide public health problem. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Alberta, Fac Pharm & Pharmacuet Sci, Dent Pharm Ctr 3126, Edmonton, AB 76G 2N8, Canada. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. RP Seubert, JM (reprint author), Univ Alberta, Fac Pharm & Pharmacuet Sci, Dent Pharm Ctr 3126, Edmonton, AB 76G 2N8, Canada. EM jseubert@pharmacy.ualberta.ca FU Intramural NIH HHS [Z01 ES025034-13] NR 82 TC 84 Z9 87 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 2007 VL 82 IS 1-4 SI SI BP 50 EP 59 DI 10.1016/j.prostaglandins.2006.05.017 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 126YY UT WOS:000243552800007 PM 17164132 ER PT J AU Baffoe-Bonnie, AB Kittles, RA Gillanders, E Ou, L George, A Robbins, C Ahaghotu, C Bennett, J Boykin, W Hoke, G Mason, T Pettaway, C Vijayakumar, S Weinrich, S Jones, MP Gildea, D Riedesel, E Albertus, J Moses, T Lockwood, E Klaric, M Faruque, M Royal, C Trent, JM Berg, K Collins, FS Furbert-Harris, PM Bailey-Wilson, JE Dunston, GM Powell, I Carpten, JD AF Baffoe-Bonnie, Agnes B. Kittles, Rick A. Gillanders, Elizabeth Ou, Liang George, Asha Robbins, Christiane Ahaghotu, Chiledum Bennett, James Boykin, William Hoke, Gerald Mason, Terry Pettaway, Curtis Vijayakumar, Srinivasan Weinrich, Sally Jones, Mary P. Gildea, Derek Riedesel, Erica Albertus, Julie Moses, Tracy Lockwood, Erica Klaric, Meghan Faruque, Mezbah Royal, Charmaine Trent, Jeffrey M. Berg, Kate Collins, Francis S. Furbert-Harris, Paulette M. Bailey-Wilson, Joan E. Dunston, Georgia M. Powell, Isaac Carpten, John D. TI Genome-wide linkage of 77 families from the African American Hereditary Prostate Cancer Study (AAHPC) SO PROSTATE LA English DT Article DE genetic susceptibility; aggressive disease; HPC2/ELAC2; metastases; genetic burden; 1-LOD support interval ID ORDERED SUBSET ANALYSIS; SUSCEPTIBILITY LOCUS; SIB-PAIR; COMPLEX TRAITS; CHROMOSOME; GENES; SURVIVAL; PROGRAM; FINLAND; WHITES AB BACKGROUND. The African American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit families with early-onset disease fulfilling criteria of >= 4 affected. METHODS. We present a similar to 10 cM genome-wide linkage (GWL) analysis on 77 families including 254 affected and 274 unaffected genotyped. RESULTS. Linkage analysis revealed three chromosomal regions with GENEHUNTER multipoint HLOD scores >= 1.3 for all 77 families at 11q22,17p11, and Xq21. One family yielded genome-wide significant evidence of linkage (LOD = 3.5) to the 17p11 region with seven other families >= 23 in this region. Twenty-nine families with no-male-to-male (MM) transmission gave a peak HLOD of 1.62 (alpha = 0.33) at the Xq21 locus. Two novel peaks >= 0.91 for the 16 families with '> 6 affected' occurred at 2p21 and 22q12. CONCLUSIONS. These chromosomal regions in the genome warrant further follow-up based on the hypothesis of multiple susceptibility genes with modest effects, or several major genes segregating in small subsets of families. C1 TGen, Genet Basis Human Dis Div, Phoenix, AZ 85004 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Howard Univ, Natl Human Genome Ctr, Washington, DC USA. Howard Univ, Div Urol, Washington, DC USA. Midtown Urol, Atlanta, GA USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Michael Reese Hosp, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Illinois, Chicago, IL USA. Univ S Carolina, Columbia, SC 29208 USA. Howard Univ, Dept Microbiol, Washington, DC 20059 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Carpten, JD (reprint author), TGen, Genet Basis Human Dis Div, 445 N 5th St, Phoenix, AZ 85004 USA. EM jcarpten@tgen.org OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS; NCI NIH HHS [CA-06927]; NCRR NIH HHS [RR03048]; NHGRI NIH HHS [N01-HG-75418] NR 36 TC 11 Z9 11 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JAN 1 PY 2007 VL 67 IS 1 BP 22 EP 31 DI 10.1002/pros.20456 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 119WL UT WOS:000243044900004 PM 17031815 ER PT J AU Krepkiy, D Gawrisch, K Yeliseev, A AF Krepkiy, Dmitriy Gawrisch, Klaus Yeliseev, Alexei TI Expression and purification of CB2 for NMR studies in micellar solution SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE cannabinoid receptor CB2; dodecylphosphocholine micelles; circular dichroism spectroscopy; H-1 NMR; ligand binding ID PERIPHERAL CANNABINOID RECEPTOR; F1F0 ATP SYNTHASE; MEMBRANE-PROTEIN; SUBUNIT-C; CHANNEL AB We demonstrate feasibility of biophysical characterization of the peripheral cannabinoid receptor CB2 produced by heterologous expression in E. coli membranes. Recombinant receptor was purified by affinity chromatography, and NMR diffusion experiments performed on CB2 solubilized in dodecylphosphocholine (DPC) micelles. Circular dichroism spectroscopy indicated high alpha-helical content (49 %) of CB2. C1 [Krepkiy, Dmitriy; Gawrisch, Klaus; Yeliseev, Alexei] NIAAA, NIH, Lab Membrane Biochem & Biophys, Sect NMR, Rockville, MD 20852 USA. RP Yeliseev, A (reprint author), NIAAA, NIH, Lab Membrane Biochem & Biophys, Sect NMR, 5625 Fishers Lane,Room 3N17, Rockville, MD 20852 USA. EM yeliseeva@mail.nih.gov RI Yeliseev, Alexei/B-3143-2009 FU Intramural NIH HHS NR 28 TC 12 Z9 12 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PY 2007 VL 14 IS 10 BP 1031 EP 1037 DI 10.2174/092986607782541051 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 268KC UT WOS:000253577700015 PM 18221003 ER PT J AU Chakraborty, A Paul, BD Nagaraja, V AF Chakraborty, Atanu Paul, Bindu Diana Nagaraja, Valakunja TI Bacteriophage Mu C protein is a new member of unusual leucine zipper-HTH class of proteins SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE C protein; helix turn helix; leucine zipper; phage Mu; transcription activation ID MOM PROMOTER REGION; DNA-BINDING; LAC REPRESSOR; MOTIF; ACTIVATION; DIMERIZATION; REPLICATION; MECHANISM; PPS10; MAX AB Transcription activator protein C of bacteriophage Mu activates transcription of the late genes, including mom, during the lytic cycle of the phage. C binding to its site leads to the alteration in DNA topology of the promoter elements resulting in RNA polymerase (RNAP) recruitment. At the next step, the transactivator enhances promoter clearance of RNAP from P-mom. The C protein binds DNA with a very high affinity using a carboxyl-terminal helix turn helix (HTH) motif which has similarity with the HTH from paired domain of Drosophila prd protein. Previous studies established that the protein is dimeric in free and DNA bound forms. We describe now the unique dimerization interface of the protein. Two heptad repeats of hydrophobic amino acids found in the protein were considered to be the candidates for dimerization region. Site-directed mutational analysis revealed that the amino-terminal coiled coil region is not the dimerization determinant. In contrast, similar mutagenesis studies indicated a role for the leucine zipper motif, located in the middle region of the protein, in dimerization. Mixed oligomerization assays confirmed the importance of leucine zipper in C dimer formation establishing the presence of an uncommon zipper-HTH domain in the transactivator. C1 Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Jawaharlal Nehru Ctr Adv Sci Res, Bangalore 560064, Karnataka, India. RP Nagaraja, V (reprint author), Indian Inst Sci, Dept Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. EM vraj@mcbl.iisc.ernet.in NR 29 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD JAN PY 2007 VL 20 IS 1 BP 1 EP 5 DI 10.1093/protein/gzl047 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 139KR UT WOS:000244431200001 PM 17218337 ER PT J AU Chakrabarti, S Lanczycki, CJ AF Chakrabarti, Saikat Lanczycki, Christopher J. TI Analysis and prediction of functionally important sites in proteins SO PROTEIN SCIENCE LA English DT Article DE functionally important sites; function prediction; active sites; metal binding sites; protein binding sites; ligand binding sites; evolutionary conservation; compositional pattern ID SEQUENCE ALIGNMENTS; GENE ONTOLOGY; ACTIVE-SITES; DATABASE; EVOLUTION; RESIDUES; FAMILIES; BINDING; CONSERVATION; REGIONS AB The rapidly increasing volume of sequence and structure information available for proteins poses the daunting task of determining their functional importance. Computational methods can prove to be very useful in understanding and characterizing the biochemical and evolutionary information contained in this wealth of data, particularly at functionally important sites. Therefore, we perform a detailed survey of compositional and evolutionary constraints at the molecular and biological function level for a large set of known functionally important sites extracted from a wide range of protein families. We compare the degree of conservation across different functional categories and provide detailed statistical insight to decipher the varying evolutionary constraints at functionally important sites. The compositional and evolutionary information at functionally important sites has been compiled into a library of functional templates. We developed a module that predicts functionally important columns (FIC) of an alignment based on the detection of a significant "template match score'' to a library template. Our template match score measures an alignment column's similarity to a library template and combines a term explicitly representing a column's residue composition with various evolutionary conservation scores (information content and position-specific scoring matrix-derived statistics). Our benchmarking studies show good sensitivity/ specificity for the prediction of functional sites and high accuracy in attributing correct molecular function type to the predicted sites. This prediction method is based on information derived from homologous sequences and no structural information is required. Therefore, this method could be extremely useful for large-scale functional annotation. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Chakrabarti, S (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM chakraba@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 42 TC 23 Z9 23 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2007 VL 16 IS 1 BP 4 EP 13 DI 10.1110/ps.062506407 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 120WI UT WOS:000243116800003 PM 17192586 ER PT J AU Houtman, JCD Brown, PH Bowden, B Yamaguchi, H Appella, E Samelson, LE Schuck, P AF Houtman, Jon C. D. Brown, Patrick H. Bowden, Brent Yamaguchi, Hiroshi Appella, Ettore Samelson, Lawrence E. Schuck, Peter TI Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: Application to adaptor protein complexes in cell signaling SO PROTEIN SCIENCE LA English DT Article DE ITC; multiprotein complexes; cooperativity; signal transduction; adaptor protein; Sos1; LAT; Grb2; protein interactions; reversible associations ID SEDIMENTATION-VELOCITY ANALYSIS; COEFFICIENT DISTRIBUTIONS C(S); SITE-SPECIFIC BINDING; LIGAND-BINDING; BIOMOLECULAR INTERACTIONS; MULTIPROTEIN COMPLEXES; THERMODYNAMIC ANALYSIS; NUCLEOTIDE-BINDING; DRUG DISCOVERY; ENERGETICS AB Multisite interactions and the formation of ternary or higher-order protein complexes are ubiquitous features of protein interactions. Cooperativity between different ligands is a hallmark for information transfer, and is frequently critical for the biological function. We describe a new computational platform for the global analysis of isothermal titration calorimetry (ITC) data for the study of binary and ternary multisite interactions, implemented as part of the public domain multimethod analysis software SEDPHAT. The global analysis of titrations performed in different orientations was explored, and the potential for unraveling cooperativity parameters in multisite interactions was assessed in theory and experiment. To demonstrate the practical potential and limitations of global analyses of ITC titrations for the study of cooperative multiprotein interactions, we have examined the interactions of three proteins that are critical for signal transduction after T-cell activation, LAT, Grb2, and Sos1. We have shown previously that multivalent interactions between these three molecules promote the assembly of large multiprotein complexes important for T-cell receptor activation. By global analysis of the heats of binding observed in sets of ITC injections in different orientations, which allowed us to follow the formation of binary and ternary complexes, we observed negative and positive cooperativity that may be important to control the pathway of assembly and disassembly of adaptor protein particles. C1 NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. NIH, Lab Cell Biol, Bethesda, MD 20892 USA. NIH, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA. RP Schuck, P (reprint author), NIH, Natl Inst Biomed Imaging & Bioengn, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU NIH HHS [Z01 OD010485-08] NR 57 TC 146 Z9 146 U1 1 U2 18 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2007 VL 16 IS 1 BP 30 EP 42 DI 10.1110/ps.062558507 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 120WI UT WOS:000243116800006 PM 17192587 ER PT J AU Wang, DN Carroll, GT Turro, NJ Koberstein, JT Kovac, P Saksena, R Adamo, R Herzenberg, LA Herzenberg, LA Steinman, L AF Wang, Denong Carroll, Gregory T. Turro, Nicholas J. Koberstein, Jeffrey T. Kovac, Pavol Saksena, Rina Adamo, Roberto Herzenberg, Leonore A. Herzenberg, Leonard A. Steinman, Lawrence TI Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium SO PROTEOMICS LA English DT Article DE antibody; bacteria; biomarker; carbohydrates; sugar chips ID TETRASACCHARIDE SIDE-CHAIN; CARBOHYDRATE MICROARRAYS; MAJOR GLYCOPROTEIN; IDENTIFICATION; PROTEINS; VACCINES; SURFACE; STERNE; SPORES; BCLA AB Using photogenerated glycan arrays, we characterized a large panel of synthetic carbohydrates for their antigenic reactivities with pathogen-specific antibodies. We discovered that rabbit IgG antibodies elicited by Bacillus anthracis spores specifically recognize a tetrasaccharide chain that decorates the outermost surfaces of the B. anthracis exosporium. Since this sugar moiety is highly specific for the spores of B. anthracis, it appears to be a key biomarker for detection of B. anthracis spores and development of novel vaccines that target anthrax spores. C1 Stanford Univ, Sch Med, Dept Genet, Beckman Ctr, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Carbohydrate Microarray Lab, Stanford, CA 94305 USA. Columbia Univ, Dept Chem, New York, NY 10027 USA. Columbia Univ, Dept Chem Engn, New York, NY USA. NIDDK, LMC, NIH, Bethesda, MD USA. RP Wang, DN (reprint author), Stanford Univ, Sch Med, Dept Genet, Beckman Ctr, 279 Campus Dr W,B011, Stanford, CA 94305 USA. EM dwang1@stanford.edu OI Carroll, Gregory/0000-0003-0419-4976 FU Intramural NIH HHS; NIAID NIH HHS [AI064104] NR 23 TC 66 Z9 67 U1 2 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JAN PY 2007 VL 7 IS 2 BP 180 EP 184 DI 10.1002/pmic.200600478 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 132QQ UT WOS:000243957700003 PM 17205603 ER PT J AU Zuvekas, SH Rupp, A Norquist, G AF Zuvekas, Samuel H. Rupp, Agnes Norquist, Grayson TI Cost shifting under managed behavioral health care SO PSYCHIATRIC SERVICES LA English DT Article ID LARGE EMPLOYER GROUP; MENTAL-HEALTH; OUT PLAN; MASSACHUSETTS; DEPRESSION; SERVICES; DISORDERS; IMPACTS; PARITY AB Objective: The study examined whether a managed behavioral health care organization (MBHO) shifted treatment costs. Methods: Four years of claims data (1991-1995) from an insurer that introduced an MBHO in 1992 to control treatment costs were analyzed. Although the MBHO was not at direct financial risk for specialty mental health treatment, it faced incentives related to reputation and contract renewal to shift costs to primary care treatment or prescription drugs. it was hypothesized that if cost shifting occurred, an increase would be noted in the use of psychotropic medications without concurrent use of specialty mental health treatment. Simple t tests and a generalized estimating equations probit specification were used to test this hypothesis. Separate tests were performed for use of any psychotropic medication, any newer antidepressant, and any stimulant in a large employer group that simultaneously implemented parity coverage (75,360 enrollees) and a group of smaller employers that did not (9,228 enrollees). Results: The use of any psychotropic medication rose 64% in relative terms (p <.001) over the four-year period among enrollees of the large employer group and by 87% in the smaller groups (p <.001). In general, there were downward secular trends in the use of psychotropic medications without specialty care. Introduction of the MBHO was not significantly associated with the use of psychotropic medication alone. For newer antidepressants, introduction of the MBHO Was associated in the large group with a 2.4 (p=.003) absolute percentage point decrease in medication use alone. Conclusions: No evidence was found to suggest that the MBHO shifted treatment costs. C1 Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD 20850 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Univ Mississippi, Dept Psychiat & Human Behav, Jackson, MS 38677 USA. RP Zuvekas, SH (reprint author), Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, 540 Gaither Rd, Rockville, MD 20850 USA. EM szuvekas@ahrq.gov NR 35 TC 3 Z9 3 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2007 VL 58 IS 1 BP 100 EP 108 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 124QE UT WOS:000243384200015 PM 17215419 ER PT J AU Fischer, MA Servi, AD Polinski, JM Wang, PS AF Fischer, Michael A. Servi, Amber D. Polinski, Jennifer M. Wang, Philip S. TI Restrictions on antidepressant medications for children: A review of medicaid policy SO PSYCHIATRIC SERVICES LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; DEPRESSION; TRIALS; RISK; ADOLESCENTS AB Objective: This study evaluated Medicaid's prior-authorization policies restricting the prescribing of antidepressant medications for children. Methods: Medicaid program prior-authorization policies for antidepressant medications were obtained for all available states. All criteria needed authorization were recorded, with a focus on policies that applied specifically to children. Results: Data from 49 states and the District of Columbia revealed that 30 states (60%) required prior authorization for antidepressants, of which eight (27%) made specific provisions for children. These provisions varied across states. In most states fluoxetine could be prescribed for children with minimal restrictions, and two states had prior-authorization policies that strongly encouraged pediatric patients to use fluoxetine. State policies regarding other selective serotonin reuptake inhibitors varied widely. Conclusions: Although relatively few states included provisions for children in prior-authorization requirements for antidepressants, in states that did, the policies implemented varied widely. These findings raise important questions about the rational development of prescription drug reimbursement policy. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Fischer, MA (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM mfischer@partners.org NR 15 TC 4 Z9 4 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2007 VL 58 IS 1 BP 135 EP 138 DI 10.1176/appi.ps.58.1.135 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 124QE UT WOS:000243384200021 PM 17215425 ER PT J AU Schoneveld, OJLM Cidlowski, JA AF Schoneveld, Onard J. L. M. Cidlowski, John A. BE Ader, R TI Glucocorticoids and Immunity: Mechanisms of Regulation SO PSYCHONEUROIMMUNOLOGY, VOLS I AND II, 4TH EDITION LA English DT Article; Book Chapter ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; NUCLEAR-LOCALIZATION SIGNALS; RECEPTOR-BINDING SITES; HEAT-SHOCK-PROTEIN; T-CELL MEMORY; C-JUN; MESSENGER-RNA AB Glucocorticoids are among the most effective pharmaceuticals used to treat inflammatory and allergic diseases. Their therapeutic effects are, however, accompanied by a number of severe side effects, including fat redistribution, weight gain, hyperglycemia, and osteoporosis. Glucocorticoids exert their effects mainly through the glucocorticoid receptor, a ligand-dependent transcriptional regulator that activates or represses target gene expression. While the adverse effects of glucocorticoid treatment are thought to be primarily caused by activation of catabolic genes, the anti-inflammatory effects are largely thought to be mediated by the transrepressive properties of glucocorticoids. Transrepression of gene expression can be achieved by association of GR with either negative regulatory sequences in target genes, or pro-inflammatory transcription factors such as NF kappa B, AP-1, and NF-AT, thereby preventing the upregulation of pro-inflammatory genes. Via these repressive mechanisms, glucocorticoids act at multiple levels in the immune system, including the regulation of cytokine signaling, cytokine receptor synthesis, and other critical mediators of the immune response. Because of their clinical importance and diverse roles as anti-inflammatory therapeutics, it is of paramount importance to understand how glucocorticoids affect the immune system. This chapter will provide a concise overview of the immune response as well as glucocorticoid signaling, and how these two systems interact. C1 [Schoneveld, Onard J. L. M.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Schoneveld, OJLM (reprint author), NIEHS, Lab Signal Transduct, Mol Endocrinol Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 172 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046501-2 PY 2007 BP 45 EP 61 PG 17 WC Immunology; Neurosciences; Psychology SC Immunology; Neurosciences & Neurology; Psychology GA BCU03 UT WOS:000311389200004 ER PT B AU Gorby, HE Sternberg, EM AF Gorby, Heather E. Sternberg, Esther M. BE Ader, R TI The Neuroendocrine System and Rheumatoid Arthritis: Focus on the Hypothalamic-Pituitary-Adrenal Axis SO PSYCHONEUROIMMUNOLOGY, VOLS I AND II, 4TH EDITION LA English DT Article; Book Chapter ID CORTICOTROPIN-RELEASING HORMONE; GENE-RELATED PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; TUMOR-NECROSIS-FACTOR; ADJUVANT-INDUCED ARTHRITIS; COLLAGEN-INDUCED ARTHRITIS; ESTROGEN REPLACEMENT THERAPY; GLUCOCORTICOID RECEPTOR-BETA; BLOOD MONONUCLEAR-CELLS; DISEASE-ACTIVITY C1 [Gorby, Heather E.; Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Rockville, MD 20852 USA. RP Gorby, HE (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Rockville, MD 20852 USA. NR 136 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046501-2; 978-0-12-088576-3 PY 2007 BP 193 EP 205 PG 13 WC Immunology; Neurosciences; Psychology SC Immunology; Neurosciences & Neurology; Psychology GA BCU03 UT WOS:000311389200011 ER PT J AU Lee, HJ Rao, JS Ertley, RN Chang, L Rapoport, SI Bazinet, RP AF Lee, Ho-Joo Rao, Jagadeesh S. Ertley, Renee N. Chang, Lisa Rapoport, Stanley I. Bazinet, Richard P. TI Chronic fluoxetine increases cytosolic phospholipase A(2) activity and arachidonic acid turnover in brain phospholipids of the unanesthetized rat SO PSYCHOPHARMACOLOGY LA English DT Article DE fluoxetine; brain; arachidonic acid; phospholipase A(2); cyclooxygenase; prostaglandin ID GROUP-SPECIFIC ASSAYS; CHRONIC LITHIUM; FATTY-ACID; DOCOSAHEXAENOIC ACID; BIPOLAR DISORDER; AWAKE RATS; SIGNAL-TRANSDUCTION; PROSTAGLANDIN RECEPTOR; CHRONIC VALPROATE; MOOD STABILIZERS AB Rationale Fluoxetine is used to treat unipolar depression and is thought to act by increasing the concentration of serotonin (5-HT) in the synaptic cleft, leading to increased serotonin signaling. The 5-HT2A/2C receptor subtypes are coupled to a phospholipase A(2) (PLA(2)). We hypothesized that chronic fluoxetine would increase the brain activity of PLA(2) and the turnover rate of arachidonic acid (AA) in phospholipids of the unanesthetized rat. Materials and methods To test this hypothesis, rats were administered fluoxetine (10 mg/kg) or vehicle intraperitoneally daily for 21 days. In the unanesthetized rat, [1-C-14]AA was infused intravenously and arterial blood plasma was sampled until the animal was killed at 5 min and its brain was subjected to chemical, radiotracer, or enzyme analysis. Results Using equations from our fatty acid model, we found that chronic fluoxetine compared with vehicle increased the turnover rate of AA within several brain phospholipids by 75-86%. The activity and protein levels of brain cytosolic PLA(2) (cPLA(2)) but not of secretory or calcium-independent PLA(2) were increased in rats administered fluoxetine. In a separate group of animals that received chronic fluoxetine followed by a 3-day saline washout, the turnover of AA and activity and protein levels of cPLA(2) were not significantly different from controls. The protein levels of cyclooxygenases 1 and 2 as well as the concentration of prostaglandin E-2 in rats chronically administered fluoxetine did not differ significantly from controls. Conclusion The results support the hypothesis that fluoxetine increases the cPLA(2)-mediated turnover of AA within brain phospholipids. C1 Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bazinet, RP (reprint author), Univ Toronto, Fac Med, Dept Nutr Sci, FitzGerald Bldg,150 Coll St,Room 306, Toronto, ON M5S 3E2, Canada. EM richard.bazinet@utoronto.ca RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 91 TC 30 Z9 30 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2007 VL 190 IS 1 BP 103 EP 115 DI 10.1007/s00213-006-0582-1 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 111GQ UT WOS:000242439800012 PM 17093977 ER PT J AU Baumann, MH Wang, XY Rothman, RB AF Baumann, Michael H. Wang, Xiaoying Rothman, Richard B. TI 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings SO PSYCHOPHARMACOLOGY LA English DT Review DE MDMA; serotonin; depletion; neurotoxicity; release; hormones; behavior ID SEROTONIN-DOPAMINE INTERACTIONS; ORALLY-ADMINISTERED MDMA; CENTRAL-NERVOUS-SYSTEM; IN-VIVO MICRODIALYSIS; DORSAL RAPHE NEURONS; ECSTASY MDMA; EXTRACELLULAR SEROTONIN; INCREASED ANXIETY; BRAIN-SLICES; (+/-)3,4-METHYLENE-DIOXYMETHAMPHETAMINE ECSTASY AB Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate. Objective.- The present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of "interspecies scaling" to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions. Results: MDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1-2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10-20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits. Conclusions: MDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks. C1 NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mbaumann@intra.nida.nih.gov NR 145 TC 141 Z9 143 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2007 VL 189 IS 4 BP 407 EP 424 DI 10.1007/s00213-006-0322-6 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 126OM UT WOS:000243523700002 PM 16541247 ER PT J AU Birbaumer, N AF Birbaumer, Niels TI For distinguished contributions to psychophysiology: Robert M. Stern SO PSYCHOPHYSIOLOGY LA English DT Biographical-Item C1 Univ Tubingen, MEG Ctr, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Birbaumer, N (reprint author), Univ Tubingen, MEG Ctr, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM niels.birbaumer@uni-Tuebingen.de 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2007 VL 44 IS 1 BP 1 EP 1 DI 10.1111/j.1469-8986.2006.00488.x PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 131JH UT WOS:000243864600001 PM 17241135 ER PT J AU Cornwell, BR Johnson, LL Grillon, C AF Cornwell, Brian R. Johnson, Linda L. Grillon, Christian TI Enhanced sensory cortical gamma oscillations during fear-conditioning revealed by spatially-filtered magnetoencephalography (MEG) SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 16-21, 2007 CL Savannah, GA DE magnetoencephalography; fear conditioning; gamma oscillations C1 NIMH, Bethesda, MD 20892 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2007 VL 44 SU 1 BP S91 EP S91 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 203VK UT WOS:000249001900418 ER PT J AU Lissek, S Rabin, S Biggs, A Alvarez, R Cornwell, BR Vythilingam, M Grillon, C AF Lissek, Shmuel Rabin, Stephanie Biggs, Arter Alvarez, Ruben Cornwell, Brian R. Vythilingam, Meena Grillon, Christian TI Generalization of conditioned fear as a pathogenic marker of PTSD SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 47th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 16-21, 2007 CL Savannah, GA C1 NIMH, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2007 VL 44 SU 1 BP S9 EP S9 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 203VK UT WOS:000249001900037 ER PT J AU Carney, RM Howells, WB Blumenthal, JA Freedland, KE Stein, PK Berkman, LF Watkins, LL Czajkowski, SM Steinmeyer, B Hayano, J Domitrovich, PP Burg, MM Jaffe, AS AF Carney, Robert M. Howells, William B. Blumenthal, James A. Freedland, Kenneth E. Stein, Phyllis K. Berkman, Lisa F. Watkins, Lana L. Czajkowski, Susan M. Steinmeyer, Brian Hayano, Junichiro Domitrovich, Peter P. Burg, Matthew M. Jaffe, Allan S. TI Heart rate turbulence, depression, and survival after acute myocardial infarction SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; acute myocardial infarction; survival; heart rate turbulence ID CORONARY-ARTERY-DISEASE; RATE-VARIABILITY; RISK-FACTOR; ENHANCING RECOVERY; MEDICAL MORBIDITY; PATIENTS ENRICHD; NERVOUS-SYSTEM; MORTALITY; MECHANISMS; EVENTS AB Objective: Depression is a risk factor for mortality after acute myocardial infarction (AMI), possibly as a result of altered autonomic nervous system (ANS) modulation of heart rate (HR) and rhythm. The purposes of this study were to determine: a) whether depressed patients are more likely to have an abnormal HR response (i.e., abnormal turbulence) to premature ventricular contractions (VPCs), and b) whether abnormal HR turbulence accounts for the effect of depression on increased mortality after AMI. Methods: Ambulatory electrocardiographic data were obtained from 666 (316 depressed, 350 nondepressed) patients with a recent AMI; 498 had VPCs with measurable HR turbulence. Of these, 260 had normal, 152 had equivocal, and 86 had abnormal HR turbulence. Patients were followed for up to 30 (median = 24) months. Results: Depressed patients were more likely to have abnormal HR turbulence (risk factor adjusted odds ratio = 1.8; 95% confidence interval [CI] = 1.0-3.0; p =.03) and have worse survival (odds ratio = 2.4; 95% Cl = 1.2-4.6; p =.02) than nondepressed patients. When HR turbulence was added to the model, the adjusted hazard ratio for depression decreased to 1.9 (95% Cl = 0.9-3.8; p =.08), and to 1.6 (95% Cl = 0.8-3.4; p =.18) when a measure of HR variability (LnVLF) was added. The hazard was found to differ over time with depression posing little risk for mortality in year I but greater risk in years 2 and 3 of the follow up. Conclusion: ANS dysregulation may partially mediate the increased risk for mortality in depressed patients with frequent VPCs after an AMI. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Epidemiol, St Louis, MO 63110 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Harvard Univ, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi 467, Japan. Yale Univ, Sch Med, New Haven, CT 06520 USA. Columbia Univ, Sch Med, New York, NY 10027 USA. Mayo Clin, Rochester, MN USA. RP Carney, RM (reprint author), Behav Med Ctr, 4625 Lindell Blvd,Suite 420, St Louis, MO 63108 USA. EM cameyr@bmc.wustl.edu FU NHLBI NIH HHS [2 R0-1HL58946] NR 40 TC 22 Z9 25 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2007 VL 69 IS 1 BP 4 EP 9 DI 10.1097/01.psy.0000249733.33811.00 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 131EX UT WOS:000243852200001 PM 17167127 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Agency Theory and Its Applications in Health Care SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID ECONOMIC-THEORY; MORAL HAZARD; INCENTIVES; CONTRACTS; COMPENSATION; PERFORMANCE; UNCERTAINTY; FRAMEWORK; MARKET; COSTS C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 151 EP 178 D2 10.1596/978-0-8213-6547-2 PG 28 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100008 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Doctors' and Patients' Utility Functions SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID MEDICAL-CARE; COMMUNICATION; INFORMATION; AGENCY C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 179 EP 194 D2 10.1596/978-0-8213-6547-2 PG 16 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100009 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Economic Models of Doctors' Behavior SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID PHYSICIANS SERVICES; DEMAND; PRICE C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD 20892 USA. NR 25 TC 2 Z9 2 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 195 EP 208 D2 10.1596/978-0-8213-6547-2 PG 14 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100010 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Economic Models of Hospital Behavior SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID SERVICES; MARKET; PRICE C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 209 EP 236 D2 10.1596/978-0-8213-6547-2 PG 28 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100011 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Motivation and Performance-Related Pay SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID MERIT AWARDS; SERVICE; DOCTORS; MANAGEMENT; PHYSICIANS C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 59 TC 1 Z9 1 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 237 EP 258 D2 10.1596/978-0-8213-6547-2 PG 22 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100012 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Payment Mechanisms and Provider Behavior SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID PRACTICE PATTERNS; COST CONTAINMENT; UNITED-STATES; PHYSICIAN; REIMBURSEMENT; MEDICARE; SERVICES; SYSTEM; CARE; INCENTIVES C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 40 TC 1 Z9 2 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 259 EP 278 D2 10.1596/978-0-8213-6547-2 PG 20 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100013 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Supplier-Induced Demand and Unnecessary Care SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID PHYSICIAN-INDUCED DEMAND; SMALL-AREA VARIATIONS; HOSPITAL UTILIZATION; MEDICAL-CARE; GEOGRAPHIC VARIATIONS; SURGICAL-PROCEDURES; UNNECESSARY SURGERY; UNITED-STATES; EVER KNOW; APPROPRIATENESS C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, New York, NY USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 85 TC 1 Z9 1 U1 1 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 279 EP 310 D2 10.1596/978-0-8213-6547-2 PG 32 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100014 ER PT J AU Liu, XZ Mills, A AF Liu, Xingzhu Mills, Anne BE Preker, AS Liu, X Velenyi, EV Baris, E TI Measuring Efficiency in Purchasing SO PUBLIC ENDS, PRIVATE MEANS: STRATEGIC PURCHASING OF HEALTH SERVICES LA English DT Article; Book Chapter ID HEALTH PRODUCTION FUNCTION; HOSPITAL EFFICIENCY; TECHNICAL EFFICIENCY; COST-FUNCTIONS; CARE; OWNERSHIP C1 [Liu, Xingzhu] ABT Associates Inc, Bethesda, MD USA. [Liu, Xingzhu] World Hlth Org, Washington, DC USA. [Liu, Xingzhu] Shandong Univ, Inst Social Med & Hlth Policy, Jinan, Peoples R China. [Mills, Anne] London Sch Hyg & Trop Med, London, England. RP Liu, XZ (reprint author), NIH, Fogarty Int Ctr Bethesda, Bethesda, MD USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6548-9 PY 2007 BP 353 EP 383 D2 10.1596/978-0-8213-6547-2 PG 31 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BAL01 UT WOS:000304464100017 ER PT J AU Csizmadi, I Kahle, L Ullman, R Dawe, U Zimmerman, TP Friedenreich, CM Bryant, H Subar, AF AF Csizmadi, Ilona Kahle, Lisa Ullman, Ruth Dawe, Ursula Zimmerman, Thea Palmer Friedenreich, Christine M. Bryant, Heather Subar, Amy F. TI Adaptation and evaluation of the National Cancer Institute's Diet History Questionnaire and nutrient database for Canadian populations SO PUBLIC HEALTH NUTRITION LA English DT Article DE food-frequency questionnaire; nutrient database; fortification; misclassification; Dietary Reference Intake ID FOOD FREQUENCY QUESTIONNAIRES; VALIDATION AB Background and objective. Despite assumed similarities in Canadian and US dietary habits, some differences in food availability and nutrient fortification exist. Food-frequency questionnaires designed for the USA may therefore not provide the most accurate estimates of dietary intake in Canadian populations. Hence, we undertook to evaluate and modify the National Cancer Institute's Diet History Questionnaire (DHQ) and nutrient database. Methods: Of the foods queried on the DHQ, those most likely to differ in nutrient composition were identified. Where possible these foods were matched to comparable foods in the Canadian Nutrient File. Nutrient values were examined and modified to reflect the Canadian content of minerals (calcium, iron, zinc) and vitamins (A, C, D, thiamin, riboflavin, niacin, B(6), folate and B(12)). DHQs completed by 13 181 Alberta Cohort Study participants aged 35-69 years were analysed to estimate nutrient intakes using the original US and modified versions of the DHQ databases. Misclassification of intake for meeting the Dietary Reference intake (DRI) was determined following analysis with the US nutrient database. Results: Twenty-five per cent of 2411 foods deemed most likely to differ in nutrient profile were subsequently modified for folate, 11% for vitamin D, 10% for calcium and riboflavin, and between 7 and 10% for the remaining nutrients of interest. Misclassification with respect to meeting the DRI varied but was highest for folate (7%) and vitamin A (7%) among men, and for vitamin D (7%) among women over 50 years of age. Conclusion: Errors in nutrient intake estimates owing to differences in food fortification between the USA and Canada can be reduced in Canadian populations by using nutrient databases that reflect Canadian fortification practices. C1 Alberta Canc Board, Div Populat Hlth & Informat, Calgary, AB T2N 4N2, Canada. Informat Management Serv Inc, Bethesda, MD USA. Westat Corp, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. RP Csizmadi, I (reprint author), Alberta Canc Board, Div Populat Hlth & Informat, 1331-29 St NW, Calgary, AB T2N 4N2, Canada. EM ilona.csizmadi@cancerboard.ab.ca NR 27 TC 49 Z9 49 U1 1 U2 9 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD JAN PY 2007 VL 10 IS 1 BP 88 EP 96 DI 10.1017/S1368980007184287 PG 9 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 133UF UT WOS:000244038700015 PM 17212847 ER PT J AU Reeve, BB Hays, RD Chang, CH Perfetto, EM AF Reeve, Bryce B. Hays, Ron D. Chang, Chih-Hung Perfetto, Eleanor M. TI Applying item response theory to enhance health outcomes assessment SO QUALITY OF LIFE RESEARCH LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. Global Outcomes Res, New York, NY USA. RP Reeve, BB (reprint author), NCI, Bethesda, MD 20892 USA. EM Bryce.Reeve@nih.gov RI Hays, Ronald/D-5629-2013 NR 8 TC 32 Z9 32 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 1 EP 3 DI 10.1007/s11136-007-9220-6 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600001 ER PT J AU Edelen, MO Reeve, BB AF Edelen, Maria Orlando Reeve, Bryce B. TI Applying item response theory (IRT) modeling to questionnaire development, evaluation, and refinement SO QUALITY OF LIFE RESEARCH LA English DT Article DE IRT; health outcomes; adolescent depression; short form ID RASCH MODEL; EM ALGORITHM; FIT INDEX; ABILITY; TESTS; PERFORMANCE; CATEGORIES; PARAMETERS; GOODNESS AB Background Health outcomes researchers are increasingly applying Item Response Theory (IRT) methods to questionnaire development, evaluation, and refinement efforts. Objective To provide a brief overview of IRT, to review some of the critical issues associated with IRT applications, and to demonstrate the basic features of IRT with an example. Methods Example data come from 6,504 adolescent respondents in the National Longitudinal Study of Adolescent Health public use data set who completed to the 19 item Feelings Scale for depression. The sample was split into a development and validation sample. Scale items were calibrated in the development sample with the Graded Response Model and the results were used to construct a 10-item short form. The short form was evaluated in the validation sample by examining the correspondence between IRT scores from the short form and the original, and by comparing the proportion of respondents identified as depressed according to the original and short form observed cut scores. Results The 19-items varied in their discrimination (slope parameter range: .86-2.66), and item location parameters reflected a considerable range of depression (-.72-3.39). However, the item set is most discriminating at higher levels of depression. In the validation sample IRT scores generated from the short and long forms were correlated at .96 and the average difference in these scores was -.01. In addition, nearly 90% of the sample was classified identically as at risk or not at risk for depression using observed score cut points from the short and long forms. Conclusions When used appropriately, IRT can be a powerful tool for questionnaire development, evaluation, and refinement, resulting in precise, valid, and relatively brief instruments that minimize response burden. C1 Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Natl Canc Inst, Bethesda, MD USA. RP Edelen, MO (reprint author), Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. EM edelen@brown.edu NR 71 TC 140 Z9 142 U1 4 U2 28 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 5 EP 18 DI 10.1007/s11136-007-9198-0 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600002 PM 17375372 ER PT J AU Bjorner, JB Chang, CH Thissen, D Reeve, BB AF Bjorner, Jakob Bue Chang, Chih-Hung Thissen, David Reeve, Bryce B. TI Developing tailored instruments: item banking and computerized adaptive assessment SO QUALITY OF LIFE RESEARCH LA English DT Article DE computerized adaptive testing; health status indicators; questionnaires; algorithms; mental health; factor analysis; statistical ID IMPACT TEST HIT(TM); PARTIAL CREDIT MODEL; GOODNESS-OF-FIT; RESPONSE THEORY; HEADACHE IMPACT; MEDICAL OUTCOMES; HEALTH SURVEY; ABILITY; PAPER; QUESTIONNAIRES AB Item banks and Computerized Adaptive Testing (CAT) have the potential to greatly improve the assessment of health outcomes. This review describes the unique features of item banks and CAT and discusses how to develop item banks. In CAT, a computer selects the items from an item bank that are most relevant for and informative about the particular respondent; thus optimizing test relevance and precision. Item response theory (IRT) provides the foundation for selecting the items that are most informative for the particular respondent and for scoring responses on a common metric. The development of an item bank is a multi-stage process that requires a clear definition of the construct to be measured, good items, a careful psychometric analysis of the items, and a clear specification of the final CAT. The psychometric analysis needs to evaluate the assumptions of the IRT model such as unidimensionality and local independence; that the items function the same way in different subgroups of the population; and that there is an adequate fit between the data and the chosen item response models. Also, interpretation guidelines need to be established to help the clinical application of the assessment. Although medical research can draw upon expertise from educational testing in the development of item banks and CAT, the medical field also encounters unique opportunities and challenges. C1 Qual Metr Inc, Lincoln, RI 02865 USA. Hlth Assessment Lab, Waltham, MA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. Univ N Carolina, Chapel Hill, NC USA. Natl Canc Inst, NIH, Bethesda, MD USA. RP Bjorner, JB (reprint author), Qual Metr Inc, 640 George Washington Highway,Suite 201, Lincoln, RI 02865 USA. EM jbjorner@qualitymetric.com FU NIA NIH HHS [AG015815]; NINDS NIH HHS [1R43NS047763-01] NR 71 TC 80 Z9 81 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 95 EP 108 DI 10.1007/s11136-007-9168-6 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600008 PM 17530450 ER PT J AU Thissen, D Reeve, BB Bjorner, JB Chang, CH AF Thissen, David Reeve, Bryce B. Bjorner, Jakob Bue Chang, Chih-Hung TI Methodological issues for building item banks and computerized adaptive scales SO QUALITY OF LIFE RESEARCH LA English DT Article DE item bank; computerized adaptive scale; computerized adaptive test; item response theory; dimensionality assessment; differential item functioning; local dependence ID IMPACT TEST HIT(TM); RESPONSE THEORY; ABILITY; MODELS; CALIBRATION; DEPENDENCE; QUESTIONS; RECOVERY; MULTILOG; LINKING AB This paper reviews important methodological considerations for developing item banks and computerized adaptive scales (commonly called computerized adaptive tests in the educational measurement literature, yielding the acronym CAT), including issues of the reference population, dimensionality, dichotomous versus polytomous response scales, differential item functioning (DIF) and conditional scoring, mode effects, the impact of local dependence, and innovative approaches to assessment using CATs in health outcomes research. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Natl Canc Inst, NIH, Bethesda, MD USA. Qual Metr Inc, Lincoln, RI USA. Hlth Assessment Lab, Waltham, MA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. RP Thissen, D (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA. EM dthissen@email.unc.edu NR 69 TC 36 Z9 36 U1 18 U2 22 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 109 EP 119 DI 10.1007/s11136-007-9169-5 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600009 PM 17294284 ER PT J AU Cook, KF Teal, CR Bjorner, JB Cella, D Chang, CH Crane, PK Gibbons, LE Hays, RD McHorney, CA Ocepek-Welikson, K Raczek, AE Teresi, JA Reeve, BB AF Cook, Karon F. Teal, Cayla R. Bjorner, Jakob B. Cella, David Chang, Chih-Hung Crane, Paul K. Gibbons, Laura E. Hays, Ron D. McHorney, Colleen A. Ocepek-Welikson, Katja Raczek, Anastasia E. Teresi, Jeanne A. Reeve, Bryce B. TI IRT health outcomes data analysis project: an overview and summary SO QUALITY OF LIFE RESEARCH LA English DT Article DE quality of life; health status; measurement; outcomes ID OF-LIFE INSTRUMENT; FIT INDEXES; MODEL; QLQ-C30; SCALE AB Background In June 2004, the National Cancer Institute and the Drug Information Association co-sponsored the conference, "Improving the Measurement of Health Outcomes through the Applications of Item Response Theory (IRT) Modeling: Exploration of Item Banks and Computer-Adaptive Assessment." A component of the conference was presentation of a psychometric and content analysis of a secondary dataset. Objectives A thorough psychometric and content analysis was conducted of two primary domains within a cancer health-related quality of life (HRQOL) dataset. Research design HRQOL scales were evaluated using factor analysis for categorical data, IRT modeling, and differential item functioning analyses. In addition, computerized adaptive administration of HRQOL item banks was simulated, and various IRT models were applied and compared. Subjects The original data were collected as part of the NCI-funded Quality of Life Evaluation in Oncology (Q-Score) Project. A total of 1,714 patients with cancer or HIV/AIDS were recruited from 5 clinical sites. Measures Items from 4 HRQOL instruments were evaluated: Cancer Rehabilitation Evaluation System-Short Form, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Functional Assessment of Cancer Therapy and Medical Outcomes Study Short-Form Health Survey. Results and conclusions Four lessons learned from the project are discussed: the importance of good developmental item banks, the ambiguity of model fit results, the limits of our knowledge regarding the practical implications of model misfit, and the importance in the measurement of HRQOL of construct definition. With respect to these lessons, areas for future research are suggested. The feasibility of developing item banks for broad definitions of health is discussed. C1 Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. Baylor Coll Med, Dept Med,Res & Dev Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Vet Affairs Hlth Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Qual Metr Inc, Lincoln, RI USA. Hlth Assessment Lab, Waltham, MA USA. Northwestern Univ, Evanston NW Healthcare, Ctr Outcomes Res & Educ, Feinberg Sch Med, Chicago, IL USA. Northwestern Univ, Buehler Ctr Aging, Feinberg Sch Med, Chicago, IL USA. Univ Washington, Div Gen Internal Med, Sch Med, Seattle, WA 98195 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, RAND Hlth Program, Los Angeles, CA USA. Merck & Co Inc, Outcomes Res, West Point, PA USA. IPRO, New York Qual Improvment Org, Lake Success, NY USA. New York State Psychiat Inst & Hosp, Riverdale, NY USA. Hebrew Home, Div Res, Riverdale, NY USA. Columbia Univ Stroud Ctr, Fac Med, Riverdale, NY USA. Natl Canc Inst, Outcomes Res Branch, Bethesda, MD USA. RP Cook, KF (reprint author), Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. EM karonc2@u.washington.edu RI Hays, Ronald/D-5629-2013; Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU NCI NIH HHS [R01 (CA60068), Y1-PC-3028-01]; NIAMS NIH HHS [1U01AR52171-01] NR 45 TC 29 Z9 29 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 121 EP 132 DI 10.1007/s11136-007-9177-5 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600010 PM 17351824 ER PT J AU Reeve, BB Burke, LB Chiang, YP Clauser, SB Colpe, LJ Elias, JW Fleishman, J Hohmann, AA Johnson-Taylor, WL Lawrence, W Claudia, SM Quatrano, LA Riley, WT Smothers, BA Werner, EM AF Reeve, Bryce B. Burke, Laurie B. Chiang, Yen-Pin Clauser, Steven B. Colpe, Lisa J. Elias, Jeffrey W. Fleishman, John Hohmann, Ann A. Johnson-Taylor, Wendy L. Lawrence, William Claudia, S. Moy Quatrano, Louis A. Riley, William T. Smothers, Barbara A. Werner, Ellen M. TI Enhancing measurement in health outcomes research supported by Agencies within the US Department of Health and Human Services SO QUALITY OF LIFE RESEARCH LA English DT Article DE item response theory; computerized adaptive testing; patient-reported outcomes; health-related quality of life ID CONSUMER ASSESSMENT; OBESITY; CARE; PERCEPTIONS; DIAGNOSIS; CRITERIA; MODELS; PLANS AB Many of the Institutes, Agencies and Centers that make up the US Department of Health and Human Services (DHHS) have recognized the need for better instrumentation in health outcomes research, and provide support, both internally and externally, for research utilizing advances in measurement theory and computer technology (informatics). In this paper, representatives from several DHHS agencies and institutes will discuss their need for better instruments within their discipline and describe current or future initiatives for exploring the benefits of these technologies. Together, the perspectives underscore the importance of developing valid, precise, and efficient measures to capture the full burden of disease and treatment on patients. Initiatives, like the Patient-Reported Outcomes Measurement Information System (PROMIS) to create health-related quality of life item banks, represent a trans-DHHS effort to develop a standard set of measures for informing decision making in clinical research, practice, and health policy. C1 NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD USA. Agcy Healthcare Res & Qual, Rockville, MD USA. NIH, Rockville, MD USA. Natl Inst Aging, Bethesda, MD USA. NIMH, Bethesda, MD 20892 USA. Div Nutr Res Coordinat, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Natl Ctr Med Rehabil Res, Bethesda, MD USA. NICHHD, Bethesda, MD 20892 USA. NINR, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Reeve, BB (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM reeveb@mail.nih.gov NR 51 TC 21 Z9 23 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PY 2007 VL 16 SU 1 BP 175 EP 186 DI 10.1007/s11136-007-9190-8 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 194VJ UT WOS:000248371600015 PM 17530449 ER PT J AU Balonov, MI Anspaugh, LR Bouville, A Likhtarev, IA AF Balonov, M. I. Anspaugh, L. R. Bouville, A. Likhtarev, I. A. TI Contribution of internal exposures to the radiological consequences of the Chernobyl accident SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT Workshop on Internal Dosimetry CY OCT 02-05, 2006 CL Montpellier, FRANCE ID SHORT-LIVED RADIOIODINES; BYELARUS; UKRAINE; I-131; RECONSTRUCTION; CS-137 AB The main pathways leading to exposure of members of the general public due to the Chernobyl accident were external exposure from radionuclides deposited on the ground and ingestion of contaminated terrestrial food products. The collective dose to the thyroid was nearly 1.5 million man Gy in Belarus, Russia and Ukraine with nearly half received by children and adolescents. The collective effective dose received in 1986-2005 by similar to five million residents living in the affected areas of the three countries was similar to 50 000 man Sv with similar to 40% from ingestion. That contribution might have been larger if countermeasures had not been applied. The main radionuclide contributing to both external and internal effective dose is Cs-137 with smaller contributions of Cs-134 and Sr-90 and negligible contribution of transuranic elements. The major demonstrated radiation-caused health effect of the Chernobyl accident has been an elevated incidence of thyroid cancer in children. C1 [Balonov, M. I.] IAEA, A-1400 Vienna, Austria. [Anspaugh, L. R.] Univ Utah, Henderson, NV 89077 USA. [Bouville, A.] NCI, Bethesda, MD 20892 USA. [Likhtarev, I. A.] Ukrainian Ctr Radiat Med, UA-04050 Kiev, Ukraine. RP Balonov, MI (reprint author), IAEA, Wagramer Str 5,POB 100, A-1400 Vienna, Austria. EM m.balonov@inca.org NR 13 TC 10 Z9 10 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2007 VL 127 IS 1-4 SI SI BP 491 EP 496 DI 10.1093/rpd/ncm301 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 314WP UT WOS:000256840200103 PM 17977893 ER PT J AU Drozdovitch, V Maceika, E Khrouch, V Zvonova, I Vlasov, O Bouville, A Cardis, E AF Drozdovitch, V. Maceika, E. Khrouch, V. Zvonova, I. Vlasov, O. Bouville, A. Cardis, E. TI Uncertainties in individual doses in a case-control study of thyroid cancer after the Chernobyl accident SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT Workshop on Internal Dosimetry CY OCT 02-05, 2006 CL Montpellier, FRANCE ID I-131; RISK AB Individual radiation doses to the thyroid were reconstructed for 2239 subjects of a case-control study of thyroid cancer among young people that was carried out in regions of Belarus and Russia contaminated by radioactive fallout from the Chernobyl accident. Although the process of dose reconstruction provides a point estimate of each subject's dose, it is obvious that there is uncertainty associated with these dose calculations. The following main sources of uncertainty in the estimated individual doses were identified: (1) shared and unshared errors associated with parameters of the dosimetry model; and (2) unshared errors that are associated with the variability, reliability and ability of information from the personal interviews. Besides setting up proper distributions for the parameters of the dosimetry model, inter-individual correlations were also defined to take into account shared errors. By the application of Monte Carlo simulations, a set of approximately log-normally distributed thyroid doses was obtained for each subject; the geometric standard deviations of the distributions are found to vary among individuals from 1.7 to 3.7. C1 [Maceika, E.] Lithuania Acad Sci, Inst Phys, LT-232600 Vilnius, Lithuania. [Khrouch, V.] Minist Publ Hlth Russia, Inst Biophys, State Res Ctr, Moscow, Russia. [Zvonova, I.] Inst Radiat Hyg, St Petersburg, Russia. [Vlasov, O.] Med Radiol Res Ctr, Obninsk, Russia. [Bouville, A.] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Drozdovitch, V.; Cardis, E.] Int Agcy Res Canc, F-69372 Lyon, France. RP Drozdovitch, V (reprint author), NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov RI Cardis, Elisabeth/C-3904-2017; OI Maceika, Evaldas/0000-0002-9251-6789 NR 8 TC 9 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2007 VL 127 IS 1-4 SI SI BP 540 EP 543 DI 10.1093/rpd/ncm360 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 314WP UT WOS:000256840200113 PM 17634207 ER PT J AU Drozdovitch, V Bouville, A Chobanova, N Filistovic, V Ilus, T Kovacic, M Malatova, I Moser, M Nedveckaite, T Volkle, H Cardis, E AF Drozdovitch, V. Bouville, A. Chobanova, N. Filistovic, V. Ilus, T. Kovacic, M. Malatova, I. Moser, M. Nedveckaite, T. Voelkle, H. Cardis, E. TI Radiation exposure to the population of Europe following the Chernobyl accident SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID THYROID-CANCER; LONG-TERM; EXTERNAL RADIATION; CS-137 DEPOSITION; INTERNAL EXPOSURE; FALLOUT; UKRAINE; BYELARUS; CONTAMINATION; RUSSIA AB On the occasion of the 20th anniversary of the Chernobyl accident an attempt has been made to evaluate the impact of the Chernobyl accident on the global burden of human cancer in Europe. This required the estimation of radiation doses in each of the 40 European countries. Dose estimation was based on the analysis and compilation of data either published in the scientific literature or provided by local experts. Considerable variability has been observed in exposure levels among the European populations. The average individual doses to the thyroid from the intake of 1311 for children aged 1 y were found to vary from similar to 0.01 mGy in Portugal up to 750 mGy in Gomel Oblast (Belarus). Thyroid doses to adults were consistently lower than the doses received by young children. The average individual effective doses from external exposure and ingestion of long-lived radiocaesium accrued in the period 1986-2005 varied from similar to 0 in Portugal to similar to 10 mSv in Gomel Oblast (Belarus) and Bryansk Oblast (Russia). The uncertainties in the dose estimates were subjectively estimated on the basis of the availability and reliability of the radiation data that were used for dose reconstruction in each country. C1 Int Agcy Res Canc, F-69372 Lyon 08, France. DHHS, NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Ctr Radiobiol & Radiat Protect, Sofia, Bulgaria. Inst Phys, LT-2053 Vilnius, Lithuania. STUK & Radiat & Nucl Safety Author, FIN-00881 Helsinki, Finland. Univ Zagreb, Gen Hosp Sveti Duh, ENT, Dept Head & Neck Surg, Zagreb 10000, Croatia. Natl Radiat Protect Inst, Prague 10000 10, Czech Republic. Swiss Fed Off Publ Hlth, Radiat Protect, CH-3003 Bern, Switzerland. Univ Fribourg, CH-1700 Fribourg, Switzerland. RP Drozdovitch, V (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM drozdovitch@iarc.fr RI Cardis, Elisabeth/C-3904-2017 NR 79 TC 13 Z9 13 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2007 VL 123 IS 4 BP 515 EP 528 DI 10.1093/rpd/ncl528 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 181XU UT WOS:000247470500015 PM 17229780 ER PT J AU Ghosh, G Li, G Myung, K Hendrickson, EA AF Ghosh, Goutam Li, Gang Myung, Kyungjae Hendrickson, Eric A. TI The lethality of Ku86 (XRCC5) loss-of-function mutations in human cells is independent of p53 (TP53) SO RADIATION RESEARCH LA English DT Article ID STRAND BREAK REPAIR; DEPENDENT PROTEIN-KINASE; DNA-LIGASE IV; TELOMERE LENGTH MAINTENANCE; END-BINDING-ACTIVITY; HUMAN SOMATIC-CELLS; X-RAY RESISTANCE; V(D)J RECOMBINATION; IONIZING-RADIATION; HOMOLOGOUS RECOMBINATION AB Ku86 is one of the two regulatory subunits of the DNA-PK (DNA-dependent protein kinase) complex that is required for DNA double-strand break repair in mammalian cells. In a previous study, by means of somatic gene targeting, we generated human cell lines deficient in Ku86 (XRCC5). Heterozygous human Ku86 cells exhibited a wide array of haploin-sufficient phenotypes, including sensitivity to ionizing radiation, defects in DNA-PK and DNA end-binding activities, elevated levels of p53 (TP53) and gamma-112AX foci, and a defect in cell proliferation with an increase in the frequency of aneuploid cells. Here we demonstrate that the overexpression of a human Ku86 cDNA complemented the deficiencies of these cells to wild-type levels. In contrast, Ku86 overexpression only partially rescued the telomere defects characteristic of Ku86 heterozygous cells and did not rescue their genetic instability. Additionally, in stark contrast to every other species described to date, we had shown earlier that homozygous human Ku86(-/-) cells are inviable, because they undergo 8 to 10 rounds of cell division before succumbing to apoptosis. The tumor suppressor protein p53 regulates the DNA damage response in mammalian cells and triggers apoptosis in the face of excessive DNA damage. Correspondingly, ablation of p53 expression has repeatedly been shown to significantly ameliorate the pathological effects of loss-of-function mutations for a large number of DNA repair genes. Surprisingly, however, even in a p53-null genetic background, the absence of Ku86 proved lethal. Thus the gene encoding Ku86 (XRCC5) is an essential gene in human somatic cells, and its absence cannot be suppressed by the loss of p53 function. These results suggest that Ku86 performs an essential role in telomere maintenance in human cells. (c) 2007 by Radiation Research Society. C1 Univ Minnesota, Sch Med, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Hendrickson, EA (reprint author), Univ Minnesota, Sch Med, Dept Biochem Mol Biol & Biophys, 6-155 Jackson Hall,321 Church St SE, Minneapolis, MN 55455 USA. EM hendr064@umn.edu FU NCI NIH HHS [P30 CA077598-09]; NHLBI NIH HHS [HL079559]; NIGMS NIH HHS [GM069576] NR 62 TC 7 Z9 7 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2007 VL 167 IS 1 BP 66 EP 79 DI 10.1667/RR0692.1 PG 14 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 123HX UT WOS:000243288100006 PM 17214517 ER PT J AU Avila, NA Dwyer, AJ Rabel, A Moss, J AF Avila, Nilo A. Dwyer, Andrew J. Rabel, Antoinette Moss, Joel TI Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: Comparison of CT features SO RADIOLOGY LA English DT Article ID MICRONODULAR PNEUMOCYTE HYPERPLASIA; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; LYMPHANGIOMYOMATOSIS; ANGIOMYOLIPOMAS; HAMARTOMAS; FREQUENCY; MUTATIONS; WOMEN; TSC2 AB Purpose: To retrospectively compare the frequencies of computed tomographic (CT) findings in patients with lymphangio-leiomyomatosis (LAM) and patients with tuberous sclerosis complex (TSC) and LAM. Materials and Methods: Institutional review board approval and informed consent were obtained for the HIPAA-compliant study. In 256 patients with LAM (mean age, 44 years) and 67 patients with TSC/LAM (mean age, 40 years), CT scans of the chest, abdomen, and pelvis were reviewed by a single radiologist. The fraction or lung involvement with cysts was estimated from high-spatial-resolution CT scans. Other findings assessed included noncalcified pulmonary nodules, pleural effusion, thoracic duct dilatation, hepatic and renal angio-myolipomas (AMLs), lymphangioleiomyoma (LALM), ascites, nephrectomy, and renal embolization. Confidence intervals and hypothesis tests of differences in frequencies, comparison of age quartiles, RIDIT analysis, analysis of variance, and correlation coefficients were used in the statistical analysis. Results: Patients with LAM had more extensive lung involvement (RIDIT score, 0.36) and higher frequency of LALM (29% vs 9%, P < .001), thoracic duct dilatation (4% vs 0, P = .3), pleural effusion (12% vs 6%, P = .2), or ascites (10% vs 6%, P = .3). Patients with TSC/LAM had higher frequency of noncalcified pulmonary nodules (12% vs 1%, P < .01), hepatic (33% vs 2%, P < .001) and renal (93% vs 32%, P < .001) AMLs, nephrectomy (25% vs 7%, P < .001), or renal artery embolization (9% vs 2%,,P < .05). Conclusion: The extent of lung disease is greater in LAM than TSC/LAM. Hepatic and renal AMLs and noncalcified lung nodules are more common in TSC/LAM, while lymphatic involvement-thoracic duct dilatation, chylous pleural effusion, ascites, and LALM-is more common in LAM. (c) RSNA, 2006. C1 NHLBI, Diagnost Radiol Dept, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Branch, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), NHLBI, Diagnost Radiol Dept, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C-660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. EM navila@nih.gov FU Intramural NIH HHS [Z01 HL002541-12] NR 30 TC 45 Z9 60 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2007 VL 242 IS 1 BP 277 EP 285 DI 10.1148/radiol.2421051767 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 131BH UT WOS:000243842500034 PM 17105849 ER PT J AU Parise, RA Egorin, MJ Eiseman, JL Joseph, E Covey, JM Beumer, JH AF Parise, Robert A. Egorin, Merrill J. Eiseman, Julie L. Joseph, Erin Covey, Joseph M. Beumer, Jan H. TI Quantitative determination of the cytidine deaminase inhibitor tetrahydrouridine (THU) in mouse plasma by liquid chromatography/electrospray ionization tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID DNA METHYLTRANSFERASE INHIBITOR; CYTOSINE-ARABINOSIDE; CLINICAL-PHARMACOLOGY; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; NSC-112907; MICE AB A number of anticancer drugs are cytidine analogues that undergo metabolic deactivation catalyzed by cytidine deaminase (CD). 3,4,5,6-Tetrahydrouridine (THU) is a potent inhibitor of CD, by acting as a transition-state analogue of its natural substrate cytidine. However, to date its pharmacokinetic properties have not been fully characterized, which has impaired its optimal preclinical evaluation and clinical use. We report a liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay for the sensitive, accurate and precise quantitation of THU in mouse plasma. Validation was performed according to FDA guidelines. The assay employed deuterated THU as the internal standard and an acetonitrile protein precipitation step. Separation, based on hydrophilic interaction chromatography, was achieved with an amino column and an isocratic mobile phase of 0.1% formic acid in acetonitrile and water followed by a wash. Chromatographic separation was followed by positive-mode electrospray ionization MS/MS detection in the multiple reaction monitoring (MRM) mode. The assay was accurate (92.5-109.9%) and precise (2.1-9.0%) in the concentration range of 0.2-50 mu g/mL. Recovery from plasma was near-complete (92.9-119.3%) and ion suppression was negligible (-17.5 to -0.2%). Plasma freeze/thaw stability (93.1-102.1%), stability for 3 months at -80 degrees C (99.5-110.9%), and stability for 4h at room temperature (92.1-102.4%) were all in order. This assay is currently being used to quantitate THU in ongoing pharmacokinetic studies. In addition, the assay is expected to be a useful tool in any future studies involving co-administration of THU with cytidine analogues. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. Natl Canc Inst, Div Canc Treatment & Diag, Dev Therapeut Program, Toxicol & Pharmacol Branch, Rockville, MD 20852 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, 517 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [N01-CM-52202] NR 23 TC 8 Z9 8 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2007 VL 21 IS 13 BP 1991 EP 1997 DI 10.1002/rcm.3054 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 181WR UT WOS:000247467500006 PM 17526067 ER PT J AU Venkatesh, S Tomer, KB Sharp, JS AF Venkatesh, Sanjay Tomer, Kenneth B. Sharp, Joshua S. TI Rapid identification of oxidation-induced conformational changes by kinetic analysis SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID MASS-SPECTROMETRY; REACTIVE OXYGEN; PHOTOCHEMICAL OXIDATION; RADICAL PROBE; RHEUMATOID-ARTHRITIS; METHIONINE RESIDUES; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; PROTEIN OXIDATION; DNA-DAMAGE AB Protein oxidation by reactive oxygen species is known to result in changes in the structure and function of the oxidized protein. Many proteins can tolerate multiple oxidation events before altering their conformation, while others suffer gross changes in conformation after a single oxidation event. Additionally, reactive oxygen species have been used in conjunction with mass spectrometry to map the accessible surface of proteins, often after verification that the oxidations do not alter the conformation. However, detection of oxidation-induced conformational changes by detailed kinetic oxidation analysis of individual proteolytic peptides or non-mass spectrometric analysis is labor-intensive and often requires significant amounts of sample. In this work, we describe a methodology to detect oxidation-induced conformational changes in proteins via direct analysis of the intact protein. The kinetics of addition of oxygen to unmodified protein are compared with the kinetics of addition of oxygen to the mono-oxidized protein. These changes in the rate of oxidation of the oxidized versus the non-oxidized protein are strongly correlated with increases in the random coil content as measured by the molar ellipticity at 198 nm. This methodology requires only small amounts of protein, and can be done rapidly without additional sample handling or derivatization. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Sharp, JS (reprint author), Univ Georgia, Complex Carbohydrate Res Ctr, 315 Riverbend Rd, Athens, GA 30602 USA. EM jsharp@ccrc.uga.edu RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS; NCRR NIH HHS [RR005351-18] NR 81 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2007 VL 21 IS 23 BP 3927 EP 3936 DI 10.1002/rcm.3291 PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 236FA UT WOS:000251287200020 PM 17985324 ER PT J AU Boyce, CA Heinssen, R Ferrell, CB Nakamura, RK AF Boyce, Cheryl A. Heinssen, Robert Ferrell, Courtney B. Nakamura, Richard K. BE Tsuang, MT Stone, WS Lyons, MJ TI Prospects for the Prevention of Mental Illness Integrating Neuroscience and Behavior SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; PARENTAL PSYCHIATRIC HISTORY; RANDOMIZED CONTROLLED-TRIAL; PERINATAL FACTORS; RISK-FACTORS; SOCIOECONOMIC-STATUS; AUTISM; CHILDREN; DEPRESSION; SYMPTOMS C1 [Boyce, Cheryl A.] NIMH, Div Mental Disorders, Bethesda, MD 20892 USA. [Boyce, Cheryl A.] NIMH, Abuse & Neglect Program, Div Pediat Translat Res & Treatment Dev, Bethesda, MD 20892 USA. [Heinssen, Robert] NIMH, Psychot Disorders Res Program, Adult Psychopathol & Prevent Res Program, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. [Ferrell, Courtney B.] NIMH, Individual Fellowships Program, Div Pediat Translat Res & Treatment Dev, Bethesda, MD 20892 USA. [Nakamura, Richard K.] NIMH, Off Director, Bethesda, MD 20892 USA. RP Boyce, CA (reprint author), NIMH, Div Mental Disorders, Bethesda, MD 20892 USA. NR 62 TC 1 Z9 1 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 241 EP 261 PG 21 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300011 ER PT J AU Volkow, ND Li, TK AF Volkow, Nora D. Li, Ting-Kai BE Tsuang, MT Stone, WS Lyons, MJ TI Drugs and Alcohol Treating and Preventing Abuse, Addiction, and Their Medical Consequences SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Article; Book Chapter ID PRENATAL COCAINE EXPOSURE; SUBSTANCE USE DISORDERS; GAMMA-VINYL GABA; GENE-EXPRESSION; UNITED-STATES; HUMAN BRAIN; FOLLOW-UP; CONTINGENCY MANAGEMENT; OUTPATIENT TREATMENT; COST-EFFECTIVENESS C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. [Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD USA. NR 125 TC 4 Z9 4 U1 3 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 263 EP 296 PG 34 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300012 ER PT J AU Li, TK Witt, E Hewitt, BG AF Li, Ting-Kai Witt, Ellen Hewitt, Brenda G. BE Tsuang, MT Stone, WS Lyons, MJ TI Alcoholism Developmental Patterns of Drinking and Prevention of Alcohol Use Disorders SO RECOGNITION AND PREVENTION OF MAJOR MENTAL AND SUBSTANCE USE DISORDERS LA English DT Article; Book Chapter ID NATIONAL EPIDEMIOLOGIC SURVEY; MONKEYS MACACA-FASCICULARIS; SEX-DIFFERENCES; UNITED-STATES; NEUROACTIVE STEROIDS; ETHANOL-CONSUMPTION; BRIEF INTERVENTIONS; C57BL/6 MICE; RISK-FACTORS; PERSONALITY-DISORDERS C1 [Li, Ting-Kai; Witt, Ellen; Hewitt, Brenda G.] NIAAA, NIH, Bethesda, MD USA. RP Li, TK (reprint author), NIAAA, NIH, Bethesda, MD USA. NR 69 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-308-2 PY 2007 BP 297 EP 316 PG 20 WC Psychology, Clinical; Substance Abuse; Psychiatry; Psychology SC Psychology; Substance Abuse; Psychiatry GA BWL81 UT WOS:000294204300013 ER PT J AU Mezey, E AF Mezey, Eva TI Bone marrow-derived stem cells in neurological diseases: stones or masons? SO REGENERATIVE MEDICINE LA English DT Review DE adult stem cells; bone marrow derived cells; cell therapy; neurological diseases; neuroprotection ID TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; FOCAL CEREBRAL-ISCHEMIA; COLONY-STIMULATING FACTOR; PROMOTE FUNCTIONAL RECOVERY; CHRONIC PARAPLEGIC RATS; STROMAL CELLS; INTRACEREBRAL TRANSPLANTATION; THERAPEUTIC BENEFIT; HEMATOPOIETIC-CELLS AB In spite of the commonly held belief that 'the brain does not regenerate', it is now accepted that postnatal neurogenesis does occur. Thus, one wonders whether cellular-replacement therapy might be used to heal the brain in diseases caused by neuronal cell loss. The existence of neural stem cells has been demonstrated by many scientists and is now generally accepted. The exact role of these cells, how their numbers are regulated and how they participate in CNS and spinal cord regeneration in postnatal life are still not well known. There are many reviews summarizing work on these cells; consequently, I will focus instead on other cells that may participate in postnatal neurogenesis: bone marrow-derived stem cells. The possibility that bone marrow-derived stem cells populate the CNS and differentiate into various neural elements is certainly not universally accepted. C1 NIDCR, CSDB, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NIDCR, CSDB, NIH, 49 Convent Dr,Bldg 49,5A76, Bethesda, MD 20892 USA. EM mezeye@mail.nih.gov FU Intramural NIH HHS NR 103 TC 20 Z9 22 U1 1 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 J9 REGEN MED JI Regen. Med. PD JAN PY 2007 VL 2 IS 1 BP 37 EP 49 DI 10.2217/17460751.2.1.37 PG 13 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA 142UP UT WOS:000244676000014 PM 17465774 ER PT S AU Ben-Dor, A Lipson, D Tsalenko, A Reimers, M Baumbusch, LO Barrett, MT Weinstein, JN Borresen-Dale, AL Yakhini, Z AF Ben-Dor, Amir Lipson, Doron Tsalenko, Anya Reimers, Mark Baumbusch, Lars O. Barrett, Michael T. Weinstein, John N. Borresen-Dale, Anne-Lise Yakhini, Zohar BE Speed, T Huang, H TI Framework for identifying common aberrations in DNA copy number data SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th Annual International Conference on Research in Computational Molecular Biology CY APR 21-25, 2007 CL Oakland, CA SP AFFYMETRIX, BioNovo, Genentech, Int Soc Computat Biol, Helicos, Merck, Roche, Wyeth, ARIADNE, QB3 Calif Inst Quantitat Biomed Res DE CGH; cancer; microarray data analysis; common aberrations; breast cancer; NCI-60 ID ARRAY-CGH DATA; COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION PATTERNS; HIGH-RESOLUTION ANALYSIS; CANCER-CELL-LINES; BREAST-CANCER; OLIGONUCLEOTIDE MICROARRAYS; SEGMENTATION; NEOPLASMS; SUBTYPES AB High-resolution array comparative genomic hybridization (aCGH) provides exon-level mapping of DNA aberrations in cells or tissues. Such aberrations are central to carcinogenesis and, in many cases, central to targeted therapy of the cancers. Some of the aberrations are sporadic, one-of-a-kind changes in particular tumor samples; others occur frequently and reflect common themes in cancer biology that have interpretable, causal ramifications. Hence, the difficult task of identifying and mapping common, overlapping genomic aberrations (including amplifications and deletions) across a sample set is an important one-, it can provide insight for the discovery of oncogenes, tumor suppressors, and the mechanisms by which they drive cancer development. In this paper we present an efficient computational framework for identification and statistical characterization of genomic aberrations that are common to multiple cancer samples in a CGH data set. We present and compare three different algorithmic approaches within the context of that framework. Finally, we apply our methods to two datasets - a collection of 20 breast cancer samples and a panel of 60 diverse human tumor cell lines (the NCI-60). Those analyses identified both known and novel common aberrations containing cancer-related genes. The potential impact of the analytical methods is well demonstrated by new insights into the patterns of deletion of CDKN2A (p16), a tumor suppressor gene crucial for the genesis of many types of cancer. C1 [Ben-Dor, Amir; Tsalenko, Anya; Barrett, Michael T.; Yakhini, Zohar] Agilent Labs, Santa Clara, CA 95051 USA. [Lipson, Doron; Yakhini, Zohar] Technion, Dept Comp Sci, Haifa, Israel. [Reimers, Mark; Weinstein, John N.] NCI, Bethesda, MD USA. [Baumbusch, Lars O.] Inst Canc Res, Dept Genet, Rikshosp Radiumhosp Med Ctr, Bethesda, MD USA. [Barrett, Michael T.] Translat Genom Res Inst, Phoenix, AZ USA. RP Ben-Dor, A (reprint author), Agilent Labs, Santa Clara, CA 95051 USA. EM amir_ben-dor@agilent.com NR 32 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-71680-8 J9 LECT NOTES COMPUT SC PY 2007 VL 4453 BP 122 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Information Systems SC Biochemistry & Molecular Biology; Computer Science GA BGI34 UT WOS:000247321200009 ER PT S AU Inbar, Y Schneidman-Duhovny, D Dror, O Nussinov, R Wolfson, HJ AF Inbar, Yuval Schneidman-Duhovny, Dina Dror, Oranit Nussinov, Ruth Wolfson, Haim J. BE Speed, T Huang, H TI Deterministic pharmacophore detection via multiple flexible alignment of drug-like molecules SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 11th Annual International Conference on Research in Computational Molecular Biology CY APR 21-25, 2007 CL Oakland, CA SP AFFYMETRIX, BioNovo, Genentech, Int Soc Computat Biol, Helicos, Merck, Roche, Wyeth, ARIADNE, QB3 Calif Inst Quantitat Biomed Res DE computer-aided drug design (CADD); rational drug discovery; 3D molecular similarity; 3D molecular superposition ID SIZED MOLECULES; IDENTIFICATION; SUPERPOSITION; 3D; SETS; SUBSTRUCTURES; SEARCH; DESIGN AB We present a novel highly efficient method for the detection of a pharmacophore from a set of ligands/drugs that interact with a target receptor. A pharmacophore is a spatial arrangement of physicochemical features in a ligand that is responsible for the interaction with a specific receptor. In the absence of a known 3D receptor structure, a pharmacophore can be identified from a multiple structural alignment of the ligand molecules. The key advantages of the presented algorithm are: (a) its ability to multiply align flexible ligands in a deterministic manner, (b) its ability to focus on subsets of the input ligands, which may share a large common substructure, resulting in the detection of both outlier molecules and alternative binding modes, and (c) its computational efficiency, which allows to detect pharmacophores shared by a large number of molecules on a standard PC. The algorithm was extensively tested on a dataset of almost 80 ligands acting on 12 different receptors. The results, which were achieved using a standard default parameter set, were consistent with reference pharmacophores that were derived from the bound ligand-receptor complexes. The pharmacophores detected by the algorithm are expected to be a key component in the discovery of new leads by screening large drug-like molecule databases. C1 [Inbar, Yuval; Schneidman-Duhovny, Dina; Dror, Oranit; Wolfson, Haim J.] Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Sackler Fac Med, Tel Aviv, Israel. [Nussinov, Ruth] NCI Frederick, SAIC Frederick Inc, Ctr Canc Res Nanobiol, Frederick, MD USA. RP Inbar, Y (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM inbaryuv@tau.ac.il FU Eshkol Fellowship; Israeli Ministry of Science; Israel Science Foundation [281/05]; Hermann Minkowski-Minerva Center for Geometry at TAU; NIAID; NIH [1UC1AI067231]; Binational US-Israel Science Foundation (BSF); National Cancer Institute; National Institutes of Health [N01-CO-12400]; Department of Health and Human Services; U.S. Government; Intramural Research Program of the NIH; Center for Cancer Research FX We want to thank D. Fishlovitch, A. Oron and H. Senderowitz for useful advice. The research of O. Dror and Y. Inbar has been supported by the Eshkol Fellowship funded by the Israeli Ministry of Science.; The research of H.J. Wolfson has been supported in part by the Israel Science Foundation (grant no. 281/05) and by the Hermann Minkowski-Minerva Center for Geometry at TAU. The research of H.J. Wolfson and R. Nussinov has been supported by the NIAID, NIH (grant No. 1UC1AI067231), and by the Binational US-Israel Science Foundation (BSF). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number N01-CO-12400. The content of this publication does not necessarily reflect the view of the policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-71680-8 J9 LECT NOTES COMPUT SC PY 2007 VL 4453 BP 412 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Information Systems SC Biochemistry & Molecular Biology; Computer Science GA BGI34 UT WOS:000247321200029 ER PT J AU Chan, CC Collins, ABD Chew, EY AF Chan, Chi-Chao Collins, Atif Ben Daniel Chew, Emily Y. TI Molecular pathology of eyes with von Hippel-Lindau (VHL) disease - A review SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; RECEPTOR INHIBITOR SU5416; SMOOTH-MUSCLE-CELLS; RETINAL HEMANGIOBLASTOMA; ERYTHROPOIETIN RECEPTOR; STEM-CELLS; EXPRESSION; THERAPY AB Background: von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited systemic cancer syndrome. Recently, many advances have contributed to the understanding of VHL pathophysiology. Methods: In this article we review recent developments and summarize our findings in VHL molecular pathology related to retinal and optic nerve diseases. Results: Loss of heterozygosity (LOH) within the VHL gene is detected in the stromal cells surrounding the capillary endothelial cells and admixed with glial cells in ocular hemangioblastomas. This finding is in line with similar findings in VHL-associated CNS hemangioblastoma and renal clear cell carcinomas. Increases of vascular endothelial growth factor (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular hemangioblastomas. Interestingly, tumorlet cells, which are composed of poorly differentiated small cells with prominent dark nuclei and little cytoplasm, as well as several stem cell markers, such as erythropoietin (Epo), Epo receptor (EpoR), and CD133, are present in ocular VHL lesions. CXCR4, a CXC chemokine receptor is also expressed in retinal VHL hemangioblastomas. Conclusions: These findings imply that VHL cells with LOH of the tumor suppressor gene, most likely originate from a hematopoietic/vascular lineage. Targeting these proteins and ischemic factors, not VEGF alone, may be a potential therapeutic approach for VHL-associated ocular hemangioblastomas. C1 NIH, NEI, Bethesda, MD 20892 USA. NIH, HHMI, Res Scholars Program, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NIH, NEI, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM Chanc@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999, Z01 EY000222-22] NR 56 TC 26 Z9 28 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2007 VL 27 IS 1 BP 1 EP 7 DI 10.1097/01.iae.0000244659.62202.ee PG 7 WC Ophthalmology SC Ophthalmology GA 175AS UT WOS:000246985000001 PM 17218907 ER PT J AU Lenfant, C AF Lenfant, Claude TI Can prevention of hypertension work? SO REVISTA LATINOAMERICANA DE HIPERTENSION LA English DT Article DE prevention; hypertesion ID WEIGHT-LOSS INTERVENTION; HIGH BLOOD-PRESSURE; SODIUM REDUCTION; NONPHARMACOLOGIC INTERVENTIONS; DIETARY-SODIUM; PHASE-II; TRIALS AB Over the years, many controlled clinical trials have demonstrated the efficacy of pharmacological treatment of hypertension. However, such treatment has its shortcomings. First, it usually requires a life-long commitment to therapy because, while this approach can control hypertension and reduce its consequences, it does not cure the condition. Next, the cost of pharmacological interventions can be very high and, thus, prohibitive for poorer individuals and nations. In addition, many patients experience problems with compliance and adherence, which almost certainly contribute to the low level of hypertension control that is so widely observed. Finally, the pharmacological approach requires a strong commitment by public health officials to detection and treatment of hypertension if there is to be any hope of limiting this condition's impact. All of these negative considerations are compounded by the fact that the prevalence of hypertension is increasing worldwide. For all these reasons, non-pharmacological interventions should be implemented to prevent or delay the occurrence of hypertension. C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD USA. RP Lenfant, C (reprint author), POB 83027, Gaithersburg, MD 20883 USA. EM lenfantc@prodigy.net NR 16 TC 0 Z9 0 U1 0 U2 1 PU SOC LATINOAMERICANA HIPERTENSION PI SAN JOSE PA ESCUELA MEDICINA JOSE MARIA VARGAS, CATEDRA FARMACOLOGIA, PISO 3 ESQ-PIRINEOUS, SAN JOSE, 00000, VENEZUELA SN 1856-4550 J9 REV LATINOAM HIPERTE JI Rev. Latinoam. Hipertens. PY 2007 VL 2 IS 1 BP 11 EP 14 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 276JA UT WOS:000254135900002 ER PT J AU Lenfant, C AF Lenfant, Claude TI Do sleep disorders have an impact on blood pressure? SO REVISTA LATINOAMERICANA DE HIPERTENSION LA English DT Article ID POSITIVE AIRWAY PRESSURE; ESSENTIAL-HYPERTENSION; APNEA PATIENTS; WEIGHT; ASSOCIATION; POPULATION; PREVALENCE; OBESITY; BURDEN; HEALTH C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), POB 83027, Gaithersburg, MD 20883 USA. EM lenfantc@prodigy.net NR 23 TC 0 Z9 0 U1 0 U2 0 PU SOC LATINOAMERICANA HIPERTENSION PI SAN JOSE PA ESCUELA MEDICINA JOSE MARIA VARGAS, CATEDRA FARMACOLOGIA, PISO 3 ESQ-PIRINEOUS, SAN JOSE, 00000, VENEZUELA SN 1856-4550 J9 REV LATINOAM HIPERTE JI Rev. Latinoam. Hipertens. PY 2007 VL 2 IS 2 BP 44 EP 48 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 283CR UT WOS:000254614700002 ER PT S AU Costa, RM AF Costa, Rui M. BE Balleine, BW Doya, K ODoherty, J Sakagami, M TI Plastic corticostriatal circuits for action learning - What's dopamine got to do with it? SO REWARD AND DECISION MAKING IN CORTICOBASAL GANGLIA NETWORKS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Reward and Decision-Making in Corticobasal Ganglia Networks CY JUN 01-04, 2006 CL Lake Arrowhead, CA SP Univ Calif, Los Angeles, Brain Res Inst, Okinawa Inst Sci & Technol, Calif Inst Technol, Tamagawa Univ Res Inst DE dopamine; striatum; synchrony; oscillatory activity; skill learning; reinforcement; action selection; goal-directed actions; habits ID PRIMARY MOTOR CORTEX; LOCAL-FIELD POTENTIALS; TERM SYNAPTIC DEPRESSION; MEDIUM SPINY NEURONS; STRIATAL CHOLINERGIC INTERNEURONS; POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA; PARKINSONS-DISEASE; HABIT FORMATION; NUCLEUS-ACCUMBENS AB Reentrant corticobasal ganglia circuits are important for voluntary action and for action selection. In vivo and ex vivo studies show that these circuits can exhibit a plethora of short- and long-lasting plastic changes. Convergent evidence at the molecular, cellular, and circuit levels indicates that corticostriatal circuits are involved in the acquisition and automatization of novel actions. There is strong evidence that activity in corticostriatal circuits changes during the learning of novel actions, but the plastic changes observed during the early stages of learning a novel action are different than those observed after extensive training. A variety of studies indicate that the neural mechanisms and the corticostriatal subcircuits involved in the initial acquisition of actions and skills differ from those involved in their automatization or in the formation of habits. Dopamine, a critical modulator of short- and long-term plasticity in corticostriatal circuits, is differentially involved in early and late stages of action learning. Changes in dopaminergic transmission have several concomitant effects in corticostriatal function, which may be important for action selection and action learning. These diverse effects may subserve different roles for dopamine in reinforcement and action learning. C1 NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Costa, RM (reprint author), NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room TS-20D,MSC 9411, Rockville, MD 20852 USA. EM costarui@mail.nih.gov OI Costa, Rui/0000-0003-0495-8374; Doya, Kenji/0000-0002-2446-6820 NR 148 TC 59 Z9 59 U1 3 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-674-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1104 BP 172 EP 191 DI 10.1196/annals.1390.015 PG 20 WC Multidisciplinary Sciences; Neurosciences; Psychology SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychology GA BGL46 UT WOS:000248194800012 PM 17435119 ER PT S AU Hikosaka, O AF Hikosaka, Okihide BE Balleine, BW Doya, K ODoherty, J Sakagami, M TI Basal ganglia mechanisms of reward-oriented eye movement SO REWARD AND DECISION MAKING IN CORTICOBASAL GANGLIA NETWORKS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Reward and Decision-Making in Corticobasal Ganglia Networks CY JUN 01-04, 2006 CL Lake Arrowhead, CA SP Univ Calif, Los Angeles, Brain Res Inst, Okinawa Inst Sci & Technol, Calif Inst Technol, Tamagawa Univ Res Inst DE saccadic eye movement; caudate nucleus; substantia nigra pars reticulata; substantia nigra pars compacta; superior colliculus; dopamine; D1 receptor; D2 receptor; GABA ID NIGRA PARS RETICULATA; MONKEY CAUDATE NEURONS; DORSOLATERAL PREFRONTAL CORTEX; SUBSTANTIA-NIGRA; DOPAMINE NEURONS; FUNCTIONAL-PROPERTIES; OCULOMOTOR FUNCTIONS; ANTICIPATORY ACTIVITY; SUPERIOR COLLICULUS; AUDITORY RESPONSES AB Expectation of reward facilitates motor behaviors that enable the animal to approach a location in space where the reward is expected. It is now known that the same expectation of reward profoundly modifies sensory, motor, and cognitive information processing in the brain. However, it is still unclear which brain regions are responsible for causing the reward-approaching behavior. One candidate is the dorsal striatum where cortical and dopaminergic inputs converge. We tested this hypothesis by injecting dopamine antagonists into the caudate nucleus (CD) while the monkey was performing a saccade task with a position-dependent asymmetric reward schedule. We previously had shown that: (1) serial GABAergic connections from the CD to the superior colliculus (SC) via the substantia nigra pars reticulata (SNr) exert powerful control over the initiation of saccadic eye movement and (2) these GABAergic neurons encode target position and are strongly influenced by expected reward, while dopaminergic neurons in the substantia nigra pars compacta (SNc) encode only reward-related information. Before injections of dopamine antagonists the latencies of saccades to a given target were shorter when the saccades were followed by a large reward than when they were followed by a small reward. After injections of dopamine D1 receptor antagonist the reward-dependent latency bias became smaller. This was due to an increase in saccade latency on large-reward trials. After injections of D2 antagonist the latency bias became larger, largely due to an increase in saccade latency on small-reward trials. These results indicate that: (1) dopamine-dependent information processing in the CD is necessary for the reward-dependent modulation of saccadic eye movement and (2) D1 and D2 receptors play differential roles depending on the positive and negative reward outcomes. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov OI Doya, Kenji/0000-0002-2446-6820 NR 102 TC 79 Z9 82 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-674-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1104 BP 229 EP 249 DI 10.1196/annals.1390.012 PG 21 WC Multidisciplinary Sciences; Neurosciences; Psychology SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychology GA BGL46 UT WOS:000248194800015 PM 17360800 ER PT J AU Jazbec, S Pantelis, C Robbins, T Weickert, T Weinberger, DR Goldberg, TE AF Jazbec, Sandra Pantelis, Christos Robbins, Trevor Weickert, Thomas Weinberger, Daniel R. Goldberg, Terry E. TI Intra-dimensional/extra-dimensional set-shifting performance in schizophrenia: Impact of distractors SO SCHIZOPHRENIA RESEARCH LA English DT Article DE CANTAB; dopamine; schizophrenia; set shifting; Wisconsin Card Sorting Test ID CARD SORTING TEST; PARKINSONS-DISEASE; PREFRONTAL CORTEX; COGNITIVE DEFICITS; EXECUTIVE FUNCTION; CAUDATE-NUCLEUS; WORKING-MEMORY; D-1 RECEPTORS; DYSFUNCTION; DEPLETION AB Background: We sought to determine if a representative group of young chronic patients with schizophrenia would demonstrate selective impairments in set shifting processes of the CANTAB Intra-dimensional/extra-dimensional (IDED) task. We predicted that patients would have prominent difficulties with Compound Discrimination (C-D) (stage of the task in which irrelevant stimuli are introduced) and Extra-Dimensional Shifting (EDS) (stage of the task in which a new stimulus dimension must be attended) on the basis of the results of cortical hypodopaminergic states in subhuman primates (for C-D) and effects of dorsolateral prefrontal cortical lesions on set shifting and prior results in schizophrenia (for EDS). Methods: We administered the IDED to 36 patients and 26 healthy controls. Additionally, we administered the Wisconsin Card Sorting Test (WCST), another test of set shifting, and a Continuous Performance Test (CPT) type task of attention to patients with schizophrenia in order to investigate which cognitive components accounted for performance difficulties at different stages of the IDED task. Results: Patients had selective difficulties oil C-D and EDS stages of the task. In schizophrenic patients early stages of the task involving the introduction and establishment of attentional set were correlated to CPT performance, while later set shifting stages were correlated with WCST categories attained. Conclusion: We found evidence that patients with schizophrenia were susceptible to introduction of unreinforced irrelevant stimuli at the C-D stage, such that the previously rewarded target stimuli no longer held hegemony as a representation. This type of processing failure may reflect difficulties in stabilizing a representation and is consistent with effects of prefrontal hypodopaminergia in primates. Secondly, "survivors" of this stage experienced marked difficulties on EDS-stage, suggestive of classic prefrontal failures. Published by Elsevier B.V. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Melbourne, St Albans, Australia. Univ Cambridge, Cambridge, England. RP Goldberg, TE (reprint author), Zucker Hillside Hosp, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM tgoldber@nshs.edu RI Pantelis, Christos/H-7722-2014 OI Pantelis, Christos/0000-0002-9565-0238 FU Medical Research Council [G0001354] NR 35 TC 46 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2007 VL 89 IS 1-3 BP 339 EP 349 DI 10.1016/j.schres.2006.08.014 PG 11 WC Psychiatry SC Psychiatry GA 128KC UT WOS:000243655600039 PM 17055703 ER PT J AU Vitiello, B Sherrill, J AF Vitiello, Benedetto Sherrill, Joel TI School-based interventions for students with attention deficit hyperactivity disorder: Research implications and prospects SO SCHOOL PSYCHOLOGY REVIEW LA English DT Editorial Material ID CHILDREN; MATTERS C1 [Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, 6001 Executive Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 13 TC 3 Z9 3 U1 0 U2 0 PU NATL ASSOC SCHOOL PSYCHOLOGISTS PI BETHESDA PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA SN 0279-6015 J9 SCHOOL PSYCHOL REV JI Sch. Psychol. Rev. PY 2007 VL 36 IS 2 BP 287 EP 290 PG 4 WC Psychology, Educational SC Psychology GA 299DV UT WOS:000255736900008 ER PT J AU Klein, HG AF Klein, Harvey G. TI Transfusion medicine in the early 21st century SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2007 VL 44 IS 1 BP 1 EP 1 DI 10.1053/j.seminhematol.2006.09.017 PG 1 WC Hematology SC Hematology GA 124KW UT WOS:000243367700001 ER PT J AU Stroncek, DF AF Stroncek, David F. TI Pulmonary transfusion reactions SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; WHITE PARTICULATE MATTER; FRESH-FROZEN PLASMA; LEUKOCYTE ANTIBODIES; NATRIURETIC PEPTIDE; BLOOD-TRANSFUSION; YERSINIA-ENTEROCOLITICA; CELL TRANSFUSION; ROUTINE STORAGE C1 NIH, Dept Transfus Med, Ctr Clin, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711m19 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 98 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2007 VL 44 IS 1 BP 2 EP 14 DI 10.1053/j.seminhematol.2006.09.014 PG 13 WC Hematology SC Hematology GA 124KW UT WOS:000243367700002 PM 17198842 ER PT J AU Alter, HJ Stramer, SL Dodd, RY AF Alter, Harvey J. Stramer, Susan L. Dodd, Roger Y. TI Emerging infectious diseases that threaten the blood supply SO SEMINARS IN HEMATOLOGY LA English DT Article ID INFLUENZA-A H5N1; WEST-NILE-VIRUS; AVIAN INFLUENZA; UNITED-STATES; TRANSFUSION; TRANSMISSION; DONORS; HUMAN-HERPESVIRUS-8; SEROPREVALENCE; REDUCTION C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Infect Dis Sect, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Sci Support Off, Rockville, MD USA. RP Alter, HJ (reprint author), NIH, Dept Transfus Med, 10 Ctr Dr,Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. EM halter@dtm.cc.nih.gov NR 33 TC 56 Z9 60 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2007 VL 44 IS 1 BP 32 EP 41 DI 10.1053/j.seminhematol.2006.09.016 PG 10 WC Hematology SC Hematology GA 124KW UT WOS:000243367700005 PM 17198845 ER PT J AU Romero, R Espinoza, J Goncalves, LF Kusanovic, JP Friel, L Hassan, S AF Romero, Roberto Espinoza, Jimmy Goncalves, Luis F. Kusanovic, Juan Pedro Friel, Lara Hassan, Sonia TI The role of inflammation and infection in preterm birth SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Review DE preterm labor; cytokines; fetal inflammatory response syndrome; chemokines; microbial invasion of the amniotic cavity ID TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; AMNIOTIC-FLUID INTERLEUKIN-6; COLONY-STIMULATING FACTOR; TOLL-LIKE RECEPTORS; INTRAUTERINE VIRAL-INFECTION; GROUP-B STREPTOCOCCI; WHITE-MATTER DAMAGE; BLOOD-CELL COUNTS; INTRAAMNIOTIC INFECTION AB Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labor and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labor, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. This article reviews the role of inflammation in preterm and term parturition. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS Hutzel Womens Hosp, Box 4,3990 John R, Detroit, MI 48201 USA. EM warfieia@mail.nih.gov FU Intramural NIH HHS NR 260 TC 350 Z9 367 U1 4 U2 26 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JAN PY 2007 VL 25 IS 1 BP 21 EP 39 DI 10.1055/s-2006-956773 PG 19 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 153FC UT WOS:000245416400005 PM 17205421 ER PT J AU Teunis, N Herdt, G AF Teunis, Niels Herdt, Gilbert BE Teunis, N Herdt, GH TI The Analysis of Sexual Inequality Introduction SO SEXUAL INEQUALITIES AND SOCIAL JUSTICE LA English DT Editorial Material; Book Chapter ID GAY; ORIENTATION; HEALTH C1 [Teunis, Niels] San Francisco State Univ, Ctr Res Gender & Sexual, San Francisco, CA 94132 USA. [Herdt, Gilbert] San Francisco State Univ, Natl Sexual Resource Ctr, San Francisco, CA USA. [Herdt, Gilbert] NIMH, Bethesda, MD USA. [Herdt, Gilbert] Stanford Univ, Stanford, CA 94305 USA. [Herdt, Gilbert] Univ Chicago, Chicago, IL 60637 USA. RP Teunis, N (reprint author), San Francisco State Univ, Ctr Res Gender & Sexual, San Francisco, CA 94132 USA. NR 102 TC 16 Z9 16 U1 0 U2 1 PU UNIV CALIFORNIA PRESS PI BERKELEY PA 2120 BERKELEY WAY, BERKELEY, CA 94720 USA BN 978-0-520-93914-1 PY 2007 BP 1 EP 30 PG 30 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA BXK29 UT WOS:000296243500002 ER PT J AU Herdt, G Russell, ST Sweat, J Marzullo, M AF Herdt, Gilbert Russell, Stephen T. Sweat, Jeffrey Marzullo, Michelle BE Teunis, N Herdt, GH TI Sexual Inequality, Youth Empowerment, and the GSA A Community Study in California SO SEXUAL INEQUALITIES AND SOCIAL JUSTICE LA English DT Article; Book Chapter C1 [Herdt, Gilbert] San Francisco State Univ, Natl Sexual Resource Ctr, San Francisco, CA 94132 USA. [Herdt, Gilbert] NIMH, Bethesda, MD USA. [Herdt, Gilbert] Stanford Univ, Stanford, CA 94305 USA. [Herdt, Gilbert] Univ Chicago, Chicago, IL 60637 USA. [Russell, Stephen T.] Univ Arizona, John & Doris Norton Sch Family & Consumer Sci, Tucson, AZ 85721 USA. RP Herdt, G (reprint author), San Francisco State Univ, Natl Sexual Resource Ctr, San Francisco, CA 94132 USA. NR 31 TC 3 Z9 4 U1 0 U2 0 PU UNIV CALIFORNIA PRESS PI BERKELEY PA 2120 BERKELEY WAY, BERKELEY, CA 94720 USA BN 978-0-520-93914-1 PY 2007 BP 233 EP 251 PG 19 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA BXK29 UT WOS:000296243500015 ER PT S AU Groll, AH Walsh, TJ AF Groll, Andreas H. Walsh, Thomas J. BE Aronson, JK TI Antifungal drugs SO SIDE EFFECTS OF DRUGS ANNUAL 29: A WORLDWIDE YEARLY SURVEY OF NEW DATA AND TRENDS IN ADVERSE DRUG REACTIONS AND INTERACTIONS SE Side Effects of Drugs Annual LA English DT Article; Book Chapter ID B LIPID COMPLEX; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; HEALTHY-SUBJECTS; PHARMACOKINETIC INTERACTION; HEMATOLOGIC MALIGNANCIES; HYDROXYLAMINE FORMATION; ESOPHAGEAL CANDIDIASIS; CANCER-PATIENTS; CYCLOSPORINE-A C1 [Groll, Andreas H.] Ctr Bone Marrow Transplantat, Infect Dis Res Program, Munster, Germany. [Groll, Andreas H.] Dept Hematol Oncol, Munster, Germany. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20891 USA. RP Groll, AH (reprint author), Ctr Bone Marrow Transplantat, Infect Dis Res Program, Munster, Germany. EM grollan@ukmuenster.de; walshtj@mail.nih.gov NR 66 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBLISHERS BV BIOMEDICAL DIVISION PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-6080 BN 978-0-08-052281-4 J9 SIDE EFFECT JI Side Eff. Drug Annu. PY 2007 VL 29 BP 280 EP 293 DI 10.1016/S0378-6080(06)29027-5 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCX07 UT WOS:000311808600028 ER PT S AU Blair, HC Sun, L Kohanski, RA AF Blair, Harry C. Sun, Li Kohanski, Ronald A. BE Zaidi, M TI Balanced regulation of proliferation, growth, differentiation, and degradation in skeletal cells SO SKELETAL BIOLOGY AND MEDICINE, PT A: ASPECTS OF BONE MORPHOGENESIS AND REMODELING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE TGF-beta; BMP; wnt; frizzled; beta-catenin; chondrocyte; parathyroid hormone; osteoclast; T lymphocyte ID TRANSCRIPTION FACTOR; ADIPOCYTE DIFFERENTIATION; OSTEOCLAST FORMATION; PARATHYROID-HORMONE; BONE-DEVELOPMENT; INDIAN HEDGEHOG; SELF-RENEWAL; STEM-CELLS; CHONDROCYTES; OSTEOBLASTS AB In cartilage and bone-producing cells, proliferation and growth are balanced with terminal differentiation. Maintaining this balance is essential for modeling, growth, and maintenance of the skeleton. Cartilage growth follows a program regulated by hormones and cytokines interacting with a counter-regulatory system in which hedgehog and parathyroid hormone (PTH)-rP signals are key elements. This maintains chondrocyte proliferation and, at specific sites, allows differentiation. Bone is produced by differentiation of mesenchymal stem cells on a scaffold of mineralizing cartilage. However, bone, once formed, is continually resorbed and replaced. Thus, maintenance of bone mass requires retention of stem cells and preosteoblasts in undifferentiated division-competent stages. Maintenance of the undifferentiated states is poorly understood, whereas the rate of osteoblast formation is regulated in part by PTH and insulin-like growth factor. The precursor pool is also subject to depletion by differentiation of mesenchymal stem cells to nonbone cells including adipocytes. In the aging skeleton, disordered balance between bone formation and resorption is in major part due to immune dysregulation that increases formation of bone-degrading osteoclasts; tumor necrosis factor (TNF)-alpha is a major intermediate in this process. C1 [Blair, Harry C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [Sun, Li] Mt Sinai Sch Med, Div Bone Metab, New York, NY USA. [Kohanski, Ronald A.] NIH, NIA, Biol Aging Program, Bethesda, MD 20892 USA. RP Blair, HC (reprint author), Univ Pittsburgh, Dept Pathol, 705 Scaife Hall, Pittsburgh, PA 15261 USA. EM hcblair@imap.pitt.edu NR 49 TC 12 Z9 12 U1 6 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-684-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1116 BP 165 EP 173 DI 10.1196/annals.1402.029 PG 9 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Orthopedics SC Endocrinology & Metabolism; Science & Technology - Other Topics; Orthopedics GA BHA44 UT WOS:000251898900012 PM 17646258 ER PT S AU Margolis, RN AF Margolis, Ronald N. BE Zaidi, M TI Nuclear receptors and bone SO SKELETAL BIOLOGY AND MEDICINE, PT A: ASPECTS OF BONE MORPHOGENESIS AND REMODELING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Conference on Skeletal Biology and Medicine CY APR 25-28, 2007 CL New York, NY SP Mt Sinai Sch Med, New York Acad Sci DE nuclear receptors; osteoporosis; Nuclear Receptor Signal Atlas; NURSA ID SIGNALING ATLAS; CIRCADIAN CLOCK; OSTEOPOROSIS; SUPERFAMILY; METABOLISM AB Nuclear receptors (NRs) represent a class of ligand-dependent and -independent transcription factors with importance to the regulation of development, reproduction, and metabolism. The emergence of new understanding of the structure, function, and role in disease of NRs provides new insights into the interaction between genetics and the environment, with NRs representing new targets for the development of therapeutic agents. NRs play key roles in bone health and contribute to our understanding of diseases and disorders that result in osteopenia and osteoporosis. The Nuclear Receptor Signaling Atlas (www.nursa.org) is an online repository of information about NRs and provides a community-wide resource designed to help catalyze new advances in biology and medicine. C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Margolis, RN (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 693, Bethesda, MD 20892 USA. EM rm76f@nih.gov NR 27 TC 0 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-684-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1116 BP 327 EP 334 DI 10.1196/annals.1402.043 PG 8 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Orthopedics SC Endocrinology & Metabolism; Science & Technology - Other Topics; Orthopedics GA BHA44 UT WOS:000251898900028 PM 17872399 ER PT J AU Applegate, B Riley, W Behar, A AF Applegate, B. Riley, W. Behar, A. TI Efficacy of a hand-held computer for the treatment of primary insomnia symptoms SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Personal Improvement Computer Syst Inc, Reston, VA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 786 BP A268 EP A269 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900787 ER PT J AU Daly, B Sloane, T Collins, B Postolache, T Weist, M AF Daly, B. Sloane, T. Collins, B. Postolache, T. Weist, M. TI School sleep/wake habits and school engagement among ethnically diverse adolescents SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Temple Univ, Philadelphia, PA 19122 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 1113 BP A383 EP A383 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224901114 ER PT J AU Picchioni, D Fukunaga, M Carr, W Braun, A Duyn, J Horovitz, S AF Picchioni, D. Fukunaga, M. Carr, W. Braun, A. Duyn, J. Horovitz, S. TI FMRI can differentiate early and late stage 1 sleep SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Walter Reed Army Inst Res, Silver Spring, MD USA. NIH, Bethesda, MD 20892 USA. Naval Med Res Ctr, Silver Spring, MD USA. RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 58 BP A20 EP A20 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900060 ER PT J AU Shaffery, J Allard, J Manaye, K Roffwarg, H AF Shaffery, J. Allard, J. Manaye, K. Roffwarg, H. TI Anatomical stress measures are not correlated with reductions in size of locus coeruleus neurons found after rem sleep deprivation SO SLEEP LA English DT Meeting Abstract CT 21st Annual Meeting of the Association-Professional-Sleep-Societies CY JUN 09-14, 2007 CL Minneapolis, MN C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2007 VL 30 SU S MA 78 BP A26 EP A27 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164HR UT WOS:000246224900080 ER PT J AU Aksu, M Demirci, S Bara-Jimenez, W AF Aksu, Murat Demirci, Sevda Bara-Jimenez, William TI Correlation between putative indicators of primary restless legs syndrome severity SO SLEEP MEDICINE LA English DT Article DE restless legs syndrome; periodic limb movement disorder; periodic movement disorder; sleep; suggested immobilization test ID SLEEP; DIAGNOSIS; EPIDEMIOLOGY; MOVEMENTS; CRITERIA AB Background and purpose: Several methods of assessing disease severity in restless legs syndrome (RLS) have been suggested. The purpose of this study was to examine the relationship between the suggested immobilization test (SIT), the International RLS Study Group rating scale (IRLS), sleep efficiency, and periodic leg movements of sleep index (PLMI). Patients and methods: Forty primary RLS patients with periodic leg movements of sleep were included in this prospective study. Study procedures were all performed during the same night, beginning with IRLS administration and following with SIT and polysomnography (PSG) evaluations, in that order. SIT was composed of two parameters: SIT mean discomfort score (SIT-MDS) and SIT periodic leg movements of wakefulness index (SIT-PLMW). PSG target measures were PLMI and sleep efficiency. Pearson's correlation was used for analysis at a P < 0.01 significance level. Results: PSG-PLMI correlated with IRLS (r = 0.462; P = 0.003) and with SIT-PLMW (r = 0.681; P = 0.0004). A correlation was also found between IRLS and SIT-MDS (r = 0.447; P = 0.004), even though SIT-PLMW and IRLS did not correlate with each other (P = 0.286). A negative correlation was found between PSG-PLMI and sleep efficiency (r = -0.435; P = 0.005). Neither SIT nor IRLS correlated with sleep efficiency. Only SIT discomfort scores from the second half of SIT correlated with SIT-PLMW (r = 0.457, P = 0.004), and they had a stronger correlation with IRLS (P = 0.003). Conclusions: This study attempted a much needed comprehensive evaluation of the relationship between various RLS severity indicators. Our findings support a strong role of motor dysfunction on sleep quality in RLS, as well as the potential use of SIT-PLMW as a sensitive indicator of RLS severity. (c) 2005 Elsevier B.V. All rights reserved. C1 Erciyes Univ, Fac Med, Dept Neurol, TR-38039 Kayseri, Turkey. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Aksu, M (reprint author), Erciyes Univ, Fac Med, Dept Neurol, TR-38039 Kayseri, Turkey. EM aksu@erciyes.edu.tr NR 22 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JAN PY 2007 VL 8 IS 1 BP 84 EP 89 DI 10.1016/j.sleep.2005.12.001 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 138YL UT WOS:000244399100013 PM 16740410 ER PT J AU Gross, GW Pancrazio, JJ AF Gross, Guenter W. Pancrazio, Joseph J. BE Knopf, GK Bassi, AS TI Neuronal Network Biosensors SO SMART BIOSENSOR TECHNOLOGY SE Optical Science and Engineering-CRC LA English DT Article; Book Chapter ID IN-VITRO; CORTICAL-NEURONS; SPINAL-CORD; COMPETITIVE ANTAGONIST; MICROELECTRODE ARRAYS; RECEPTOR-SITE; RAT-BRAIN; GABA; CLASSIFICATION; DERIVATIVES C1 [Gross, Guenter W.] Univ N Texas, Dept Biol Sci, Ctr Network Neurosci, Denton, TX 76203 USA. [Pancrazio, Joseph J.] NINDS, Ctr Neurosci, Rockville, MD USA. RP Gross, GW (reprint author), Univ N Texas, Dept Biol Sci, Ctr Network Neurosci, Denton, TX 76203 USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-0-8493-3759-8 J9 OPT SCI ENG-CRC PY 2007 VL 118 BP 177 EP 201 PG 25 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BKV99 UT WOS:000269449100008 ER PT J AU Ostir, GV Ottenbacher, KJ Fried, LP Guralnik, JM AF Ostir, Glenn V. Ottenbacher, Kenneth J. Fried, Linda P. Guralnik, Jack M. TI The effect of depressive symptoms on the association between functional status and social participation SO SOCIAL INDICATORS RESEARCH LA English DT Article DE aged; consumer participation; depression; quality of life ID NONDISABLED OLDER PERSONS; LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; LONGITUDINAL ANALYSIS; PHYSICAL-DISABILITY; WOMENS HEALTH; SUPPORT; CARE; PERFORMANCE; COMMUNITY AB The aim of the current study was to examine the interactive effects of depressive symptoms and lower extremity functioning on social participation for a group of moderately to severely disabled older women. The study used a cross-sectional community based sample, enrolled in the Women's Health and Aging Study I, randomly selected from the Centers for Medicare & Medicaid Services enrollment files for women living in the Baltimore, Maryland area. The participants were women aged 65 or older who completed the in-person interview (n = 999). After adjusting for demographics and risk factors, each unit increase in the Short Physical Performance Battery (SPPB) score was associated with a 0.31 point increase in satisfaction with social participation for the non-depressed group, and 2.04 points for the depressed group. Depressive symptoms and lower extremity functioning interact to affect satisfaction with social participation. Among women with high depressive symptoms the gradient of association with social participation increased sharply with better lower extremity function compared with non-depressed women, where the gradient of association was moderate. The findings suggest the potential value of programs that focus on improving lower extremity function among older high risk groups. C1 Univ Texas, Med Branch, Sealy Ctr Aging, Galveston, TX 77555 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Ostir, GV (reprint author), Univ Texas, Med Branch, Sealy Ctr Aging, Galveston, TX 77555 USA. EM gostir@utmb.edu FU NIA NIH HHS [K02 AG019736, K02 AG019736-02, R01 AG031178, R01 AG031178-02, R03 AG023888, R03 AG023888-01A1]; NICHD NIH HHS [K01 HD046682, K01 HD046682-01A1] NR 41 TC 6 Z9 8 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0303-8300 J9 SOC INDIC RES JI Soc. Indic. Res. PD JAN PY 2007 VL 80 IS 2 BP 379 EP 392 DI 10.1007/s11205-005-6189-9 PG 14 WC Social Sciences, Interdisciplinary; Sociology SC Social Sciences - Other Topics; Sociology GA 127BF UT WOS:000243559600006 PM 17330150 ER PT J AU Wiener, L Zobel, M Battles, H Ryder, C AF Wiener, Lori Zobel, Melissa Battles, Haven Ryder, Celia TI Transition from a pediatric HIV intramural clinical research program to adolescent and adult community-based care services: Assessing transition readiness SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE transition readiness; pediatric; adolescent; HIV; chronic illness ID HEALTH-CARE; YOUNG-ADULTS; CHRONIC ILLNESS; POSITION PAPER; YOUTH; NEEDS; MEDICINE; CHILDREN; SOCIETY; ACCESS AB As treatment options have improved, there has been a significant increase in the life expectancy of HIV-infected children and adolescents. For most adolescents, the time comes when it is appropriate to transition from pediatric care to an adult or community-based provider. In response to a program closure, a transition readiness scale was developed. A total of 39 caregivers of HIV-infected youth (ages 10-18) and 12 youth over the age of 18 years were interviewed at two time points. Barriers associated with transition were identified and addressed between visits. Transition readiness improved and state anxiety decreased significantly from the first time point to the last visit (approximately 7 months later). Not having a home social worker was the most reported concern/need identified. Barriers to transition and interventions utilized to assist with transitioning care are discussed. C1 NCI, HIV AIDS Malignancy Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Wiener, L (reprint author), NCI, HIV AIDS Malignancy Branch, Canc Res Ctr, 9000 Rockville Pike,Bldg 10 Pediatr Clin I-SE,Roo, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 33 TC 43 Z9 44 U1 3 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2007 VL 46 IS 1 BP 1 EP 19 DI 10.1300/J010v46n01_01 PG 19 WC Social Work SC Social Work GA 217NS UT WOS:000249955200001 PM 18032153 ER PT J AU BrintzenhofeSzoc, K Aron, M Jacobsen, MP Koziol, DE Callahan, C AF BrintzenhofeSzoc, Karlynn Aron, Margo Jacobsen, Mark P. Koziol, Deloris E. Callahan, Christine TI The development of the profile of adaptation to life within a medically ill population: PAL-M SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE psychosocial screening; psychosocial assessment; medical patients; social work ID CANCER-PATIENTS; BREAST-CANCER; ADJUSTMENT; DISTRESS AB The social work department at a biomedical research hospital was challenged to improve efficiency and accountability regarding psychosocial care of its patients. This article presents the process of selecting and revising the Profile of Adaptation to Life (PAL) into a screening instrument that identifies the hospital's most vulnerable patients Who need to have a full psychosocial assessment completed by the social worker. The PAL was selected because it includes identifiable risk factors across the psychosocial spectrum, is cost-effective, and easy to administer and score. Factor analysis and reliability analysis resulted in a promising instrument, the Profile for Adaptation to Life-Medical (PAL-M), for use in rapid, psychosocial risk screening with medically ill patients. Based on the analysis, the authors updated the PAL's original language, clarified introductory wording of some questions, and expanded demographic information. C1 Catholic Univ Amer, Nat Catholic Sch Social Serv, Washington, DC 20064 USA. NIH, Ctr Clin, Dept Social Work, Bethesda, MD 20892 USA. SAMHSA, Washington, DC USA. RP BrintzenhofeSzoc, K (reprint author), Catholic Univ Amer, Nat Catholic Sch Social Serv, Shahan Hall, Washington, DC 20064 USA. EM brintzek@cua.edu NR 22 TC 1 Z9 1 U1 0 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2007 VL 45 IS 2 BP 43 EP 58 DI 10.1300/J010v45n02_03 PG 16 WC Social Work SC Social Work GA 204FT UT WOS:000249029900003 PM 17954442 ER PT S AU Ruknudin, AM Lakattaa, EG AF Ruknudin, Abdul M. Lakattaa, Edward G. BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI The regulation of the Na/Ca exchanger and plasmalemmal Ca2+ ATPase by other proteins SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE calcium transport; phosphorylation; signal transduction ID SODIUM-CALCIUM EXCHANGE; SARCOLEMMAL NA+-CA2+ EXCHANGER; CARDIAC NA+/CA2+ EXCHANGER; PHOSPHORYLATION-DEPENDENT REGULATION; CALMODULIN BINDING DOMAIN; NITRIC-OXIDE SYNTHASE; SODIUM/CALCIUM EXCHANGER; KINASE-C; INHIBITORY INTERACTION; VENTRICULAR MYOCYTES AB Na/Ca exchanger (NCX) and plasma membrane Ca2+ ATPase are the Ca2+ efflux mechanisms known in mammalian cells. NCX is the main transporter to efflux intracellular Ca2+ in the heart. NCX protein contains nine putative transmembrane domains and a large intracellular loop joining two sets of the transmembrane domains. The intracellular loop regulates the activity of the NCX by interacting with other proteins and nonprotein factors, such as ions, PIP2. Several proteins that are associated with NCX have been identified recently. Similarly, plasmalemmal Ca2+ ATPase (PMCA) has 10 putative transmembrane domains, and the C-terminal intracellular region inhibits transporter activity. There are several proteins associated with PMCA, and the roles of the associated proteins of PMCA vary from specific localization to involving PMCA in signal transduction. Elucidation of structural and functional roles played by these associated proteins of NCX and PMCA will provide opportunities to develop drugs of potential therapeutic value. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Ruknudin, AM (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. EM aruknudi@umaryland.edu FU Intramural NIH HHS NR 85 TC 5 Z9 6 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 86 EP 102 DI 10.1196/annals.1387.045 PG 17 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300012 PM 17446448 ER PT S AU Ruknudin, AM Wei, SK Haigney, MC Lederer, WJ Schulze, DH AF Ruknudin, Abdul M. Wei, Sha-Kui Haigney, Mark C. Lederer, W. J. Schulze, Dan H. BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI Phosphorylation and other conundrums of Na/Ca exchanger, NCX1 SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE protein kinase A; regulation; NCX1 knockout; mode-specific inhibition; NCX macromolecular complex; beta-adrenergic stimulation ID SODIUM-CALCIUM EXCHANGE; CARDIAC NA+/CA2+ EXCHANGER; PROTEIN-KINASE-C; NA+-CA2+ EXCHANGER; VENTRICULAR MYOCYTES; DEPENDENT REGULATION; DYNAMIC PROPERTIES; STEADY-STATE; SODIUM/CALCIUM EXCHANGER; FUNCTIONAL EXPRESSION AB The Na+/Ca2+ exchanger (NCX) is an important Ca2+ transport mechanism in virtually all cells in the body. There are three genes that control the expression of NCX in mammals. There are at least 16 alternatively spliced isoforms of NCX1 that target muscle and nerve and other tissues. Here we briefly discuss three remarkable regulatorv issues or '' conundrums '' that involve the most prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation? We suggest that the macromolecular complex of NCX1 plays a critical role in the regulation of NCX. The role of the macromolecular complex and evidence supporting its existence and functional importance is presented. (2) Can there be transport block of a single '' mode '' of NCX1 transport by drugs or therapeutic agents? The simple answer is '' no.'' A brief explanation is provided. (3) How can NCX1 knockout mice live? The answer is '' by other compensatory regulatory mechanisms.'' These conundrums highlight important features in NCX1 and lay the foundation for new experiments to elucidate function and regulation of NCX1 and provide a context for investigations that seek to understand novel therapeutic agents. C1 Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD 21201 USA. NIA, Ctr Gerontol Res, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. RP Ruknudin, AM (reprint author), Univ Maryland, Dept Microbiol & Immunol, 660 W Redwood St, Baltimore, MD 21201 USA. EM aruknudi@umaryland.edu RI Lederer, William/B-1285-2010 NR 45 TC 13 Z9 13 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 103 EP 118 DI 10.1196/annals.1387.036 PG 16 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300013 PM 17446449 ER PT S AU Rahamimoff, H Elbaz, B Alperovich, A Kimchi-Sarfaty, C Gottesman, MM Lichtenstein, Y Eskin-Shwartz, M Kasir, J AF Rahamimoff, H. Elbaz, B. Alperovich, A. Kimchi-Sarfaty, C. Gottesman, M. M. Lichtenstein, Y. Eskin-Shwartz, M. Kasir, J. BE Herchuelz, A Blaustein, MP Lytton, J Philipson, KD TI Cyclosporin A-dependent Downregulation of the Na+/Ca2+ exchanger expression SO SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Sodium-Calcium Exchange CY AUG 23-27, 2006 CL Brussels, BELGIUM DE Na+/Ca2+ exchanger expression; cyclosporin A; cyclophilin A; proline mutagenesis ID CIS-TRANS ISOMERASE; NA+-CA2+ EXCHANGER; SURFACE EXPRESSION; FUNCTIONAL EXPRESSION; RAT; PROTEIN; CLONING; CYCLOPHILIN; CHANNELS; RBE-1 AB Cyclosporin A (CsA) is an immunosuppressive drug commonly given to transplant patients. Its application is accompanied by severe side effects related to calcium, among them hypertension and nephrotoxicity. The Na+/Ca (2+) exchanger (NCX) is a major calcium regulator expressed in the surface membrane of all excitable and many nonexcitable tissues. Three genes, NCX1, NCX2, and NCX3 code for Na+/Ca2+ exchange activity. NCX1 gene products are the most abundant. We have shown previously that exposure of NCX1-transfected HEK 293 cells to CsA, leads to concentration-dependent reduction of Na+/Ca2+ exchange activity and surface expression, without a reduction in total cell-expressed NCX1 protein. We show now that the effect of CsA on NCX1 protein expression is not restricted to transfected cells overexpressing the NCX1 protein but exhibited also in cells expressing endogenously the NCX1 protein (L6, H9c2, and primary smooth muscle cells). Exposure of NCX2- and NCX3-transfected cells to CsA results also in reduction of Na+/Ca2+ exchange activity and surface expression, though the sensitivity to the drug was lower than in NCX1-transfected cells. Studying the molecular mechanism of CsA-NCX interaction suggests that cyclophilin (Cyp) is involved in NCX1 protein expression and its modulation by CsA. Deletion of 426 amino acids from the large cytoplasmic loop of the protein retains the CsA-dependent downregulation of the truncated NCX1 suggesting that CsA-Cyp-NCX interaction involves the remaining protein domains. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol, Bethesda, MD 20892 USA. RP Rahamimoff, H (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. EM Hannah.Rahamimoff@huji.ac.il OI Elbaz, Benayahu/0000-0001-5202-4598 NR 19 TC 7 Z9 8 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-649-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1099 BP 204 EP 214 DI 10.1196/annals.1387.046 PG 11 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BGC24 UT WOS:000245982300024 PM 17446460 ER PT J AU Brough, B Christman, KL Wong, TS Kolodziej, CM Forbes, JG Wang, K Maynard, HD Ho, CM AF Brough, Branden Christman, Karen L. Wong, Tak Sing Kolodziej, Christopher M. Forbes, Jeffrey G. Wang, Kuan Maynard, Heather D. Ho, Chih-Ming TI Surface initiated actin polymerization from top-down manufactured nanopatterns SO SOFT MATTER LA English DT Article ID TORSIONAL RIGIDITY; MUSCLE ACTIN; FILAMENTS; PROTEINS; BINDING; PEPTIDES AB Protocols to fabricate high aspect-ratio biologically-based nanostructures using a top-down fabricated polymer platform and surface-initiated actin polymerization were developed. C1 NIAMS, Muscle Proteom & Nanotechnol Sect, Lab Muscle Biol B50, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Ctr Scalable & Integrated Nanomfg, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Sch Engn & Appl Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA USA. RP Wang, K (reprint author), NIAMS, Muscle Proteom & Nanotechnol Sect, Lab Muscle Biol B50, NIH, Room 1140, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov; maynard@chem.ucla.edu; chihming@ucla.edu RI Wong, Tak Sing/L-9488-2013; Ho, Chih-ming/I-6537-2012 OI Wong, Tak Sing/0000-0001-5500-0575; NR 29 TC 20 Z9 21 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2007 VL 3 IS 5 BP 541 EP 546 DI 10.1039/b618524j PG 6 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 166HD UT WOS:000246368400005 ER PT J AU Dunson, DB AF Dunson, David B. TI Bayesian methods for latent trait modelling of longitudinal data SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID STRUCTURAL EQUATION MODELS; MULTIPLE CONTINUOUS OUTCOMES; LINEAR MIXED MODELS; VARIABLE MODELS; FACTOR ANALYZERS; PRIOR DISTRIBUTIONS; MULTIVARIATE DATA; POLYTOMOUS DATA; MISSING DATA; DISCRETE AB Latent trait models have long been used in the social science literature for studying variables that can only be measured indirectly through multiple items. However, such models are also very useful in accounting for correlation in multivariate and longitudinal data, particularly when outcomes have mixed measurement scales. Bayesian methods implemented with Markov chain Monte Carlo provide a flexible framework for routine fitting of a broad class of latent variable (LV) models, including very general structural equation models. However, in considering LV models, a number of challenging issues arise, including identifiability, confounding between the mean and variance, uncertainty in different aspects of the model, and difficulty in computation. Motivated by the problem of modelling multidimensional longitudinal data, this article reviews the recent literature, provides some recommendations and highlights areas in need of additional research, focusing on methods for model uncertainty. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunsonl@niehs.nih.gov NR 74 TC 16 Z9 16 U1 0 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2007 VL 16 IS 5 BP 399 EP 415 DI 10.1177/0962280206075309 PG 17 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 224IS UT WOS:000250441300003 PM 17656454 ER PT J AU Albert, PS Follmann, DA AF Albert, Paul S. Follmann, Dean A. TI Random effects and latent processes approaches for analyzing binary longitudinal data with missingness: a comparison of approaches using opiate clinical trial data SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID INFORMATIVE MISSINGNESS; LINEAR-MODEL; SUBJECT AB The analysis of longitudinal data with non-ignorable missingness remains an active area in biostatistics research. This article discusses various random effects and latent process models which have been proposed for analyzing longitudinal binary data subject to both non-ignorable intermittent missing data and dropout. These models account for non-ignorable missingness by introducing random effects or a latent process which is shared between the response model and the model for the missing-data mechanism. We discuss various random effects and latent processes approaches and compare these approaches with analyses from an opiate clinical trial data set, which had high proportion of intermittent missingness and dropout. We also compare these random effect and latent process approaches with other methods for accounting for non-ignorable missingness using this data set. C1 Natl Canc Inst, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Natl Canc Inst, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov NR 24 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2007 VL 16 IS 5 BP 417 EP 439 DI 10.1177/0962280206075308 PG 23 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 224IS UT WOS:000250441300004 PM 17656452 ER PT J AU Rodriguez-Gomez, JA Lu, JQ Velasco, I Rivera, S Zoghbi, SS Liow, JS Musachio, JL Chin, FT Toyama, H Seidel, J Green, MV Thanos, PK Ichise, M Pike, VW Innis, RB McKay, RDG AF Rodriguez-Gomez, Jose A. Lu, Jian-Qiang Velasco, Ivan Rivera, Seth Zoghbi, Sami S. Liow, Jeih-San Musachio, John L. Chin, Frederick T. Toyama, Hiroshi Seidel, Jurgen Green, Michael V. Thanos, Panayotis K. Ichise, Masanori Pike, Victor W. Innis, Robert B. McKay, Ron D. G. TI Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease SO STEM CELLS LA English DT Article DE Parkinson disease; embryonic stem cell; transplantation; microdialysis; positron emission tomography; dopamine transporter ID POSITRON-EMISSION-TOMOGRAPHY; INTRASTRIATAL NIGRAL GRAFTS; ANIMAL PET SCANNER; RAT STRIATUM; IN-VITRO; NEURAL TRANSPLANTATION; INTRACEREBRAL DIALYSIS; MESENCEPHALIC GRAFTS; INVIVO MEASUREMENT; CONSTANT INFUSION AB The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D-2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons. C1 NINDS, Lab Mol Biol, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. NIAAA, Lab Neuroimaging, NIH, Bethesda, MD USA. RP McKay, RDG (reprint author), NINDS, Lab Mol Biol, Porter Neurosci Res Ctr, 35 Convent Dr,Bldg 35,Room 3A-201,MSC 3703, Bethesda, MD 20892 USA. EM mckayr@ninds.nih.gov RI Velasco, Ivan/D-3593-2014; Rodriguez-Gomez, Jose/C-8313-2015 OI Velasco, Ivan/0000-0002-8953-6578; FU Intramural NIH HHS [Z01 MH002795-07]; NIMH NIH HHS [Z01 MH002795] NR 77 TC 95 Z9 100 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 4 BP 918 EP 928 DI 10.1634/stemcells.2006-0386 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 158BR UT WOS:000245766400014 PM 17170065 ER PT J AU Telford, WG Bradford, J Godfrey, W Robey, RW Bates, SE AF Telford, William G. Bradford, Jolene Godfrey, William Robey, Robert W. Bates, Susan E. TI Side population analysis using a violet-excited cell-permeable DNA binding dye SO STEM CELLS LA English DT Article DE stem cell; Hoechst 33342; side population; DyeCycle; bone marrow; cord blood ID HEMATOPOIETIC STEM-CELLS; ULTRAVIOLET LASER-DIODES; FLOW-CYTOMETRY; BONE-MARROW; TRANSPORTER; ABCG2; PHENOTYPE; HOECHST-33342; PROGENITORS; EFFLUX AB Hoechst 33342 side population (SP) analysis is a common method for identifying stem cells in mammalian hematopoietic and nonhematopoietic tissues. Although widely employed for stem cell analysis, this method requires an ultraviolet (UV) laser to excite Hoechst 33342. Flow cytometers equipped with UV sources are not common because of the cost of both the laser and optics that can transmit light UV light. Violet laser sources are inexpensive and are now common fixtures on flow cytometers, but have been previously shown to provide insufficient Hoechst dye excitation for consistent resolution of SP cells. One solution to this problem is to identify additional fluorescent substrates with the same pump specificity as Hoechst 33342, but with better violet excitation characteristics. DyeCycle Violet reagent has emission characteristics similar to those of Hoechst 33342, but with a longer wavelength excitation maxima (369 nm). When this dye is loaded into hematopoietic cells, a sharply resolved side population was also observed, similar in appearance to that seen with Hoechst 33342. Unlike Hoechst SP, DCV SP was similar in appearance with both violet and UV excitation. DCV SP could be inhibited fumitremorgin C, and showed the same membrane pump specificity as Hoechst 33342. Simultaneous immunophenotyping with stem cell markers in mouse bone marrow demonstrated that DCV SP was restricted to the stem cell lineage(-) Sca-1(+) c-kit(+) cells population, as is Hoechst SP. Pending confirmation by functional analysis of DCV SP cells, these results suggest that DCV efflux identified approximately the same stem cell population as did Hoechst 33342 efflux. Substituting DCV for Hoechst 33342 in the SP technique may, therefore, allow side population analysis on flow cytometers with violet lasers. C1 NCI, Expt Translat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. Mol Probes Invitrogen, Eugene, OR USA. RP Telford, WG (reprint author), NCI, Expt Translat & Immunol Branch, NIH, Bldg 10,Room 3-3297,9000 Rockville Pike, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov FU Intramural NIH HHS NR 19 TC 56 Z9 64 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 4 BP 1029 EP 1036 DI 10.1634/stemcells.2006-0567 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 158BR UT WOS:000245766400026 PM 17185610 ER PT J AU Hedlund, E Pruszak, J Ferree, A Vinuela, A Hong, SH Isacson, O Kim, KS AF Hedlund, Eva Pruszak, Jan Ferree, Andrew Vinuela, Angel Hong, Sunghoi Isacson, Ole Kim, Kwang-Soo TI Selection of embryonic stem cell-derived enhanced green fluorescent protein-positive dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populations SO STEM CELLS LA English DT Article DE genetic engineering; fluorescence-activated cell sorting; Parkinson disease; stage-specific embryonic antigen 1; CD-15 ID CATECHOLAMINERGIC TC CELLS; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; TUMOR-FORMATION; IMMUNOREACTIVE NEURONS; TRANSIENT EXPRESSION; MONOCLONAL-ANTIBODY; ENTERIC NEURONS; FLOW-CYTOMETRY; ANTIGEN SSEA-1 AB Transplantation of mouse embryonic stem (mES) cells can restore function in Parkinson disease models, but can generate teratomas. Purification of dopamine neurons derived from embryonic stem cells by fluorescence-activated cell sorting ( FACS) could provide a functional cell population for transplantation while eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in mES cells. First, we evaluated 2.5-kilobase (kb) and 9-kb TH promoter fragments and showed that clones generated using the 9-kb fragment produced significantly more eGFP+/TH+ neurons. We selected the 9-kb TH clone with the highest eGFP/TH overlap for further differentiation, FACS, and transplantation experiments. Grafts contained large numbers of eGFP+ dopamine neurons of an appropriate phenotype. However, there were also numerous eGFP+ cells that did not express TH and did not have a neuronal morphology. In addition, we found cells in the grafts representing all three germ layers. Based on these findings, we examined the expression of stem cell markers in our eGFP+ population. We found that a majority of eGFP+ cells were stage-specific embryonic antigen-positive (SSEA-1+) and that the genetically engineered clones contained more SSEA-1+ cells after differentiation than the original D3 mES cells. By negative selection of SSEA-1, we could isolate a neuronal eGFP+ population of high purity. These results illustrate the complexity of using genetic selection to purify mES cell-derived dopamine neurons and provide a comprehensive analysis of cell selection strategies based on tyrosine hydroxylase expression. C1 Harvard Univ, McLean Hosp, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Sch Med, Mol Neurobiol Labs, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Sch Med, Neurogenerat Labs, Belmont, MA 02478 USA. RP Kim, KS (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mol Neurobiol Lab, 115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu; kskim@mclean.harvard.edu RI Pruszak, Jan/G-6972-2015; OI Pruszak, Jan/0000-0003-4297-4009; Hedlund, Eva/0000-0001-6347-0075 FU NINDS NIH HHS [P50 NS039793, P50 NS039793-07, P50 NS39793] NR 71 TC 50 Z9 53 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 5 BP 1126 EP 1135 DI 10.1634/stemcells.2006-0540 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 165GR UT WOS:000246292700006 PM 17234989 ER PT J AU Shin, S Sun, Y Liu, Y Khaner, H Svant, S Cai, JL Xu, XQ Davidson, BP Stice, SL Smith, AK Goldman, SA Reubinoff, BE Zhan, M Rao, MS Chesnut, JD AF Shin, Soojung Sun, Yu Liu, Ying Khaner, Hanita Svant, Smita Cai, Jingli Xu, Xiu Qin Davidson, Bruce P. Stice, Steven L. Smith, Alan K. Goldman, Steven A. Reubinoff, Benjamin E. Zhan, Ming Rao, Mahendra S. Chesnut, Jonathan D. TI Whole genome analysis of human neural stem cells derived from embryonic stem cells and stem and progenitor cells isolated from fetal tissue SO STEM CELLS LA English DT Article DE large scale genomic analysis; neural stem cells; human embryonic stem cells; adult stem cells; differentiation; lineage restricted precursor cells ID PRECURSOR CELLS; GENE-EXPRESSION; IN-VITRO; DIRECTED DIFFERENTIATION; NEURONS; RAT; LINES; BRAIN; TRANSPLANTATION; PROLIFERATION AB Multipotent neural stem cells (NSC) have been derived from human embryonic stem cells (hESC) as well as isolated from fetal tissues. However, there have been few exclusive markers of NSC identified to date, and the differences between NSC from various sources are poorly understood. Although cells isolated from these two sources share many important characteristics, it is not clear how closely they are related in terms of gene expression. Here, we compare the gene expression profiles of 11 lines of NSC derived from hESC (ES_NSC), four lines of NSC isolated from fetus (F_NSC), and two lines of restricted progenitors in order to characterize these cell populations and identify differences between NSC derived from these two sources. We showed that ES_NSC were clustered together with high transcriptional similarities but were distinguished from F_NSC, oligodendrocyte precursor cells, and astrocyte precursor cells. There were 17 genes expressed in both ES_NSC and F_NSC whose expression was not identified in restricted neural progenitors. Furthermore, the major differences between ES_NSC and F_NSC were mostly observed in genes related to the key neural differentiation pathways. Here, we show that comparison of global gene expression profiles of ES_NSC, F_NSC, and restricted neural progenitor cells makes it possible to identify some of the common characteristics of NSC and differences between similar stem cell populations derived from hESCs or isolated from fetal tissue. C1 Stem Cells & Regenerat Med, Carlsbad, CA USA. NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, Hadassah Human Embryon Stem Cell Res Ctr, Dept Gynaecol, IL-91120 Jerusalem, Israel. Theradigm Inc, Baltimore, MD USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. ES Cell Int Pte Ltd, Singapore, Singapore. Univ Georgia, Athens, Greece. Univ Rochester, Rochester, NY USA. RP Chesnut, JD (reprint author), 1610 Faraday Ave, Carlsbad, CA 92008 USA. EM jon.chesnut@invitrogen.com NR 42 TC 53 Z9 54 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 5 BP 1298 EP 1306 DI 10.1634/stemcells.2006-0660 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 165GR UT WOS:000246292700024 PM 17272497 ER PT J AU Bozorgmehr, F Laufs, S Sellers, SE Roeder, I Zeller, WJ Dunbar, CE Fruehauf, S AF Bozorgmehr, Farastuk Laufs, Stefanie Sellers, Stephanie E. Roeder, Ingo Zeller, Werner J. Dunbar, Cynthia E. Fruehauf, Stefan TI No evidence of clonal dominance in primates up to 4 years following transplantation of multidrug resistance 1 retrovirally transduced long-term repopulating cells SO STEM CELLS LA English DT Article DE gene therapy; multidrug resistance 1; CD34+; rhesus macaque ID POLYMERASE-CHAIN-REACTION; RESISTANCE MDR-1 GENE; BONE-MARROW-CELLS; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; HEMATOPOIETIC-CELLS; BREAST-CANCER; IN-VIVO; INSERTIONAL MUTAGENESIS; IMMUNODEFICIENT MICE AB Previous murine studies have suggested that retroviral multidrug resistance 1 ( MDR1) gene transfer may be associated with a myeloproliferative disorder. Analyses at a clonal level and prolonged long-term follow-up in a model with more direct relevance to human biology were lacking. In this study, we analyzed the contribution of individual CD34selected peripheral blood progenitor cells to long-term rhesus macaque hematopoiesis after transduction with a retroviral vector either expressing the multidrug resistance 1 gene ( HaMDR1 vector) or expressing the neomycin resistance ( NeoR) gene ( G1Na vector). We found a total of 122 contributing clones from 8 weeks up to 4 years after transplantation. One hundred two clones contained the G1Na vector, whereas only 20 clones contained the HaMDR1 vector. Here, we show for the first time realtime polymerase chain reaction based quantification of individual transduced cell clones constituting 0.0008% +/- 0.0003% to 0.0041% +/- 0.00032% of primate peripheral blood cells. No clonal dominance was observed. C1 German Canc Res Ctr, Res Grp Pharmacol, Heidelberg, Germany. Univ Heidelberg, Dept Expt Surg, Mannheim Fac, D-6900 Heidelberg, Germany. DKFZ, Mol Oncol Solid Tumors Unit, Heidelberg, Germany. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-7010 Leipzig, Germany. Univ Heidelberg, Dept Internal Med 5, D-6900 Heidelberg, Germany. Paracelsus Klin, Ctr Tumor Diagnost, Osnabruck, Germany. RP Laufs, S (reprint author), Paracelus Klin, Ctr Tumor Diagnost & Therapy, Natruper Holz 69, D-49076 Osnabruck, Germany. EM prof.stefan.fruehauf@pk-mx.de NR 51 TC 17 Z9 17 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 10 BP 2610 EP 2618 DI 10.1634/stemcells.2007-0017 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 217DZ UT WOS:000249929900024 PM 17615269 ER PT J AU Yao, YG Childs, RW Kajigaya, S Mccoy, JP Younga, NS AF Yao, Yong-Gang Childs, Richard W. Kajigaya, Sachiko Mccoy, J. Philip, Jr. Younga, Neal S. TI Mitochondrial DNA sequence heterogeneity of single CD34(+) cells after nonmyeloablative allogeneic stem cell transplantation SO STEM CELLS LA English DT Article DE single-cell analysis; mitochondrial DNA; nonmyeloablative allogeneic stem cell transplantation; CD34(+) cell; kinetics ID BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; HEMATOPOIETIC CHIMERISM; MTDNA MUTATIONS; LEUKEMIA; ENGRAFTMENT; PERSISTENCE; DISEASE; CANCER; MICE AB We applied a single-cell method to detect mitochondrial DNA (mtDNA) mutations to evaluate the reconstitution of hematopoietic stem cells (HSCs) and committed progenitor cells after nonmyeloablative allogeneic stem cell transplantation in humans. In a total of 1,958 single CD34(+) cells from six human leukocyte antigen-matched sibling donor and recipient pairs, individual CD34(+) clones were recognized based on the observed donor-or recipient-specific mtDNA sequence somatic alteration. There was no overall reduction of mtDNA heterogeneity among CD34(+) cells from the recipient after transplantation. Samples collected from two donors over time showed the persistence of certain CD34(+) clones marked by specific mutations. Our results demonstrate the feasibility of distinguishing donor and recipient individual CD34(+) clones based on mtDNA mutations during engraftment. HSCs were not limited in number, and similar mtDNA heterogeneity levels suggested representation of the total stem cell compartment during rapid hematopoietic reconstitution in the recipient. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Yao, YG (reprint author), NHLBI, Hematol Branch, NIH, Bldg 20 CRC,Room 3E-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM yaoy3@nhlbi.nih.gov NR 52 TC 5 Z9 6 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 10 BP 2670 EP 2676 DI 10.1634/stemcells.2007-0269 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 217DZ UT WOS:000249929900030 PM 17628021 ER PT J AU Davani, B Ikonomou, L Raaka, BM Geras-Raaka, E Morton, RA Marcus-Samuels, B Gershengorn, MC AF Davani, Behrous Ikonomou, Laertis Raaka, Bruce M. Geras-Raaka, Elizabeth Morton, Russell A. Marcus-Samuels, Bernice Gershengorn, Marvin C. TI Human islet-derived precursor cells are mesenchymal stromal cells that differentiate and mature to hormone-expressing cells in vivo SO STEM CELLS LA English DT Article DE islet precursor cells; mesenchymal stromal cells; insulin; cell replacement therapy; diabetes ID INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; STEM-CELLS; BONE-MARROW; MULTIPOTENTIAL NESTIN; VITRO; TRANSITION; TRANSPLANTATION; ENDOCRINE; EXPANSION AB Islet transplantation offers improved glucose homeostasis in diabetic patients, but transplantation of islets is limited by the supply of donor pancreases. Undifferentiated precursors hold promise for cell therapy because they can expand before differentiation to produce a large supply of functional insulin-producing cells. Previously, we described proliferative populations of human islet-derived precursor cells (hIPCs) from adult islets. To show the differentiation potential of hIPCs, which do not express insulin mRNA after at least 1,000-fold expansion, we generated epithelial cell clusters (ECCs) during 4 days of differentiation in vitro. After transplantation into mice, 22 of 35 ECC preparations differentiated and matured into functional cells that secreted human C-peptide in response to glucose. Transcripts for insulin, glucagon, and somatostatin in recovered ECC grafts increased with time in vivo, reaching levels approximately 1% of those in adult islets. We show that hIPCs are mesenchymal stromal cells (MSCs) that adhere to plastic, express CD73, CD90, and CD105, and can differentiate in vitro into adipocytes, chondrocytes, and osteocytes. Moreover, we find a minor population of CD105(+)/ CD73(+)/ CD90(+) cells in adult human islets (prior to incubation in vitro) that express insulin mRNA at low levels. We conclude that hIPCs are a specific type of pancreas-derived MSC that are capable of differentiating into hormone-expressing cells. Their ability to mature into functional insulin-secreting cells in vivo identifies them as an important adult precursor or stem cell population that could offer a virtually unlimited supply of human islet-like cells for replacement therapy in type 1 diabetes. C1 [Davani, Behrous; Ikonomou, Laertis; Raaka, Bruce M.; Geras-Raaka, Elizabeth; Morton, Russell A.; Marcus-Samuels, Bernice; Gershengorn, Marvin C.] NIH, NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIH, NIDDK, Clin Endocrinol Branch, Bldg 50, Rm 4133, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Ikonomou, Laertis/D-4579-2009 OI Ikonomou, Laertis/0000-0003-0993-6713 NR 33 TC 73 Z9 81 U1 0 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 12 BP 3215 EP 3222 DI 10.1634/stemcells.2007-0323 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 242EL UT WOS:000251707200026 PM 17901402 ER PT J AU Mutskov, V Raaka, BM Felsenfeld, G Gershengorn, MC AF Mutskov, Vesco Raaka, Bruce M. Felsenfeld, Gary Gershengorn, Marvin C. TI The human insulin gene displays transcriptionally active epigenetic marks in islet-derived mesenchymal precursor cells in the absence of insulin expression SO STEM CELLS LA English DT Article DE islet-derived precursor cells; mesenchymal stromal cells; epigenetic; histone modifications; insulin gene ID PANCREATIC BETA-CELLS; EMBRYONIC STEM-CELLS; HISTONE MODIFICATIONS; IN-VITRO; CELLULAR MEMORY; PROMOTER DNA; BONE-MARROW; METHYLATION; CHROMATIN; TRANSPLANTATION AB Human islet-derived precursor cells (hIPCs), mesenchymal cells derived in vitro from adult pancreas, proliferate freely and do not express insulin but can be differentiated to epithelial cells that express insulin. hIPCs have been studied with the goal of obtaining large quantities of insulin-producing cells suitable for transplantation into patients suffering from type 1 diabetes. It appeared that undifferentiated hIPCs are '' committed '' to a pancreatic endocrine phenotype through multiple cell divisions, suggesting that epigenetic modifications at the insulin locus could be responsible. We determined patterns of histone modifications over the insulin gene in human islets and hIPCs and compared them with HeLa and human bone marrow-derived mesenchymal stem cells (hBM-MSCs), neither of which expresses insulin. The insulin gene in islets displays high levels of histone modifications (H4 hyperacetylation and dimethylation of H3 lysine 4) typical of active genes. These are not present in HeLa and hBM-MSCs, which instead have elevated levels of H3 lysine 9 dimethylation, a mark of inactive genes. hIPCs, in contrast, show significant levels of active chromatin modifications, as much as half those seen in islets, and show no measurable H3 K9 methylation. Cells expanded from a minor population of mesenchymal stromal cells found in islets exhibit the same histone modifications as established hIPCs. We conclude that hIPCs, which do not express the insulin gene, nonetheless uniquely exhibit epigenetic marks that could poise them for activation of insulin expression. This epigenetic signature may be a general mechanism whereby tissue-derived precursor cells are committed to a distinct specification. C1 [Mutskov, Vesco; Felsenfeld, Gary] NIH, NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. [Raaka, Bruce M.; Gershengorn, Marvin C.] NIH, NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIH, NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov; marving@intra.niddk.nih.gov NR 39 TC 45 Z9 51 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2007 VL 25 IS 12 BP 3223 EP 3233 DI 10.1634/stemcells.2007-0325 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 242EL UT WOS:000251707200027 PM 17901401 ER PT S AU Workman, P Burrows, F Neckers, L Rosen, N AF Workman, Paul Burrows, Francis Neckers, Len Rosen, Neal BE Csermely, P Korcsmaros, T Sulyok, K TI Drugging the cancer chaperone HSP90 combinatorial therapeutic exploitation of oncogene addiction and tumor stress SO STRESS RESPONSES IN BIOLOGY AND MEDICINE: STRESS OF LIFE IN MOLECULES, CELLS, ORGANISMS, AND PSYCHOSOCIAL COMMUNITIES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 2nd World Conference on Stress CY AUG 23-26, 2007 CL Budapest, HUNGARY ID SHOCK-PROTEIN 90; MOLECULAR CHAPERONE; BREAST-CANCER; HEAT-SHOCK-PROTEIN-90 INHIBITORS; IN-VITRO; ANTITUMOR AGENT; B-RAF; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; CELLS; EXPRESSION AB The molecular chaperone HSP90 has emerged as an exciting target for cancer treatment. We review the potential advantages of HSP90 inhibitors, particularly the simultaneous combinatorial depletion of multiple oncogenic "client" proteins, leading to blockade of many cancer-causing pathways and the antagonism of all of the hallmark pathological traits of malignancy. Cancer selectivity is achieved by exploiting cancer "dependencies," including oncogene addiction and the stressed state of malignant cells. The multiple downstream effects of HSP90 inhibitors should make the development of resistance more difficult than with agents having more restricted effects. We review the various classes of HSP90 inhibitor that have been developed, including the natural products geldanamycin and radicicol and also the purine scaffold and pyrazole/isoxazole class of synthetic small molecule inhibitors. A first-in-class HSP90 drug, the geldanamycin analog 17-AAG, has provided proof of concept for HSP90 inhibition in patients at well tolerated doses and therapeutic activity has been seen. Other inhibitors show promise in preclinical and clinical development. Opportunities and challenges for HSP90 inhibitors are discussed, including use in combination with other agents. Most of the current HSP90 inhibitors act by blocking the essential nucleotide binding and ATPase activity required for chaperone function. Potential new approaches are discussed, for example, interference with cochaperone binding and function in the superchaperone complex. Biomarkers for use with HSP90 inhibitors are described. C1 Canc Res UK, Ctr Canc Therapeut, Inst Canc Res, Haddow Labs, Sutton, Surrey, England. Biogen IDEC, San Diego, CA USA. NCI, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Workman, P (reprint author), Canc Res UK, Ctr Canc Therapeut, Inst Canc Res, Haddow Labs, 15 Cotswold Rd, Sutton, Surrey, England. EM paul.workman@icr.ac.uk NR 88 TC 316 Z9 324 U1 5 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-675-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1113 BP 202 EP 216 DI 10.1196/annals.1391.012 PG 15 WC Psychology, Biological; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences; Psychology, Social SC Psychology; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGX56 UT WOS:000251158200019 PM 17513464 ER PT S AU Nepomnaschy, PA Sheiner, E Mastorakos, G Arck, PC AF Nepomnaschy, Pablo A. Sheiner, Eyal Mastorakos, George Arck, Petra C. BE Csermely, P Korcsmaros, T Sulyok, K TI Stress, immune function, and women's reproduction SO STRESS RESPONSES IN BIOLOGY AND MEDICINE: STRESS OF LIFE IN MOLECULES, CELLS, ORGANISMS, AND PSYCHOSOCIAL COMMUNITIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd World Conference on Stress CY AUG 23-26, 2007 CL Budapest, HUNGARY DE stress; immune function; reproductive function; evolution ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; VASOACTIVE-INTESTINAL-PEPTIDE; NERVE GROWTH-FACTOR; REGULATORY T-CELLS; MATERNAL-FETAL INTERFACE; DENDRITIC CELLS; EARLY-PREGNANCY; FETOMATERNAL INTERFACE; STEROID-BIOSYNTHESIS AB Only 23% of women will begin a successful pregnancy during the first menstrual cycle in their attempt to conceive.(1) A large number of these failed reproductive attempts are attributed to a broad set of pathologies, but across studies an important proportion of unsuccessful cycles is consistently left unexplained. Stress has become a commonly cited factor when discussing unexplained reproductive failures. Early research on the effect of stress on reproduction was plagued with methodological problems and lacked a solid theoretical framework. However, recent experimental, clinical and population-based research provides new evidence and suggests novel biological mechanisms, which merit a fresh evaluation of the purported association. Here we briefly review the latest advancements in the study of the interplay between stress, the immune system and women's reproduction, discuss a proposed evolutionary origin for their relationship and examine the biological pathways that may mediate the connection between these three systems. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. Univ Athens, Sch Med, Dept Obstet Gynecol 2, GR-11527 Athens, Greece. Charite Univ Med Berlin, Div PsychoNeuroImmunol, Berlin, Germany. RP Nepomnaschy, PA (reprint author), POB 12233,MD A3-05,Rm 309 111 TW Alexander Dr RTP, Res Triangle Pk, NC 27709 USA. EM nepomnaschyp@niehs.nih.gov RI Arck, Petra/D-7094-2013; SHEINER, EYAL/F-1488-2012 NR 80 TC 25 Z9 27 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-675-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1113 BP 350 EP 364 DI 10.1196/annals.1391.028 PG 15 WC Psychology, Biological; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences; Psychology, Social SC Psychology; Behavioral Sciences; Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGX56 UT WOS:000251158200029 PM 17978283 ER PT J AU Goldstein, DS Kopin, IJ AF Goldstein, David S. Kopin, Irwin J. TI Evolution of concepts of stress SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE allostasis; baroreceptors; cardiovascular disease; distress; exercise; homeostasis ID REPEATEDLY IMMOBILIZED RATS; SYMPATHETIC-NERVE ACTIVITY; SYMPATHOADRENAL SYSTEM; ALLOSTATIC LOAD; GENE-EXPRESSION; ADRENOMEDULLARY ACTIVATION; TYROSINE-HYDROXYLASE; ADRENAL-MEDULLA; PANIC DISORDER; BLOOD-PRESSURE AB This essay describes the evolution of stress as a medical scientific idea. Claude Bernard, Walter B. Cannon and Hans Selye provided key founding concepts for the current view. Bernard introduced the idea of the internal environment bathing cells the milieu interieur - maintained by continual compensatory changes of bodily functions. Cannon coined the word, "homeostasis," referring to a set of acceptable ranges of values for internal variables. Cannon taught that threats to homeostasis evoke activation of the sympathoadrenal system as a functional unit. Selye defined stress as a state characterized by a uniform response pattern, regardless of the particular stressor, that could lead to long-term pathologic changes. "Allostasis" was introduced as a concept in recognition that there is no single ideal set of steady-state conditions in life; instead, setpoints and other response criteria change continuously. Stress is now viewed neither as a perturbation nor a stereotyped response pattern but as a condition characterized by a perceived discrepancy between information about a monitored variable and criteria for eliciting patterned effector responses. Different stressors elicit different patterns of activation of the sympathetic nervous, adrenomedullary hormonal, hypothalamic-pituitary-adrenocortical and other effectors, closing negative feedback loops. This systems concept of stress yields predictions that observation or experimentation can test and that are applicable to normal physiology and to a variety of acute and chronic disorders. C1 NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, 10-6N252,10 Ctr Dr MSC-1620, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 67 TC 80 Z9 88 U1 8 U2 42 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2007 VL 10 IS 2 BP 109 EP 120 DI 10.1080/10253890701288935 PG 12 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 176DO UT WOS:000247064300002 PM 17514579 ER PT J AU Aguilera, G Kiss, A Liu, Y Kamitakahara, A AF Aguilera, Greti Kiss, Alexander Liu, Ying Kamitakahara, Anna TI Negative regulation of corticotropin releasing factor expression and limitation of stress response SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE adrenalectomy; chronic stress; corticosterone; corticotrophs; CRF receptors; glucocorticoid receptor ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; HORMONE GENE; ARGININE-VASOPRESSIN; REPEATED RESTRAINT; RECEPTOR EXPRESSION; RAT HYPOTHALAMUS; ATT-20 CELLS; FACTOR CRF; PITUITARY AB Corticotropin releasing factor (CRF) coordinates behavioral, autonomic and hormonal responses to stress. Activation of the hypothalamic pituitary adrenal (HPA) axis with stimulation of CRF and vasopressin (VP) release from hypothalamic parvocellular neurons, and consequent secretion of ACTH from the anterior pituitary and glucocorticoid from the adrenal cortex, is the major endocrine response to stress. Current evidence indicates that the main regulator of ACTH secretion in acute and chronic conditions is CRF, in spite of the fact that the selective increases in expression of parvocellular VP and pituitary VP V1b receptors observed during prolonged activation of the HPA axis have suggested that VP becomes the predominant regulator. Following CRF release, activation of CRF transcription is required to restore mRNA and peptide levels, but termination of the response is essential to prevent pathology associated with chronic elevation of CRF and glucocorticoid production. While glucocorticoid feedback plays an important role in regulating CRF expression, the relative importance of direct transcriptional repression of the CRF gene by glucocorticoids in the overall feedback mechanism is not clear. In addition to glucocorticoids, intracellular feedback mechanisms in the CRF neuron, involving induction of repressor forms of cAMP response element modulator (CREM) limit CRF transcriptional responses by competing with the positive regulator, phospho-CREB. Rapid repression of CRF transcription following stress-induced activation is likely to contribute to limiting the stress response and to preventing disorders associated with excessive CRF production. C1 NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Rm 1E-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM greti_aguilera@nih.gov FU Intramural NIH HHS NR 63 TC 36 Z9 40 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2007 VL 10 IS 2 BP 153 EP 161 DI 10.1080/10253890701391192 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 176DO UT WOS:000247064300007 PM 17514584 ER PT J AU Saavedra, JM Benicky, J AF Saavedra, Juan M. Benicky, Julius TI Brain and peripheral angiotensin II play a major role in stress SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE angiotensin receptor types; candesartan; cold-restraint stress; hypothalamic; pituitary; adrenal axis; isolation stress; paraventricular nucleus ID INDUCED GASTRIC INJURY; PARAVENTRICULAR NUCLEUS; RECEPTOR ANTAGONIST; RAT-BRAIN; BENZODIAZEPINE BINDING; SUBFORNICAL ORGAN; HYPERTENSIVE-RATS; AT(2) RECEPTORS; BLOOD-FLOW; AT(1) AB Angiotensin II (Ang II), the active principle of the renin-angiotensin system (RAS), was discovered as a vasoconstrictive, fluid retentive circulating hormone. It was revealed later that there are local RAS in many organs, including the brain. The physiological receptor for Ang II, the AT(1) receptor type, was found to be highly expressed in many tissues and brain areas involved in the hypothalamic-pituitary-adrenal axis response to stress and in the sympathoadrenal system. The production of circulating and local Ang II, and the expression of AT(1) receptors increase during stress. Blockade of peripheral and brain AT1 receptors with receptor antagonists administered peripherally prevented the hormonal and sympathoadrenal response to isolation stress, the stress-related alterations in cortical CRF1 and benzodiazepine receptors, part of the GABA(A) complex, and reduced anxiety in rodents. AT(1) receptor blockade prevented the ulcerations of the gastric mucosa produced by cold-restraint stress, by preservation of the gastric blood flow, prevention of the stress-induced inflammatory response of the gastric mucosa, and partial blockade of the sympathoadrenal response to the stress. Our observations demonstrate that Ang II is an important stress hormone, and that blockade of AT(1) receptors could be proposed as a potentially useful therapy for stress-induced disorders. C1 NIMH, Pharmacol Sect, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Dept Hlth & Human Serv, 10 Ctr Dr,Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov FU Intramural NIH HHS NR 64 TC 73 Z9 75 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2007 VL 10 IS 2 BP 185 EP 193 DI 10.1080/10253890701350735 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 176DO UT WOS:000247064300010 PM 17514587 ER PT J AU Zelinka, T Eisenhofer, G Pacak, K AF Zelinka, T. Eisenhofer, G. Pacak, K. TI Pheochromocytoma as a catecholamine producing tumor: Implications for clinical practice SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE adrenoceptor antagonists; catecholamines; dopamine; epinephrine; genetic testing; laparoscopic surgery ID ENDOCRINE NEOPLASIA TYPE-2; MALIGNANT PHEOCHROMOCYTOMA; BIOCHEMICAL-DIAGNOSIS; PRIMARY ALDOSTERONISM; I-123 METAIODOBENZYLGUANIDINE; HYPERTENSIVE PATIENTS; PARAGANGLIOMAS; MANAGEMENT; LOCALIZATION; MUTATIONS AB Pheochromocytomas are catecholamine-producing tumors presenting with various clinical symptoms, but mostly with headache, sweating, palpitations and hypertension. If not properly diagnosed, secretion of catecholamines may lead to fatal cardiovascular consequences. Biochemical testing for pheochromocytoma should be performed not only in symptomatic subjects or in subjects with adrenal incidentaloma but also in subjects with a genetic predisposition for pheochromocytoma (multiple endocrine neoplasia type 2, Von Hippel - Lindau (VHL) syndrome, neurofibromatosis type 1 (NF 1) and mutations of succinate dehydrogenase (SDH) genes). Once a pheochromocytoma is proven, computed tomography (CT), magnetic resonance imaging (MRI) and functional imaging with [I-123]-MIBG may be used for tumor localization. Adequate medical pre-treatment is essential for successful operation which is performed in most cases by laparoscopy. After tumor removal, further follow-up is necessary due to possible recurrence. Although prognosis after tumor resection is excellent, a significant proportion of pheochromocytomas recur, some as metastases. Thus, appropriate follow-up is mandatory. C1 NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, CRC, Bethesda, MD 20892 USA. Gen Fac Hosp, Dept Med 3, Prague, Czech Republic. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, CRC, 10 Ctr Dr,Bldg 10,RM 1-E3140,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Zelinka, Tomas/D-4276-2017 OI Zelinka, Tomas/0000-0003-3395-8373 FU Intramural NIH HHS NR 74 TC 31 Z9 36 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2007 VL 10 IS 2 BP 195 EP 203 DI 10.1080/10253890701395896 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 176DO UT WOS:000247064300011 PM 17514588 ER PT J AU Chrousos, GP Kino, T AF Chrousos, George P. Kino, Tomoshige TI Glucocorticoid action networks and complex psychiatric and/or somatic disorders SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE chronic stress; cortisol; Cushing's syndrome; hypothalamic-pituitary-adrenal axis; inflammation; insulin resistance ID PITUITARY-ADRENAL AXIS; FRAGMENT-LENGTH-POLYMORPHISM; RECEPTOR GENE; TRANSCRIPTIONAL ACTIVITY; N363S POLYMORPHISM; METABOLIC SYNDROME; CLINICAL-IMPLICATIONS; BODY-COMPOSITION; IN-VIVO; STRESS AB Glucocorticoids contribute fundamentally to the maintenance of basal and stress-related homeostasis in all higher organisms. These hormones influence a large percentage of the expressed human genome and their effects spare almost no organs or tissues. Glucocorticoids influence many functions of the central nervous system, such as arousal, cognition, mood and sleep, the activity and direction of intermediary metabolism, the maintenance of a normal cardiovascular tone, the activity and quality of the immune and inflammatory reaction, including the manifestations of the sickness syndrome, as well as growth and reproduction. The numerous actions of glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor (GR) isoforms forming homo- or hetero-dimers. The GRs consist of multifunctional domain proteins operating as ligand-dependent transcription factors that interact with many other cell signaling systems. The presence of multiple GR monomers and dimers expressed in a cell-specific fashion at different quantities with quantitatively and qualitatively different transcriptional activities suggests that the glucocorticoid signaling system is highly stochastic. Based on ample evidence, we present our conception that glucocorticoids are heavily involved in human pathophysiology and influence life expectancy. Common psychiatric and/or somatic complex disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis with its cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and allergic disorders, all appear to have a glucocorticoid component. C1 NICHHD, Clin Res Ctr, NIH, Pediat Endocrinol Sect,Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Chrousos, GP (reprint author), NICHHD, Clin Res Ctr, NIH, Pediat Endocrinol Sect,Reprod Biol & Med Branch, Bldg 10,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM chrousog@mail.nih.gov FU Intramural NIH HHS NR 47 TC 147 Z9 153 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2007 VL 10 IS 2 BP 213 EP 219 DI 10.1080/10253890701292119 PG 7 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 176DO UT WOS:000247064300013 PM 17514590 ER PT J AU Leker, RR Soldner, F Velasco, I Gavin, DK Androutsellis-Theotokis, A McKay, RDG AF Leker, Ronen R. Soldner, Frank Velasco, Ivan Gavin, Denise K. Androutsellis-Theotokis, Andreas McKay, Ronald D. G. TI Long-lasting regeneration after ischemia in the cerebral cortex SO STROKE LA English DT Article DE growth factors; neural progenitors; neural stem cells; neurogenesis; stroke ID ADULT BRAIN; SUBVENTRICULAR ZONE; NEURAL PROGENITORS; STEM-CELLS; STROKE; NEUROGENESIS; REPLACEMENT; INDUCTION; NEURONS; INJURY AB Background and Purpose-Because fibroblast growth factor 2 is a mitogen for central nervous system stern cells, we explored whether long-term fibroblast growth factor 2 delivery to the brain can improve functional outcome and induce cortical neurogenesis after ischemia. Methods-Rats underwent permanent distal middle cerebral artery occlusion resulting in an ischemic injury limited to the cortex. We used an adeno-associated virus transfection system to induce long-term fibroblast growth factor 2 expression and monitored behavioral and histological changes. Results-Treatment increased the number of proliferating cells and improved motor behavior. Neurogenesis continued throughout 90 days after the ischemia, and the occurrence of newly generated cells with characteristics of neural precursors and immature neurons was most evident 90 days after treatment. Conclusions-Focal cortical ischemia elicits an ongoing neurogenic response that can be enhanced with fibroblast growth factor 2 leading to improved functional outcome. C1 Hadassah Univ, Med Ctr, Dept Neurol, IL-91120 Jerusalem, Israel. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Leker, RR (reprint author), Hadassah Univ, Med Ctr, Dept Neurol, POB 12000, IL-91120 Jerusalem, Israel. EM leker@cc.huji.ac.il RI Velasco, Ivan/D-3593-2014 OI Velasco, Ivan/0000-0002-8953-6578 NR 21 TC 120 Z9 137 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2007 VL 38 IS 1 BP 153 EP 161 DI 10.1161/01.STR.0000252156.65953.a9 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 124HP UT WOS:000243359200033 PM 17122419 ER PT J AU Thorner, ED Jaszyna-Gasior, M Epstein, DH Moolchan, ET AF Thorner, Elissa D. Jaszyna-Gasior, Maria Epstein, David H. Moolchan, Eric T. TI Progression to daily smoking: Is there a gender difference among cessation treatment seekers? SO SUBSTANCE USE & MISUSE LA English DT Article DE adolescents; cessation; gender; prevention; smoking trajectory; teenagers; treatment; tobacco dependence ID NICOTINE DEPENDENCE; AGE AB The goal of this study was to develop an understanding the developmental trajectory of smoking behaviors in adolescents who seek smoking cessation treatment to inform tailored prevention and treatment efforts; this includes identifying gender differences in smoking behaviors. Smoking trajectory was examined retrospectively in 639 treatment-seeking adolescents (59% female; 44% African American, 50% European American, mean +/- SD daily cigarettes per day [CPD] 19.16 +/- 7.2 for both girls and boys). Smoking trajectory variables examined included age at first cigarette, age at daily smoking (a proxy measure for onset of dependence), and age at treatment request. The time interval from first cigarette to daily smoking was shorter for girls than for boys (mean +/- SD 0.9 +/- 1.1 years for girls, 1.3 +/- 1.5 years for boys, p < 0.01). From this clinical sample of adolescent smokers, findings suggest only a brief window of opportunity for secondary preventive interventions before the development of tobacco dependence. Additional research is needed to explore the specific factors that differentially affect smoking trajectory in girls compared to boys. C1 NIDA, Teen Tobacco Addict Treatment Res Clin, DHHS, NIH,IRP, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, DHHS, NIH,IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov FU Intramural NIH HHS NR 17 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2007 VL 42 IS 5 BP 829 EP 835 DI 10.1080/10826080701202486 PG 7 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 188HX UT WOS:000247912100003 PM 17613947 ER PT J AU Grotta, J Marler, J AF Grotta, James Marler, John TI Intravenous rt-PA: a tenth anniversary reflection SO SURGICAL NEUROLOGY LA English DT Article DE stroke; rt-PA; treatment ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; CEREBRAL-ISCHEMIA; URGENT THERAPY; MERCI TRIAL; TPA STROKE; T-PA; EXPERIENCE; MANAGEMENT AB Background: Clinical trials with rt-PA for treating AIS began 20 years ago in 1987, and the pivotal NINDS rt-PA Stroke Study was completed and published in 1995 with FDA approval in 1996, about 10 years ago. A large number of articles emanated from that study and have established the efficacy and generalizability of this treatment. Methods: Here we summarize the background of how the NINDS trial was developed and carried out and its main findings. Results: The NINDS rt-PA Stroke Study resulted from preclincal and pilot studies and paralleled similar studies carried out around the world. Its positive results, compared with the other trials, probably were due to the early time window for treatment and well-organized clinical and statistical centers. Many controversies have surrounded its use since its approval. As a result of the NINDS rt-PA Stroke Study, many new approaches to thrombolytic therapy are under evaluation. Conclusion: The results of the NINDS rt-PA Stroke Study have affected the management of patients with acute stroke worldwide. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Texas, Sch Med, Dept Neurol, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. RP Grotta, J (reprint author), Univ Texas, Sch Med, Dept Neurol, Houston, TX 77030 USA. EM james.c.grotta@uth.tme.edu FU NINDS NIH HHS [P50 NS044227-01] NR 52 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PY 2007 VL 68 SU 1 BP S12 EP S16 DI 10.1016/j.sumeu.2007.07.079 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 235OA UT WOS:000251242600003 PM 17963915 ER PT J AU Tsilou, E Zhou, M Gahl, W Sieving, PC Chan, CC AF Tsilou, Ekaterini Zhou, Min Gahl, William Sieving, Pamela C. Chan, Chi-Chao TI Ophthalmic manifestations and histopathology of infantile nephropathic cystinosis: Report of a case and review of the literature SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE cystine; cystinosis; eye; histopathology; infantile nephropathic cystinosis; lysosome ID CYSTEAMINE EYE DROPS; CORNEAL CRYSTALS; OCULAR MANIFESTATIONS; LONG-TERM; TOPICAL CYSTEAMINE; CHILDHOOD CYSTINOSIS; CONFOCAL MICROSCOPY; ELECTRON-MICROSCOPY; MULTIPLE-MYELOMA; CLINICAL-TRIAL AB Cystmosis is a rare autosomal recessive metabolic disorder characterized by the intracellular accumulation of cystine, the disulfide of the amino acid cysteine, in many organs and tissues. Infantile nephropathic cystinosis is the most severe phenotype. Corneal crystal accumulation and pigmentary retinopathy were originally the most commonly described ophthalmic manifestations, but successful kidney transplantation significantly changed the natural history of the disease. As cystinosis patients now live longer, long-term complications in extrarenal tissues, including the eye, have become apparent. A case of an adult patient with infantile nephropathic cystinosis is reported. He presented with many long-term ocular complications of cystinosis. After 4 years of follow-up, the patient died from sepsis. Pathology of the phthisical eyes demonstrated numerous electron-transparent polygonal spaces, bounded by single membrane, in corneal cells, retinal pigment epithelial cells, and even choroidal endothelial cells. The ophthalmic manifestations and pathology of infantile nephropathic cystinosis are discussed and reviewed in light of the current report and other cases in the literature. C1 NHGRI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. NHGRI, Immunopathol Sect, Immunol Lab, Bethesda, MD 20892 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. NIH, Natl Inst Hlth Lib, Bethesda, MD 20892 USA. RP Tsilou, E (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. OI Sieving, Pamela/0000-0003-3794-5000 FU Intramural NIH HHS [Z99 HD999999, Z01 EY000222-22] NR 98 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JAN-FEB PY 2007 VL 52 IS 1 BP 97 EP 105 DI 10.1016/j.survophthal.2006.10.006 PG 9 WC Ophthalmology SC Ophthalmology GA 133VZ UT WOS:000244043300006 PM 17212992 ER PT J AU Slakter, JS Carvalho, C Coleman, H AF Slakter, Jason S. Carvalho, Cynthia Coleman, Hannah TI The Digital Angiography Reading Center (DARC) role in the anecortave acetate clinical trials SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE anecortave acetate; clinical trials; digitial angiography; imaging systems ID RECURRENT CHOROIDAL NEOVASCULARIZATION; INDOCYANINE GREEN ANGIOGRAPHY; MACULAR DEGENERATION; HYPERFLUORESCENCE AB Advances in digital camera and computer technology have resulted in imaging systems providing clinically relevant information equivalent to traditional film-based techniques. The Digital Angiography Reading Center (DARC) was created to provide the next generation in reading center assessment for clinical trials of retinal disease. A fully digital angiographic imaging protocol was implemented with the anecortave acetate clinical studies. For image evaluation readers followed a standard manual of definitions and guidelines. Eligibility was determined based on protocol specific criteria. Rapid communication of images between the study sites and DARC permitted screening for eligibility and pre-treatment stratification of all patients prior to enrollment. This screening process was designed to eliminate angiographically ineligible patients from the clinical trials. The result was a reduction in the total number of patients needed to obtain sufficient evaluable patients for statistical assessment of treatment outcome. Digital angiography can be successfully used in clinical trials for retinal disease. C1 Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. Vanderbilt Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Nashville, TN USA. NEI, Bethesda, MD 20892 USA. RP Slakter, JS (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,5th Floor, New York, NY 10022 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JAN PY 2007 VL 52 SU 1 BP S91 EP S98 DI 10.1016/j.survophthal.2006.10.016 PG 8 WC Ophthalmology SC Ophthalmology GA 135KZ UT WOS:000244153800011 PM 17240261 ER PT J AU Springer, MS Burk-Herrick, A Meredith, R Eizirik, E Teeling, E O'Brien, SJ Murphy, WJ AF Springer, Mark S. Burk-Herrick, Angela Meredith, Robert Eizirik, Eduardo Teeling, Emma O'Brien, Stephen J. Murphy, William J. TI The adequacy of morphology for reconstructing the early history of placental mammals SO SYSTEMATIC BIOLOGY LA English DT Article ID PHYLOGENY RECONSTRUCTION; NUCLEAR GENES; MITOCHONDRIAL; ORIGIN; AFROTHERIA; RADIATION; SEQUENCES; MODELS; CLADE; TREE C1 Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. Pontificia Univ Catolica Rio Grande do Sul, Fac Med, BR-90619 Porto Alegre, RS, Brazil. Univ Coll Dublin, Sch Biol & Environm Sci, Dublin, Ireland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. RP Springer, MS (reprint author), Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. EM mark.springer@ucr.edu RI Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 NR 50 TC 66 Z9 70 U1 1 U2 24 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1063-5157 J9 SYSTEMATIC BIOL JI Syst. Biol. PY 2007 VL 56 IS 4 BP 673 EP 684 DI 10.1080/10635150701491149 PG 12 WC Evolutionary Biology SC Evolutionary Biology GA 194QW UT WOS:000248359900010 PM 17661234 ER PT S AU Zotenko, E Guimaraes, KS Jothi, R Przytycka, TM AF Zotenko, Elena Guimaraes, Katia S. Jothi, Raja Przytycka, Teresa M. BE Eskin, E Ideker, T Raphael, B Workman, C TI Decomposition of overlapping protein complexes: A graph theoretical method for analyzing static and dynamic protein associations SO SYSTEMS BIOLOGY AND REGULATORY GENOMICS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT Joint Annual Workshop on Systems Biology and on Regulatory Genomics CY DEC 02-04, 2005 CL San Diego, CA SP Ind Univ Cooperat Res Program, Calif Inst Telecommun & Informat Technol ID SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORKS; FUNCTIONAL MODULES; SCALE-FREE; YEAST; ORGANIZATION; INTERACTOME; PATHWAY AB We propose a new method for identifying and representing overlapping functional groups within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. We illustrate the effectiveness of our method by applying it to TNF alpha/NF-kappa B and pheromone signaling pathways. C1 [Zotenko, Elena; Guimaraes, Katia S.; Jothi, Raja; Przytycka, Teresa M.] Natl Lib Med, NCBI, NIH, Bethesda, MD 20209 USA. [Zotenko, Elena] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Guimaraes, Katia S.] Univ Fed Pernambuco, Ctr Informat, Recife, PE, Brazil. RP Zotenko, E (reprint author), Natl Lib Med, NCBI, NIH, Bethesda, MD 20209 USA. OI Zotenko, Elena/0000-0002-0256-3195 FU intramural research program of the National Institutes of Health; National Library of Medicine FX This work was supported by the intramural research program of the National Institutes of Health, the National Library of Medicine. Visualization of protein interaction networks was performed using the Pajek program [27]. The authors would like to thank Dianne P. O'Leary for constructive comments. NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-48293-2 J9 LECT NOTES COMPUT SC PY 2007 VL 4023 BP 23 EP + PG 4 WC Biochemical Research Methods; Biology; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Computer Science GA BFV49 UT WOS:000244806900003 ER PT S AU Kennedy, CL Koopman, P Mishina, Y O'Bryan, MK AF Kennedy, Claire L. Koopman, Peter Mishina, Yuji O'Bryan, Moira K. BE Eddy, EM Griswold, MD TI Sox8 and Sertoli-cell function SO TESTICULAR CHROMOSOME STRUCTURE AND GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 19th North American Testis Workshop CY APR 18-20, 2007 CL Tampa, FL SP Amer Soc Androl, Amer Soc Reprod Med, Conrad, Organon, NIH, Natl Inst Diabet, Kidney & Digest Dis DE testis; fertility; Sox; sperm; adhesion; Sertoli cells ID SEX-DETERMINING REGION; MOBILITY-GROUP DOMAIN; ECTOPLASMIC SPECIALIZATION; TRANSCRIPTION FACTORS; NUCLEAR IMPORT; MOUSE; TESTIS; SRY; PROTEINS; FAMILY AB SOX8 is a transcription factor that belongs to the SoxE group of high mobility group (HMG) superfamily of genes. As Sox8 is widely expressed during development, and has male-specific expression at the critical period for sex determination, it was initially hypothesized that its inactivation would result in abnormal sex determination. Though knockout males showed normal sexual development, they did however display a progressive seminiferous tubule failure and infertility. Young males could occasionally sire litters, though fecundity decreased with age in parallel with an increase in the degeneration and disorganization of the seminiferous epithelium. SOX8 is a product of the adult Sertoli cells. Sox8 knockout males showed a progressive dysregulation of the spermatogenic cycle, including sloughing of spermatocytes and round spermatids into the epididymis and spermiation failure. Sperm that did reach the epididymis showed an age-dependent decrease in both total and progressive motility in addition to overall number. We conclude that SOX8 transactivated genes have key roles in adult Sertoli-cell function and its elimination results in progressive male infertility. C1 [Kennedy, Claire L.; O'Bryan, Moira K.] Monash Univ, Monash Inst Med Res, Melbourne, Vic 3004, Australia. [Kennedy, Claire L.; Koopman, Peter; O'Bryan, Moira K.] Australian Res Council Ctr Excellence Biotechnol, Brisbane, Qld, Australia. [Koopman, Peter] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Mishina, Yuji] NIEHS, Mol Dev Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP O'Bryan, MK (reprint author), Monash Univ, Monash Inst Med Res, 27-31 Wright St, Clayton, Vic 3181, Australia. EM moira.obryan@med.monash.edu.au RI Koopman, Peter /C-9416-2009; O'Bryan, Moira/F-8256-2012 OI Koopman, Peter /0000-0001-6939-0914; O'Bryan, Moira/0000-0001-7298-4940 NR 22 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-693-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1120 BP 104 EP 113 DI 10.1196/annals.1411.007 PG 10 WC Andrology; Genetics & Heredity; Multidisciplinary Sciences; Physiology SC Endocrinology & Metabolism; Genetics & Heredity; Science & Technology - Other Topics; Physiology GA BHD16 UT WOS:000252263700009 PM 17905940 ER PT J AU Purdue, MP Gold, L Jarvholm, B Alavanja, MCR Ward, MH Vermeulen, R AF Purdue, Mark P. Gold, Laura Jarvholm, Bengt Alavanja, Michael C. R. Ward, Mary H. Vermeulen, Roel TI Impaired lung function and lung cancer incidence in a cohort of Swedish construction workers SO THORAX LA English DT Article ID NUTRITION EXAMINATION SURVEY; OBSTRUCTIVE PULMONARY-DISEASE; FORCED EXPIRATORY VOLUME; 1ST NATIONAL-HEALTH; SURVEY FOLLOW-UP; UNITED-STATES; RESPIRATORY SYMPTOMS; AIRWAY-OBSTRUCTION; CIGARETTE SMOKERS; NONSMOKING WOMEN AB Background: Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow-up were available, were analysed. Methods: Cancer incidence for 1971-2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non-lung tobacco-related cancers, other cancers, total mortality) were also investigated. Results: 834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow-up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality. Conclusions: Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8121,6120 Execut Blvd, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; Purdue, Mark/C-9228-2016 OI Vermeulen, Roel/0000-0003-4082-8163; Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS NR 53 TC 73 Z9 77 U1 2 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD JAN PY 2007 VL 62 IS 1 BP 51 EP 56 DI 10.1136/thx.2006.064196 PG 6 WC Respiratory System SC Respiratory System GA 119VX UT WOS:000243043500011 PM 16928722 ER PT J AU Stone, MJ Frenkel, V Dromi, S Thomas, P Lewis, RP Li, KCP Horne, M Wood, BJ AF Stone, Michael J. Frenkel, Victor Dromi, Sergio Thomas, Peter Lewis, Ryan P. Li, King C. P. Horne, McDonald, III Wood, Bradford J. TI Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study SO THROMBOSIS RESEARCH LA English DT Article DE high intensity focused ultrasound (HIFU); thrombolysis; tissue plasminogen activator (tPA); clot model; rabbit ear vein ID TISSUE-PLASMINOGEN ACTIVATOR; HIGH-FREQUENCY ULTRASOUND; 2-MHZ ULTRASOUND; FIBRINOLYSIS; DELIVERY; DNA; MICROBUBBLES; DISSOLUTION; DISRUPTION; THROMBOSIS AB Thrombotic disease continues to account for significant morbidity and mortality. Ultrasound energy has been investigated as a potential primary and adjunctive treatment for thrombotic disease. We have previously shown that pulsed-high intensity focused ultrasound (HIFU) enhances thrombolysis induced by tissue plasminogen activator (tPA) in vitro, including describing the non-destructive mechanism by which tPA availability and consequent activity are increased. In this study we aimed to determine,if the same effects could be achieved in vivo. Materials and methods: In this study, pulsed-HIFU exposures combined with tPA boluses were compared to treatment with tPA alone, HIFU alone and control in a novel in vivo clot model. Clots were formed in the rabbit marginal ear vein and verified using venography and infrared imaging. The efficacy of thrombolytic treatment was monitored via high resolution ultrasonography for 5 h post-treatment. The cross-sectional area of clots at 4 points along the vein was measured and normalized to the pre-treatment size. Results: At 5 h the complete recanalization of clots treated with pulsed-HIFU and tPA was significantly different from the partial recanalization seen with tPA treatment atone. tPA treatment atone showed a significant decrease in clot versus control, where HIFU was not significantly different than control. Histological analysis of the vessel walls in the treated veins showed no apparent irreversible damage to endothelial cells or extravascular tissue. Conclusions: This study demonstrates that tPA mediated thrombolysis can be significantly enhanced when combined with non-invasive pulsed-HIFU exposures. Published by Elsevier Ltd. C1 [Stone, Michael J.; Frenkel, Victor; Dromi, Sergio; Lewis, Ryan P.; Li, King C. P.; Wood, Bradford J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Thomas, Peter] NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. [Horne, McDonald, III] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Stone, Michael J.] Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD 20815 USA. RP Frenkel, V (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1N306A,10 Ctr Dr, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 36 TC 51 Z9 53 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2007 VL 121 IS 2 BP 193 EP 202 DI 10.1016/j.thromres.2007.03.023 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 246BP UT WOS:000251982800007 PM 17481699 ER PT J AU Horne, MK Merryman, PK Cullinane, AM Cai, J Martinez, PE Kling, MA Gold, PW AF Horne, McDonald K., III Merryman, Paula K. Cullinane, Ann M. Cai, June Martinez, Pedro E. Kling, Mitchel A. Gold, Philip W. TI Activation of blood coagulation in patients with major depressive disorder during euglycemic hyperinsulinemia SO THROMBOSIS RESEARCH LA English DT Article DE hypercoagulability; major depressive disorder; Hyperinsulinemia ID CORONARY-ARTERY-DISEASE; PSYCHOLOGICAL STRESS; HEMOSTASIS; INSULIN; WOMEN; MEN C1 NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 FU Intramural NIH HHS [, NIH0010153849]; PHS HHS [NIH0010153849] NR 17 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2007 VL 120 IS 4 BP 517 EP 521 DI 10.1016/j.thromres.2006.09.016 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 206FX UT WOS:000249170400010 PM 17157901 ER PT J AU Vanjani, R Park, M Holt, B Cullinane, A Merryman, P Horne, M AF Vanjani, Rachna Park, Melissa Holt, Brittany Cullinane, Ann Merryman, Paula Horne, McDonald TI Enhanced fibrinolysis in fingerstick blood samples: A possible role for matrix metalloproteinase-9 SO THROMBOSIS RESEARCH LA English DT Article ID STROMELYSIN-1 MMP-3; PLASMINOGEN-ACTIVATOR; NEUTROPHILS; METALLOPROTEINASES; BINDING; SERUM C1 NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. RP Horne, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM mhorne@maii.cc.nih.gov FU Intramural NIH HHS [Z01 CL010348-03] NR 17 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2007 VL 120 IS 5 BP 773 EP 778 DI 10.1016/j.thromres.2006.12.018 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 211SH UT WOS:000249543100017 PM 17407789 ER PT J AU Carneiro-Lobo, TC Konig, S Sogayar, MC Francischetti, IMB Monteiro, RQ AF Carneiro-Lobo, T. C. Konig, S. Sogayar, M. C. Francischetti, I. M. B. Monteiro, R. Q. TI Procoagulant properties of U87MG human glioblastoma cells and molecular targets of the anticoagulant and antitumor agent Ixolaris SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Thrombosis and Hemostasis Issues in Cancer CY OCT 26-28, 2007 CL Bergamo, ITALY C1 [Carneiro-Lobo, T. C.; Monteiro, R. Q.] UFRJ, Inst Bioquim Med, Rio De Janeiro, Brazil. [Konig, S.] UFRJ, Dept Anat, Rio De Janeiro, Brazil. [Sogayar, M. C.] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, Brazil. [Francischetti, I. M. B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2007 VL 120 SU 2 BP S165 EP S165 DI 10.1016/S0049-3848(07)70215-3 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248IT UT WOS:000252147500094 ER PT S AU Philp, D St-Surin, S Cha, HJ Moon, HS Kleinman, HK Elkin, M AF Philp, Deborah St-Surin, Sharleen Cha, Hee-Jae Moon, Hye-Sung Kleinman, Hynda K. Elkin, Michael BE Goldstein, AL Garaci, E TI Thymosin beta 4 induces hair growth via stem cell migration and differentiation SO THYMOSINS IN HEALTH AND DISEASE: FIRST INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Thymosins in Health and Disease CY 2007 CL Washington, DC DE cell migration; hair follicle growth; angiogenesis; wound healing; stem cells; cell survival; inflammation; gene expression; laminin-5; proteases; zyxin; endothelial cells; thymosin beta 4; keratinocytes; MMPs; TIMPs ID ENDOTHELIAL-CELLS; WOUND REPAIR; ANGIOGENESIS; METASTASIS; EXPRESSION; FOLLICLES; BETA-4; MORPHOGENESIS; BETA(4) AB Thymosin beta 4 is a small 43-amino-acid molecule that has multiple biological activities, including promotion of cell migration angiogenesis, cell survival, protease production, and wound healing. We have found that thymosin beta 4 promotes hair growth in various rat and mice models including a transgenic thymosin beta 4 overexpressing mouse. We have also determined the mechanism by which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth, migration, differentiation, and protease production. C1 NIDCR, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDCR, Cell Biol Sect, NIH, Bldg 30,Room 433,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 30 TC 31 Z9 35 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-701-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1112 BP 95 EP 103 DI 10.1196/annals.1415.009 PG 9 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGV24 UT WOS:000250750600010 PM 17947589 ER PT S AU Moody, TW AF Moody, Terry W. BE Goldstein, AL Garaci, E TI Thymosin alpha 1 as a chemopreventive agent in lung and breast cancer SO THYMOSINS IN HEALTH AND DISEASE: FIRST INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Thymosins in Health and Disease CY 2007 CL Washington, DC DE thymosin alpha 1; chemoprevention; lung cancer; breast cancer; carcinogenesis ID A/J MICE; MAMMARY CARCINOGENESIS; PROGNOSTIC MARKER; PROTHYMOSIN-ALPHA; PHASE-II; GROWTH; MUTATIONS; GEFITINIB; CARCINOMA; CELLS AB The ability of thymosin alpha 1 (T alpha 1) to prevent lung and breast cancer was investigated. Lung adenomas developed in A/J mice injected with carcinogens, such as urethane. The lung adenoma number was reduced by 15-45% if animals were daily treated subcutaneously (s.c.) with T alpha 1 (0.4 mg/kg). T alpha 1 (1 mu M) directly inhibited the growth of mouse lung cell lines. These results suggest that Tot I may prevent mouse lung carcinogenesis because it directly inhibits the growth of lung cancer cells. T alpha 1 prevented mammary carcinogenesis in two animal models. In the Fisher rat, an animal model of mammary cancer that is estrogen receptor dependent, tumors were initiated by the injection of N-methylurea (NMU). The rat survival was significantly increased by the daily injection of T alpha 1. In the SV40T antigen mouse, a transgenic female mouse that spontaneously gets mammary cancer in an estrogen receptor-independent manner, survival was increased and tumor burden was significantly decreased by daily injection of T alpha 1. These results indicate that Tu I is a chemopreventive agent in animal models for lung and breast carcinogenesis. C1 NCI Off Director, CCR, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI Off Director, CCR, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 38 TC 12 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-701-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1112 BP 297 EP 304 DI 10.1196/annals.1415.040 PG 8 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGV24 UT WOS:000250750600028 PM 17567944 ER PT S AU Ershler, WB Gravenstein, S Geloo, ZS AF Ershler, William B. Gravenstein, Stefan Geloo, Zeba S. BE Goldstein, AL Garaci, E TI Thymosin alpha 1 as an adjunct to influenza vaccination in the elderly - ationale and trial summaries SO THYMOSINS IN HEALTH AND DISEASE: FIRST INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Thymosins in Health and Disease CY 2007 CL Washington, DC DE aging; vaccine; influenza; thymosin alpha 1 ID ANTIBODY-SYNTHESIS INVITRO; A VIRUS; IMMUNE-RESPONSE; NURSING-HOME; ALPHA-ONE; UNITED-STATES; AGED MICE; T-CELLS; ADULTS; HEMAGGLUTININ AB From a clinical perspective, the immune deficiency of aging (immune senescence) is not profound. In fact, it may be of little clinical consequence. However, older people are prone to chronic and debilitating disorders which alone, or in concert with the medications used in their treatment, may add to the age effect and create a more clinically relevant immune deficiency. As a result, many older people are susceptible to infection. Furthermore, it is now well recognized that older people respond less well to immunization protocols. Protection against influenza by vaccination with hemagluttinin is the prototype example. Despite programs that have raised vaccination rates dramatically over the past three decades, influenza remains a major cause of morbidity and mortality in the elderly. This, in part, is due to the fact that vaccine responses are reduced in older recipients. Strategies are under development to enhance vaccine efficacy in this population and one such strategy is the adjuvant use of thymosin alpha I (Tot 1). In both animal experiments and human trials, there has been demonstrated enhancement of vaccine responses. The findings to date warrant additional efforts to further examine the role of Tot 1 in augmenting specific vaccine responses both in the elderly or in younger subjects in situations in which there are suboptimal quantities of immunizing antigen available. C1 NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ershler, WB (reprint author), Harbor Hosp, NIA, NM545,3100 Hanover St, Baltimore, MD 21225 USA. EM ershlerwi@grc.nia.nih.gov NR 51 TC 13 Z9 14 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-701-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1112 BP 375 EP 384 DI 10.1196/annals.1415.050 PG 10 WC Biochemistry & Molecular Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Immunology; Science & Technology - Other Topics GA BGV24 UT WOS:000250750600036 PM 17600281 ER PT S AU Husain, FT AF Husain, Fatima T. BE Langguth, B Hajak, G Kleinjung, T Cacace, A Moller, AR TI Neural network models of tinnitus SO TINNITUS: PATHOPHYSIOLOGY AND TREATMENT SE Progress in Brain Research LA English DT Review; Book Chapter DE neuroimaging; electrophysiological; fMRI; auditory; cerebral cortex; thalamus ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL BLOOD-FLOW; INFERIOR COLLICULUS; AUDITORY-SYSTEM; LATERAL INHIBITION; ACOUSTIC TRAUMA; INTENSE SOUND; ANIMAL-MODEL; WORKING-MEMORY; HEARING-LOSS AB In this chapter we review the relatively recent effort on the part of neuroscientists to use computational neural network modeling to investigate the neural basis of subjective tinnitus. There are advantages and challenges in using a modeling framework to understand this complex auditory disorder. The foremost challenge to modeling a subjective condition such as tinnitus is the evaluation of the occurrence of tinnitus in the model. We propose comparing measures of the model's activities (simulated neuronal activity, behavioral activity, or neuroimaging activity) with experimental data obtained from studies of tinnitus in humans and animals; strong agreement with experimental data will provide support for the validity of the simulation of tinnitus in a particular model. A major advantage of neural network modeling is that it allows experimentation not possible in animals. Models make it possible to evaluate the contribution of different neural mechanisms affecting tinnitus in a principled manner. A model makes predictions that can be tested by experiments thus leading to the designing of focused experiments. We review several neural models of tinnitus and discuss published findings from simulations using these models. We conclude with a proposed scheme for investigating tinnitus that combines neural network modeling with brain imaging experiments. C1 [Husain, Fatima T.] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Husain, FT (reprint author), Univ Illinois, Dept Speech & Hearing Sci, Champaign, IL 61820 USA. EM husainf@nidcd.nih.gov FU Intramural NIH HHS NR 81 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53167-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 166 BP 125 EP 140 DI 10.1016/S0079-6123(07)66011-7 PG 16 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA BQC09 UT WOS:000280613600013 PM 17956777 ER PT J AU Robbins, FM Hartzman, RJ AF Robbins, F. -M. Hartzman, R. J. TI CD31/PECAM-1 genotyping and haplotype analyses show population diversity SO TISSUE ANTIGENS LA English DT Article DE CD31 alleles; haplotype tag single nucleotide polymorphisms; molecular haplotyping; polymerase chain reaction-sequence-specific oligonucleotide probing; single nucleotide polymorphism frequencies ID CELL-ADHESION MOLECULE-1; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; INFLAMMATORY GENE POLYMORPHISMS; MIGRATION IN-VITRO; CYTOPLASMIC DOMAIN; ENDOTHELIAL-CELLS; PECAM-1 CD31; RISK-FACTOR; PCR AB Using direct sequencing of complementary DNA products, the sequences of human CD31 from exon 1 through exon 16 of 179 individuals (139 unrelated) were systematically examined. Of the 14 biallelic single nucleotide polymorphic sites detected, 7 polymorphic sites involved amino acid substitution. These 14 polymorphic sites yielded 18 observed CD31 alleles and 9 predicted CD31 polypeptide sequences. Based on molecular haplotyping and family pedigree analysis, linkage disequilibrium among some single nucleotide polymorphic sites was observed. Single nucleotide polymorphism frequencies between populations were also measured using dot-blot hybridization with DNA or peptide nucleic acid probes. C1 Georgetown Univ, Med Ctr, CW Bill Young Marrow Donor Recruitment & Res Prog, Dept Pediat, Washington, DC 20007 USA. Naval Med Res Ctr, CW Bill Young Marrow Donor Recruitment & Res Prog, Silver Spring, MD USA. RP Robbins, FM (reprint author), NIH, HLA Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM frobbins@mail.cc.nih.gov NR 43 TC 7 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JAN PY 2007 VL 69 IS 1 BP 28 EP 37 DI 10.1111/j.1399-0039.2006.00722.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 119PN UT WOS:000243024400004 PM 17212705 ER PT S AU Murphy, E Korach, KS AF Murphy, E. Korach, K. S. BE Korach, KS Wintermantel, T TI Actions of estrogen and estrogen receptors in nonclassical target tissues SO TISSUE-SPECIFIC ESTROGEN ACTION: NOVEL MECHANISMS, NOVEL LIGANDS, NOVEL THERAPIES SE Ernst Schering Foundation Symposium Proceedings LA English DT Proceedings Paper CT International Symposium on Tissue-Specific Estrogen Action CY MAR 01-03, 2006 CL Berlin, GERMANY ID ISCHEMIA-REPERFUSION INJURY; CYTOSOLIC FREE CALCIUM; ISCHEMIA/REPERFUSION INJURY; GENDER-DIFFERENCES; BETA(2)-ADRENERGIC RECEPTOR; MYOCARDIAL-INFARCTION; UP-REGULATION; BETA AGONIST; RABBIT HEART; NITRIC-OXIDE AB Hormonal effects on classical endocrine target organs such as the female reproductive tract, mammary gland, ovary, and neuroendocrine system have been thoroughly studied, with significant advancements in our understanding of estrogen actions and disease conditions from both cell culture as well as new experimental animal models. Knowledge of the highly appreciated effects of estrogen in nonclassical endocrine organ systems, arising from epidemiological and clinical findings in the cardiovascular, immune, GI tract, and liver, is only now becoming clarified from the development and use of knock-out or transgenic animal models for the study of both estrogen and ER activities. There are considerable epidemiological data showing that premenopausal females (Barrett-Connor 1997; Crabbe et al. 2003) have reduced risk for cardiovascular disease. However, a recent large clinical trial failed to show cardioprotection for postmenopausal females on estrogen-progestin replacement (Rossouw et al. 2002). In fact, the Women's Health Initiative Study showed increased cardiovascular risk for females taking an estrogen-progestin combination. These studies suggest that we need a better understanding of the mechanisms responsible for cardioprotection in females. C1 [Murphy, E.; Korach, K. S.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), Natl Inst Hlth, Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov NR 46 TC 1 Z9 1 U1 2 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-9425 BN 978-3-540-49547-5 J9 ERNST SCHERING FOUND JI Ernst Schering Found. Symp. Proc. PY 2007 VL 1 BP 13 EP + DI 10.1007/2789_2006_014 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BGT18 UT WOS:000250402800002 ER PT J AU Johnson, KA AF Johnson, Kennita A. TI Imaging techniques for small animal imaging models of pulmonary disease: Micro-CT SO TOXICOLOGIC PATHOLOGY LA English DT Article DE in vivo; in vitro; 3D imaging; bleomycin; hyperoxia ID COMPUTED-TOMOGRAPHY AB Microcomputed tomography (micro-CT) is ideal for quantifying pulmonary disease because of the inherent contrast between tissue and air that exists in the lungs. Both in vivo and in vitro studies can be performed using micro-CT. Live animal studies show function, while fixed specimen studies show structure. Through the use of image processing techniques, both acute and chronic lung diseases can be quantified. The information provided by micro-CT is complementary to histological evaluation, since CT is nondestructive. This paper discusses two examples, in vivo and in vitro, of how micro-CT can be used to assess pulmonary diseases in small animal models. With the use of micro-CT, we were able to quantify pulmonary fibrosis in the live rat and investigate the microstructure of the airway in fixed mouse lungs. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Johnson, KA (reprint author), 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM johnso58@niehs.nih.gov FU Intramural NIH HHS [NIH0011625334]; PHS HHS [NIH0011625334] NR 12 TC 38 Z9 38 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 BP 59 EP 64 DI 10.1080/01926230601184262 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300007 PM 17325973 ER PT J AU Flake, GP Rivera, MP Funkhouser, WK Maygarden, SJ Meadows, KL Long, EH Stockton, PS Jones, TC Yim, HW Slebos, RJC Taylor, JA AF Flake, Gordon P. Rivera, M. Patricia Funkhouser, William K. Maygarden, Susan J. Meadows, Kellen L. Long, Elizabeth H. Stockton, Pat S. Jones, Tina C. Yim, Hyeon Woo Slebos, Robbert J. C. Taylor, Jack A. TI Detection of pre-invasive lung cancer: Technical aspects of the LIFE project SO TOXICOLOGIC PATHOLOGY LA English DT Article DE pre-invasive lung cancer; bronchial dysplasia; fluorescence endoscopy; frozen sections; laser capture microdissection ID LASER-CAPTURE MICRODISSECTION; POLYMERASE-CHAIN-REACTION; PARAFFIN-EMBEDDED TISSUES; FLUORESCENCE BRONCHOSCOPY; MOLECULAR ANALYSIS; RESIDUAL DISEASE; FROZEN-SECTION; DNA; SPECIMENS; RESECTION AB Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The LIFE (Light Induced Fluorescence Endoscopy) Project was initiated at the University of North Carolina Medical Center in November, 1999, for the dual purposes of (1) detecting pre-invasive lung cancer in high- risk patients and (2) studying the molecular biology of pre-invasive lesions of the bronchus for possible development of molecular biomarkers. Of the 47 patients enrolled, all were current or former tobacco smokers, except for 1. Fluorescence endoscopy was utilized, in addition to white light bronchoscopy, to increase the detection of intraepithelial lesions. Adjacent biopsies were submitted for permanent and frozen sections, respectively, from four predetermined sites as well as from any abnormal areas. The snap-frozen specimens were cryostat sectioned, and the mucosal epithelial cells laser capture microdissected for DNA analysis. The great majority of specimens yielded sufficiently abundant and intact DNA to accomplish the molecular objectives. Histologic concordance of adjacent permanent and frozen sections was equivalent to the concordance of adjacent permanent sections, suggesting that frozen section diagnosis was adequate for the research purpose of correlating histology with molecular analysis. C1 NIH, Natl Inst Environm Sci, Lab Expt Pathol, Chapel Hill, NC 27709 USA. Univ N Carolina Hosp, Multidisciplinary Thorac Oncol Program, Chapel Hill, NC 27514 USA. NIH, Natl Inst Environm Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Social Sci Systems Inc, Durham, NC 27703 USA. Vanderbilt Univ, Ctr Med, Vanderbilt Ingram Canc Ctr, Dept Canc Biol & Otolaryngol, Nashville, TN 37232 USA. NIEHS, NIH, Dept Hlth & Human Serv, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Flake, GP (reprint author), NIEHS, Lab Exptl Pathol, POB 12233,MD B3-06,111 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. EM flake@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS NR 39 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 BP 65 EP 74 DI 10.1080/01926230601052659 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300008 PM 17325974 ER PT J AU Wakamatsu, N Devereux, TR Hong, HHL Sills, RC AF Wakamatsu, Nobuko Devereux, Theodora R. Hong, Hue-Hua L. Sills, Robert C. TI Overview of the molecular carcinogenesis of mouse lung tumor models of human lung cancer SO TOXICOLOGIC PATHOLOGY LA English DT Article DE lung tumor; oncogenes; tumor suppressor genes; K-ras; p53 ID SQUAMOUS-CELL CARCINOMA; CHLORIDE-INDUCED LUNG; FEMALE B6C3F1 MICE; K-RAS MUTATIONS; P53 MUTATIONS; HIGH-FREQUENCY; DAP-KINASE; A/J MOUSE; PROMOTER HYPERMETHYLATION; CHEMOPREVENTIVE EFFICACY AB Lung cancer is the leading cause of cancer death worldwide, and the need to develop better diagnostic techniques and therapies is urgent. Mouse models have been utilized for studying carcinogenesis of human lung cancers, and many of the major genetic alterations detected in human lung cancers have also been identified in mouse lung tumors. The importance of mouse models for understanding human lung carcinogenic processes and in developing early diagnostic techniques, preventive measures and therapies cannot be overstated. In this report, the major known molecular alterations in lung tumorigenesis of mice are reviewed and compared to those in humans. C1 NIEHS, Lab Exptl Pathol, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, Lab Exptl Pathol, MD B306,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 70 TC 23 Z9 24 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 BP 75 EP 80 DI 10.1080/01926230601059993 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300009 PM 17325975 ER PT J AU Hong, HHL Houle, CD Ton, TVT Sills, RC AF Hong, Hue-Hua L. Houle, Christopher D. Ton, Thai-Vu T. Sills, Robert C. TI K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse SO TOXICOLOGIC PATHOLOGY LA English DT Article DE k-ras; ethylene oxide; mice; carcinogen; Harderian gland; lung; uterus; neoplasm ID IN-VIVO MUTAGENICITY; INHALATION EXPOSURE; PROTOONCOGENE ACTIVATION; MOLECULAR DOSIMETRY; POINT MUTATION; HIGH-FREQUENCY; DNA-ADDUCTS; BONE-MARROW; MICE; RATS AB Ethylene oxide is a multisite carcinogen in rodents and classified as a human carcinogen by the National Toxicology Program. In 2-year mouse studies, ethylene oxide (EO) induced lung, Harderian gland (HG), and uterine neoplasms. We evaluated representative EO-induced and equivalent spontaneous neoplasms for K-ras mutations in codons 12, 13, and 61. K-ras mutations were identified in 100% (23/23) of the EO-induced lung neoplasms and 25% (27/108) of the spontaneous lung neoplasms. Codon 12 G to T transversions were common in EO-induced lung neoplasms (21/23) but infrequent in spontaneous lung neoplasms (1/108). K-ras mutations were found in 86% (18/21) of the EO-induced HG neoplasms and 7% (2/27) of the spontaneous HG neoplasms. Codon 13 G to C and codon 12 G to T transversions were predominant in the EO-induced HG neoplasms but absent in spontaneous HG neoplasms (0/27). K-ras mutations occurred in 83% (5/6) of the EO-induced uterine carcinomas and all were codon 13 C to T transitions. These data show a strong predilection for development of K-ras mutations in EO-induced lung, Harderian gland, and uterine neoplasms. This suggests that EO specifically targets the K-ras gene in multiple tissue types and that this event is a critical component of EO-induced tumorigenesis. C1 Exp Pathol Lab Inc, Res Triangle Pk, NC USA. NIH, NIEHS, Lab Exptl Pathol, Res Triangle Pk, NC 27709 USA. RP Hong, HHL (reprint author), NIH, NIEHS, Lab Exptl Pathol, Res Triangle Pk, NC 27709 USA. EM hong5@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 36 TC 14 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 BP 81 EP 85 DI 10.1080/01926230601063839 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300010 PM 17325976 ER PT J AU Sells, DM Brix, AE Nyska, A Jokinen, MP Orzech, DP Walker, NJ AF Sells, Donald M. Brix, Amy E. Nyska, Abraham Jokinen, Micheal P. Orzech, Denise P. Walker, Nigel J. TI Respiratory tract lesions in noninhalation studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE toxicology; pathology; respiratory tract; rats; mice; lung; nasal epithelium ID F344 RATS; NASAL CAVITY; METHACRYLONITRILE; CARCINOGENICITY; MICE; CYTOCHROME-P450; METAPLASIA; EPITHELIUM; TOXICOLOGY; RELEVANCE AB This paper reviews respiratory tract lesions observed in rodents administered various chemicals by noninhalation routes. Chemicals administered by inhalation caused lesions in the respiratory tract and were well described; however, when chemicals were administered by noninhalation routes the effort to evaluate tissues for lesions may have been less or not considered, especially in the upper respiratory tract, and some lesions may have gone undetected. Lesions described in this review mostly occurred in rodent chronic noninhalation studies conducted by the National Toxicology Program; however, some were noted in studies of shorter duration. The nasal cavity was vulnerable to damage when chemicals were administered by noninhalation routes. Changes included respiratory epithelial hyperplasia, degeneration and necrosis of olfactory epithelium, olfactory epithelial metaplasia, adenoma, adenocarcinoma, squamous cell carcinoma, and neuroblastoma. In the lung, compound-related lesions included alveolar histiocytosis, alveolar epithelial hyperplasia, bronchiolar metaplasia of the alveolar epithelium, squamous metaplasia, alveolar/bronchial adenoma and carcinoma, and squamous tumors. Pathogenesis of these lesions included regurgitation of volatiles, metabolites arriving from the blood stream, and additional metabolism by olfactory epithelium or Clara cells. The presence of respiratory tract lesions in noninhalation studies emphasizes the need for a thorough examination of the respiratory tract including nasal passages, regardless of the route of administration. C1 Battelle Mem Inst, Columbus Labs, Columbus, OH 43201 USA. Expt Pathol Labs, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Charles River Labs, Pathol Associates, Durham, NC 27703 USA. RP Walker, NJ (reprint author), NIEHS, NIH, US Dept HHS, POB 12233,111 Alexander Dr,MD EC-34, Res Triangle Pk, NC 27709 USA. EM walker3@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999] NR 24 TC 14 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 BP 170 EP 177 DI 10.1080/01926230601059969 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300020 PM 17325986 ER PT J AU Cimon, KY Malarkey, DE Miller, RA AF Cimon, K. Y. Malarkey, D. E. Miller, R. A. TI Incidences of mesenchymal neoplasms in the nasal cavity in NTP rodent studies SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Expt Pathol Labs, Res Triangle Pk, NC USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P5 BP 180 EP 180 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300027 ER PT J AU Johnson, KA Mahler, B Cho, HY Kleeberger, SR Maronpot, RR AF Johnson, K. A. Mahler, B. Cho, H. Y. Kleeberger, S. R. Maronpot, R. R. TI Structural model of hyperoxic lung injury in mice using micro-CT SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P21 BP 183 EP 183 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300043 ER PT J AU Ramot, Y Lewis, D Ortel, T Moser, G Streiker, M Ward, S Elmore, S Peddada, S Nyska, A AF Ramot, Y. Lewis, D. Ortel, T. Moser, G. Streiker, M. Ward, S. Elmore, S. Peddada, S. Nyska, A. TI Age and dose sensitivities in 2-butoxyethanol F344 rat model of hemdytic anemia and disseminated thrombosis SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Hadassah Med Ctr, Jerusalem, Israel. Duke Univ, Med Ctr, Div Hematol, Durham, NC USA. Integrated Lab Syst, Res Triangle Pk, NC USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RI Peddada, Shyamal/D-1278-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P25 BP 184 EP 184 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300047 ER PT J AU Cesta, MF Davis, JP Cunningham, ML AF Cesta, M. F. Davis, J. P. Cunningham, M. L. TI Detection of quantum dots after IV administration in F344/N rats SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Integrated Lab Syst Inc, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P31 BP 185 EP 186 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300053 ER PT J AU Clayton, N Yoshizawa, K Burka, T Kissling, G Chan, PC Nyska, A AF Clayton, N. Yoshizawa, K. Burka, T. Kissling, G. Chan, P. C. Nyska, A. TI Hepatocellular hypertrophy induced by oral treatment with kava extract in F344 rats: Immunohistochemical analysis of expressions of hepatic cytochrome P450 SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Drug Metab & Pharmacokinet Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Toxical Operat Branch, Res Triangle Pk, NC 27709 USA. Astellas Pharma Inc, Drug Safety Res Labs, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P35 BP 186 EP 187 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300057 ER PT J AU Travlos, GS Betz, L Hard, GC AF Travlos, G. S. Betz, L. Hard, G. C. TI The influence of diet or route of exposure on chronic progressive nephropathy, kidney weight, blood urea nitrogen and creatinine concentrations in 13-week toxicity studies for control F344/N male rats SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Constella Hlth Sci, Durham, NC USA. EPL Inc, NTP Archives, Durham, NC USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P52 BP 190 EP 191 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300074 ER PT J AU Singh, BP Bushel, PR Malarkey, DE AF Singh, B. P. Bushel, P. R. Malarkey, D. E. TI Correlation of transcriptome profiles and histologic alterations for seven known rodent hepatotoxicants SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P62 BP 193 EP 193 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300084 ER PT J AU Wancket, LM Davis, JP Guenther, BD Woznicki, GL Johnson, BW Wahlstrand, BD Maronpot, RR AF Wancket, L. M. Davis, J. P. Guenther, B. D. Woznicki, G. L. Johnson, B. W. Wahlstrand, B. D. Maronpot, R. R. TI Monitoring growth of DEN-induced mouse liver tumors using magnetic resonance microscopy (MRM) SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Integrated Lab Syst Inc, Res Triangle Pk, NC USA. MRPath Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA 67 BP 194 EP 194 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300089 ER PT J AU Yoshizawa, K Walker, NJ Jokinen, MP Brix, AE Sells, DM Nyska, A Wyde, ME AF Yoshizawa, K. Walker, N. J. Jokinen, M. P. Brix, A. E. Sells, D. M. Nyska, A. Wyde, M. E. TI Thyroid follicular lesions induced by oral treatment for two years with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds in female harlan Sprague-Dawley rats SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Astellas Pharma Inc, Osaka, Japan. Charles River Co, Pathol Assoc, Cary, NC USA. Expt Pathol Lab, Res Triangle Pk, NC USA. Battelle Columbus Labs, Columbus, OH USA. NIH, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Toxicol Pathol, Timrat, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P69 BP 194 EP 195 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300091 ER PT J AU Golomb, E Schneider, A Houminer, E Dunnick, J Kissling, GE Borman, J Nyska, A Schwalb, H AF Golomb, E. Schneider, A. Houminer, E. Dunnick, J. Kissling, G. E. Borman, J. Nyska, A. Schwalb, H. TI Bis(2-chloroethoxy) methane impairs cardiac mitochondrial response to ischemic injury; Ex vivo assessment of the functional mitochondrial effect of a cardiotoxic agent SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Hadassah Med Ctr, IL-91120 Jerusalem, Israel. Shaare Zedek Med Ctr, Jerusalem, Israel. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P72 BP 195 EP 195 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300094 ER PT J AU Kodavanti, U Nyska, A Ledbetter, A Schladweiler, M Gottipolu, R Wallenborn, G Thomas, R Jaskot, R Richards, J Crissman, K Hatch, G Kissling, G Maronpot, R AF Kodavanti, U. Nyska, A. Ledbetter, A. Schladweiler, M. Gottipolu, R. Wallenborn, G. Thomas, R. Jaskot, R. Richards, J. Crissman, K. Hatch, G. Kissling, G. Maronpot, R. TI Cardiovascular diseases, susceptibility to oxidative injury and compensatory mechanisms: Insights from rodent models SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. Toxicol Pathol, Timrat, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA P74 BP 195 EP 196 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300096 ER PT J AU Flagler, ND Ney, E Mahler, BW Maronpot, RR AF Flagler, N. D. Ney, E. Mahler, B. W. Maronpot, R. R. TI Publication images: The good, the bad, and the impossible SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. Expt Pathol Labs Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA 80 BP 197 EP 197 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300102 ER PT J AU Flagler, ND Ney, E Mahler, BW Maronpot, RR AF Flagler, N. D. Ney, E. Mahler, B. W. Maronpot, R. R. TI Image ethics: To adjust or not to adjust SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. Expt Pathol Labs Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 1 MA 79 BP 197 EP 197 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 145UP UT WOS:000244891300101 ER PT J AU Mori, K Blackshear, PE Lobenhofer, EK Parker, JS Orzech, DP Roycroft, JH Walker, KL Johnson, KA Marsh, TA Irwin, RD Boorman, GA AF Mori, Kazuhiko Blackshear, Pamela E. Lobenhofer, Edward K. Parker, Joel S. Orzech, Denise P. Roycroft, Joseph H. Walker, Kimwa L. Johnson, Kennita A. Marsh, Tiwanda A. Irwin, Richard D. Boorman, Gary A. TI Hepatic transcript levels for genes coding for enzymes associated with xenobiotic metabolism are altered with age SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; rat; transcriptome; aging; cytochrome P450; xenobiotic metabolism ID WISTAR RATS; DRUG-METABOLISM; CYTOCHROME-P450 ISOFORMS; SENESCENT MALE; FEMALE RATS; EXPRESSION; LIVER; SEX; INDUCTION; TOXICITY AB Metabolism studies are crucial for data interpretation from rodent toxicity and carcinogenicity studies. Metabolism studies are usually conducted in 6 to 8 week old rodents. Long-term studies often continue beyond 100 weeks of age. The potential for age-related changes in transcript levels of genes encoding for enzymes associated with metabolism was evaluated in the liver of male F344/N rats at 32, 58, and 84 weeks of age. Differential expression was found between the young and old rats for genes whose products are involved in both phase I and phase II metabolic pathways. Thirteen cytochrome P450 genes from CYP families 1-3 showed alterations in expression in the older rats. A marked age-related decrease in expression was found for 4 members of the Cyp3a family that are critical for drug metabolism in the rat. Immunohistochemical results confirmed a significant decrease in Cyp3a2 and Cyp2c11 protein levels with age. This indicates that the metabolic capacity of male rats changes throughout a long-term study. Conducting multiple hepatic microarray analyses during the conduct of a long-term study can provide a global view of potential metabolic changes that might occur. Alterations that are considered crucial to the interpretation of long-term study results could then be confirmed by subsequent metabolic studies. C1 Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Cogenics, Morrisville, NC 27564 USA. Constella Grp Inc, Res Triangle Pk, NC 27709 USA. RP Boorman, GA (reprint author), Natl Inst Environm Hlth Sci, Environm Toxicol Program, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM boorman@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [ES-35513, N01-ES-25497] NR 53 TC 28 Z9 28 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 2 BP 242 EP 251 DI 10.1080/01926230601156286 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 148ZZ UT WOS:000245117200005 PM 17366318 ER PT J AU Heinloth, AN Boorman, GA Foley, JF Flagler, ND Paules, RS AF Heinloth, Alexandra N. Boorman, Gary A. Foley, Julie F. Flagler, Norris D. Paules, Richard S. TI Gene expression analysis offers unique advantages to histopathology in liver biopsy evaluations SO TOXICOLOGIC PATHOLOGY LA English DT Article DE histopathology; toxicogenomics; liver; microarray; biopsy; acetaminophen ID CHRONIC HEPATITIS-C; SAMPLING VARIABILITY; CELL-DEATH; ACETAMINOPHEN; APOPTOSIS; TOXICITY; NECROSIS; INJURY; HEPATOTOXICITY; INVOLVEMENT AB Liver diseases that induce nonuniform lesions often give rise to greatly varying histopathology results in needle biopsy samples from the same patient. This study examines whether gene expression analysis of such biopsies could provide a more representative picture of the overall condition of the liver. We utilized acetaminophen (APAP) as a model hepatotoxicant that gives a multifocal pattern of necrosis following toxic doses. Rats were treated with a single toxic or subtoxic dose of APAP and sacrificed 6, 24, or 48 hours after exposure. Left liver lobes were harvested, and both gene expression and histopathological analysis were per-formed on biopsy-sized samples. While histopathological evaluation of such small samples revealed significant sample to sample differences after toxic doses of APAR gene expression analysis provided a very homogeneous picture and allowed clear distinction between subtoxic and toxic doses. The main biological function differentiating animals that received sub-toxic from those that had received toxic doses was an acute stress response at 6 hours and signs of energy depletion at later time points. Our results suggest that the use of genomic analysis of biopsy samples together with histopathological analysis could provide a more precise representation of the overall condition of a patient's liver than histopathological evaluation alone. C1 Natl Inst Environm Hlth Sci, NIEHS, Natl Ctr Toxicogenom, Microarray Grp, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Paules, RS (reprint author), Natl Inst Environm Hlth Sci, NIEHS, Natl Ctr Toxicogenom, Microarray Grp, 111 Alexander Dr,Mail Drop D2-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01-ES-95446, ES-25497] NR 26 TC 15 Z9 15 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 2 BP 276 EP 283 DI 10.1080/01926230601178207 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 148ZZ UT WOS:000245117200009 PM 17366322 ER PT J AU Elmore, S AF Elmore, Susan TI Apoptosis: A review of programmed cell death SO TOXICOLOGIC PATHOLOGY LA English DT Review DE apoptosis; programmed cell death; intrinsic/extrinsic pathway; granzyme; A/B; perforin; autophagy ID MITOCHONDRIAL PERMEABILITY TRANSITION; ISCHEMIA-REPERFUSION INJURY; LASER-SCANNING CYTOMETRY; LI-FRAUMENI-SYNDROME; MEDIATED APOPTOSIS; CYTOCHROME-C; GRANZYME-A; DNA-DAMAGE; IN-VIVO; CASPASE ACTIVATION AB The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis. C1 NIEHS, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Elmore, S (reprint author), NIEHS, PO Box 12233, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 170 TC 2491 Z9 2621 U1 172 U2 767 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 4 BP 495 EP 516 DI 10.1080/01926230701320337 PG 22 WC Pathology; Toxicology SC Pathology; Toxicology GA 190GQ UT WOS:000248047700003 PM 17562483 ER PT J AU Doi, AM Hill, G Seely, J Hailey, JR Kissling, G Bucher, JR AF Doi, Adriana M. Hill, Georgette Seely, John Hailey, James R. Kissling, Grace Bucher, John R. TI alpha 2u-globulin nephropathy and renal tumors in national toxicology program studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE alpha 2u-globulin nephropathy; male rats; renal tubular cell tumors; pathogenesis ID ALPHA(2U)-GLOBULIN NEPHROPATHY; ALPHA-2-MU-GLOBULIN NEPHROPATHY; ALTERNATIVE HYPOTHESIS; CARCINOGENIC MODES; HUMAN RELEVANCE; WHITE RAVENS; RATS; INFORMATION; MECHANISMS; EXPOSURE AB Chemically induced renal neoplasms in male rats, developed coincident with alpha 2(u)-globulin nephropathy, are not considered predictive of risk to humans by the International Agency for Research on Cancer (IARC) and the U. S. Environmental Protection Agency. Criteria have been defined to establish the role of alpha 2(u)-globulin nephropathy in renal carcinogenesis, based on a proposed mode of action involving sustained tubular cell proliferation resulting from alpha 2(u)-induced nephropathy, with consequent development of neoplastic lesions. Recent NTP studies demonstrated inconsistencies with this proposed mechanism, including in some cases, far weaker kidney tumor responses than expected based on the extent of alpha 2(u)-globulin nephropathy. NTP studies with decalin, propylene glycol mono-t-butyl ether and Stoddard solvent IIC included extended evaluations of alpha 2(u)-related nephropathy, and were thus used in assessing the linkage between key events in 90-day studies with renal tumors in 2-year studies. This review revealed no or at best weak associations of tumor responses with renal alpha 2(u)-globulin concentrations, indices of cell turnover, or microscopic evidence of alpha 2(u)-associated nephropathy in prechronic studies. While tumor responses corresponded somewhat with a measure of cumulative alpha 2(u)-associated nephropathy ( linear mineralization of the papilla) at the end of the 2-year studies, the severity of chronic nephropathy was generally in best agreement with the pattern of tumor response. These results suggest that while alpha 2(u)-globulin nephropathy may contribute to the renal tumor response, the critical component(s) of the nephropathy most closely associated with the development of tumors could not be clearly identified in this review. C1 NIEHS, NIH, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, Natl Toxicol Program, 79 Alexander Dr,Mail Drop EC-34, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 31 TC 15 Z9 15 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 4 BP 533 EP 540 DI 10.1080/01926230701338941 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 190GQ UT WOS:000248047700006 PM 17562486 ER PT J AU Dunnick, JK Kissling, G Gerken, DK Vallant, MA Nyska, A AF Dunnick, J. K. Kissling, G. Gerken, D. K. Vallant, M. A. Nyska, A. TI Cardiotoxicity of Ma Huang/caffeine or ephedrine/caffeine in a rodent model system SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cardiotoxicity; Ma Huang; ephedra; ephedrine; caffeine ID DIETARY-SUPPLEMENTS; EPHEDRA ALKALOIDS; CALCIUM-ENTRY; CA2+ RELEASE; HEK293 CELLS; CAFFEINE; PHARMACOKINETICS; COMBINATION; PATHWAYS; RATS AB Ma Huang (equivalent to 0, 12.5, 25, or 50 mg/kg ephedrine) or ephedrine (0, 6.25, 12.5, 25 mg/kg) were administered as one bolus oral dose to male F344 rats with and without caffeine. The herbal medicine Ma Huang (ephedra) in combination with caffeine caused rapid clinical signs of toxicity including salivation, hyperactivity, ataxia, and eventually lethargy, and failure to respond to stimuli. When this syndrome of clinical signs emerged, animals were moribund sacrificed, and a histological analysis for heart lesions performed. Cardiotoxicity included hemorrhage, necrosis, and degeneration in the ventricles or interventricular septum within 2-4 hours after treatment with Ma Huang (ephedra)/caffeine or ephedrine (the principal active component in Ma Huang)/caffeine. There was a steep dose response curve for cardiotoxicity with minimal toxicity seen at levels of Ma Huang (equivalent to 12.5 mg/kg ephedrine) with caffeine. However, cardiotoxic lesions occurred in 28% of animals with Ma Huang dosages equivalent to 25 mg/kg ephedrine with 15 or 30 mg/kg caffeine, and in 90% of animals at Ma Huang exposures equivalent to 50 mg/kg ephedrine with 15 or 30 mg/kg caffeine. Cardiotoxic lesions occurred in 47% of animals in the 25 mg/kg ephedrine groups with caffeine at 7.25, 15, or 30 mg/kg. There was no statistical difference in the occurrence of cardiotoxic lesions when 15 or 30 mg/kg caffeine was combined with Ma Huang equivalent to 25 or 50 mg/kg ephedrine; likewise there was no statistical difference in the occurrence of cardiotoxic lesions when 7.25, 15, or 30 mg/kg caffeine was combined with 25 mg/kg ephedrine. These results show that the cardiotoxic effects of the herbal medicine, Ma Huang, are similar to that of ephedrine, the principal active ingredient in the herbal medicine. The combination of Ma Huang or ephedrine with caffeine enhanced the cardiotoxicity over that with the herbal medicine or the active ingredient alone. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Columbus, OH 43201 USA. RP Dunnick, JK (reprint author), PO Box 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [N01-ES-65406, N01ES55547] NR 35 TC 20 Z9 22 U1 0 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 5 BP 657 EP 664 DI 10.1080/0192623001459978 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 217KU UT WOS:000249947600004 PM 17676524 ER PT J AU Morrison, JP Satoh, H Foley, J Horton, JL Dunnick, JK Kissling, GE Malarkey, DE AF Morrison, James P. Satoh, Hiroshi Foley, Julie Horton, John L. Dunnick, June K. Kissling, Grace E. Malarkey, David E. TI N-ethyl-N-nitrosourea (ENU)-induced meningiomatosis and meningioma in p16(INK4a)/p19(ARF) tumor suppressor gene-deficient mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE animal model; central nervous system; meningioma; meningiomatosis; mouse; tumor suppressor gene deficiency; ethylnitrosourea ID TUMORIGENESIS; LOCUS; EXPRESSION; P14(ARF); GROWTH; CDKN2B; CELLS AB The cyclin-dependent kinase (CDK) inhibitor p16(INK4a) and the MDM2 ubiquitin ligase inhibitor p19(ARF) are critical to the regulation of cell cycle progression. Their loss by deletion, mutation or epigenetic silencing is a common molecular alteration in many human cancers. To investigate the role of p16(INK4a)/p19(ARF) deficiency in CNS tumor pathogenesis, pregnant mice bearing p16(-/-)/ p19(-/-), p16(+/-)/ p19(+/-), and p16(+/+)/ p19(+/+) embryos were exposed transplacentally on gestation day 14 to a single dose of the potent carcinogen, ethylnitrosourea (ENU). p16+/-/ p19+/- male mice treated with ENU developed meningial proliferative lesions with a high incidence (5/10). The incidence was lower in other ENU-treated animals of both sexes and none occurred in saline-treated control animals. The lesions ranged from widespread meningeal proliferation and plaque-like thickening by neoplastic spindle cells consistent with meningiomatosis to a larger discrete mass consistent with a meningioma. Ultrastructural analysis revealed the presence of intercellular junctions between cells, supporting a meningothelial histogenesis. Spontaneous meningiomas occur rarely in wild-type mice but are a common neoplasm afflicting humans, accounting for between 13 and 26% of primary intracranial neoplasms. This ENU inducible meningeal lesion in p16(+/-)/ p19(+/-) mice may provide additional insight into the pathogenesis of meningeal neoplasia and aid the development of therapeutics. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Pathol Associates Inc, Charles River Labs, Durham, NC 27703 USA. Daiichi Pharmaceut Co Ltd, Drug Safety Res Lab, Tokyo 1348630, Japan. RP Malarkey, DE (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MD-B3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM malarkey@niehs.nih.gov NR 29 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 6 BP 838 EP 845 DI 10.1080/01926230701584130 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 221AQ UT WOS:000250199200011 ER PT J AU Yoshizawa, K Heatherly, A Malarkey, DE Walker, NJ Nyska, A AF Yoshizawa, Katsuhiko Heatherly, Allison Malarkey, David E. Walker, Nigel J. Nyska, Abraham TI A critical comparison of murine pathology and epidemiological data of TCDD, PCB126, and PeCDF SO TOXICOLOGIC PATHOLOGY LA English DT Review DE carcinogenesis; dioxin; human; PCB126; PeCDF; rodent; TCDD ID SPRAGUE-DAWLEY-RATS; ARYL-HYDROCARBON RECEPTOR; DIOXIN-LIKE COMPOUNDS; GONADOTROPIN-RELEASING-HORMONE; POLYCHLORINATED-BIPHENYLS PCBS; TOXIC EQUIVALENCY FACTORS; MOLAR TOOTH DEVELOPMENT; ZEBRAFISH DANIO-RERIO; AIR-FORCE VETERANS; DIBENZO-P-DIOXINS AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) and dioxin-like compounds (DLCs) induce numerous toxicities, including developmental, endocrine, immunological, and multi-organ carcinogenic, in animals and/or humans. Multiple studies completed by the National Toxicology Program (NTP) focused on the effects caused in Harlan Sprague-Dawley rats by specific DLCs, among them the prototypical dioxin, TCDD. Because humans are exposed daily to a combination of DLCs, primarily via ingestion of food, the Toxic Equivalency Factor (TEF) was developed in order to evaluate health hazards caused by these mixtures. Herein we review the pathological effects reported in humans exposed to TCDD; 3,3 ', 4,4', 5-pentachlorobiphenyl (PCB 126); and 2,3,4,7,8,-pentachlorodibenzofuran (PeCDF) and compare them to similar changes seen in NTP murine studies performed with the same compounds. While there were differences in specific pathologies observed, clear consistency in the target organs affected (liver, oral cavity, cardiovascular system, immune system, thyroid, pancreas, and lung) could be seen in both human studies and rodent toxicity and carcinogenicity investigations. C1 [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Drug Safety Res Labs, Osaka 5328415, Japan. [Yoshizawa, Katsuhiko] Kansai Univ, Moriguchi, Osaka 5708506, Japan. [Heatherly, Allison; Malarkey, David E.] NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), Haharuv 18 PO Box 184, IL-23840 Timrat, Israel. EM anyska@bczcqmt.net RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999] NR 128 TC 23 Z9 23 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 7 BP 865 EP 879 DI 10.1080/01926230701618516 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA 243JO UT WOS:000251792800003 PM 18098033 ER PT J AU Walker, NJ Yoshizawa, K Miller, RA Brix, AE Sells, DM Jokinen, MP Wyde, ME Easterling, M Nyska, A AF Walker, Nigel J. Yoshizawa, Katsuhiko Miller, Rodney A. Brix, Amy E. Sells, Donald M. Jokinen, Micheal P. Wyde, Michael E. Easterling, Michael Nyska, Abraham TI Pulmonary lesions in female Harlan Sprague-Dawley rats following two-year oral treatment with dioxin-like compounds SO TOXICOLOGIC PATHOLOGY LA English DT Article DE lung; cystic keratinizing epithelioma; bronchiolar metaplasia; carcinogenesis; mixtures; TEFs ID ARYL-HYDROCARBON RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; POLYCHLORINATED-BIPHENYLS; CHRONIC TOXICITY; RETINOIC ACID; DOSE LEVELS; LUNG; EXPOSURE; INDUCTION; VITAMIN AB Dioxin and dioxin-related compounds have been associated with high incidences of pulmonary dysfunctions and/or cancers in humans. To evaluate the relative potencies of effects of these compounds, the National Toxicology Program completed a series of two-year bioassays which were conducted using female Harlan Sprague-Dawley rats. The rats were treated orally for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3', 4,4', 5-pentachlorobiphenyl (PCB126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and a ternary mixture of TCDD, PCB126 and PeCDF. In addition to treatment-related effects reported in other organs, a variety of pulmonary lesions were observed that were related to exposure. Pulmonary CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) activity was increased in all dosed groups. The most common non-neoplastic lesions, which occurred in all studies, were bronchiolar metaplasia and squamous metaplasia of the alveolar epithelium. Cystic keratinizing epithelioma was the most commonly observed neoplasm which occurred in all studies. A low incidence of squamous cell carcinoma was associated only with PCB126 treatment. Potential mechanisms leading to altered differentiation and/or proliferation of bronchiolar and alveolar epithelia may be through CYP1A1 induction or disruption of retinoid metabolism. C1 [Walker, Nigel J.; Wyde, Michael E.; Nyska, Abraham] Natl Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Drug Safety Labs, Osaka, Japan. [Yoshizawa, Katsuhiko] Kansai Med Univ, Osaka, Japan. [Miller, Rodney A.; Brix, Amy E.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. [Sells, Donald M.] Columbus Labs, Columbus, OH USA. [Jokinen, Micheal P.] A Charles River Co, Pathol Assoc Inc, Durham, NC USA. [Easterling, Michael] Constella Grp, Res Triangle Pk, NC USA. RP Walker, NJ (reprint author), Natl Inst Environm Hlth Sci, 111 Alexander Dr Po Box 12233, Res Triangle Pk, NC 27709 USA. EM walker3@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999] NR 70 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 7 BP 880 EP 889 DI 10.1080/01926230701748396 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 243JO UT WOS:000251792800004 PM 18098034 ER PT J AU Hardisty, JF Elwell, MR Ernst, H Greaves, P Kolenda-Roberts, H Malarkey, DE Mann, PC Tellier, PA AF Hardisty, Jerry F. Elwell, Michael R. Ernst, Heinrich Greaves, Peter Kolenda-Roberts, Holly Malarkey, David E. Mann, Peter C. Tellier, Pierre A. TI Histopathology of hemangiosarcomas in mice and hamsters and liposarcomas/fibrosarcomas in rats associated with PPAR agonists SO TOXICOLOGIC PATHOLOGY LA English DT Article DE PPAR agonists; hemangiosarcoma; liposarcoma; fibrosarcoma; rodent; carcinogenesis; diagnostic criteria ID VASCULAR TUMORS; S-100 PROTEIN; TROGLITAZONE; LIPOSARCOMA; TISSUE AB Peroxisome proliferator-activated receptors (PPAR) are involved in the pathogenesis of insulin resistance, diabetes, and related complications. Consequently, the identification of PPAR subtypes and the potential for their activation provides promising therapeutic targets for the management of type 2 diabetes mellitus. Available data from rodent carcinogenicity studies, however, demonstrate that PPAR agonists can be tumorigenic in one or more species of rodents at multiple sites. In 2005, the Health and Environmental Sciences Institute (HESI) PPAR Agonist Project Committee was established by a group of pharmaceutical companies to advance research on and to understand the modes of action and human relevance of this emerging rodent tumor data for PPAR agonists. Since the most commonly observed tumor types reported in rodents are hemangiosarcomas, fibrosarcomas and liposarcomas, the PPAR Agonist Project Committee approved a Pathology Working Group (PWG) to develop consensus of morphologic criteria for tumor diagnoses and consistency of diagnoses across multiple studies for hemangiosarcomas in mice and hamsters and liposarcomas/fibrosarcomas in rats. Therefore, the focus of the PWG review was to establish consistent tumor diagnostic criteria, to assess evidence of potentially preneoplastic changes and to identify distinguishing morphologic differences which may exist between spontaneous changes present in control animals with similar changes from treated animals. Specific diagnostic criteria and nomenclature are recommended for the classification of proliferative vascular lesions which may be present in mice or hamsters and for proliferative mesenchymal changes in rats in studies that are conducted with PPAR agonists. C1 [Hardisty, Jerry F.; Kolenda-Roberts, Holly] Expt Path Labs Inc, Res Triangle Pk, NC 27709 USA. [Elwell, Michael R.] Covenance Labs, Vienna, VA 22182 USA. [Ernst, Heinrich] Fraunhofer Inst Toxicol & Expt Med, D-30625 Hannover, Germany. [Greaves, Peter] Leicester Royal Infirm, Dept Canc Studies & Mol Med, Leicester, Leics, England. [Malarkey, David E.] NIEHS, Res Triangle Pk, NC 27709 USA. [Mann, Peter C.] EPL NW, Seattle, WA USA. [Tellier, Pierre A.] Charls River Labs, Senneville, PQ H9X 3R3, Canada. RP Hardisty, JF (reprint author), POB 12766, Res Triangle Pk, NC USA. EM jhardisty@epl-inc.com FU Intramural NIH HHS [Z99 ES999999] NR 36 TC 29 Z9 29 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2007 VL 35 IS 7 BP 928 EP 941 DI 10.1080/01926230701748156 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 243JO UT WOS:000251792800009 PM 18098039 ER PT J AU Herr, DW Graff, JE Moser, VC Crofton, KM Little, PB Morgan, DL Sills, RC AF Herr, David W. Graff, Jaimie E. Moser, Virginia C. Crofton, Kevin M. Little, Peter B. Morgan, Daniel L. Sills, Robert C. TI Inhalational exposure to carbonyl sulfide produces altered brainstem auditory and somatosensory-evoked potentials in Fischer 344N rats SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-of-Toxicology CY MAR 06-10, 2005 CL New Orleans, LA SP Soc Toxicol DE carbonyl sulfide; evoked potentials; BAER; SEP; CNAP; NCV ID LONG-EVANS RATS; DISULFIDE NEUROTOXICITY; PSYCHOPHYSIOLOGICAL RESEARCH; MIDBRAIN DEAFNESS; VISUAL-SYSTEM; WORD DEAFNESS; HOODED RATS; WAVE-FORM; FLASH; STIMULATION AB Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131-145; Sills et al., 2004, Toxicol. Pathol. 32, 1-10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash-evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage. C1 US EPA, NHEERL, NTD, NPTB,Neurotoxicol Div,ORD, Res Triangle Pk, NC 27711 USA. Chalk River Labs, Pathol Associates Div, Durham, NC 27713 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Herr, DW (reprint author), US EPA, NHEERL, NTD, NPTB,Neurotoxicol Div,ORD, 109 TW Alexander Dr,MD B105-05, Res Triangle Pk, NC 27711 USA. EM herr.david@epamail.epa.gov RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 85 TC 10 Z9 10 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2007 VL 95 IS 1 BP 118 EP 135 DI 10.1093/toxsci/kfl146 PG 18 WC Toxicology SC Toxicology GA 120GK UT WOS:000243072300012 PM 17079700 ER PT S AU Valasek, L Szamecz, B Hinnebusch, AG Nielsen, KH AF Valasek, Leos Szamecz, Beta Hinnebusch, Alan G. Nielsen, Klaus H. BE Lorsch, J TI In vivo stabilization of preinitiation complexes by formaldehyde cross-linking SO TRANSLATION INITIATION: EXTRACT SYSTEMS AND MOLECULAR GENETICS SE Methods in Enzymology LA English DT Review; Book Chapter ID INITIATION-FACTOR 3; TRANSLATION INITIATION; RIBOSOMAL-SUBUNITS; CODON SELECTION; MESSENGER-RNA; 40S SUBUNITS; EIF3; BINDING; YEAST; PROTEIN AB Translation initiation starts with the formation of the 43S preinitiation complex (PIC) consisting of several soluble factors, including the ternary complex (TC; eIF2-GTP-Met-tRNA(i)(Met)), which associate with the small ribosomal subunit. In the next step, mRNA is recruited to form the 48S PIC and the entire machinery starts scanning the 5' untranslated region of the mRNA until the AUG start codon is encountered. The most widely used method to separate 40S and 60S ribosomal subunits from soluble factors, monosomes and polysomes, is sucrose density centrifugation (SDC). Since PICs are intrinsically unstable complexes that cannot withstand the forces imposed by SDC, a stabilization agent must be employed to detect the association of factors with the 40S subunit after SDC. This was initially achieved by adding heparin (a highly sulfated glycosaminoglycan) directly to the breaking buffer of cells treated with cycloheximide (a translation elongation inhibitor). However, the mechanism of stabilization is not understood and, moreover, there are indications that the use of heparin may lead to artifactual factor associations that do not reflect the factor occupancy of the 43S/48S PICs in the cell at the time of lysis. Therefore, we developed an alternative method for PIC stabilization using formaldehyde (HCHO) to cross-link factors associated with 40S ribosomal subunits in vivo before the disruption of the yeast cells. Results obtained using HCHO stabilization strongly indicate that the factors detected on the 43S/48S PIC after SDC approximate a real-time in vivo "snapshot" of the 43S/48S PIC composition. In this chapter, we will present the protocol for HCHO cross-linking in detail and demonstrate the difference between heparin and HCHO stabilization procedures. In addition, different conditions for displaying the polysome profile or PIC analysis by SDC, used to address different questions, will be outlined. C1 AS CR, Inst Microbiol, Prague, Czech Republic. NICHHD, NIH, Bethesda, MD 20892 USA. Aarhus Univ, Dept Mol Biol, Aarhus C, Denmark. RP Valasek, L (reprint author), AS CR, Inst Microbiol, Prague, Czech Republic. RI Valasek, Leos/I-5743-2014 FU FIC NIH HHS [1R01 TW007271-01]; Wellcome Trust [076456, 076456/Z/05/Z] NR 30 TC 35 Z9 35 U1 1 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374191-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 429 BP 163 EP 183 DI 10.1016/S0076-6879(07)29008-1 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGT14 UT WOS:000250401900008 PM 17913623 ER PT S AU Shin, BS Dever, TE AF Shin, Byung-Sik Dever, Thomas E. BE Lorsch, J TI Molecular genetic structure-function analysis of translation initiation factor EIF5B SO TRANSLATION INITIATION: EXTRACT SYSTEMS AND MOLECULAR GENETICS SE Methods in Enzymology LA English DT Review; Book Chapter ID RIBOSOMAL-SUBUNITS; FACTOR IF2; YEAST; RELEASE; BINDING; RECOGNITION; MUTATIONS; GTPASE; STEP AB Recently, significant progress has been made in obtaining three-dimensional (3-D) structures of the factors that promote translation initiation, elongation, and termination. These structures, when interpreted in light of previous biochemical characterizations of the factors, provide significant insight into the function of the factors and the molecular mechanism of specific steps in the translation process. In addition, genetic analyses in yeast have helped elucidate the in vivo roles of the factors in various steps of the translation pathway. We have combined these two approaches and use molecular genetic studies to define the structure-function properties of translation initiation factors in the yeast Saccharomyces cerevisiae. In this chapter, we describe our multistep approach in which we first characterize a site-directed mutant of the factor of interest using in vivo and in vitro assays of protein synthesis. Next, we subject the mutant gene to random mutagenesis and screen for second-site mutations that restore the factor's function in vivo. Following biochemical and in vivo characterization of the suppressor mutant, we interpret the results in light of the 3-D structure of the factor to define the structure-function properties of the factor and to provide new molecular insights into the mechanism of translation. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shin, BS (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. OI Dever, Thomas/0000-0001-7120-9678 NR 22 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374191-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2007 VL 429 BP 185 EP 201 DI 10.1016/S0076-6879(07)29009-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BGT14 UT WOS:000250401900009 PM 17913624 ER PT J AU Olsen, ECB Lee, SE Simons-Morton, BG AF Olsen, Erik C. B. Lee, Suzanne E. Simons-Morton, Bruce G. TI Eye movement patterns for novice teen drivers - Does 6 months of driving experience make a difference? SO TRANSPORTATION RESEARCH RECORD LA English DT Article ID DECISION-MAKING; VISUAL-SEARCH; TASKS AB Attention to the road is essential to safe driving, but the development of appropriate eye glance scanning behaviors may require substantial driving experience. Novice teen drivers may focus almost exclusively on the road ahead rather than scanning the mirrors, and when performing secondary tasks, they may spend more time with eyes on the task than on the road. This paper examines the extent to which the scanning of novice teens improves with experience. For this study, 18 novice teen (younger than 17.5 years old) and 18 experienced adult drivers performed a set of in-vehicle tasks and a baseline driving segment on a test track, the teens within 4 weeks of licensure and then again 6 months later. This paper addresses the following questions: Did teen eye glance performance improve from initial assessment? Did teens and adults still differ after 6 months? Results for some tasks showed that rearview and left mirror-window (LM-W) glances improved for teens from initial testing to the 6-month follow-up and that some differences between teens and adults at initial testing were no longer significant at the 6-month follow-up, suggesting significant learning effects. The frequency of rearview and LM-W glances during secondary tasks improved among teens at the 6-month follow-up, but teens still had significantly fewer glances to Mirrors than did adults when engaged in a secondary task. C1 [Olsen, Erik C. B.; Simons-Morton, Bruce G.] NICHHD, Bethesda, MD 20892 USA. [Lee, Suzanne E.] Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA. RP Olsen, ECB (reprint author), NICHHD, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM olsene@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 37 TC 5 Z9 6 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0361-1981 J9 TRANSPORT RES REC JI Transp. Res. Record PY 2007 IS 2009 BP 8 EP 14 DI 10.3141/2009-02 PG 7 WC Engineering, Civil; Transportation; Transportation Science & Technology SC Engineering; Transportation GA 258YZ UT WOS:000252907600002 ER PT J AU Resnicow, KR Shaikh, A AF Resnicow, Ken R. Shaikh, Abdul BE Kushner, RF Bessesen, DH TI Motivational Interviewing in Medical Settings Application to Obesity Conceptual Issues and Evidence Review SO TREATMENT OF THE OBESE PATIENT SE Contemporary Endocrinology Series LA English DT Article; Book Chapter DE Obesity; motivational interviewing; counseling; client-centered ID PRENATAL SMOKING-CESSATION; HEALTH-CARE PROFESSIONALS; AFRICAN-AMERICAN CHURCHES; WEIGHT-CONTROL PROGRAM; GENERAL-PRACTICE; PHYSICAL-ACTIVITY; BLACK CHURCHES; PEDIATRIC OBESITY; CONTROLLED-TRIAL; UNITED-STATES AB Counseling by health care professionals represents a potentially important component of the public health response to rising rates of obesity in the United States. One promising approach to weight control counseling is motivational interviewing (MI). This manuscript explores conceptual issues related to the application of MI for the prevention and treatment of obesity in medical practice. Given the paucity of studies on MI and obesity, we examine what is known about the application of MI to adult diet and physical activity behaviors, as well as the use of MI to modify weight, diet, and activity in children and adolescents. We begin with a brief overview of MI and describe some nuances of applying this approach to obesity counseling. Recommendations for future research and clinical practice are also presented. C1 [Resnicow, Ken R.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Shaikh, Abdul] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Resnicow, KR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. NR 71 TC 1 Z9 1 U1 3 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-59745-400-1 J9 CONTEMP ENDOCRINOL S PY 2007 BP 321 EP 339 DI 10.1007/978-1-59745-400-1_17 D2 10.1007/978-1-59745-400-1 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BNO59 UT WOS:000275130100018 ER PT S AU Vahabzadeh, M Lin, JL Epstein, DH Mezghanni, M Schmittner, J Preston, KL AF Vahabzadeh, Massoud Lin, Jia-Ling Epstein, David H. Mezghanni, Mustapha Schmittner, John Preston, Kenzie L. BE Kokol, P Podgorelec, V MiceticTurk, D Zorman, M Verlic, M TI Computerized Contingency Management for Motivating Behavior Change: Automated Tracking and Dynamic Reward Reinforcement Management SO TWENTIETH IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 20th IEEE International Symposium on Computer-Based Medical Systems CY JUN 20-22, 2007 CL Maribor, SLOVENIA SP IEEE Comp Soc TCCM, Fac Elect Engn & Comp Sci, Fac Hlth Sci ID THERAPY AB Contingency management has been successfully used to reinforce abstinence in drug-dependent patients. The major challenge associated with this technique, however, is its likely prohibitive cost especially, when the reinforcement follows an escalating amount schedule. At our clinic, we have implemented a less costly approach involving prize draws as the reinforcer. Workflow, challenges of such an implementation are extensive considering varying conditions concurrently used in various protocols for meeting inclusion criteria, stratifying into various groups, tracking categories of prizes, determining eligibility for bonus draws based on laboratory results, etc. To address these challenges we implemented the Automated Contingency Management (A CM) decision support system for dynamic reward reinforcement in the study of treatment of cocaine and opiates. A discussion of the results of our research as well as possible insight into some of our findings provided by ACM is presented in this C1 [Vahabzadeh, Massoud; Lin, Jia-Ling; Epstein, David H.; Schmittner, John; Preston, Kenzie L.] Natl Inst Drug Abuse, Natl Inst Hlth, DHHS, Intramural Res Program, Baltimore, MD 21224 USA. [Mezghanni, Mustapha] Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. RP Vahabzadeh, M (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, DHHS, Intramural Res Program, Baltimore, MD 21224 USA. EM massoudv@nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural Research Program of the NIH; National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 11 TC 0 Z9 0 U1 1 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 978-0-7695-2905-9 J9 COMP MED SY PY 2007 BP 85 EP + DI 10.1109/CBMS.2007.35 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Computer Science, Information Systems; Engineering, Biomedical SC Computer Science; Engineering GA BGL02 UT WOS:000248094800015 ER PT S AU Vahabzadeh, M Lin, JL Mezghanni, M Contoreggi, C Leff, M AF Vahabzadeh, Massoud Lin, Jia-Ling Mezghanni, Mustapha Contoreggi, Carlo Leff, Michelle BE Kokol, P Podgorelec, V MiceticTurk, D Zorman, M Verlic, M TI An EHR-Based multi-site recruiting system for clinical trials SO TWENTIETH IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 20th IEEE International Symposium on Computer-Based Medical Systems CY JUN 20-22, 2007 CL Maribor, SLOVENIA SP IEEE Comp Soc TCCM, Fac Elect Engn & Comp Sci, Fac Hlth Sci ID INTERVIEW AB Optimizing screening and evaluation process is essential in maximizing recruiting potential participants into clinical trials. We developed a clinical recruiting system used in the management of human research studies whereby recruiting for various protocols are conducted at multiple sites by different groups with process interdependencies. The system is developed based on a multi-tier architecture with a series of real-time and on-demand decision support systems to increase the efficiency of screening and evaluation of participants during a recruiting process. It simulates various conditions by using derivation rules and recruiting templates for automatic generation of checklists in order to recommend the optimum selection rules based on existing participants' data and is seamlessly integrated into our large Human Research Information System, a comprehensive electronic health record (EHR) system for research participants. C1 [Vahabzadeh, Massoud; Lin, Jia-Ling; Contoreggi, Carlo; Leff, Michelle] NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Mezghanni, Mustapha] Johns Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. RP Vahabzadeh, M (reprint author), NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. EM massoudv@nih.gov FU NIH; National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 10 TC 0 Z9 0 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 978-0-7695-2905-9 J9 COMP MED SY PY 2007 BP 331 EP + DI 10.1109/CBMS.2007.20 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Computer Science, Information Systems; Engineering, Biomedical SC Computer Science; Engineering GA BGL02 UT WOS:000248094800055 ER PT J AU Waltz, P Chodick, G AF Waltz, Paul Chodick, Gabriel TI International comparisons of prostate cancer mortality rates with dietary practices and sunlight levels SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Waltz, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN-FEB PY 2007 VL 25 IS 1 BP 85 EP 85 DI 10.1016/j.urolonc.2006.09.010 PG 1 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 129AY UT WOS:000243702000014 PM 17208145 ER PT S AU Caspi, RR AF Caspi, Rachel R. BE Pleyer, U Foster, CS TI Immunotherapy of Uveitis: is Gene Therapy in our Future? SO UVEITIS AND IMMUNOLOGICAL DISORDERS SE Essentials in Ophthalmology LA English DT Article; Book Chapter ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; KOYANAGI-HARADA-DISEASE; T-CELLS; IN-VIVO; ADENOASSOCIATED VIRUS; POSTERIOR UVEITIS; ELECTRIC PULSE; TGF-BETA; ANTIGEN; EXPRESSION C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 56 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1612-3212 BN 978-3-540-30798-3 J9 ESSENT OPHTHALMOL PY 2007 BP 193 EP 210 DI 10.1007/978-3-540-30798-3_13 D2 10.1007/978-3-540-30798-3 PG 18 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BNP79 UT WOS:000275189200013 ER PT S AU Cohen, MD AF Cohen, Mitchell D. BE Kustin, K Pessoa, JC Crans, DC TI Toxicity of Vanadium Compounds: Pulmonary and Immune System Targets SO VANADIUM: THE VERASTILE METAL SE ACS SYMPOSIUM SERIES LA English DT Proceedings Paper CT 5th International Symposium on Chemistry and Biological Chemistry of Vanadium CY SEP 10-14, 2006 CL San Francisco, CA ID OIL FLY-ASH; PROTEIN-TYROSINE PHOSPHATASES; RABBIT ALVEOLAR MACROPHAGES; MESSENGER-RNA EXPRESSION; AIRWAY EPITHELIAL-CELLS; AMMONIUM META-VANADATE; NF-KAPPA-B; IN-VITRO; RAT LUNG; GENE-EXPRESSION AB Inhalation is the most prevalent route of human exposure to insoluble pentavalent vanadium(V) oxides and soluble salts in urban/occupational settings. While initial pulmonary clearance of both soluble and insoluble forms of V is fairly rapid, complete clearance/degree of absorption of any V agent is ultimately a function of its solubility. Nevertheless, there are still several general toxicologic outcomes that arise from lung deposition of various V agents (as pure compounds or V-contaminated dusts). Workers exposed to V-bearing dusts or fumes display an. increased incidence of several lung diseases (e.g., asthma, bronchitis, pneumonia). Similarly, after deposition of urban particulate matter (PM) or residual oil fly ash (ROFA), animals develop states of immunomodulation (inflammation, neutrophilic alveolitis, modified resistance to infection) that correlate with the levels of V in the particles. This presentation focused on how general (and in some cases agent-specific) mechanisms have been formulated to explain how entrained V agents induce toxicity and immunomodulation in the lungs. C1 NYU, NIEHS, Ctr Excellence, Dept Environm Med,Sch Med, Tuxedo Pk, NY 10987 USA. RP Cohen, MD (reprint author), NYU, NIEHS, Ctr Excellence, Dept Environm Med,Sch Med, Tuxedo Pk, NY 10987 USA. NR 125 TC 3 Z9 3 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-7446-4 J9 ACS SYM SER PY 2007 VL 974 BP 217 EP 239 PG 23 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Physical SC Biochemistry & Molecular Biology; Chemistry GA BKS16 UT WOS:000269059400017 ER PT J AU Ballantyne, C Nambi, V Chambless, L Hu, Y Coresh, J Ni, H Folsom, A Sharrett, A Boerwinkle, E Hoogeveen, R AF Ballantyne, Christie Nambi, Vijay Chambless, Lloyd Hu, Yijuan Coresh, Josef Ni, Hanyu Folsom, Aaron Sharrett, A. Boerwinkle, Eric Hoogeveen, Ron TI Inflammatory biomarkers LpPLA2 and CRP for prediction of first ischemic stroke SO VASCULAR MEDICINE LA English DT Meeting Abstract C1 Methodist DeBakey Heart Ctr, Houston, TX USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NHLBI, NIH, Bethesda, MD USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2007 VL 12 IS 2 MA 20 BP 146 EP 146 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 181XT UT WOS:000247470400027 ER PT J AU Starost, MF AF Starost, M. F. TI Solitary biliary hamartoma with cholelithiasis in a domestic rabbit (Oryctolagus cuniculus) SO VETERINARY PATHOLOGY LA English DT Article DE biliary; hamartoma; liver; Oryctolagus; rabbits ID GALLBLADDER MUCOSAL FUNCTION; BILE-DUCT HAMARTOMA; MEYENBURG COMPLEXES; VASCULAR HAMARTOMAS; LIVER; DOG; CHOLESTEROL; ADENOFIBROMA; CALF AB Hamartomas of the liver and biliary system are extremely rare entities in both animals and humans. Biliary hamartomas in humans are usually multiple and constitute the von Meyenburg complexes. This report describes the presence of a large solitary mass arising from the edge of the right medial liver lobe of a domestic rabbit. Histologically, the mass was composed of an extensive network of large varying sized cystic structures lined by simple cuboidal to columnar epithelium within an abundant fibrous stroma. Within many of the cyst lumina were varying sized, pale white to greenish hard concretions identified as choleliths and were analyzed and found to be composed of calcium carbonate. This is the first known report of biliary hamartoma, with cholelithiasis in rabbits. C1 NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. RP Starost, MF (reprint author), NIH, Off Res Serv, Div Vet Resources, Bldg 28A,Room 106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM starostm@mail.nih.gov FU Intramural NIH HHS NR 32 TC 5 Z9 6 U1 0 U2 2 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JAN PY 2007 VL 44 IS 1 BP 92 EP 95 DI 10.1354/vp.44-1-92 PG 4 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 123NB UT WOS:000243301500012 PM 17197630 ER PT S AU Kline, K Lawson, KA Yu, WP Sanders, BG AF Kline, Kimberly Lawson, Karla A. Yu, Weiping Sanders, Bob G. BE Litwack, G TI Vitamin E and cancer SO VITAMIN E: VITAMINS AND HORMONES ADVANCES IN RESEARCH AND APPLICATIONS SE Vitamins and Hormones LA English DT Review; Book Chapter ID ALPHA-TOCOPHERYL-SUCCINATE; MAMMARY-TUMOR BURDEN; RANDOMIZED CONTROLLED-TRIAL; SIGNAL-REGULATED KINASE; GROWTH-FACTOR-BETA; BREAST-CANCER; PROSTATE-CANCER; GAMMA-TOCOPHEROL; INDUCED APOPTOSIS; E ANALOGS AB Perhaps not Surprisingly. vitamin E which has been touted to be potentially beneficial for a variety of disorders, including cancer, heart disease, and even Alzheimer's disorder, based on its function as an antioxidant has failed to withstand the scrutiny of recent, double-blinded, placebo-controlled clinical trials, including failure to provide science-based support for vitamin E as a potent anticancer agent. Although less studied, vitamin E forms other than RRR-alpha-tocopherol or synthetic all-rac-alpha-tocopherol show promise as anticancer agents in preclinical studies. This chapter will (1) review basic information about natural and synthetic vitamin E compounds as well as vitamin E analogues, (2) summarize the current status of human intervention trials, (3) review data from preclinical cell culture and animal model studies of vitamin E compounds and novel vitamin E-based analogues in regards to future potential for cancer treatment, and (4) summarize some of the insights that have been gained into the anticancer mechanisms of action of vitamin E-based compounds which are providing interesting insights into their potent proapoptotic effects, which include restoration of apoptotic signaling pathways and blockage of prosurvival signaling events. (C) 2007 Elsevier Inc. C1 [Kline, Kimberly] Univ Texas Austin, Div Nutr, Austin, TX 78712 USA. [Lawson, Karla A.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Yu, Weiping; Sanders, Bob G.] Univ Texas Austin, Sch Biol Sci, Austin, TX 78712 USA. RP Kline, K (reprint author), Univ Texas Austin, Div Nutr, Austin, TX 78712 USA. FU Public Health Service [CA59739]; Foundation for Research; American Institute for Cancer Research FX This work is Supported by Public Health Service Grant CA59739 (to K.K. and B.G.S.), the Foundation for Research (to K.K. and B.G.S.), and American Institute for Cancer Research Grant (to W.Y.). NR 119 TC 43 Z9 44 U1 2 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-373592-8 J9 VITAM HORM JI Vitam. Horm. PY 2007 VL 76 BP 435 EP 461 DI 10.1016/S0083-6729(07)76017-X PG 27 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BID45 UT WOS:000258685900017 PM 17628185 ER PT J AU Wingood, GM DiClemente, RJ Mikhail, I McCree, DH Davies, SL Hardin, JW Peterson, SH Hook, EW Saag, M AF Wingood, Gina M. DiClemente, Ralph J. Mikhail, Isis McCree, Donna Hubbard Davies, Susan L. Hardin, James W. Peterson, Shani Harris Hook, Edward W. Saag, Mike TI HIV discrimination and the health of women living with HIV SO WOMEN & HEALTH LA English DT Article DE HIV discrimination; women ID GENDER DISCRIMINATION; RISK-FACTORS; STIGMA; MEN; CARDIA; AIDS AB Women living, with HIV are especially vulnerable to discrimination because of the stigma associated with the disease, as well as their race, gender and class status. To investigate the association between self-reported HIV discrimination and health outcomes among African-American and white women living with HIV, 366 women living with HIV were recruited from HIV/AIDS clinics in Georgia and Alabama. In this cross-sectional study, participants completed an interview that assessed self-reported HIV discrimination and depressive symptomatology, suicidal ideation, self-esteem, stress, quality of life, sexual health and HIV/AIDS related health care seeking. Nearly-a sixth of the sample reported experiencing HIV discrimination. Women reporting HIV discrimination had higher mean scores for stress, suicidal ideation, depressive symptoms, number of unprotected sexual episodes; they had lower mean scores for self-esteem, and quality of life, and were more likely to have not sought medical care for HIV/AIDS. In race-specific analyses, none of the relationships between HIV discrimination and health outcomes were significant for white women. African-American women who reported HIV discrimination had higher mean scores for stress, suicidal ideation, depressive symptoms, number of unprotected sexual episodes: they had lower mean scores for self-esteem, and quality of life, and were more likely not to have Sought medical care for HIV/AIDS. The findings indicated that HIV discrimination adversely affects women's mental, sexual and physical health. However. separate race-specific analyses indicated that compared to white women, African-American women were markedly more likely to experience the adverse affects of HIV discrimination. Eradication of HIV discrimination remains an important public health priority. C1 [Wingood, Gina M.; DiClemente, Ralph J.; Peterson, Shani Harris] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Wingood, Gina M.; DiClemente, Ralph J.] Emory Univ, Rollins Sch Publ Hlth, Emory Ctr AIDS Res, Atlanta, GA 30322 USA. [DiClemente, Ralph J.] Emory Univ, Dept Med, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. [Mikhail, Isis] NCI, US Natl Inst Hlth, Bethesda, MD USA. [McCree, Donna Hubbard] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. [Davies, Susan L.] Univ Alabama, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA. [Hardin, James W.] Univ So Calif, Dept Epidemiol & Biostat, Los Angeles, CA USA. [Hook, Edward W.] Univ Alabama, Dept Med, Sch Med, Div Infect Dis, Birmingham, AL 35294 USA. RP Wingood, GM (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd,NE,BSHE Room 556, Atlanta, GA 30322 USA. EM gwingoo@sph.ernory.edu RI Hardin, James/Q-7617-2016 OI Hardin, James/0000-0003-0506-5500 NR 26 TC 44 Z9 44 U1 1 U2 11 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2007 VL 46 IS 2-3 BP 99 EP 112 DI 10.1300/J013v46n02_07 PG 14 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 247WO UT WOS:000252113500008 PM 18160372 ER PT J AU Ekker, SC Stemple, DL Clark, M Chien, CB Rasooly, RS Javois, LC AF Ekker, Stephen C. Stemple, Derek L. Clark, Matthew Chien, Chi-Bin Rasooly, Rebekah S. Javois, Lorette C. TI Zebrafish Genome Project: Bringing New Biology to the Vertebrate Genome Field SO ZEBRAFISH LA English DT Editorial Material C1 [Ekker, Stephen C.] Mayo Clin, Ctr Canc, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. [Stemple, Derek L.; Clark, Matthew] Wellcome Trust Sanger Inst, Cambridge, England. [Chien, Chi-Bin] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT USA. [Rasooly, Rebekah S.] NIDDK, DKUH, NIH, Bethesda, MD USA. [Javois, Lorette C.] NICHD, NIH, Bethesda, MD USA. RP Ekker, SC (reprint author), Mayo Clin, Ctr Canc, Dept Biochem & Mol Biol, 200 1st St SW, Rochester, MN 55905 USA. EM Ekker.Stephen@mayo.edu OI Rasooly, Rebekah/0000-0002-6357-5528 NR 0 TC 12 Z9 12 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2007 VL 4 IS 4 BP 239 EP 251 DI 10.1089/zeb.2007.9979 PG 13 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18EA UT WOS:000207986900002 PM 18284331 ER PT J AU Luzzio, FA Duveau, DY Figg, WD AF Luzzio, Frederick A. Duveau, Damien Y. Figg, William D. TI A chiral pool approach toward the synthesis of thalidomide metabolites SO HETEROCYCLES LA English DT Article DE thalidomide; angiogenesis; nitroaldol; valerolactam; phthaloylation ID ANGIOGENESIS; ANALOGS; DERIVATIVES; FUMAGILLIN; INHIBITOR; CANCER; ALPHA; CELLS; ACID AB A synthetic strategy toward the glutarimide-derived metabolite of thalidomide, 5'-hydroxythalidomide (5'-OH THD, 2) was developed which utilizes aspartic acid as a "chiral pool"-type starting material. The synthesis incorporates a Henry reaction as the key carbon-carbon bond-forming step followed by a tandem reduction-cyclization of the intermediate nitroalcohol in forming the heterocyclic core of 5'-OH THD. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Luzzio, FA (reprint author), Univ Louisville, Dept Chem, 2320 S Brook St, Louisville, KY 40292 USA. RI Figg Sr, William/M-2411-2016 NR 18 TC 4 Z9 4 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 31 PY 2006 VL 70 BP 321 EP + PG 15 WC Chemistry, Organic SC Chemistry GA 139OY UT WOS:000244442800036 ER PT J AU Toyooka, N Zhou, DJ Nemoto, H Garraffo, HM Spande, TF Daly, JW AF Toyooka, Naoki Zhou, Dejun Nemoto, Hideo Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Chiral synthesis of poison-frog alkaloids 251N and 221K SO HETEROCYCLES LA English DT Article DE poison-frog alkaloid; 251N; 221K; 5,8-disubstituted indolizidine; nicotinic receptor ID NICOTINIC ACETYLCHOLINE-RECEPTORS; POTENT AB The chiral synthesis of 8-butyl 5-substituted poison-frog alkaloids 251N and 221K has been achieved, and the relative stereochemistry of natural 251N was determined by the present chiral synthesis. C1 Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM toyooka@pha.u-toyama.ac.jp NR 7 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 31 PY 2006 VL 70 BP 541 EP + PG 9 WC Chemistry, Organic SC Chemistry GA 139OY UT WOS:000244442800050 ER PT J AU Isaac, J AF Isaac, John TI Rapid, activity-dependent plasticity in timing precision in neonatal barrel cortex SO MOLECULAR PAIN LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD DEC 30 PY 2006 VL 2 AR 38 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 165CB UT WOS:000246280300016 ER PT J AU Woo, N AF Woo, Newton TI Regulation of bi-directional plasticity by BDNF SO MOLECULAR PAIN LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD DEC 30 PY 2006 VL 2 AR 38 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 165CB UT WOS:000246280300038 ER PT J AU Lee, JY Yang, W AF Lee, Jae Young Yang, Wei TI UvrD helicase unwinds DNA one base pair at a time by a two-part power stroke SO CELL LA English DT Article ID ESCHERICHIA-COLI UVRD; SINGLE-STRANDED-DNA; CRYSTAL-STRUCTURE; REP HELICASE; STEP-SIZE; ATP HYDROLYSIS; RECBCD ENZYME; PCRA HELICASE; GENE-PRODUCT; DUPLEX DNA AB Helicases use the energy derived from nucleoside triphosphate hydrolysis to unwind double helices in essentially every metabolic pathway involving nucleic acids. Earlier crystal structures have suggested that DNA helicases translocate along a single-stranded DNA in an inchworm fashion, We report here a series of crystal structures of the UvrD helicase complexed with DNA and ATP hydrolysis intermediates. These structures reveal that ATP binding alone leads to unwinding of 1 base pair by directional rotation and translation of the DNA duplex, and ADP and Pi release leads to translocation of the developing single strand. Thus DNA unwinding is achieved by a two-part power stroke in a combined wrench-and-inchworm mechanism. The rotational angle and translational distance of DNA define the unwinding step to be 1 base pair per ATP hydrolyzed. Finally, a gateway for ssDNA translocation and an alternative strand-displacement mode may explain the varying step sizes reported previously. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK036119-10] NR 52 TC 209 Z9 210 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 29 PY 2006 VL 127 IS 7 BP 1349 EP 1360 DI 10.1016/j.cell.2006.10.049 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 128WI UT WOS:000243690000015 PM 17190599 ER PT J AU Sramko, M Markus, J Kabat, J Wolff, L Bies, J AF Sramko, Marek Markus, Jan Kabat, Juraj Wolff, Linda Bies, Juraj TI Stress-induced inactivation of the c-Myb transcription factor through conjugation of SUMO-2/3 proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEGATIVE REGULATORY DOMAIN; V-MYB; PHOSPHORYLATION SITE; HEMATOPOIETIC-CELLS; SIGNAL-TRANSDUCTION; TOPOISOMERASE-II; BINDING PROTEIN; HEAT-SHOCK; ACTIVATION; TRANSACTIVATION AB Post-translational modifications, such as phosphorylation, acetylation, ubiquitination, and SUMOylation, play an important role in regulation of the stability and the transcriptional activity of c-Myb. Conjugation of small ubiquitin-like modifier type 1 (SUMO-1) to lysines in the negative regulatory domain strongly suppresses its transcriptional activity. Here we report conjugation of two other members of the SUMO protein family, SUMO-2 and SUMO-3, and provide evidence that this post-translational modification negatively affects transcriptional activity of c-Myb. Conjugation of SUMO-2/3 proteins is strongly enhanced by several different cellular stresses and occurs primarily on two lysines, Lys523 and Lys499. These lysines are in the negative regulatory domain of c-Myb and also serve as acceptor sites for SUMO-1. Stress-induced SUMO-2/3 conjugation is very rapid and independent of activation of stress-activated protein kinases of the SAPK and JNK families. PIAS-3 protein was identified as a new c-Myb-specific SUMO-E3 ligase that both catalyzes conjugation of SUMO-2/3 proteins to c-Myb and exerts a negative effect on c-Myb-induced reporter gene activation. Interestingly, co-expression of a SPRING finger mutant of PIAS-3 significantly suppresses SUMOylation of c-Myb under stress. These results argue that PIAS-3 SUMO-E3 ligase plays a critical role in stress-induced conjugation of SUMO-2/3 to c-Myb. We also detected stress-induced conjugation of SUMO-2/3 to c-Myb in hematopoietic cells at the levels of endogenously expressed proteins. Furthermore, according to the negative role of SUMO conjugation on c-Myb capacity, we have observed rapid stress-induced down-regulation of the targets genes c-myc and bcl-2 of c-Myb. Our findings demonstrate that SUMO-2/3 proteins conjugate to c-Myb and negatively regulate its activity in cells under stress. C1 Slovak Acad Sci, Canc Res Inst, Ctr Mol Med, Bratislava 83391, Slovakia. NIAID, Biol Imaging Facil, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Bies, J (reprint author), Bldg 37,Rm 4124,37 Convent Dr, Bethesda, MD 20892 USA. EM bies@helix.nih.gov NR 58 TC 33 Z9 34 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 DEC 29 PY 2006 VL 281 IS 52 BP 40065 EP 40075 DI 10.1074/jbc.M609404200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119SP UT WOS:000243033900036 PM 17077080 ER PT J AU Kar, S Choi, EJ Guo, F Dimitriadis, EK Kotova, SL Adhya, S AF Kar, Sudeshna Choi, Eugene J. Guo, Fusheng Dimitriadis, Emilios K. Kotova, Svetlana L. Adhya, Sankar TI Right-handed DNA supercoiling by an octameric form of histonelike protein HU - Modulation of cellular transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; BINDING; CHROMATIN; RECOMBINATION; EXPRESSION AB In bacteria, the contribution of global nucleoid organization in determining cellular transcription programs is unclear. Using a mutant form of the most abundant nucleoid-associated protein HU, HU alpha(E38K,V42L), we previously showed that nucleoid remodeling by the mutant protein re-organizes the global transcription pattern. Here, we demonstrate that, unlike the dimeric wild-type HU, HU alpha(E38K,V42L), is an octamer and wraps DNA around its surface. The formation of wrapped nucleoprotein complexes by HU alpha(E38K,V42L) leads to a high degree of DNA condensation. The DNA wrapping is right-handed, which restrains positive supercoils. In vivo, HU alpha(E38K,V42L) shows altered association and distribution patterns with the genetic loci whose transcription are differentially affected in the mutant strain. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Instrumentat Res & Dev Resource, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), 37 Convent Dr,Rm 5138, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 28 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 2006 VL 281 IS 52 BP 40144 EP 40153 DI 10.1074/jbc.M605576200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119SP UT WOS:000243033900044 PM 17062578 ER PT J AU Johnston, D Tavano, C Wickner, S Trun, N AF Johnston, Danielle Tavano, Christine Wickner, Sue Trun, Nancy TI Specificity of DNA binding and dimerization by CspE from Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-STRANDED-DNA; SHOCK PROTEIN; BACILLUS-SUBTILIS; TRANSCRIPTION COMPLEXES; CRYSTAL-STRUCTURE; RNA; FAMILY; GENE; IDENTIFICATION; REPLICATION AB The CspE protein from Escherichia coli K12 is a single-stranded nucleic acid-binding protein that plays a role in chromosome condensation in vivo. We report here that CspE binds to single-stranded DNA containing 6 or more contiguous dT residues with high affinity (K-D < 30 nM). The interactions are predominantly through base-specific contacts. When an oligonucleotide contains fewer than 6 contiguous dT residues, the CspE interactions with single-stranded DNA are primarily electrostatic. The minimal length of single-stranded DNA to which CspE binds in a salt-resistant manner is eight nucleotides. We also show that CspE exists as a dimer in solution. We present a possible mechanism to explain the role of CspE in chromosome condensation in vivo by CspE binding to distant DNA regions in the chromosome and dimerizing, thereby condensing the intervening DNA. C1 Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20895 USA. RP Trun, N (reprint author), Duquesne Univ, Dept Biol Sci, 600 Forbes Ave,256 Mellon Hall, Pittsburgh, PA 15282 USA. EM trun@duq.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM65121-01] NR 40 TC 7 Z9 8 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 2006 VL 281 IS 52 BP 40208 EP 40215 DI 10.1074/jbc.M606414200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119SP UT WOS:000243033900051 PM 17088256 ER PT J AU Hassan, MQ Tare, RS Lee, SH Mandeville, M Morasso, MI Javed, A van Wijnen, AJ Stein, JL Stein, GS Lian, JB AF Hassan, Mohammad Q. Tare, Rahul S. Lee, Suk Hee Mandeville, Matthew Morasso, Maria I. Javed, Amjad van Wijnen, Andre J. Stein, Janet L. Stein, Gary S. Lian, Jane B. TI BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; OSTEOBLAST DIFFERENTIATION; OSTEOCALCIN GENE; CHONDROCYTE DIFFERENTIATION; PROGRESSIVE DEVELOPMENT; OVERLAPPING EXPRESSION; VERTEBRATE DEVELOPMENT; PROMOTES OSTEOGENESIS; SKELETAL DEVELOPMENT; HOMEOBOX GENES AB Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2. However, there is a gap in our knowledge of the regulatory cascade from BMP2 signaling to the onset of osteogenesis. Here we show that BMP2 induces DLX3, a homeodomain protein that activates Runx2 gene transcription. Small interfering RNA knockdown studies in osteoblasts validate that DLX3 is a potent regulator of Runx2. Furthermore in Runx2 null cells, DLX3 forced expression suffices to induce transcription of Runx2, osteocalcin, and alkaline phosphatase genes, thus defining DLX3 as an osteogenic regulator independent of RUNX2. Our studies further show regulation of the Runx2 gene by several homeodomain proteins: MSX2 and CDP/cut repress whereas DLX3 and DLX5 activate endogenous Runx2 expression and promoter activity in non-osseous cells and osteoblasts. These HD proteins exhibit distinct temporal expression profiles during osteoblast differentiation as well as selective association with Runx2 chromatin that is related to Runx2 transcriptional activity and recruitment of RNA polymerase II. Runx2 promoter mutagenesis shows that multiple HD elements control expression of Runx2 in relation to the stages of osteoblast maturation. Our studies establish mechanisms for commitment to the osteogenic lineage directly through BMP2 induction of HD proteins DLX3 and DLX5 that activate Runx2, thus delineating a transcriptional regulatory pathway mediating osteoblast differentiation. We propose that the three homeodomain proteins MSX2, DLX3, and DLX5 provide a key series of molecular switches that regulate expression of Runx2 throughout bone formation. C1 Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01655 USA. NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. RP Lian, JB (reprint author), Univ Massachusetts, Sch Med, Dept Cell Biol, 55 Lake Ave N, Worcester, MA 01655 USA. EM jane.lian@umassmed.edu OI Javed, Amjad/0000-0002-0847-8266 FU NIAMS NIH HHS [AR48818, R01 AR049069, AR39588]; NIDCR NIH HHS [DE12528] NR 62 TC 128 Z9 135 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 29 PY 2006 VL 281 IS 52 BP 40515 EP 40526 DI 10.1074//jbc.M604508200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119SP UT WOS:000243033900081 PM 17060321 ER PT J AU Kikusui, T Winslow, JT Mori, Y AF Kikusui, Takefumi Winslow, James T. Mori, Yuji TI Social buffering: relief from stress and anxiety SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE social buffering; stress responses; social affiliation; glucocorticoids; oxytocin ID PITUITARY-ADRENAL AXIS; MESSENGER-RNA EXPRESSION; HAMSTER PHODOPUS-SUNGORUS; UNFAMILIAR ADULT FEMALE; BEHAVIORAL-RESPONSES; SQUIRREL-MONKEY; ALARM PHEROMONE; GUINEA-PIGS; MALE-RATS; RHESUS-MONKEYS AB Communication is essential to members of a society not only for the expression of personal information, but also for the protection from environmental threats. Highly social mammals have a distinct characteristic: when conspecific animals are together, they show a better recovery from experiences of distress. This phenomenon, termed 'social buffering', has been found in rodents, birds, non-human primates and also in humans. This paper reviews classical findings on social buffering and focuses, in particular, on social buffering effects in relation to neuroendocrine stress responses. The social cues that transmit social buffering signals, the neural mechanisms of social buffering and a partner's efficacy with respect to social buffering are also detailed. Social contact appears to have a very positive influence on the psychological and the physiological aspects of social animals, including human beings. Research leading towards further understanding of the mechanisms of social buffering could provide alternative medical treatments based on the natural, individual characteristics of social animals, which could improve the quality of life. C1 Univ Tokyo, Lab Vet Ethol, Bunkyo Ku, Tokyo 1138657, Japan. NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. RP Kikusui, T (reprint author), Univ Tokyo, Lab Vet Ethol, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan. EM akikus@mail.ecc.u-tokyo.ac.jp NR 190 TC 149 Z9 150 U1 11 U2 53 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 EI 1471-2970 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD DEC 29 PY 2006 VL 361 IS 1476 BP 2215 EP 2228 DI 10.1098/rstb.2006.1941 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 114SI UT WOS:000242685500012 PM 17118934 ER PT J AU Dagdug, L Berezhkovskii, AM AF Dagdug, Leonardo Berezhkovskii, Alexander M. TI Diffusion-limited binding to a site on the wall of a membrane channel SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE NUMBER FLUCTUATIONS; ION-CHANNEL; TRANSPORT; DYNAMICS; KINETICS; ESCAPE AB The authors develop a theory of diffusion-controlled reactions with a site located on the wall of a cylindrical membrane channel that connects two reservoirs containing diffusing particles which are trapped by the site at the first contact. An expression for the Laplace transform of the rate coefficient, k(t), is derived assuming that the size of the site is small compared to the channel radius. The expression is used to find the stationary value of the rate coefficient, k(infinity), as a function of the length and radius of the channel, the radius of the site, and its position inside the channel (distances from the two ends of the channel) as well as the particle diffusion constants in the bulk and in the channel. Their derivation is based on the one-dimensional description of the particle motion in the channel, which is generalized to include binding to the site into consideration. The validity of the approximate one-dimensional description of diffusion and binding was checked by three-dimensional Brownian dynamics simulations. They found that the one-dimensional description works reasonably well when the size of the site does not exceed 0.2 of the channel radius. (c) 2006 American Institute of Physics. C1 Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dagdug, L (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. FU Intramural NIH HHS NR 23 TC 8 Z9 8 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 28 PY 2006 VL 125 IS 24 AR 244705 DI 10.1063/1.2409682 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 121LB UT WOS:000243158000035 PM 17199366 ER PT J AU Somu, RV Wilson, DJ Bennett, EM Boshoff, HI Celia, L Beck, BJ Barry, CE Aldrich, CC AF Somu, Ravindranadh V. Wilson, Daniel J. Bennett, Eric M. Boshoff, Helena I. Celia, Laura Beck, Brian J. Barry, Clifton E., III Aldrich, Courtney C. TI Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of the glycosyl domain SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NONRIBOSOMAL PEPTIDE SYNTHETASES; TRANSFER-RNA SYNTHETASE; MYCOBACTERIUM-TUBERCULOSIS; ADENYLATION DOMAINS; IRON ACQUISITION; SALICYLATE SYNTHASE; CRYSTAL-STRUCTURE; STAPHYLOCOCCUS-AUREUS; BIOLOGICAL EVALUATION; YERSINIA-PESTIS AB Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction. C1 Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA. NIAID, Tuberculosis Res Stn, Rockville, MD 20852 USA. Amer Type Culture Collect, Bacteriol Program, Manassas, VA 20110 USA. RP Aldrich, CC (reprint author), Univ Minnesota, Ctr Drug Design, Acad Hlth Ctr, Minneapolis, MN 55455 USA. EM aldri015@umn.edu RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-15]; NIAID NIH HHS [R01 AI 070219, R01 AI070219, R01 AI070219-01] NR 79 TC 47 Z9 50 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 28 PY 2006 VL 49 IS 26 BP 7623 EP 7635 DI 10.1021/jm061068d PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 118WL UT WOS:000242974100010 PM 17181146 ER PT J AU Morrell, A Antony, S Kohlhagen, G Pommier, Y Cushman, M AF Morrell, Andrew Antony, Smitha Kohlhagen, Glenda Pommier, Yves Cushman, Mark TI A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA COVALENT COMPLEX; BIOLOGICAL EVALUATION; MJ-III-65 NSC-706744; ANTICANCER ACTIVITY; CLEAVAGE COMPLEXES; CAMPTOTHECIN; DESIGN; MECHANISM; BASE; ORIENTATION AB The biological activity of indenoisoquinoline topoisomerase I inhibitors is significantly enhanced by nitration of the isoquinoline ring. In the present study, nitrated analogues were synthesized with the indenone ring substituted with methoxy groups to further explore a previously identified structure-activity relationship between the nitrated isoquinoline ring and a methylenedioxy-substituted indenone ring. The results indicate that a single methoxy group at the 9-position of an indenoisoquinoline affords superior biological activity. Hypothetical binding models have been developed to rationalize these results, and they indicate that pi-stacking between the indenoisoquinolines and the DNA base pairs, as visualized by electrostatic complementarity, is important for the intercalation and biological activity of the indenoisoquinoline analogues. Collectively, the analysis of methoxy groups on the indenone ring also illustrates a strict steric requirement for substituents extending toward the nonscissile DNA backbone and emphasizes a need for planarity to afford potent biological activity. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharmaceut Sci, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharmaceut Sci, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [ST32 CA 09634-12, T32 CA009634, U01 CA 89566, U01 CA089566, U01 CA089566-01A1, U01 CA089566-02, U01 CA089566-03, N01 CO 56000, U01 CA089566-04, U01 CA089566-05]; NCRR NIH HHS [C06 RR 14499] NR 38 TC 53 Z9 53 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 28 PY 2006 VL 49 IS 26 BP 7740 EP 7753 DI 10.1021/jm060974n PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 118WL UT WOS:000242974100020 PM 17181156 ER PT J AU Andreani, A Burnelli, S Granaiola, M Leoni, A Locatelli, A Morigi, R Rambaldi, M Varoli, L Farruggia, G Stefanelli, C Masotti, L Kunkel, MW AF Andreani, Aldo Burnelli, Silvia Granaiola, Massimiliano Leoni, Alberto Locatelli, Alessandra Morigi, Rita Rambaldi, Mirella Varoli, Lucilla Farruggia, Giovanna Stefanelli, Claudio Masotti, Lanfranco Kunkel, Mark W. TI Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-CELL-LINES; AGENTS; DRUGS; INHIBITORS; DEATH AB The design and synthesis of antitumor imidazothiazole guanylhydrazones are reported. The compounds were submitted to NCI for testing. All but one were more active than methyl-GAG. A few compounds were selected for further studies in search of a possible mechanism of action. The results from these studies and a final search with the NCI COMPARE algorithm suggest that the guanylhydrazones described in this paper are acting through a novel mechanism of action. C1 Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy. Univ Bologna, Dipartimento Biochim G Moruzzi, I-40126 Bologna, Italy. NCI, Dev Therapeut Program, Informat Technol Branch, Div Canc Treatment & Diagnosis, Rockville, MD 20892 USA. RP Andreani, A (reprint author), Univ Bologna, Dipartimento Sci Farmaceut, Via Belmeloro 6, I-40126 Bologna, Italy. EM aldo.andreani@unibo.it OI STEFANELLI, CLAUDIO/0000-0001-5864-2178; LEONI, ALBERTO/0000-0001-8528-8207; Farruggia, Giovanna/0000-0003-3599-7034 NR 21 TC 17 Z9 17 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 28 PY 2006 VL 49 IS 26 BP 7897 EP 7901 DI 10.1021/jm061077m PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 118WL UT WOS:000242974100037 PM 17181173 ER PT J AU Toptygin, D Gronenborn, AM Brand, L AF Toptygin, Dmitri Gronenborn, Angela M. Brand, Ludwig TI Nanosecond relaxation dynamics of protein GB1 identified by the time-dependent red shift in the fluorescence of tryptophan and 5-fluorotryptophan SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID IMMUNOGLOBULIN-BINDING DOMAIN; LIVER ALCOHOL-DEHYDROGENASE; POLAR SOLVATION DYNAMICS; BOVINE SERUM-ALBUMIN; RESOLVED FLUORESCENCE; SOLVENT RELAXATION; ENERGY LANDSCAPES; EMISSION-SPECTRA; DECAY; MATRIX AB The B1 domain of Streptococcal protein G (GB1) is a small, thermostable protein containing a single tryptophan residue. We recorded time-resolved fluorescence of the wild-type GB1 and its 5-fluorotryptophan (5FTrp) variant at more than 30 emission wavelengths between 300 and 470 nm. The time-resolved emission spectra reveal no signs of heterogeneity, but show a time-dependent red shift characteristic of microscopic dielectric relaxation. This is true for both 5FTrp and unmodified Trp in GB1. The time-dependent red shifts in the fluorescence of 5FTrp and unmodified Trp are essentially identical, confirming that the shift is caused by the relaxation of the protein matrix rather than by the fluorophore itself. The total amplitude (but not the rate) of the time-dependent red shift depends on the fluorophore, specifically, on the magnitude of the vector difference between its excited state and ground state electric dipole moments; for 5FTrp this is estimated to be about 88% of that for the unmodified Trp. The decay of the excited state fluorophore population is not monoexponential for either fluorophore; however, the deviation from the monoexponential decay law is larger in the case of unmodified Trp. The relaxation dynamics of GB1 was found to be considerably faster than that of other proteins studied previously, consistent with the small size, tightly packed core, and high thermodynamic stability of GB1. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Toptygin, D (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. EM toptygin@jhu.edu OI Gronenborn, Angela M/0000-0001-9072-3525 FU Intramural NIH HHS NR 45 TC 45 Z9 45 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 28 PY 2006 VL 110 IS 51 BP 26292 EP 26302 DI 10.1021/jp064528n PG 11 WC Chemistry, Physical SC Chemistry GA 118WN UT WOS:000242974300106 PM 17181288 ER PT J AU Young, WS Li, J Wersinger, SR Palkovits, M AF Young, W. S. Li, J. Wersinger, S. R. Palkovits, M. TI The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy SO NEUROSCIENCE LA English DT Article DE social memory; aggression; corpora amylacea; paraventricular nucleus ID HAMSTERS MESOCRICETUS-AURATUS; PASSIVE-AVOIDANCE BEHAVIOR; TEMPORAL-LOBE EPILEPSY; FLANK-MARKING BEHAVIOR; SOCIAL RECOGNITION; LATERAL SEPTUM; MESSENGER-RNA; V1B RECEPTOR; SELECTIVE VULNERABILITY; MAGNOCELLULAR NEURONS AB The vasopressin 1b receptor (Avpr1b) is one of two principal receptors mediating the behavioral effects of vasopressin (Avp) in the brain. Avpr1b has recently been shown to strongly influence social forms of aggression in mice and hamsters. This receptor appears to play a role in social recognition and motivation as well as in regulating the hypothalamic-pituitary-adrenal axis. Most of these studies have been performed in knockout mice, a species in which the localization of the Avpr1b has not been described, thus precluding correlations with the behaviors. We performed in situ hybridization histochemistry (ISHH) with specific probes and found especially prominent expression within the CA2 pyramidal neurons of the hippocampus, with much lower expression in the hypothalamic paraventricular nucleus and amygdala. Reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed expression in those as well other areas in which the ISHH was not sensitive enough to detect labeled cells (e.g. piriform cortex, septum, caudate-putamen and lower brainstem areas). Mouse Avpr1b transcript levels were not altered in the CA2 field by restraint stress or adrenalectomy. Finally, ISHH and RT-PCR showed expression of the Avpr1b gene in the rat and human hippocampi as well. We suggest that the CA2 field may form or retrieve associations (memories) between olfactory cues and social encounters. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Neuromorphol Lab, H-1094 Budapest, Hungary. Semmelweis Univ, H-1094 Budapest, Hungary. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, 9000 Rockville Pike,Bldg 49,Room 5A56, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; chen, xuanlan/H-4158-2011; Palkovits, Miklos/F-2707-2013; OI Young, W Scott/0000-0001-6614-5112; Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002498, Z01 MH002498-16] NR 67 TC 95 Z9 97 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 28 PY 2006 VL 143 IS 4 BP 1031 EP 1039 DI 10.1016/j.neuroscience.2006.08.040 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 116SN UT WOS:000242822700010 PM 17027167 ER PT J AU Barnes, AM Chang, WZ Morello, R Cabral, WA Weis, MA Eyre, DR Leikin, S Makareeva, E Kuznetsova, N Uveges, TE Ashok, A Flor, AW Mulvihill, JJ Wilson, PL Sundaram, UT Lee, B Marini, JC AF Barnes, Aileen M. Cliang, Weizhong Morello, Roy Cabral, Wayne A. Weis, MaryAnn Eyre, David R. Leikin, Sergey Makareeva, Elena Kuznetsova, Natalia Uveges, Thomas E. Ashok, Aarthi Flor, Armando W. Mulvihill, John J. Wilson, Patrick L. Sundaram, Usha T. Lee, Brendan Marini, Joan C. TI Brief report: Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BRITTLE BONE-DISEASE; I PROCOLLAGEN; CDNA CLONING; TRIPLE-HELIX; COLLAGEN; MUTATIONS; GENES; CRTAP; FORM; ENZYME AB Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Rm 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Leikin, Sergey/A-5518-2008; Makareeva, Elena/F-5183-2011 OI Leikin, Sergey/0000-0001-7095-0739; FU NIAMS NIH HHS [R01 AR036794, AR37318, R37 AR037318]; NICHD NIH HHS [HD22657]; NIDCR NIH HHS [DE016990] NR 25 TC 159 Z9 168 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 28 PY 2006 VL 355 IS 26 BP 2757 EP 2764 DI 10.1056/NEJMoa063804 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 120UA UT WOS:000243110500008 PM 17192541 ER PT J AU Bennett, JE AF Bennett, John E. TI Echinocandins for candidemia - The author replies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID VORICONAZOLE C1 NIAID, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 28 PY 2006 VL 355 IS 26 BP 2792 EP 2792 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 120UA UT WOS:000243110500029 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI Libya, HIV, and open communication SO RETROVIROLOGY LA English DT Editorial Material ID HCV AB This year-end editorial discusses several points including the recent Libyan verdict sentencing five Bulgarian nurses and a Palestinian doctor to death for allegedly infecting 426 children with HIV. It also comments on the role played by open communication for bridging cultural misunderstandings and summarizes briefly Retrovirology's progress in 2006. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 9 TC 2 Z9 2 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 28 PY 2006 VL 3 AR 99 DI 10.1186/1742-4690-3-99 PG 2 WC Virology SC Virology GA 129IU UT WOS:000243723000001 PM 17194303 ER PT J AU Nyaga, SG Lohani, A Jaruga, P Trzeciak, AR Dizdaroglu, M Evans, MK AF Nyaga, Simon G. Lohani, Althaf Jaruga, Pawel Trzeciak, Andrzej R. Dizdaroglu, Miral Evans, Michele K. TI Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937 SO BMC CANCER LA English DT Article ID OXIDATIVE DNA-DAMAGE; AP LYASE ACTIVITY; SACCHAROMYCES-CEREVISIAE; GLYCOSYLASE ACTIVITY; BASE LESIONS; OGG1 PROTEIN; 8-OXOGUANINE; BRCA1; GENE; EXCISION AB Background: Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua), which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134. Methods: We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/ mass spectrometry (LC/MS) was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H2O2 followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RTPCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H2O2-mediated oxidative stress. Results: We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H2O2 treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H2O2 and have upregulated SOD1 and SOD2. Conclusion: This study provides evidence for inefficient repair of 8-OH-Gua in HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect. C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. Nicolas Copernicus Univ, Collegium Medicum, Dept Clin Biochem, Bydgoszcz, Poland. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM nyagas@grc.nia.nih.gov; lohania@grc.nia.nih.gov; pawel.jaruga@nist.gov; trzeciakan@grc.nia.nih.gov; miral.dizdar@nist.gov; me42v@nih.gov RI Jaruga, Pawel/M-4378-2015 FU Intramural NIH HHS NR 52 TC 19 Z9 21 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 27 PY 2006 VL 6 AR 297 DI 10.1186/1471-2407-6-297 PG 15 WC Oncology SC Oncology GA 128KX UT WOS:000243657700001 PM 17192190 ER PT J AU Pearson, SD Miller, FG Emanuel, EJ AF Pearson, Steven D. Miller, Franklin G. Emanuel, Ezekiel J. TI Medicare requirement for research participation - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM spearson99@yahoo.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 27 PY 2006 VL 296 IS 24 BP 2924 EP 2925 DI 10.1001/jama.296.24.2924-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 120FD UT WOS:000243069000019 ER PT J AU Carandang, R Seshadri, S Beiser, A Kelly-Hayes, M Kase, CS Kannel, WB Wolf, PA AF Carandang, Raphael Seshadri, Sudha Beiser, Alexa Kelly-Hayes, Margaret Kase, Carlos S. Kannel, William B. Wolf, Philip A. TI Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ACUTE ISCHEMIC-STROKE; CASE-FATALITY; INCIDENCE RATES; CARDIOVASCULAR-DISEASE; INTERNATIONAL TRENDS; PRIMARY PREVENTION; UNITED-STATES; NEW-ZEALAND; LUND-ORUP AB Context Prior estimates of long-term trends in the incidence and severity of stroke have varied; trends in lifetime risk have not been reported. Objective To determine long-term trends in the incidence, lifetime risk, severity, and 30-day mortality of clinical stroke. Design, Setting, and Participants Prospective evaluation of the community-based Framingham Study original and offspring cohorts. Participants were 9152 men and women free of prevalent stroke and undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977, 1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data and active surveillance for incident clinical stroke and cause-specific mortality. Main Outcome Measures Incidence (age-adjusted, sex-specific), severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of stroke in each of the specified periods. Results There were 1030 incident clinical strokes ( 450 [44%] in men, 629 atherothrombotic brain infarctions [61%]) in 9152 persons 55 years or older over 174 917 person-years of follow-up. The age-adjusted incidence of first stroke per 1000 person-years in each of the 3 periods was 7.6, 6.2, and 5.3, respectively, in men (P=. 02 for trend) and 6.2, 5.8, and 5.1 in women ( P=. 01 for trend). The lifetime risk at age 65 years decreased from 19.5% to 14.5% in men ( P=. 11) and from 18.0% to 16.1% in women ( P=. 61). Age-adjusted stroke severity did not vary across periods; however, 30-day mortality decreased significantly in men ( from 23% to 14%; P=. 01) but not significantly in women ( from 21% to 20%; P=. 32). Conclusions In this cohort of men and women free of prevalent clinical stroke at initial examination, incidence of stroke has decreased over the past 50 years but the lifetime risk has not declined to the same degree, perhaps due to improved life expectancy. The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Wolf, PA (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-608, Boston, MA 02118 USA. EM pawolf@bu.edu FU NHLBI NIH HHS [N01-HC-25195]; NINDS NIH HHS [5R01-NS17950] NR 56 TC 231 Z9 237 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 27 PY 2006 VL 296 IS 24 BP 2939 EP 2946 DI 10.1001/jama.296.24.2939 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 120FD UT WOS:000243069000025 PM 17190894 ER PT J AU Rhyu, MR Lu, J Webster, DE Fabricant, DS Farnsworth, NR Wang, ZJ AF Rhyu, Mee-Ra Lu, Jian Webster, Donna E. Fabricant, Daniel S. Farnsworth, Norman R. Wang, Z. Jim TI Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE black cohosh; menopause; hot flashes; opiate; botanical dietary supplement ID MENOPAUSAL HOT FLASHES; UP HERS-II; POSTMENOPAUSAL WOMEN; ESTROGEN/PROGESTIN REPLACEMENT; HORMONE-THERAPY; CLIMACTERIC COMPLAINTS; DISEASE OUTCOMES; RANDOMIZED-TRIAL; SYMPTOMS; ESTROGEN AB Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Because the opiate system in the brain is intimately associated with mood, temperature, and sex hormonal levels, the activity of black cohosh extracts at the human mu opiate receptor (hMOR) expressed in Chinese hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2-propanol extracts of black cohosh effectively displaced the specific binding of [H-3]DAMGO to hMOR. Further studies of the clinically used ethanol extract indicated that black cohosh acted as a mixed competitive ligand, displacing 77 +/- 4% [H-3]DAMGO to hMOR (K-i = 62.9 mu g/mL). Using the [S-35]GTP gamma S assay, the action of black cohosh was found to be consistent with an agonist, with an EC50 of 68.8 +/- 7.7 mu g/mL. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms. C1 Univ Illinois, Dept Biopharmaceut Sci, Coll Pharm, Chicago, IL 60612 USA. NIH, UIC, Dept Med Chem & Pharmacognosy, Ctr Bot Dietary Supplements Res, Chicago, IL USA. Univ Illinois, Program Collaborat Res Pharmaceut Sci, Coll Pharm, Chicago, IL 60612 USA. RP Wang, ZJ (reprint author), Univ Illinois, Dept Biopharmaceut Sci, Coll Pharm, 833 S Woods St, Chicago, IL 60612 USA. EM zjwang@uic.edu OI Lu, Jian/0000-0003-3468-137X FU NCCIH NIH HHS [R21 AT002406, AT000155, AT003476, F31 AT002669, F31AT002669, P50 AT000155, R21 AT002406-02, R21 AT003476, R21 AT003476-01, R21 AT003476-02]; NIDA NIH HHS [DA005050] NR 58 TC 26 Z9 29 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD DEC 27 PY 2006 VL 54 IS 26 BP 9852 EP 9857 DI 10.1021/jf062808u PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 118KR UT WOS:000242941700032 PM 17177511 ER PT J AU Wen, R Song, Y Kjellstrom, S Tanikawa, A Liu, Y Li, YW Zhao, L Bush, RA Laties, AM Sieving, PA AF Wen, Rong Song, Ying Kjellstrom, Sten Tanikawa, Atsuhiro Liu, Yun Li, Yiwen Zhao, Lian Bush, Ronald A. Laties, Alan M. Sieving, Paul A. TI Regulation of rod phototransduction machinery by ciliary neurotrophic factor SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CNTF; phototransduction; Muller cells; ERG; electroretinogram; retina; rod ID RHODOPSIN KNOCKOUT MOUSE; CELLS IN-VITRO; RETINAL-DEGENERATION; RETINITIS-PIGMENTOSA; OUTER SEGMENTS; B-WAVE; PHOTORECEPTOR DEGENERATION; SYMPATHETIC NEURONS; DARK-ADAPTATION; MOTOR-NEURONS AB Ciliary neurotrophic factor ( CNTF) promotes photoreceptor survival but also suppresses electroretinogram ( ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it is considered to be a potential treatment for retinal degenerative disorders. Here we report that the suppression of ERG responses is attributable to negative regulation of the phototransduction machinery in rod photoreceptors. Intravitreal injection of recombinant human CNTF protein in rat results in a series of biochemical and morphological changes in rod photoreceptors. CNTF induces a decrease in rhodopsin expression and an increase in arrestin level. Morphologically, CNTF treatment causes a shortening of rod outer segments (ROS). All of these changes are fully reversible. The lower rhodopsin level and shortened ROS reduce the photon catch of rods. Less rhodopsin and more arrestin dramatically increase the arrestin-to-rhodopsin ratio so that more arrestin molecules are available to quench the photoexcited rhodopsin. The overall effect of CNTF is to negatively regulate the phototransduction machinery, which reduces the photoresponsiveness of rods, resulting in lower ERG amplitude at a given intensity of light stimulus. The CNTF-induced changes in rods are similar to those in light-induced photoreceptor plasticity. Whether CNTF-induced changes in rods are through the same mechanism that mediates light-induced photoreceptor plasticity remains to be answered. C1 Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Wen, R (reprint author), Univ Penn, Sch Med, Dept Ophthalmol, D-603 Richards Bldg, Philadelphia, PA 19104 USA. EM rwen@mail.med.upenn.edu FU Intramural NIH HHS; NEI NIH HHS [EY-015289, EY-12727] NR 65 TC 55 Z9 57 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 27 PY 2006 VL 26 IS 52 BP 13523 EP 13530 DI 10.1523/JNEUROSCI.4021-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 123DZ UT WOS:000243277800013 PM 17192435 ER PT J AU Englund, EA Xu, Q Witschi, MA Appella, DH AF Englund, Ethan A. Xu, Qun Witschi, Mark A. Appella, Daniel H. TI PNA-DNA duplexes, triplexes, and quadruplexes are stabilized with trans-cyclopentane units SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PEPTIDE NUCLEIC-ACIDS; BINDING; DISCRIMINATION; OLIGOMER; INVASION; IMPROVES; DNA/RNA; PH C1 NIDDK, Bioorgan Chem Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov RI Xu, Qun /C-6996-2011 FU Intramural NIH HHS NR 18 TC 25 Z9 25 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 27 PY 2006 VL 128 IS 51 BP 16456 EP 16457 DI 10.1021/ja064317w PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 118KQ UT WOS:000242941600022 PM 17177367 ER PT J AU Lazar, KL Kurutz, JW Tycko, R Meredith, SC AF Lazar, Kristi L. Kurutz, Josh W. Tycko, Robert Meredith, Stephen C. TI Encapsulation and NMR on an aggregating peptide before fibrillogenesis SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEINS; MECHANISM; DISEASE; MEMORY; BRAIN C1 Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Chicago, Dept Chem, Chicago, IL 60637 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Meredith, SC (reprint author), Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. EM scmeredi@uchicago.edu FU NHLBI NIH HHS [HL 07237]; NINDS NIH HHS [NS 042852] NR 13 TC 4 Z9 4 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 27 PY 2006 VL 128 IS 51 BP 16460 EP 16461 DI 10.1021/ja064999n PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 118KQ UT WOS:000242941600024 PM 17177369 ER PT J AU Lehrmann, E Colantuoni, C Deep-Soboslay, A Becker, KG Lowe, R Huestis, MA Hyde, TM Kleinman, JE Freed, WJ AF Lehrmann, Elin Colantuoni, Carlo Deep-Soboslay, Amy Becker, Kevin G. Lowe, Ross Huestis, Marilyn A. Hyde, Thomas M. Kleinman, Joel E. Freed, William J. TI Transcriptional Changes Common to Human Cocaine, Cannabis and Phencyclidine Abuse SO PLOS ONE LA English DT Article AB A major goal of drug abuse research is to identify and understand drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex ( aPFC) from 42 human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and drug abuse history. Common transcriptional changes were demonstrated for a majority of drug abuse cases (N = 34), representing a number of consistently changed functional classes: Calmodulin-related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased. Quantitative PCR validated decreases in calmodulin 2 (CALM2) mRNA and increases in apolipoprotein L, 2 (APOL2) and semaphorin 3B (SEMA3B) mRNA for individual cases. A comparison between control cases with and without cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a decrease in transcription of calmodulin-related genes and increased transcription related to lipid/cholesterol and Golgi/ER function. These changes represent common molecular features of drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers. C1 [Lehrmann, Elin; Freed, William J.] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. [Colantuoni, Carlo; Deep-Soboslay, Amy; Hyde, Thomas M.; Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, GCAP, Intramural Res Program,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Becker, Kevin G.] NIA, Res Resources Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Lehrmann, Elin; Lowe, Ross; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Lehrmann, E (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. EM elehrman@intra.nida.nih.gov OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656 FU Intramural Research Programs at the NIDA, NIMH; NIA, NIH, DHHS FX This study was funded by the Intramural Research Programs at the NIDA, NIMH and NIA, NIH, DHHS. NR 46 TC 27 Z9 30 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 27 PY 2006 VL 1 IS 2 AR e114 DI 10.1371/journal.pone.0000114 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DC UT WOS:000207443700008 PM 17205118 ER PT J AU Radhakrishnan, R Arora, K Wang, YL Beard, WA Wilson, SH Schlick, T AF Radhakrishnan, Ravi Arora, Karunesh Wang, Yanli Beard, William A. Wilson, Samuel H. Schlick, Tamar TI Regulation of DNA repair fidelity by molecular checkpoints: "Gates" in DNA polymerase beta's substrate selection SO BIOCHEMISTRY LA English DT Article ID INDUCED-FIT MECHANISM; BASE EXCISION-REPAIR; ACTIVE-SITE; DYNAMICS SIMULATIONS; CRYSTAL-STRUCTURE; NUCLEOTIDE INCORPORATION; STRUCTURAL INSIGHTS; SUBDOMAIN MOTIONS; KINETIC ANALYSES; SINGLE-MOLECULE AB With an increasing number of structural, kinetic, and modeling studies of diverse DNA polymerases in various contexts, a complex dynamical view of how atomic motions might define molecular "gates" or checkpoints that contribute to polymerase specificity and efficiency is emerging. Such atomic-level information can offer insights into rate-limiting conformational and chemical steps to help piece together mechanistic views of polymerases in action. With recent advances, modeling and dynamics simulations, subject to the well-appreciated limitations, can access transition states and transient intermediates along a reaction pathway, both conformational and chemical, and such information can help bridge the gap between experimentally determined equilibrium structures and mechanistic enzymology data. Focusing on DNA polymerase beta (pol beta), we present an emerging view of the geometric, energetic, and dynamic selection criteria governing insertion rate and fidelity mechanisms of DNA polymerases, as gleaned from various computational studies and based on the large body of existing kinetic and structural data. The landscape of nucleotide insertion for pol beta includes conformational changes, prechemistry, and chemistry "avenues", each with a unique deterministic or stochastic pathway that includes checkpoints for selective control of nucleotide insertion efficiency. For both correct and incorrect incoming nucleotides, pol beta's conformational rearrangements before chemistry include a cascade of slow and subtle side chain rearrangements, followed by active site adjustments to overcome higher chemical barriers, which include critical ion-polymerase geometries; this latter notion of a prechemistry avenue fits well with recent structural and NMR data. The chemical step involves an associative mechanism with several possibilities for the initial proton transfer and for the interaction among the active site residues and bridging water molecules. The conformational and chemical events and associated barriers define checkpoints that control enzymatic efficiency and fidelity. Understanding the nature of such active site rearrangements can facilitate interpretation of existing data and stimulate new experiments that aim to probe enzyme features that contribute to fidelity discrimination across various polymerases via such geometric, dynamic, and energetic selection criteria. C1 NYU, Dept Chem, New York, NY 10012 USA. NYU, Courant Inst Math Sci, New York, NY 10012 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Schlick, T (reprint author), NYU, Dept Chem, 550 1St Ave, New York, NY 10012 USA. EM schlick@nyu.edu RI Radhakrishnan, Ravi/A-2964-2011 FU Intramural NIH HHS [Z01 ES050158-09]; NIEHS NIH HHS [R01 ES012692, R01 ES012692-03]; NIGMS NIH HHS [R01 GM055164, R01 GM055164-06, R01 GM55164] NR 86 TC 53 Z9 53 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 DEC 26 PY 2006 VL 45 IS 51 BP 15142 EP 15156 DI 10.1021/bi061353z PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600002 PM 17176036 ER PT J AU Lee, DY Park, SJ Jeong, W Sung, HJ Oho, T Wu, XW Rhee, SG Gruschus, JM AF Lee, Duck-Yeon Park, Sung Jun Jeong, Woojin Sung, Ho Jin Oho, Taena Wu, Xiongwu Rhee, Sue Goo Gruschus, James M. TI Mutagenesis and modeling of the peroxiredoxin (Prx) complex with the NMR structure of ATP-bound human sulfiredoxin implicate aspartate 187 of Prx I as the catalytic residue in ATP hydrolysis SO BIOCHEMISTRY LA English DT Article ID CYSTEINE SULFINIC ACID; CHEMICAL-SHIFT; MAMMALIAN SULFIREDOXIN; 2-CYS PEROXIREDOXIN; HYDROGEN-PEROXIDE; CRYSTAL-STRUCTURE; PROTEIN; MECHANISM; C-13; DOCKING AB The catalytic cysteine of certain members of the peroxiredoxin (Prx) family can be hyperoxidized to cysteinesulfinic acid during reduction of peroxides. Sulfiredoxin is responsible for the ATP-dependent reduction of cysteinesulfinic acid (SO2H) of hyperoxidized Prx. Here we report the NMR solution structure of human sulfiredoxin (hSrx), both with and without bound ATP, and we model the complex of ATP-bound hSrx with Prx. Binding ATP causes only small changes in the NMR structure of hSrx, and the bound ATP conformation is quite similar to that seen for the previously reported X-ray structure of the ADP-hSrx complex. Although hSrx binds ATP, it does not catalyze hydrolysis by itself and has no catalytic acid residue typical of most ATPase and kinase family proteins. For modeling the complex, the ATP-bound hSrx was docked to hyperoxidized Prx II using EMAP of CHARMM. In the model complex, Asn186 of Prx II (Asp187 of Prx I) is in contact with the hSrx-bound ATP beta- and gamma-phosphate groups. Asp187 of Prx I was mutated to alanine and asparagine, and binding and activity of the mutants with hSrx were compared to those of the wild type. For the D187N mutant, both binding and hydrolysis and reduction activities were comparable to those of the wild type, whereas for D187A, binding was unimpaired but ATP hydrolysis and reduction did not occur. The modeling and mutagenesis analyses strongly implicate Asp187 of Prx I as the catalytic residue responsible for ATP hydrolysis in the cysteinesulfinic acid reduction of Prx by hSrx. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Gruschus, JM (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 38 TC 18 Z9 18 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15301 EP 15309 DI 10.1021/bi061824h PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600018 PM 17176052 ER PT J AU Cutalo, JM Darden, TA Kunkel, TA Tomer, KB AF Cutalo, Jenny M. Darden, Thomas A. Kunkel, Thomas A. Tomer, Kenneth B. TI Mapping the dimer interface in the C-terminal domains of the yeast MLH1-PMS1 heterodimer SO BIOCHEMISTRY LA English DT Article ID DNA MISMATCH REPAIR; NUCLEIC ACID INTERACTIONS; MASS-SPECTROMETRY; CHEMICAL-MODIFICATION; MOLECULAR CHARACTERIZATION; MUTL HOMOLOGS; COMPLEXES; GLYCOPROTEIN; PROTEINS; ANTIBODY AB Yeast MutL alpha is a heterodimer of MLH1 and PMS1 that participates in a variety of DNA transactions, including DNA mismatch repair. Formation of the MutL alpha heterodimer requires that the C-terminal domains of MLH1 and PMS1 interact in a manner that is not yet fully understood. Here we investigate the interactions involved in heterodimerization. Using protein surface modification and mass spectrometry, we identify numerous lysine residues that are exposed to solvent in monomeric MLH1. A corresponding analysis of the MLH1-PMS1 heterodimer reveals that three of these exposed residues, K665, K675, and K704, are no longer solvent accessible in the heterodimer, suggesting that they are within the dimer interface. We refine secondary structure predictions and sequence alignments of C-terminal residues of seven eukaryotic MutL homologues and then develop homology models for the N- and C-terminal domains of MLH1. On the basis of this information, we present a model for interaction of the C-terminal domains of MLH1 and PMS1. C1 NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Oral Biol, Chapel Hill, NC 27599 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 32 TC 9 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15458 EP 15467 DI 10.1021/bi061392a PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600033 PM 17176067 ER PT J AU DeMarco, ML Silveira, J Caughey, B Daggett, V AF DeMarco, Mari L. Silveira, Jay Caughey, Byron Daggett, Valerie TI Structural properties of prion protein protofibrils and fibrils: An experimental assessment of atomic models SO BIOCHEMISTRY LA English DT Article ID INDUCED CONFORMATIONAL CONVERSION; SCRAPIE-ASSOCIATED FORM; IN-VITRO FORMATION; X-RAY-DIFFRACTION; AMYLOID FIBRIL; COMMON MECHANISM; EARLY STEPS; PRP; ANTIBODIES; AGGREGATION AB Decades after the prion protein was implicated in transmissible spongiform encephalopathies, the structure of its toxic isoform and its mechanism of toxicity remain unknown. By gathering available experimental data, albeit low resolution, a few pieces of the prion puzzle can be put in place. Currently, there are two fundamentally different models of a prion protofibril. One has its building blocks derived from a molecular dynamics simulation of the prion protein under amyloidogenic conditions, termed the spiral model. The other model was constructed by threading a portion of the prion sequence through a beta-helical structure from the Protein Data Bank. Here we compare and contrast these models with respect to all of the available experimental information, including electron micrographs, symmetries, secondary structure, oligomerization interfaces, enzymatic digestion, epitope exposure, and disaggregation profiles. Much of this information was not available when the two models were introduced. Overall, we find that the spiral model is consistent with all of the experimental results. In contrast, it is difficult to reconcile several of the experimental observables with the beta-helix model. While the experimental constraints are of low resolution, in bringing together the previously disconnected experiments, we have developed a clearer picture of prion aggregates. Both the improved characterization of prion aggregates and the existing atomic models can be used to devise further experiments to better elucidate the misfolding pathway and the structure of prion protofibrils. C1 Univ Washington, Dept Med Chem, Biomol Struct & Design Program, Seattle, WA 98195 USA. NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. RP Daggett, V (reprint author), Univ Washington, Dept Med Chem, Biomol Struct & Design Program, Seattle, WA 98195 USA. EM daggett@u.washington.edu FU NIGMS NIH HHS [GM-50789, T32 GM-07750] NR 67 TC 48 Z9 48 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15573 EP 15582 DI 10.1021/bi0612723 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600044 PM 17176078 ER PT J AU Soubias, O Polozov, IV Teague, WE Yeliseev, AA Gawrisch, K AF Soubias, Olivier Polozov, Ivan V. Teague, Walter E. Yeliseev, Alexei A. Gawrisch, Klaus TI Functional reconstitution of rhodopsin into tubular lipid bilayers supported by nanoporous media SO BIOCHEMISTRY LA English DT Article ID SOLID-STATE NMR; PROTEIN-COUPLED RECEPTOR; METARHODOPSIN II FORMATION; ALUMINUM-OXIDE NANOPORES; ANGLE NEUTRON-SCATTERING; DETERGENT REMOVAL; NANOTUBE ARRAYS; POROUS ALUMINA; MEMBRANES; SPECTROSCOPY AB We report on a novel reconstitution method for G-protein-coupled receptors (GPCRs) that yields detergent-free, single, tubular membranes in porous anodic aluminum oxide (AAO) filters at concentrations sufficient for structural studies by solid-state NMR. The tubular membranes line the inner surface of pores that traverse the filters, permitting easy removal of detergents during sample preparation as well as delivery of ligands for functional studies. Reconstitution of bovine rhodopsin into AAO filters did not interfere with rhodopsin function. Photoactivation of rhodopsin in AAO pores, monitored by UV-vis spectrophotometry, was indistinguishable from rhodopsin in unsupported unilamellar liposomes. The rhodopsin in AAO pores is G-protein binding competent as shown by a [S-35]GTP gamma S binding assay. The lipid-rhodopsin interaction was investigated by H-2 NMR on sn-1- or sn-2-chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phospholine as a matrix lipid. Rhodopsin incorporation increased mosaic spread of bilayer orientations and contributed to spectral density of motions with correlation times in the range of nano- to microseconds, detected as a significant reduction in spin-spin relaxation times. The change in lipid chain order parameters due to interaction with rhodopsin was insignificant. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov RI Yeliseev, Alexei/B-3143-2009 FU Intramural NIH HHS NR 53 TC 17 Z9 17 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15583 EP 15590 DI 10.1021/bi061416d PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600045 PM 17176079 ER PT J AU Kimura, T AF Kimura, Tomohiro TI Human opioid peptide Met-enkephalin binds to anionic phosphatidylserine in high preference to zwitterionic phosphatidylcholine: Natural-abundance C-13 NMR study on the binding state in large unilamellar vesicles SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; METHIONINE-ENKEPHALIN; PHOSPHOLIPID-BILAYER; MOLECULAR-DYNAMICS; LEUCINE-ENKEPHALIN; AQUEOUS-SOLUTIONS; ASPARTIC-ACID; ACHATIN-I; MEMBRANES; CONFORMATION AB A human opioid neuropeptide, Met-enkephalin (M-Enk: Tyr(1)-Gly(2)-Gly(3)-Phe(4)-Met(5)), having no net charge binds to anionic phosphatidylserine (PS) in high preference to zwitterionic phosphatidylcholine (PC). The binding mechanism in the PS and PC bilayers was studied on the basis of the inter- and intramolecular interaction data obtained by natural-abundance C-13 nuclear magnetic resonance (NMR) of the peptide. Prominent upfield changes of the C-13 resonance were observed in the C-terminal residue upon binding to PS, whereas no such marked change was observed upon binding to PC. The upfield chemical shift changes with their characteristic carbon site dependence are ascribed to the electrostatic binding between the peptide C-terminal CO2- and the PS headgroup NH3+. Despite the net negative charge of the PS bilayer surface, M-Enk thus anchors the negatively charged C-terminus. In the N-terminal residue, on the other hand, marked downfield chemical shift changes are observed upon binding to both the PS and PC bilayers, the magnitude of the changes being much larger in the PS system. The downfield changes with their characteristic carbon site dependence are ascribed to the electrostatic binding between the peptide N-terminal NH3+ and the lipid headgroup negative charge(s) (CO2- or PO4- in PS, PO4- in PC). Perturbation on the signal half-widths due to membrane binding also indicates the preferential and deeper binding of M-Enk on the PS membrane surface than on the PC membrane surface. Local charge cancellation takes place efficiently between M-Enk termini and the PS headgroups and compensates for the strong electrostatic hydration of the ionic groups. Distribution of the charged (positive and negative) and uncharged sites in the headgroups along the bilayer normal is responsible for the marked difference between PS and PC headgroups in controlling the binding state of the zwitterionic M-Enk. C1 Kyoto Univ, Chem Res Inst, Uji, Kyoto 6110011, Japan. RP Kimura, T (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM kimurato@mail.nih.gov NR 44 TC 11 Z9 11 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15601 EP 15609 DI 10.1021/bi061641v PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600047 PM 17176081 ER PT J AU Smith, SV Robinson, RC Smith, TG Burks, SM Friedman, FK AF Smith, Stanley V. Robinson, Richard C. Smith, Tina G. Burks, Stephanie M. Friedman, Fred K. TI Rapid conformational dynamics of cytochrome p450 2E1 in a natural biological membrane environment SO BIOCHEMISTRY LA English DT Article ID DRUG-DRUG INTERACTIONS; CO BINDING-KINETICS; FLASH-PHOTOLYSIS; HALOTHANE HEPATITIS; OXIDATIVE STRESS; ETHANOL; CYP2E1; P450; METABOLISM; 3A4 AB Among the members of the cytochrome P450 superfamily, P450 2E1 is most often associated with the production of reactive oxygen species and subsequent cellular toxicity. We sought to identify a structural basis for this distinguishing feature of P450 2E1 by examining its carbon monoxide binding kinetics as a probe of conformation/dynamics. We employed liver microsomes from wild-type and P450 2E1 knockout mice in order to characterize this P450 in a natural membrane environment. The CO binding kinetics of the P450s of wild-type microsomes had a rapid component that was absent in the knockout microsomes. Data analysis using the maximum entropy method (MEM) correspondingly identified two distinct kinetic components in the wild-type microsomes and only one component in the knockout microsomes. The rapid kinetic component in wild-type microsomes was attributed to endogenous P450 2E1, while the slower component was derived from the remaining P450s. In addition, rapid binding kinetics and a single component were also observed for human P450 2E1 in a baculovirus expression system, in the absence of other P450s. Binding kinetics of both mouse and human P450 2E1 were slowed in the presence of ethanol, a modulator of this P450. The unusually rapid CO binding kinetics of P450 2E1 indicate that it is more dynamically mobile than other P450s and thus able to more readily interconvert among alternate conformations. This suggests that conformational switching during the catalytic cycle may promote substrate release from a short-lived binding site, allowing activated oxygen to attack other targets with toxic consequences. C1 Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Smith, SV (reprint author), Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. EM svsmith@pharmacology.umsmed.edu RI Friedman, Fred/D-4208-2016 FU Intramural NIH HHS; PHS HHS [R06/CCR419466] NR 55 TC 4 Z9 7 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 26 PY 2006 VL 45 IS 51 BP 15617 EP 15623 DI 10.1021/bi061873u PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118IL UT WOS:000242935600049 PM 17176083 ER PT J AU Quillin, ML Wingfield, PT Matthews, BW AF Quillin, Michael L. Wingfield, Paul T. Matthews, Brian W. TI Determination of solvent content in cavities in IL-1 beta using experimentally phased electron density SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hydration; protein folding; water ID HUMAN INTERLEUKIN-1-BETA; 3-DIMENSIONAL STRUCTURE; HYDROPHOBIC CAVITY; DISORDERED WATER; NMR-SPECTROSCOPY; SIDE-CHAINS; PROTEINS; REFINEMENT; RESOLUTION; MUTATIONS AB The extent to which water is present within apolar cavities in proteins remains unclear. in the case of interleukin-1 beta (IL-1 beta), four independent structures solved by x-ray crystallography indicate that water is not present in the central apolar cavity. In contrast, results from NMR spectroscopy suggest that water has high occupancy within the cavity but is positionally disordered, making it undetectable by standard crystallographic methods. A theoretically based crystallographic-phase refinement technique also suggested that there was the equivalent of two fully occupied water molecules within the apolar cavity. To resolve these discrepancies we sought to obtain an experimentally phased electron density map that was free of possible bias caused by mathematical modeling of the protein or the solvent. By combining native diffraction data with multiple wavelength anomalous data from a platinum derivative, accurate phases were obtained. Using these experimental phases, we estimate that occupancy of the apolar cavity in IL-1 beta by solvent is close or equal to zero. Polar cavities in the protein that contain ordered solvent molecules serve as internal controls. C1 Univ Oregon, Howard Hughes Med Inst, Inst Mol Biol, Eugene, OR 97403 USA. Univ Oregon, Dept Phys, Eugene, OR 97403 USA. Natl Inst Arthritis & Musculoskelatal, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Matthews, BW (reprint author), Univ Oregon, Howard Hughes Med Inst, Inst Mol Biol, Eugene, OR 97403 USA. EM brian@uoregon.edu FU NIGMS NIH HHS [GM021967, R01 GM021967] NR 40 TC 20 Z9 21 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2006 VL 103 IS 52 BP 19749 EP 19753 DI 10.1073/pnas.0609442104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500027 PM 17179045 ER PT J AU Shewmaker, F Wickner, RB Tycko, R AF Shewmaker, Frank Wickner, Reed B. Tycko, Robert TI Amyloid of the prion domain of Sup35p has an in-register parallel beta-sheet structure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE solid-state NMR ID SOLID-STATE NMR; CHAIN RELEASE FACTOR; HET-S PRION; YEAST PRION; SACCHAROMYCES-CEREVISIAE; EXPERIMENTAL CONSTRAINTS; SECONDARY STRUCTURE; POLAR ZIPPERS; FIBRILS; PROTEIN AB The [PSI+] prion of Saccharomyces cerevisiae is a self-propagating amyloid form of Sup35p, a subunit of the translation termination factor. Using solid-state NMR we have examined the structure of amyloid fibrils formed in vitro from purified recombinant Sup35(1-253), consisting of the glutamine- and asparagine-rich N-terminal 123-residue prion domain (N) and the adjacent 130-residue highly charged M domain. Measurements of magnetic dipole-dipole couplings among C-13 nuclei in a series of Sup35NM fibril samples, C-13-labeled at backbone carbonyl sites of Tyr, Leu, or Phe residues or at side-chain methyl sites of Ala residues, indicate intermolecular C-13-C-13 distances of approximate to 0.5 nm for nearly all sites in the N domain. Certain sites in the M domain also exhibit intermolecular distances of approximate to 0.5 nm. These results indicate that an in-register parallel beta-sheet structure underlies the [PSI+] prion phenomenon. C1 Natl Inst Diab & Digest & Kidney DIs, Lab Chem Phys, NIH, Bethesda, MD 20892 USA. Natl Inst Diab & Digest & Kidney DIs, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), Natl Inst Diab & Digest & Kidney DIs, Lab Chem Phys, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov; robertty@mail.nih.gov NR 59 TC 186 Z9 191 U1 4 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2006 VL 103 IS 52 BP 19754 EP 19759 DI 10.1073/pnas.0609638103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500028 PM 17170131 ER PT J AU Shu, S Mahadeo, DC Liu, X Liu, WL Parent, CA Korn, ED AF Shu, Shi Mahadeo, Dana C. Liu, Xiong Liu, Wenli Parent, Carole A. Korn, Edward D. TI S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemotaxis; Dictyostelium; neutrophils; tubercidin ID ADENOSYL-L-HOMOCYSTEINE; GREEN FLUORESCENT PROTEIN; DICTYOSTELIUM-DISCOIDEUM; PHOSPHOLIPID METHYLATION; CYCLIC-AMP; ACTIN; LEUKOCYTES; ACID; CARBOXYMETHYLATION; IDENTIFICATION AB Chemotaxis of bacteria requires regulated methylation of chemoreceptors. However, despite considerable effort in the 1980s, transmethylation has never been established as a component of eukaryotic cell chemotaxis. S-adenosylhomocysteine (SAH), the product formed when the methyl group of the universal donor S-adenosylmethionine (SAM) is transferred to an acceptor molecule, is a potent inhibitor of all transmethylation reactions. In eukaryotic cells, this inhibition is relieved by hydrolysis of SAH to adenosine and homocysteine catalyzed by SAH hydrolase (SAHH). We now report that SAHH, which is diffuse in the cytoplasm of nonmotile Dictyostelium amoebae and human neutrophils, concentrates with F-actin in pseudopods at the front of motile, chemotaxing cells, but is not present in filopodia or at the very leading edge. Tubercidin, an inhibitor of SAHH, inhibits both chemotaxis and chemotaxis-dependent cell streaming of Dictyostelium, and chemotaxis of neutrophils at concentrations that have little effect on cell viability. Tubercidin does not inhibit starvation-induced expression of the cAMP receptor, cAR1, or G protein-mediated stimulation of adenylyl cyclase activity and actin polymerization in Dictyostelium. Tubercidin has no effect on either capping of Con A receptors or phagocytosis in Dictyostelium. These results add SAHH to the list of proteins that redistribute in response to chemotactic signals in Dictyostelium and neutrophils and strongly suggest a role for transmethylation in chemotaxis of eukaryotic cells. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012 FU Intramural NIH HHS NR 52 TC 17 Z9 18 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2006 VL 103 IS 52 BP 19788 EP 19793 DI 10.1073/pnas.0609385103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500034 PM 17172447 ER PT J AU Hyun, DH Emerson, SS Jo, DG Mattson, MP de Cabo, R AF Hyun, Dong-Hoon Emerson, Scott S. Jo, Dong-Gyu Mattson, Mark P. de Cabo, Rafael TI Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's disease; reactive oxygen species; coenzyme Q10; oxidoreductase ID DIETARY RESTRICTION; ELECTRON-TRANSPORT; NEURODEGENERATIVE DISEASES; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; ANTIOXIDANT SYSTEM; LIPID-PEROXIDATION; CORTICAL-NEURONS; FOOD RESTRICTION; COENZYME-Q AB The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and alpha-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (alpha-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress. C1 NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 55 TC 119 Z9 123 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2006 VL 103 IS 52 BP 19908 EP 19912 DI 10.1073/pnas.0608008103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 123GX UT WOS:000243285500054 PM 17167053 ER PT J AU Sherman, ME Kahler, J Gustafson, KS Wang, SS AF Sherman, Mark E. Kahler, Jessica Gustafson, Karen S. Wang, Sophia S. TI "Sip volume" as a quality indicator in liquid-based cervical cytology SO CANCER CYTOPATHOLOGY LA English DT Article DE cervix; screening; quality assurance; human papillomavirus ID GLACIAL ACETIC-ACID; PAPANICOLAOU SMEARS; ABNORMALITIES; POPULATION; SPECIMENS; EFFICACY; LESIONS; TRIAGE AB BACKGROUND. introduction of nonmicroscopic cervical screening techniques creates the potential for liquid-based cytology specimens to be sent for human papillomavirus (HPV) testing, automated screening, or other assays prior to microscopic quality assessment. It was hypothesized that the volumes required to prepare ThinPreps ("sip volumes") represent indicators of specimen quality. METHODS. A stratified random sample of 505 enrollment ThinPreps were assessed in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) to evaluate associations between sip volume and slide cellularity, cellular distribution, and clinical outcomes. Masked assessments included counting cells and qualitative evaluations. RESULTS. Sip volumes were highest among women aged 18-19 or >= 35 years (P = .01), higher during the secretory menstrual phase (P < .0001), and lower among women with a history of Chlamydia infection (P = .04). Low cellularity was associated with Atypical squamous cells-cannot exclude high-grade squamous intra-epithelial lesion (ASC-H) interpretations at the clinical centers (P = .04). Sip volumes were related to cellularity (P < .0001) and cellular distribution (P < .0001). Sip volumes <= 2.0 mL were associated with lower cellularity and both low and high sip volumes yielded less homogeneous cell deposition. However, sip volume was unrelated to the overall performance of cytology and HPV testing. CONCLUSIONS. Extremely low sip volumes are associated with hypocellular ThinPreps, and very low and high sip volumes more often show uneven cellular distribution. Although results of cytology and HPV testing in ALTS were generally unrelated to sip volume, results with other protocols or assays may vary; suggesting that microscopic assessment of specimens with extreme sip volumes prior to nonmicroscopic testing may be useful. C1 NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Div Cytopathol, Dept Pathol, Baltimore, MD 21205 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov NR 25 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2006 VL 108 IS 6 BP 462 EP 467 DI 10.1002/cncr.22283 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 117MU UT WOS:000242878100003 PM 17096435 ER PT J AU Shreeram, S Hee, WK Demidov, ON Kek, C Yamaguchi, H Fornace, AJ Anderson, CW Appella, E Bulavin, DV AF Shreeram, Sathyavageeswaran Hee, Weng Kee Demidov, Oleg N. Kek, Calvina Yamaguchi, Hiroshi Fornace, Albert J., Jr. Anderson, Carl W. Appella, Ettore Bulavin, Dmitry V. TI Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-CYCLE CHECKPOINTS; ATAXIA-TELANGIECTASIA; ATM ACTIVATION; P53; AUTOPHOSPHORYLATION; PATHWAY; APOPTOSIS; CANCER; PPM1D; TUMORIGENESIS AB The ataxia telangiectasia mutated (ATM) kinase is a key tumor suppressor that regulates numerous cell cycle checkpoints as well as apoptosis. Here, we report that ATM is a critical player in the regulation of apoptosis and lymphomagenesis in the presence of c-myc. In turn, deletion of the inhibitory ATM phosphatase, Wip1, results in ATM up-regulation and suppression of E mu-myc-induced B cell lymphomas. Using mouse genetic crosses, we show that the onset of myc-induced lymphomas is dramatically delayed in Wip1-null mice in an ATM- and p53-, but not p38 MAPK- or Arf-, dependent manner. We propose that Wip1 phosphatase is critical for regulating the ATM- mediated tumor surveillance network. C1 Inst Cell & Mol Biol, Singapore 138673, Singapore. NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Bulavin, DV (reprint author), Inst Cell & Mol Biol, Singapore 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Sathyavageeswaran, Shreeram/0000-0002-6111-1818; Demidov, Oleg/0000-0003-4323-7174 FU Intramural NIH HHS NR 26 TC 77 Z9 82 U1 0 U2 5 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 DEC 25 PY 2006 VL 203 IS 13 BP 2793 EP 2799 DI 10.1084/jem.20061563 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 120QH UT WOS:000243099400002 PM 17158963 ER PT J AU Chieppa, M Rescigno, M Huang, AYC Germain, RN AF Chieppa, Marcello Rescigno, Maria Huang, Alex Y. C. Germain, Ronald N. TI Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTOR-5; NF-KAPPA-B; T-CELLS; SALMONELLA-TYPHIMURIUM; IN-VIVO; COMMENSAL BACTERIA; IMMUNE-RESPONSE; LAMINA PROPRIA; HOST-DEFENSE; PEYERS PATCH AB Cells lining the gastrointestinal tract serve as both a barrier to and a pathway for infectious agent entry. Dendritic cells (DCs) present in the lamina propria under the columnar villus epithelium of the small bowel extend processes across this epithelium and capture bacteria, but previous studies provided limited information on the nature of the stimuli, receptors, and signaling events involved in promoting this phenomenon. Here, we use immunohistochemical as well as dynamic explant and intravital two-photon imaging to investigate this issue. Analysis of CD11c-enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual "balloon" shape, varies along the length of the small bowel. High numbers of such extensions were found in the proximal jejunum, but only a few were present in the terminal ileum. The extensions in the terminal ileum markedly increased upon the introduction of invasive or noninvasive Salmonella organisms, and chimeric mouse studies revealed the key role of MyD88-dependent Toll-like receptor (TLR) signaling by nonhematopoietic (epithelial) elements in the DC extension response. Collectively, these findings support a model in which epithelial cell TLR signaling upon exposure to microbial stimuli induces active DC sampling of the gut lumen at sites distant from organized lymphoid tissues. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov RI Chieppa, Marcello/K-4846-2012; Rescigno, Maria/J-9704-2012; OI Rescigno, Maria/0000-0002-6464-509X; Chieppa, Marcello/0000-0001-9819-0823; Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS NR 58 TC 386 Z9 399 U1 0 U2 24 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 DEC 25 PY 2006 VL 203 IS 13 BP 2841 EP 2852 DI 10.1084/jem.20061884 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 120QH UT WOS:000243099400007 PM 17145958 ER PT J AU Casazza, JP Betts, MR Price, DA Precopio, ML Ruff, LE Brenchley, JM Hill, BJ Roederer, M Douek, DC Koup, RA AF Casazza, Joseph P. Betts, Michael R. Price, David A. Precopio, Melissa L. Ruff, Laura E. Brenchley, Jason M. Hill, Brenna J. Roederer, Mario Douek, Daniel C. Koup, Richard A. TI Acquisition of direct antiviral effector functions by CMV-specific CD4(+) T lymphocytes with cellular maturation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; EX-VIVO ANALYSIS; CYTOMEGALOVIRUS-INFECTION; HIV-1-INFECTED SUBJECTS; CYTOTOXIC ACTIVITY; IN-VIVO; CELLS; MEMORY; IMMUNITY AB The role of CD4(+) T cells in the control of persistent viral infections beyond the provision of cognate help remains unclear. We used polychromatic flow cytometry to evaluate the production of the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2, the chemokine macrophage inflammatory protein (MIP)-1 beta, and surface mobilization of the degranulation marker CD107a by CD4(+) T cells in response to stimulation with cytomegalovirus (CMV)-specific major histocompatibility complex class II peptide epitopes. Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4(+) T cell maturation. The functional profile of virus-specific CD4(+) T cells in chronic CMV infection was unique compared with that observed in other viral infections. Salient features of this profile were: ( a) the simultaneous production of MIP-1 beta, TNF-alpha, and IFN-gamma in the absence of IL-2; and (b) direct cytolytic activity associated with surface mobilization of CD107a and intracellular expression of perforin and granzymes. This polyfunctional profile was associated with a terminally differentiated phenotype that was not characterized by a distinct clonotypic composition. Thus, mature CMV-specific CD4(+) T cells exhibit distinct functional properties reminiscent of antiviral CD8(+) T lymphocytes. C1 NIAID, Immunobiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. RP Koup, RA (reprint author), NIAID, Immunobiol Lab, NIH, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Intramural NIH HHS; Medical Research Council [G108/441] NR 61 TC 205 Z9 213 U1 1 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 25 PY 2006 VL 203 IS 13 BP 2865 EP 2877 DI 10.1081/jem.20052246 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 120QH UT WOS:000243099400009 PM 17158960 ER PT J AU Xue, L Hu, N Song, Y Zou, S Shou, J Qian, L Ren, L Lin, D Tong, T He, Z Zhan, QM Taylor, PR Lu, N AF Xue, Li-yan Hu, Nan Song, Yong-mei Zou, Shuang-mei Shou, Jian-zhong Qian, Lu-xia Ren, Li-qun Lin, Dong-mei Tong, Tong He, Zu-gen Zhan, Qimin Taylor, Philip R. Lu, Ning TI Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma SO BMC CANCER LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; PROGNOSTIC-SIGNIFICANCE; IMMUNOHISTOCHEMICAL ANALYSIS; INTRAEPITHELIAL NEOPLASIA; DIFFERENTIAL EXPRESSION; ENHANCED EXPRESSION; ANNEXIN-I; CANCER; OVEREXPRESSION; LAMININ-5 AB Background: The development of esophageal squamous cell carcinoma ( ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia ( DYS) and carcinoma in situ ( CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. Methods: Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5.2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin5.2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. Results: In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5.2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions ( ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5.2 and SPARC. Conclusion: Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5.2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC. C1 Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst Hosp, Dept Pathol, Beijing 100037, Peoples R China. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst Hosp, State Key Lab Mol Oncol, Beijing 100037, Peoples R China. Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst Hosp, Dept Urol, Beijing 100037, Peoples R China. RP Lu, N (reprint author), Chinese Acad Med Sci, Peking Union Med Coll, Canc Inst Hosp, Dept Pathol, Beijing 100037, Peoples R China. EM xueliyan2003@yahoo.com.cn; nhu@mail.nih.gov; symlh2006@yahoo.com.cn; smzou@hotmail.com; shoujianzhong@hotmail.com; qianl@mail.nih.gov; renlq2004@126.com; lindm3@yahoo.com; tongt5@yahoo.com; hezugen2002@hotmail.com; zhanqimin@pumc.edu.cn; ptaylor@mail.nih.gov; nlu03@126.com NR 47 TC 41 Z9 45 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 22 PY 2006 VL 6 AR 296 DI 10.1186/1471-2407-6-296 PG 15 WC Oncology SC Oncology GA 125IP UT WOS:000243435900001 PM 17187659 ER PT J AU Jabba, SV Oelke, A Singh, R Maganti, RJ Fleming, S Wall, SM Everett, LA Green, ED Wangemann, P AF Jabba, Sairam V. Oelke, Alisha Singh, Ruchira Maganti, Rajanikanth J. Fleming, Sherry Wall, Susan M. Everett, Lorraine A. Green, Eric D. Wangemann, Philine TI Macrophage invasion contributes to degeneration of stria vascularis in Pendred syndrome mouse model SO BMC MEDICINE LA English DT Article ID SYNDROME GENE PDS; INNER-EAR; EXPRESSION; TRANSPORTER; PROTEIN; IODIDE; CELLS; SECRETION; DEAFNESS; INSIGHT AB Background: Pendred syndrome, an autosomal-recessive disorder characterized by deafness and goiter, is caused by a mutation of SLC26A4, which codes for the anion exchanger pendrin. We investigated the relationship between pendrin expression and deafness using mice that have (Slc26a4(+/+) or Slc26a4(+/-)) or lack (Slc26a4(-/-)) a complete Slc26a4 gene. Previously, we reported that stria vascularis of adult Slc26a4-/- mice is hyperpigmented and that marginal cells appear disorganized. Here we determine the time course of hyperpigmentation and marginal cell disorganization, and test the hypothesis that inflammation contributes to this tissue degeneration. Methods: Slc26a4(-/-) and age-matched control (Slc26a4(+/+) or Slc26a4(+/-)) mice were studied at four postnatal ( P) developmental stages: before and after the age that marks the onset of hearing (P10 and P15, respectively), after weaning (P28-41) and adult (P74-170). Degeneration and hyperpigmentation stria vascularis was evaluated by confocal microscopy. Gene expression in stria vascularis was analyzed by microarray and quantitative RT-PCR. In addition, the expression of a select group of genes was quantified in spiral ligament, spleen and liver to evaluate whether expression changes seen in stria vascularis are specific for stria vascularis or systemic in nature. Results: Degeneration of stria vascularis defined as hyperpigmentation and marginal cells disorganization was not seen at P10 or P15, but occurred after weaning and was associated with staining for CD68, a marker for macrophages. Marginal cells in Slc26a4(-/-), however, had a larger apical surface area at P10 and P15. No difference in the expression of Lyzs, C3 and Cd45 was found in stria vascularis of P15 Slc26a4+/- and Slc26a4-/- mice. However, differences in expression were found after weaning and in adult mice. No difference in the expression of markers for acute inflammation, including Il1a, Il6, Il12a, Nos2 and Nos3 were found at P15, after weaning or in adults. The expression of macrophage markers including Ptprc (= Cd45), Cd68, Cd83, Lyzs, Lgals3 (= Mac2 antigen), Msr2, Cathepsins B, S, and K (Ctsb, Ctss, Ctsk) and complement components C1r, C3 and C4 was significantly increased in stria vascularis of adult Slc26a4(-/-) mice compared to Slc26a4(+/+) mice. Expression of macrophage markers Cd45 and Cd84 and complement components C1r and C3 was increased in stria vascularis but not in spiral ligament, liver or spleen of Slc26a4(-/-) compared to Slc26a4(+/-) mice. The expression of Lyzs was increased in stria vascularis and spiral ligament but not in liver or spleen. Conclusion: The data demonstrate that hyperpigmentation of stria vascularis and marginal cell reorganization in Slc26a4(-/-) mice occur after weaning, coinciding with an invasion of macrophages. The data suggest that macrophage invasion contributes to tissue degeneration in stria vascularis, and that macrophage invasion is restricted to stria vascularis and is not systemic in nature. The delayed onset of degeneration of stria vascularis suggests that a window of opportunity exists to restore/preserve hearing in mice and therefore possibly in humans suffering from Pendred syndrome. C1 Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Wangemann, P (reprint author), Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. EM sjabba@vet.ksu.edu; OelkeAlisha@rossmed.edu.dm; rsingh@vet.ksu.edu; rmaganti@vet.ksu.edu; sdflemin@ksu.edu; smwall@emory.edu; wange@vet.ksu.edu; egreen@nhgri.nih.gov; wange@vet.ksu.edu RI Wangemann, Philine/N-2826-2013; Jabba, Sairam/B-5790-2015 FU NCRR NIH HHS [NIH-P20-RR017686, P20 RR017686]; NIDCD NIH HHS [NIH-R01-DC01098, R01 DC001098]; NIDDK NIH HHS [NIH-R01-DK52935, R01 DK052935] NR 30 TC 30 Z9 32 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD DEC 22 PY 2006 VL 4 AR 37 DI 10.1186/1741-7015-4-37 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 145OB UT WOS:000244873300001 PM 17187680 ER PT J AU Fung, HC Chen, CM Hardy, J Singleton, AB Wu, YR AF Fung, Hon-Chung Chen, Chiung-Mei Hardy, John Singleton, Andrew B. Wu, Yih-Ru TI A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan SO BMC NEUROLOGY LA English DT Article ID MUTATIONS; PREVALENCE AB Background: Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized clinically by resting tremor, bradykinesia, postural instability and rigidity. The prevalence of PD is approximately 2% of the population over 65 years of age and 1.7 million PD patients ( age >= 55 years) live in China. Recently, a common LRRK2 variant Gly2385Arg was reported in ethnic Chinese PD population in Taiwan. We analyzed the frequency of this variant in our independent PD case-control population of Han Chinese from Taiwan. Methods: 305 patients and 176 genetically unrelated healthy controls were examined by neurologists and the diagnosis of PD was based on the published criteria. The region of interest was amplified with standard polymerase chain reaction (PCR). PCR fragments then were directly sequenced in both forward and reverse directions. Differences in genotype frequencies between groups were assessed by the X(2) test, while X(2) analysis was used to test for the Hardy-Weinberg equilibrium. Results: Of the 305 patients screened we identified 27 (9%) with heterozygous G2385R variant. This mutation was only found in 1 (0.5%) in our healthy control samples ( odds ratio = 16.99, 95% CI: 2.29 to 126.21, p = 0.0002). Sequencing of the entire open reading frame of LRRK2 in G2385R carriers revealed no other variants. Conclusion: These data suggest that the G2385R variant contributes significantly to the etiology of PD in ethnic Han Chinese individuals. With consideration of the enormous and expanding aging Chinese population in mainland China and in Taiwan, this variant is probably the most common known genetic factor for PD worldwide. C1 Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei 10591, Taiwan. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London WC1N 1PJ, England. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. RP Wu, YR (reprint author), Chang Gung Mem Hosp, Dept Neurol, 199 Tung Hwa N Rd, Taipei 10591, Taiwan. EM fungp@mail.nih.gov; cmchen@adm.cgmh.org.tw; hardyj@mail.nih.gov; singleta@mail.nih.gov; yihruwu@adm.cgmh.org.tw RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 13 TC 50 Z9 53 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD DEC 22 PY 2006 VL 6 AR 47 DI 10.1186/1471-2377-6-47 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 128SP UT WOS:000243679200001 PM 17187665 ER PT J AU Tan, WF Martin, D Gutkind, JS AF Tan, Wenfu Martin, Daniel Gutkind, J. Silvio TI The G alpha(13)-Rho signaling axis is required for SDF-1-induced migration through CXCR4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DERIVED FACTOR-1-ALPHA; HETEROTRIMERIC G-PROTEINS; CHEMOKINE RECEPTOR CXCR4; EXCHANGE FACTOR; DEPENDENT ACTIVATION; B-LYMPHOPOIESIS; RHO ACTIVITY; FACTOR-I; RAC; CHEMOTAXIS AB The CXC chemokine stromal cell-derived factor-1 alpha (SDF-1) binds to CXCR4, a seven-transmembrane G protein-coupled receptor that plays a critical role in many physiological processes that involve cell migration and cell fate decisions, ranging from stem cell homing, angiogenesis, and neuronal development to immune cell trafficking. CXCR4 is also implicated in various pathological conditions, including metastatic spread and human immunodeficiency virus infection. Although SDF-1-induced cell migration in CXCR4-expressing cells is sensitive to pertussis toxin treatment, hence involving heterotrimeric G proteins of the Gi family, whether other G proteins participate in the chemotactic response to SDF-1 is still unknown. In this study, we took advantage of the potent chemotactic activity of SDF-1 in Jurkat T-cells to examine the nature of the heterotrimeric G protein subunits contributing to CXCR4-mediated cell migration. We observed that whereas G(i) and G beta gamma subunits are involved in SDF-1-induced Rac activation and cell migration, CXCR4 can also stimulate Rho potently leading to the phosphorylation of myosin light chain through the Rho effector, Rho kinase, but independently of Gi. Furthermore, we found that G alpha(13) mediates the activation of Rho by CXCR4 and that the functional activity of both G alpha(13) and Rho is required for directional cell migration in response to SDF-1. Collectively, our data indicate that signaling by CXCR4 to Rho through G alpha(13) contributes to cell migration when stimulated by SDF-1, thus identifying the G alpha(13)-Rho signaling axis as a potential pharmacological target in many human diseases that involve the aberrant function of CXCR4. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, Dept Hlth & Human Serv, 30 Convent Dr,Bldg 30,Rm 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS NR 54 TC 83 Z9 87 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 22 PY 2006 VL 281 IS 51 BP 39542 EP 39549 DI 10.1074/jbc.M609062200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117UL UT WOS:000242898700062 PM 17056591 ER PT J AU Duncan, T Fariss, R Wiggert, B AF Duncan, Todd Fariss, Robert N. Wiggert, Barbara TI Confocal immunolocalization of bovine serum albumin, serum retinol-binding protein, and interphotoreceptor retinoid-binding protein in bovine retina SO MOLECULAR VISION LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID PIGMENT-EPITHELIUM; MESSENGER-RNA; BARRIER BREAKDOWN; RABBIT RETINA; HUMAN PLASMA; RAT EYE; IRBP; MATRIX; LOCALIZATION; RELEASE AB Purpose: Recently it has been shown that the transport as well as clearance of retinol from isolated rod photoreceptors requires an extracellular factor. Interphotoreceptor retinoid-binding protein (IRBP) is a component of the interphotoreceptor matrix (IPM) and is known to bind visual cycle retinoids. Serum albumin and serum retinol-binding protein (sRBP), proteins capable of binding retinoids, have also been reported to be components of the IPM. It is of interest to know the components present in the IPM that are capable of binding visual cycle retinoids and that also facilitate rhodopsin regeneration. The purpose of this study was to determine the localization of serum albumin, sRBP, and IRBP in bovine retina using immunofluorescence analysis. Methods: Fresh bovine eyes, obtained from a local abattoir, were fixed immediately after enucleation. Tissue sections (100 mu m) were incubated with primary antibodies to bovine serum albumin (BSA), sRBP, and IRBP. Sections were washed then incubated 4 h with 4'-6-Diamidino-2-phenylindole (DAPI), Alexa Fluor (R) 488 goat antimouse, and Alexa Fluor (R) 568 goat antirabbit secondary antibodies. Sections were analyzed using a laser scanning confocal microscope equipped with Nomarski optics. Western immunoblot analysis of bovine retinal tissues and protein standards was performed using the primary antibodies to BSA, sRBP, and IRBP to show specificity to their respective antigens. Results: Immunoblot analysis showed that monoclonal anti-BSA was highly specific for BSA detecting only a single band at about 67 kDa. Antihuman sRBP and antibovine IRBP were also highly specific, recognizing a single band at about 25 and about 133 kDa, respectively. No immunopositive bands were observed in bovine neural retinal when probed with the anti-sRBP antibody; however, a single immunoreactive band at about 67 and about 133 kDa was detected in bovine neural retina by the anti-BSA and IRBP antibodies, respectively. Immunofluorescence analysis showed labeling for IRBP throughout the IPM. IRBP labeling was especially associated with the outer segments of photoreceptors and also with the apical surface of the retinal pigment epithelium. Immunofluorescence labeling for serum albumin was associated only with the lumen of retinal and choroidal blood vessels. Staining for both serum albumin and sRBP in the IPM was negative. Conclusions: Immunofluorescence analysis of fresh bovine eyes using antibodies to BSA and sRBP clearly shows that serum albumin and sRBP are not components of bovine IPM. IRBP, on the other hand, is localized to the IPM where it is available for the binding and transport of visual cycle retinoids. From these data we conclude that serum albumin and sRBP are not factors that could participate in the binding as well as transport of visual cycle retinoids in the IPM of bovine retina. C1 NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. RP Duncan, T (reprint author), NEI, Lab Retinal Cell & Mol Biol, NIH, 7 Mem Dr,MSC0706,Bldg 7,Room 337, Bethesda, MD 20892 USA. EM duncant@nei.nih.gov FU Intramural NIH HHS NR 47 TC 6 Z9 7 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 22 PY 2006 VL 12 IS 187-90 BP 1632 EP 1639 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 121ZG UT WOS:000243194900001 PM 17200663 ER PT J AU Rouault, TA AF Rouault, Tracey A. TI If the RNA fits, use it SO SCIENCE LA English DT Editorial Material ID IRON REGULATORY PROTEINS; ACONITASE; DIVERSITY C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM trou@helix.nih.gov NR 9 TC 2 Z9 2 U1 1 U2 3 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 DEC 22 PY 2006 VL 314 IS 5807 BP 1886 EP 1887 DI 10.1126/science.1137174 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 119EY UT WOS:000242996800034 PM 17185590 ER PT J AU Koelle, K Cobey, S Grenfell, B Pascual, M AF Koelle, Katia Cobey, Sarah Grenfell, Bryan Pascual, Mercedes TI Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans SO SCIENCE LA English DT Article ID SEQUENCE SPACE; NEUTRAL EVOLUTION; UNITED-STATES; VIRUS; PROTEIN; DYNAMICS; HEMAGGLUTININ; EMERGENCE; MORTALITY; MODEL AB Human influenza A ( subtype H3N2) is characterized genetically by the limited standing diversity of its hemagglutinin and antigenically by clusters that emerge and replace each other within 2 to 8 years. By introducing an epidemiological model that allows for differences between the genetic and antigenic properties of the virus's hemagglutinin, we show that these patterns can arise from cluster-specific immunity alone. Central to the formulation is a genotype-to-phenotype mapping, based on neutral networks, with antigenic phenotypes, not genotypes, determining the degree of strain cross-immunity. The model parsimoniously explains well-known, as well as previously unremarked, features of interpandemic influenza dynamics and evolution. It captures the observed boom-and-bust pattern of viral evolution, with periods of antigenic stasis during which genetic diversity grows, and with episodic contraction of this diversity during cluster transitions. C1 Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. Penn State Univ, Dept Biol, Mueller Lab 208, Eberly Coll Sci, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Koelle, K (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, 2019 Kraus Nat Sci Bldg,830 N Univ Ave, Ann Arbor, MI 48109 USA. EM kkoelle@psu.edu NR 49 TC 243 Z9 251 U1 0 U2 30 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 DEC 22 PY 2006 VL 314 IS 5807 BP 1898 EP 1903 DI 10.1126/science.1132745 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 119EY UT WOS:000242996800040 PM 17185596 ER PT J AU Nackley, AG Shabalina, SA Tchivileva, IE Satterfield, K Korchynskyi, O Makarov, SS Maixner, W Diatchenko, L AF Nackley, A. G. Shabalina, S. A. Tchivileva, I. E. Satterfield, K. Korchynskyi, O. Makarov, S. S. Maixner, W. Diatchenko, L. TI Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure SO SCIENCE LA English DT Article ID PAIN PATIENTS; GENE; COMT; POLYMORPHISMS; TRANSLATION; PREDICTION; PATTERN AB Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations. C1 Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ N Carolina, Thurston Arthrit Ctr, Chapel Hill, NC 27599 USA. Attagene Inc, Res Triangle Pk, NC 27560 USA. RP Diatchenko, L (reprint author), Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA. EM lbdiatch@email.unc.edu RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 NR 20 TC 517 Z9 536 U1 7 U2 35 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 DEC 22 PY 2006 VL 314 IS 5807 BP 1930 EP 1933 DI 10.1126/science.1131262 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 119EY UT WOS:000242996800050 PM 17185601 ER PT J AU Zhang, QQ Djuth, FT Zhou, QF Hu, CH Cha, JH Shung, KK AF Zhang, Q. Q. Djuth, F. T. Zhou, Q. F. Hu, C. H. Cha, J. H. Shung, K. K. TI High frequency broadband PZT thick film ultrasonic transducers for medical imaging applications SO ULTRASONICS LA English DT Article; Proceedings Paper CT Ultrasonics International (UI 05)/ World Congress on Ultrasonics (WCU 2005) CY AUG 29-SEP 01, 2005 CL Beijing, PEOPLES R CHINA DE PZT; thick films; sol-gel; high frequency; transducer ID FABRICATION AB A modified sol-gel method is used to prepare PZT thick film on Pt-coated silicon substrate. A new method of vacuum filling sol-gel precursor solution is introduced to improve film quality. The effects of the filling on PZT thick film structure and ferroelectric properties are discussed. The fabrication of a high frequency transducer with the PZT film as the actuating layer is described. The performance of the transducer is measured and results show that the transducer backed by E-Solder without a matching layer has a center frequency of 103 MHz and a bandwidth of 70%. Beam pro. le measurements show that the transducer has an axial resolution of 9.2 mu m and a lateral resolution of 33 mu m. (c) 2006 Elsevier B. V. All rights reserved. C1 Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. Geospace Res Inc, El Segundo, CA 90245 USA. RP Zhou, QF (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM qifazhou@usc.edu FU NCI NIH HHS [1R43CA110214-01]; NIBIB NIH HHS [P41-EB2182] NR 8 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD DEC 22 PY 2006 VL 44 SU 1 BP E711 EP E715 DI 10.1016/j.ultras.2006.05.130 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 200ZX UT WOS:000248802400136 PM 16793087 ER PT J AU Ablan, S Rawat, SS Viard, M Wang, JM Puri, A Blumenthal, R AF Ablan, Sherimay Rawat, Satinder S. Viard, Mathias Wang, Ji Ming Puri, Anu Blumenthal, Robert TI The role of cholesterol and sphingolipids in chemokine receptor function and HIV-I envelope glycoprotein-mediated fusion SO VIROLOGY JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEMBRANE CHOLESTEROL; LIPID RAFTS; CELL-LINES; T-CELLS; CD4; TYPE-1; ENTRY; INFECTION; PROTEIN AB Background: HIV-1 entry into cells is a multifaceted process involving target cell CD4 and the chemokine receptors, CXCR4 or CCR5. The lipid composition of the host cell plays a significant role in the HIV fusion process as it orchestrates the appropriate disposition of CD4 and co-receptors required for HIV-1 envelope glycoprotein (Env)-mediated fusion. The cell membrane is primarily composed of sphingolipids and cholesterol. The effects of lipid modulation on CD4 disposition in the membrane and their role in HIV-1 entry have extensively been studied. To focus on the role of lipid composition on chemokine receptor function, we have by-passed the CD4 requirement for HIV-1 Env-mediated fusion by using a CD4-independent strain of HIV-1 Env. Results: Cell fusion mediated by a CD4- independent strain of HIV-1 Env was monitored by observing dye transfer between Env-expressing cells and NIH3T3 cells bearing CXCR4 or CCR5 in the presence or absence of CD4. Chemokine receptor signaling was assessed by monitoring changes in intracellular [Ca2+] mobilization induced by CCR5 or CXCR4 ligand. To modulate target membrane cholesterol or sphingolipids we used Methyl- beta-cyclodextrin (M beta CD) or 1-phenyl-2hexadecanoylamino- 3-morpholino-1-propanol ( PPMP), respectively. Treatment of the target cells with these agents did not change the levels of CD4 or CXCR4, but reduced levels of CCR5 on the cell surface. Chemokine receptor signalling was inhibited by cholesterol removal but not by treatment with PPMP. HIV-1 Env mediated fusion was inhibited by > 50% by cholesterol removal. Overall, PPMP treatment appeared to slow down the rates of CD4- independent HIV-1 Env-mediated Fusion. However, in the case of CXCR4-dependent fusion, the differences between untreated and PPMP-treated cells did not appear to be significant. Conclusion: Although modulation of cholesterol and sphingolipids has similar effects on CD4 dependent HIV-1 Env-mediated fusion, sphingolipid modulation had little effect on CD4-independent HIV-1 Env-mediated fusion. Chemokine receptor function remained intact following treatment of cells with PPMP. Therefore such treatment may be considered a more suitable agent to inhibit CD4 dependent HIV-1 infection. C1 NCI, Canc Res Ctr, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21701 USA. NCI, Canc Res Ctr, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA. RP Blumenthal, R (reprint author), NCI, Canc Res Ctr, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21701 USA. EM sablan@ncifcrf.gov; Satinder.Rawat@umassmed.edu; viardm@mail.ncifcrf.gov; wangji@mail.ncifcrf.gov; apuri@helix.nih.gov; blumen@helix.nih.gov NR 37 TC 15 Z9 15 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 DEC 22 PY 2006 VL 3 AR 104 DI 10.1186/1743-422X-3-104 PG 8 WC Virology SC Virology GA 182OL UT WOS:000247513800001 PM 17187670 ER PT J AU Horkay, F Hecht, AM Rochas, C Basser, PJ Geissler, E AF Horkay, Ferenc Hecht, Anne Marie Rochas, Cyrille Basser, Peter J. Geissler, Erik TI Anomalous small angle x-ray scattering determination of ion distribution around a polyelectrolyte biopolymer in salt solution SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID NEUTRON-SCATTERING; PERSISTENCE LENGTH; CHARGED COLLOIDS; HYALURONIC-ACID; DNA FRAGMENTS; LIMITING LAWS; CONDENSATION; COUNTERIONS; ROD; SIMULATIONS AB The distribution of counterions in solutions of high molecular mass hyaluronic acid, in near-physiological conditions where mono- and divalent ions are simultaneously present, is studied by small angle neutron scattering and anomalous small angle x-ray scattering. The solutions contain either sodium or rubidium chloride together with varying concentrations of calcium or strontium chloride. The effects of monovalent-divalent ion exchange dominate the amplitude and the form of the counterion cloud. In the absence of divalent ions, the shape of the anomalous scattering signal from the monovalent ions is consistent with the distribution calculated from the Poisson-Boltzmann equation, as found by other workers. In mixtures of monovalent and divalent ions, however, as the divalent ion concentration increases, both the diameter and the amplitude of the monovalent ion cloud decrease. The divalent counterions always occupy the immediate neighborhood of the charged polyanion. Above a given concentration their anomalous scattering signal saturates. Even in a large excess of divalent ions, ion exchange is incomplete. (c) 2006 American Institute of Physics. C1 NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, Lab Spect Phys, UMR 5588, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM erik.geissler@ujf-grenoble.fr RI Basser, Peter/H-5477-2011; d2am, beamline/I-6445-2015 FU Intramural NIH HHS NR 38 TC 19 Z9 19 U1 1 U2 5 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 21 PY 2006 VL 125 IS 23 AR 234904 DI 10.1063/1.2402921 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 125BA UT WOS:000243415300037 PM 17190574 ER PT J AU Conwit, RA AF Conwit, Robin A. TI Preventing familial ALS: A clinical trial may be feasible but is an efficacy trial warranted? SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Editorial Material C1 NIH, NINDS, Ctr Neurosci, Bethesda, MD 20892 USA. RP Conwit, RA (reprint author), NIH, NINDS, Ctr Neurosci, Bethesda, MD 20892 USA. EM conwit@ninds.nih.gov NR 0 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 21 PY 2006 VL 251 IS 1-2 BP 1 EP 2 DI 10.1016/j.jns.2006.07.009 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 120BR UT WOS:000243059000001 PM 17070848 ER PT J AU Bertram, R Pedersen, MG Luciani, DS Sherman, A AF Bertram, Richard Gram Pedersen, Morten Luciani, Dan S. Sherman, Arthur TI A simplified model for mitochondrial ATP production SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE metabolism; calcium; mathematical model ID NICOTINAMIDE NUCLEOTIDE TRANSHYDROGENASE; BETA-CELL; FREE CA2+; ELECTRICAL-ACTIVITY; OXYGEN-CONSUMPTION; GLYCOLYTIC PATHWAY; INSULIN-SECRETION; ENERGY-METABOLISM; PANCREATIC-ISLETS; OSCILLATIONS AB Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration. A detailed model of this reaction, which includes dynamic equations for the key mitochondrial variables, was developed earlier by Magnus and Keizer. However, this model is extraordinarily complicated. We develop a simpler model that captures the behavior of the original model but is easier to use and to understand. We then use it to investigate the mitochondrial responses to glycolytic and calcium input. We use the model to explain experimental observations of the opposite effects of raising cytosolic Ca2+ in low and high glucose, and to predict the effects of a mutation in the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (Nnt) in pancreatic beta-cells. (c) 2006 Elsevier Ltd. All rights reserved. C1 Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Programs Neurosci & Mol Biophys, Tallahassee, FL 32306 USA. Tech Univ Denmark, Dept Math, DK-2800 Lyngby, Denmark. Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada. Natl Inst Hlth, Lab Biol Modeling, Bethesda, MD USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu RI Pedersen, Morten/F-4134-2012; OI Pedersen, Morten/0000-0002-2639-2394; Luciani, Dan/0000-0002-4318-4159 FU Intramural NIH HHS NR 20 TC 37 Z9 37 U1 0 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD DEC 21 PY 2006 VL 243 IS 4 BP 575 EP 586 DI 10.1016/j.jtbi.2006.07.019 PG 12 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 115YI UT WOS:000242769300011 PM 16945388 ER PT J AU Wang, TJ Gona, P Larson, MG Tofler, GH Levy, D Newton-Cheh, C Jacques, PF Rifai, N Selhub, J Robins, SJ Benjamin, EJ D'Agostino, RB Vasan, RS AF Wang, Thomas J. Gona, Philimon Larson, Martin G. Tofler, Geoffrey H. Levy, Daniel Newton-Cheh, Christopher Jacques, Paul F. Rifai, Nader Selhub, Jacob Robins, Sander J. Benjamin, Emelia J. D'Agostino, Ralph B. Vasan, Ramachandran S. TI Multiple biomarkers for the prediction of first major cardiovascular events and death SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; PLASMINOGEN-ACTIVATOR INHIBITOR; DENSITY-LIPOPROTEIN CHOLESTEROL; BRAIN NATRIURETIC PEPTIDE; CONVENTIONAL RISK-FACTORS; MYOCARDIAL-INFARCTION; PHOSPHOLIPASE A(2); ARTERY DISEASE; FOLLOW-UP AB BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, d-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with ``multimarker'' scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. NHLBI, Bethesda, MD 20892 USA. Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer Dept Agr, Boston, MA 02111 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Div Endocrinol Nutr & Diabet, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [R01-HL-48157, 2K24-HL-04334, K23-HL-074077, N01-HC-25195, R01-HL-076784] NR 40 TC 745 Z9 768 U1 7 U2 46 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 2006 VL 355 IS 25 BP 2631 EP 2639 DI 10.1056/NEJMoa055373 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200004 PM 17182988 ER PT J AU Cookson, MR Hardy, J AF Cookson, Mark R. Hardy, John TI Clinical implications of basic research: The persistence of memory SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UBIQUITIN C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RI Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 4 TC 2 Z9 2 U1 0 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 DEC 21 PY 2006 VL 355 IS 25 BP 2697 EP 2698 DI 10.1056/NEJMcibr065999 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200015 PM 17182998 ER PT J AU Hoofnagle, JH AF Hoofnagle, Jay H. TI Overweight, obesity, and mortality SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 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 DEC 21 PY 2006 VL 355 IS 25 BP 2699 EP 2699 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200017 PM 17186585 ER PT J AU Adams, KF Schatzkin, A Leitzmann, MF AF Adams, Kenneth F. Schatzkin, Arthur Leitzmann, Michael F. TI Overweight, obesity, and mortality - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID BRITISH DOCTORS; SMOKING C1 NCI, Rockville, MD 20850 USA. RP Adams, KF (reprint author), NCI, Rockville, MD 20850 USA. EM adamske@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 21 PY 2006 VL 355 IS 25 BP 2700 EP 2701 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 118QG UT WOS:000242956200020 ER PT J AU Melzer, D Murray, A Hurst, AJ Weedon, MN Bandinelli, S Corsi, AM Ferrucci, L Paolisso, G Guralnik, JM Frayling, TM AF Melzer, David Murray, Anna Hurst, Alison J. Weedon, Michael N. Bandinelli, Stefania Corsi, Anna Maria Ferrucci, Luigi Paolisso, Guiseppe Guralnik, Jack M. Frayling, Timothy M. TI Effects of the diabetes linked TCF7L2 polymorphism in a representative older population SO BMC MEDICINE LA English DT Article ID INSULIN-SECRETION; RISK; MELLITUS; GENE; COMPLICATIONS; ASSOCIATION; DIAGNOSIS; GLUCOSE; EPIDEMIOLOGY; REPLICATION AB Background: A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has been found to be associated with type 2 diabetes in case-control studies. We aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with fasting glucose, lipids, diabetes prevalence and complications in an older general population. Methods: In total, 944 subjects aged >= 65 years from the population representative InCHIANTI study were enrolled in this study. Those with fasting blood glucose of >= 7 mmol/l or physician diagnosis were considered diabetic. Cut-off points for impaired fasting glucose (IFG) were >= 5.6 mmol/l to < 7 mmol/l. Results: In the general population sample, minor (T) allele carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting poorer beta-cell function. T allele carriers also had smaller waist circumference (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4% in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T allele carriers had metabolic syndrome features (p = 0.047) or had experienced a myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024). Conclusion: The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels, smaller waist circumference, and lower risk lipid profiles in the general elderly population. Patients with diabetes who are carriers of the minor allele are less likely to have metabolic-syndrome features, but may experience more microvascular complications, although the number of cases was small. If replicated, these findings may have implications for developing treatment approaches tailored by genotype. C1 Peninsula Med Sch, Exeter EX2 5DW, Devon, England. Italian Natl Res Council Aging, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Univ Florence, Dept Med & Surg Crit Care, Florence, Italy. NIA, Longitudial Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Naples Federico 2, Dept Geriatr Med & Metabol Dis, Naples, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Peninsula Med Sch, RD&E Wonford Site,Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk; anna.murray@pms.ac.uk; alison.hurst@pms.ac.uk; michael.weedon@pms.ac.uk; stefania.bandinelli@asf.toscana.it; annamaria.corsi@asf.it; FerrucciLu@grc.nia.nih.gov; giuseppe.paolisso@unina2.it; GuralniJ@nia.nih.gov; tim.frayling@pms.ac.uk OI Murray, Anna/0000-0002-2351-2522; Paolisso, Giuseppe/0000-0002-2137-455X; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413, R01 AG024233, R01 AG24233-01]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 31 TC 55 Z9 59 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD DEC 20 PY 2006 VL 4 AR 34 DI 10.1186/1741-7015-4-34 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 145NZ UT WOS:000244873100002 PM 17181866 ER PT J AU Willis, SL Tennstedt, SL Marsiske, M Ball, K Elias, J Koepke, KM Morris, JN Rebok, GW Unverzagt, FW Stoddard, AM Wright, E AF Willis, Sherry L. Tennstedt, Sharon L. Marsiske, Michael Ball, Karlene Elias, Jeffrey Koepke, Kathy Mann Morris, John N. Rebok, George W. Unverzagt, Frederick W. Stoddard, Anne M. Wright, Elizabeth CA ACTIVE Study Grp TI Long-term effects of cognitive training on everyday functional outcomes in older adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMER-DISEASE; INSTRUMENTAL ACTIVITIES; INTELLECTUAL ABILITY; AFRICAN-AMERICANS; PERFORMANCE; RISK; INTERVENTION; DEMENTIA; SPEED AB Context Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated. Objective To determine the effects of cognitive training on daily function and durability of training on cognitive abilities. Design, Setting, and Participants Five-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons ( mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample. Interventions Ten-session training for memory ( verbal episodic memory), reasoning ( inductive reasoning), or speed of processing ( visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training. Main Outcome Measures Self-reported and performance-based measures of daily function and cognitive abilities. Results The reasoning group reported significantly less difficulty in the instrumental activities of daily living ( IADL) than the control group ( effect size, 0.29; 99% confidence interval [CI], 0.03- 0.55). Neither speed of processing training ( effect size, 0.26; 99% CI, - 0.002 to 0.51) nor memory training ( effect size, 0.20; 99% CI, - 0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing ( effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years ( memory: effect size, 0.23 [ 99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [ 99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [ 99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance ( effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance ( effect size, 0.85; 99% CI, 0.61-1.09). Conclusions Reasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention. C1 Penn State Univ, Dept Human Dev & Family Studies, State Coll, PA 16801 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Florida, Inst Aging, Gainesville, FL USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. NIA, Bethesda, MD 20892 USA. NINR, Bethesda, MD 20892 USA. Hebrew Senior Life, Boston, MA USA. Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Willis, SL (reprint author), Penn State Univ, Dept Human Dev & Family Studies, 135 E Nittany Ave,Suite 405, State Coll, PA 16801 USA. EM slw@psu.edu OI Marsiske, Michael/0000-0001-5973-2116 FU NIA NIH HHS [U01 AG014263, R37 AG024102, U01 AG014260, U01 AG014276, U01 AG014276-04, U01 AG014276-05, U01 AG014276-05S1, U01 AG014276-05S2, U01 AG014276-05S3, U01 AG014276-06A1, U01 AG014276-07, U01 AG014276-07S1, U01 AG014276-08, U01 AG014276-08S1, U01 AG014282, U01 AG014289, U01 AG14263, U01 AG14282, U01 AG14289, U01AG14260, U01AG14276]; NINR NIH HHS [U01 NR004507, U01 NR004508, U01 NR04507, U01 NR04508] NR 55 TC 591 Z9 618 U1 9 U2 100 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 20 PY 2006 VL 296 IS 23 BP 2805 EP 2814 DI 10.1001/jama.296.23.2805 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 116TR UT WOS:000242826400022 PM 17179457 ER PT J AU Walshe, JM Denduluri, N Swain, SM AF Walshe, Janice M. Denduluri, Neelima Swain, Sandra M. TI Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID INDUCED OVARIAN FAILURE; HIGH-DOSE CHEMOTHERAPY; DISEASE-FREE SURVIVAL; MUSTARD L-PAM; RANDOMIZED-TRIAL; FOLLOW-UP; AROMATASE INHIBITORS; PROGNOSTIC IMPACT; CYCLOPHOSPHAMIDE; THERAPY AB Chemotherapy and ovarian ablation both independently improve survival in premenopausal women with hormone-sensitive breast cancer. Amenorrhea is a well-recognized occurrence after chemotherapy. The rate of chemotherapy-induced amenorrhea varies with patient age and chemotherapy regimens administered. However, the impact of chemotherapy-induced amenorrhea on prognosis is still being defined. Older studies in premenopausal women argue that the benefit with chemotherapy is a result of direct cytotoxicity alone. However, studies that restrict outcome analysis to hormone receptor-positive tumors suggest that chemotherapy has a dual mechanism in women with hormone-responsive tumors; indirect endocrine manipulation secondary to chemotherapy-induced ovarian suppression and direct cytotoxicity. The significant health ramifications involved with the induction of premature menopause as well as potential benefits necessitate a comprehensive evaluation of chemotherapy-induced amenorrhea. This review will discuss the incidence of amenorrhea with commonly-used adjuvant chemotherapeutic regimens, the possible benefits of chemotherapy-induced amenorrhea, and the challenges of interpreting the existing data in breast cancer trials. C1 NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20889 USA. RP Swain, SM (reprint author), NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 85 TC 175 Z9 185 U1 0 U2 9 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 DEC 20 PY 2006 VL 24 IS 36 BP 5769 EP 5779 DI 10.1200/JCO.2006.07.2793 PG 11 WC Oncology SC Oncology GA 119EG UT WOS:000242994400022 PM 17130515 ER PT J AU Pentz, RD Joffe, S Emanuel, EJ Schnipper, LE Haskell, CM Tannock, IF AF Pentz, Rebecca D. Joffe, Steven Emanuel, Ezekiel J. Schnipper, Lowell E. Haskell, Charles M. Tannock, Ian F. TI ASCO core values SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. RP Pentz, RD (reprint author), Emory Univ, Winship Canc Inst, 1365 C Clifton Rd NE,Rm C 3008, Atlanta, GA 30322 USA. EM rebecca.pentz@emoryhealthcare.org OI Joffe, Steven/0000-0002-0667-7384 NR 9 TC 6 Z9 6 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 DEC 20 PY 2006 VL 24 IS 36 BP 5780 EP 5782 DI 10.1200/JCO.2006.08.5068 PG 3 WC Oncology SC Oncology GA 119EG UT WOS:000242994400023 PM 17179111 ER PT J AU Zhang, MY Choudhry, V Sidorov, IA Tenev, V Vu, BK Choudhary, A Lu, H Stiegler, GM Katinger, HWD Jiang, S Broder, CC Dimitrov, DS AF Zhang, Mei-Yun Choudhry, Vidita Sidorov, Igor A. Tenev, Vladimir Vu, Bang K. Choudhary, Anil Lu, Hong Stiegler, Gabriela M. Katinger, Hermann W. D. Jiang, Shibo Broder, Christopher C. Dimitrov, Dimiter S. TI Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE HIV; antibody; phage display; gp41; inhibitors; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; TYPE-1; GP120; GP41; GLYCOPROTEIN; EPITOPE; BINDING; FAB; IDENTIFICATION AB The HIV envelope glycoprotein (Env) is composed of two non-covalently associated subunits: gp 120 and gp41. Panning of phage-displayed antibody libraries against Env-based antigens has resulted mostly in selection of anti-gp120 antibodies. Native gp41 in the absence of gp120 is unstable. The use of gp41 fragments as antigens has resulted in selection of antibodies with only relatively modest neutralizing activity. To enhance selection of antibodies specific for gp41 in the context of the whole Env we developed a methodology termed competitive antigen panning (CAP). Using CAP, we identified a novel gp41-specific human monoclonal antibody (hmAb), m48, from an immune library derived from long-term nonprogressors with high titers of broadly cross-reactive neutralizing antibodies (bcnAbs). Selection of m48 was only successful using CAP and not through the conventional pre-incubation methodology. In assays based on spreading infection in peripheral blood mononuclear cells (PBMCs) m48 neutralized a panel of HIV-1 primary isolates from different clades more potently than the well-characterized broadly cross-reactive HIV-1-neutralizing antibodies IgG1 4E10 and Fab Z13. These results may have implications for the selection of novel gp41-specific bcnAbs and other antibodies, and for the development of HIV-1 inhibitors and vaccine immunogens. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, CCRNP, CCR, NIH,Prot Interact Grp, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Viral Immunol, New York, NY 10021 USA. Inst Appl Microbiol, Vienna, Austria. RP Zhang, MY (reprint author), NCI, CCRNP, CCR, NIH,Prot Interact Grp, Bldg 469,Rm 131,POB B,Miller Dr, Frederick, MD 21702 USA. EM zhangm@nciferf.gov; dimitrov@ncifcrf.gov RI Jiang, Shibo/L-4500-2014; OI Sidorov, Igor/0000-0001-6519-4983 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, Z01 BC010257-10, N01-CO-12400]; NIAID NIH HHS [AI48380] NR 37 TC 26 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 20 PY 2006 VL 317 IS 1-2 BP 21 EP 30 DI 10.1016/j.jim.2006.09.016 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 121HM UT WOS:000243148700003 PM 17078964 ER PT J AU Mastronardi, C Smiley, GG Raber, J Kusakabe, T Kawaguchi, A Matagne, V Dietzel, A Heger, S Mungenast, AE Cabrera, R Kimura, S Ojeda, SR AF Mastronardi, Claudio Smiley, Gregory G. Raber, Jacob Kusakabe, Takashi Kawaguchi, Akio Matagne, Valerie Dietzel, Anja Heger, Sabine Mungenast, Alison E. Cabrera, Ricardo Kimura, Shioko Ojeda, Sergio R. TI Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction without impairing basal ganglia function SO JOURNAL OF NEUROSCIENCE LA English DT Article DE TTF1; homeobox genes; conditional gene deletion; hypothalamus; basal ganglia; female puberty ID PROTEIN-COUPLED RECEPTOR; TRANSCRIPTION FACTOR-I; GROWTH-FACTOR-ALPHA; ENHANCER-BINDING PROTEIN; NEUROENDOCRINE BRAIN; ALZHEIMERS-DISEASE; TRANSGENIC MICE; CEREBRAL-CORTEX; LHRH NEURONS; EXPRESSION AB Thyroid transcription factor 1 ( TTF1) [ also known as Nkx2.1 ( related to the NK-2 class of homeobox genes) and T/ebp ( thyroid- specific enhancer- binding protein)], a homeodomain gene required for basal forebrain morphogenesis, remains expressed in the hypothalamus after birth, suggesting a role in neuroendocrine function. Here, we show an involvement of TTF1 in the control of mammalian puberty and adult reproductive function. Gene expression profiling of the nonhuman primate hypothalamus revealed that TTF1 expression increases at puberty. Mice in which the Ttf1 gene was ablated from differentiated neurons grew normally and had normal basal ganglia/ hypothalamic morphology but exhibited delayed puberty, reduced reproductive capacity, and a short reproductive span. These defects were associated with reduced hypothalamic expression of genes required for sexual development and deregulation of a gene involved in restraining puberty. No extrapyramidal impairments associated with basal ganglia dysfunction were apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in the ventral telencephalon, once this function is satisfied in the hypothalamus, TTF1 remains active as part of the transcriptional machinery controlling female sexual development. C1 Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Hosp Children & Adolescents, D-04317 Leipzig, Germany. RP Ojeda, SR (reprint author), Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM ojedas@ohsu.edu FU Intramural NIH HHS; NCRR NIH HHS [RR00163]; NIA NIH HHS [AG20904]; NICHD NIH HHS [U54 HD18185, HD25123] NR 67 TC 42 Z9 43 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 20 PY 2006 VL 26 IS 51 BP 13167 EP 13179 DI 10.1523/JNEUROSCI.4238-06.2006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 119EW UT WOS:000242996300006 PM 17182767 ER PT J AU Zhang, JH Zhang, L Jiao, HY Zhang, Q Zhang, DS Lou, DW Katz, JL Xu, M AF Zhang, Jianhua Zhang, Lu Jiao, Hongyuan Zhang, Qi Zhang, Dongsheng Lou, Danwen Katz, Jonathan L. Xu, Ming TI c-Fos facilitates the acquisition and extinction of cocaine-induced persistent changes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; dopamine D-1 receptors; signal transduction; c-Fos; gene expression; dendritic morphology; behaviors ID DOPAMINE D1 RECEPTOR; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR; GENE-EXPRESSION; PSYCHOMOTOR STIMULANT; INDUCED REINSTATEMENT; DENDRITIC SPINES; MICE LACKING; MUTANT MICE AB Development of drug addiction involves persistent neurobiological changes. The dopamineD(1) receptor is involved in mediating cocaineinduced neuroadaptation, yet the underlying intracellular mechanisms remain unclear. We examined a potential role of the immediate early gene Fos, which is robustly and rapidly induced by cocaine via D-1 receptors, in mediating cocaine- induced persistent neurobiological changes by creating and analyzing a mouse in which Fos is primarily disrupted in D-1 receptor- expressing neurons in the brain. We show that the expression levels of several transcription factors, neurotransmitter receptors, and intracellular signaling molecules induced by repeated cocaine administration are altered in Fos- deficient brains. Dendritic remodeling of medium spiny neurons induced by repeated exposure to cocaine is blunted in the mutant mice. The mutant mice exhibit attenuated behavioral sensitization after repeated exposure to cocaine and more persistent memory of cocaine- induced conditioned place preference. Our findings indicate that c- Fos produced in D-1 receptor- expressing neurons integrates mechanisms to facilitate both the acquisition and extinction of cocaine- induced persistent changes. C1 Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Univ Alabama, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. NIDA, Medicat Discovery Res Branch, Baltimore, MD 21224 USA. RP Xu, M (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. EM mxu@dacc.uchicago.edu RI zhang, jianhua/D-3404-2009; OI Katz, Jonathan/0000-0002-1068-1159; Zhang, Jianhua/0000-0002-2128-9574 FU NIDA NIH HHS [DA14644, DA17323] NR 56 TC 63 Z9 70 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 20 PY 2006 VL 26 IS 51 BP 13287 EP 13296 DI 10.1523/JNEUROSCI.3795-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 119EW UT WOS:000242996300018 PM 17182779 ER PT J AU Mentis, GZ Siembab, VC Zerda, R O'Donovan, MJ Alvarez, FJ AF Mentis, George Z. Siembab, Valerie C. Zerda, Ricardo O'Donovan, Michael J. Alvarez, Francisco J. TI Primary afferent synapses on developing and adult Renshaw cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spinal cord; development; proprioceptive; interneurons; recurrent inhibition; motoneuron ID MAMMALIAN SPINAL-CORD; MUSCLE-SPINDLE AFFERENTS; MOTOR-NEURONS; GLYCINE RECEPTOR; MICROSCOPIC OBSERVATIONS; INHIBITORY INTERNEURONS; HORSERADISH-PEROXIDASE; POSTNATAL MATURATION; RECURRENT INHIBITION; POSTSYNAPTIC CHANGES AB The mechanisms that diversify adult interneurons from a few pools of embryonic neurons are unknown. Renshaw cells, Ia inhibitory interneurons ( IaINs), and possibly other types of mammalian spinal interneurons have common embryonic origins within the V1 group. However, in contrast to IaINs and other V1-derived interneurons, adult Renshaw cells receive motor axon synapses and lack proprioceptive inputs. Here, we investigated how this specific pattern of connectivity emerges during the development of Renshaw cells. Tract tracing and immunocytochemical markers [ parvalbumin and vesicular glutamate transporter 1 ( VGLUT1)] showed that most embryonic ( embryonic day 18) Renshaw cells lack dorsal root inputs, but more than half received dorsal root synapses by postnatal day 0 ( P0) and this input spread to all Renshaw cells by P10 - P15. Electrophysiological recordings in neonates indicated that this input is functional and evokes Renshaw cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but thereafter decreased because of limited synapse proliferation coupled with the enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic densities apposed to VGLUT1-IR synapses became smaller in adult compared with P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell growth. Like other V1 neurons, Renshaw cells are thus competent to receive sensory synapses. However, after P15, these sensory inputs appear deselected through arrested proliferation and synapse weakening. Thus, Renshaw cells shift from integrating sensory and motor inputs in neonates to predominantly motor inputs in adult. Similar synaptic weight shifts on interneurons may be involved in the maturation of motor reflexes and locomotor circuitry. C1 Wright State Univ, Dept Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA. NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Alvarez, FJ (reprint author), Wright State Univ, Dept Neurosci Cell Biol & Physiol, 3640 Colonel Glenn Highway, Dayton, OH 45435 USA. EM francisco.alvarez@wright.edu RI o'donovan, michael/A-2357-2015; Alvarez, Francisco/H-4929-2011 OI o'donovan, michael/0000-0003-2487-7547; FU Intramural NIH HHS; NINDS NIH HHS [NS047357, R01 NS047357, R01 NS047357-03, R01 NS047357-04, R56 NS047357] NR 69 TC 40 Z9 40 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 20 PY 2006 VL 26 IS 51 BP 13297 EP 13310 DI 10.1523/JNEUROSCI.2945-06.2006 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 119EW UT WOS:000242996300019 PM 17182780 ER PT J AU Thiebaut, ACM Schatzkin, A Ballard-Barbash, R Kipnis, V AF Thiebaut, Anne C. M. Schatzkin, Arthur Ballard-Barbash, Rachel Kipnis, Victor TI Dietary fat and breast cancer: Contributions from a survival trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LIFE-STYLE MODIFICATION; POOLED ANALYSIS; RISK; WOMEN; HEALTH; FIBER; METFORMIN; PATTERNS; WEIGHT; COHORT C1 NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Control & Populat Sci, Bethesda, MD 20892 USA. RP Kipnis, V (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, 6130 Execut Blvd,EPN 3124, Bethesda, MD 20892 USA. EM kipnisv@mail.nih.gov NR 26 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 2006 VL 98 IS 24 BP 1753 EP 1755 DI 10.1093/jnci/djj504 PG 3 WC Oncology SC Oncology GA 118WE UT WOS:000242973400001 PM 17179470 ER PT J AU Platz, EA Leitzmann, MF Fisvanathan, K Rimm, EB Stampfer, MJ Willett, WC Giovannucci, E AF Platz, Elizabeth A. Leitzmann, Michael F. Fisvanathan, Kala Rimm, Eric B. Stampfer, Meir J. Willett, Walter C. Giovannucci, Edward TI Statin drugs and risk of advanced prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; RANDOMIZED-TRIALS; COLORECTAL-CANCER; LOWERING DRUGS; UNITED-STATES; FOLLOW-UP; CHOLESTEROL; SURVIVAL; METAANALYSIS; INHIBITORS AB Background. Statins are commonly used cholesterol-lowering drugs that have proapoptotic and antimetastatic activities that could affect cancer risk or progression. Results from previous epidemiologic studies of the association between statin use and cancer have been inconsistent. We investigated the association of statin use with total and advanced prostate cancer, the latter being the most important endpoint to prevent. Methods: We analyzed data from an ongoing prospective cohort study of 34 989 US male health professionals who were cancer free in 1990 and were followed to 2002. Participants reported their use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis was confirmed by medical record review. Multivariable-adjusted relative risks (RRs) were estimated from Cox proportional hazards regression models. Statistical tests were two-sided. Results: During 376939 person-years of follow-up, we ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally invasive, metastatic, or fatal). The age-standardized incidence rates of advanced prostate cancer were 38 and 89 per 100 000 person-years in current statin users and in past or never users, respectively. The multivariable-adjusted relative risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use. The associations remained after adjusting for prostate-specific antigen screening history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower with longer statin use (P-trend = .003); compared with never use, the relative risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09). Conclusions: In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sidnek Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E6138,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu FU NCI NIH HHS [CA55075, P50 CA58236]; NHLBI NIH HHS [HL35464] NR 30 TC 234 Z9 237 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 20 PY 2006 VL 98 IS 24 BP 1819 EP 1825 DI 10.1093/jnci/djj499 PG 7 WC Oncology SC Oncology GA 118WE UT WOS:000242973400013 PM 17179483 ER PT J AU Vikram, B AF Vikram, Bhadrasain TI Re: Incidence of initial local therapy among men with lower-risk prostate cancer in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Clin Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Vikram, B (reprint author), NCI, Clin Radiat Oncol Branch, 6130 Execut Blvd,Suite 6002, Bethesda, MD 20892 USA. EM vikramb@mail.nih.gov NR 1 TC 1 Z9 1 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 DEC 20 PY 2006 VL 98 IS 24 BP 1826 EP 1826 DI 10.1093/jnci/djj490 PG 1 WC Oncology SC Oncology GA 118WE UT WOS:000242973400014 PM 17179485 ER PT J AU Momeni, P Bell, J Duckworth, J Hutton, M Mann, D Brown, SP Hardy, J AF Momeni, Parastoo Bell, Jason Duckworth, Jaime Hutton, Mike Mann, David Brown, Stuart Pickering Hardy, John TI Sequence analysis of all identified open reading frames on the frontal temporal dementia haplotype on chromosome 3 fails to identify unique coding variants except in CHMP2B SO NEUROSCIENCE LETTERS LA English DT Article DE dementia; CHMP2B; genetics ID FRONTOTEMPORAL DEMENTIA; MUTATIONS AB A segregating splice site mutation in the CHMP2B gene has been shown in the single Danish family which has been reported to show linkage between dementia and chromosome 3 markers. Despite extensive analysis, no other segregating mutations have been found in other kindreds, although some point variants have been found both in sporadic cases and in controls. We recently found a premature stop codon in a person without dementia and this led us to investigate whether the splice site mutation in the Danish kindred did not explain the disease, but rather was hitchhiking on the segregating disease haplotype. We determined to test this possibility by sequencing every other gene on the haplotype in a case from the kindred. We did not find any other unique variants. The implications of these findings for the likely mode of pathogenesis of frontal temporal dementia are discussed. Published by Elsevier Ireland Ltd. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. Univ Manchester, Div Lab & Regenerat Med, Manchester M13 9PT, Lancs, England. Univ Manchester, Hope Hosp, Greater Manchester Neurosci Ctr, Salford M6 8HD, Lancs, England. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg 35,Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009; OI Pickering-Brown, Stuart/0000-0003-1561-6054 FU Medical Research Council [G0701075] NR 8 TC 11 Z9 11 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 20 PY 2006 VL 410 IS 2 BP 77 EP 79 DI 10.1016/j.neulet.2006.06.065 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 114LV UT WOS:000242668600001 PM 17095158 ER PT J AU Chen, S Liu, HL Yang, YH Hsu, YY Chuang, KS AF Chen, Sharon Liu, Ho-Ling Yang, Yihong Hsu, Yuan-Yu Chuang, Keh-Shih TI Determination of arterial input function in dynamic susceptibility contrast MRI using group independent component analysis technique SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article; Proceedings Paper CT 3rd International Conference on Imaging Technologies in Biomedical Sciences CY SEP 25-29, 2005 CL Milos, GREECE DE AIF; group ICA technique; CBF; perfusion MRI ID CEREBRAL-BLOOD-FLOW; INFERENCES AB Quantification of cerebral blood flow (CBF) with dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) requires the determination of the arterial input function (AIF). The segmentation of surrounding tissue by manual selection is error-prone due to the partial volume artifacts. Independent component analysis (ICA) has the advantage in automatically decomposing the signals into interpretable components. Recently group ICA technique has been applied to fMRI study and showed reduced variance caused by motion artifact and noise. In this work, we investigated the feasibility and efficacy of the use of group ICA technique to extract the AIF. Both simulated and in vivo data were analyzed in this study. The simulation data of eight phantoms were generated using randomized lesion locations and time activity curves. The clinical data were obtained from spin-echo EPI MR scans performed in seven normal subjects. Group ICA technique was applied to analyze data through concatenating across seven subjects. The AIFs were calculated from the weighted average of the signals in the region selected by ICA. Preliminary results of this study showed that group ICA technique could not extract accurate AIF information from regions around the vessel. The mismatched location of vessels within the group reduced the benefits of group study. (c) 2006 Elsevier B.V. All rights reserved. C1 Natl Tsing Hua Univ, Dept Nucl Sci, Hsinchu 30043, Taiwan. NIH, Neuroimaging Res Branch, Baltimore, MD USA. Buddhist Tzu Chi Gen Hosp, Dept Radiol, Taipei, Taiwan. RP Chuang, KS (reprint author), Natl Tsing Hua Univ, Dept Nucl Sci, 101 Sector 2 Guangfu Rd, Hsinchu 30043, Taiwan. EM kschuang@mx.nthu.edu.tw NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD DEC 20 PY 2006 VL 569 IS 2 SI SI BP 617 EP 621 DI 10.1016/j.nima.2006.08.136 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 122QK UT WOS:000243241300102 ER PT J AU Matoba, R Niwa, H Masui, S Ohtsuka, S Carter, MG Sharov, AA Ko, MSH AF Matoba, Ryo Niwa, Hitoshi Masui, Shinji Ohtsuka, Satoshi Carter, Mark G. Sharov, Alexei A. Ko, Minoru S. H. TI Dissecting Oct3/4-Regulated Gene Networks in Embryonic Stem Cells by Expression Profiling SO PLOS ONE LA English DT Article AB POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks. C1 [Matoba, Ryo; Carter, Mark G.; Sharov, Alexei A.; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. [Niwa, Hitoshi; Masui, Shinji; Ohtsuka, Satoshi] RIKEN, Ctr Dev Biol, Lab Pluripotent Cell Studies, Kobe, Hyogo, Japan. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural Research Program of the National Institute on Aging, NIH FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, NIH. NR 71 TC 123 Z9 126 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2006 VL 1 IS 1 AR e26 DI 10.1371/journal.pone.0000026 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DB UT WOS:000207443600026 PM 17183653 ER PT J AU Russell, CA Real, LA Smith, DL AF Russell, Colin A. Real, Leslie A. Smith, David L. TI Spatial Control of Rabies on Heterogeneous Landscapes SO PLOS ONE LA English DT Article AB Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics. C1 [Russell, Colin A.] Univ Cambridge, Dept Zool, Cambridge, England. [Real, Leslie A.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Smith, David L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Russell, CA (reprint author), Univ Cambridge, Dept Zool, Cambridge, England. EM car44@cam.ac.uk RI Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Russell, Colin/0000-0002-2113-162X FU Gates Cambridge Trust FX Funding: This work was supported by a Gates Cambridge Trust Fellowship to CAR. NR 25 TC 29 Z9 29 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 20 PY 2006 VL 1 IS 1 AR e27 DI 10.1371/journal.pone.0000027 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DB UT WOS:000207443600027 PM 17183654 ER PT J AU Bennasser, Y Jeang, KT AF Bennasser, Yamina Jeang, Kuan-Teh TI HIV-I tat interaction with Dicer: requirement for RNA SO RETROVIROLOGY LA English DT Article ID BINDING PROTEIN; MESSENGER-RNAS; INTERFERENCE; SIRNA; TRBP; EXPRESSION; IMMUNITY; PATHWAY; COMPLEX; STRAND AB Dicer is an RNase III which processes two classes of cellular small RNAs: the microRNAs (miRNA) and short interfering RNAs (siRNA). Previously, we observed that over-expressed HIV-1 Tat protein can suppress the processing of small RNAs inside cells. Here, we have investigated the requirements for Tat interaction with Dicer. We report that Tat-Dicer interaction depends on RNA, requires the helicase domain of Dicer, and is independent of Tat's transactivation domain. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ybennasser@mail.nih.gov; kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 25 TC 67 Z9 71 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 20 PY 2006 VL 3 AR 95 DI 10.1186/1742-4690-3-95 PG 6 WC Virology SC Virology GA 129IR UT WOS:000243722700001 PM 17181864 ER PT J AU Stephens, GE Xiao, H Lankenau, DH Wu, C Elgin, SCR AF Stephens, Gena E. Xiao, Hua Lankenau, Dirk-H. Wu, Carl Elgin, Sarah C. R. TI Heterochromatin protein 2 interacts with Nap-1 and NURF: A link between heterochromatin-induced gene silencing and the chromatin remodeling machinery in Drosophila SO BIOCHEMISTRY LA English DT Article ID ASSEMBLY FACTOR-I; POSITION-EFFECT VARIEGATION; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; NUCLEOSOME; MELANOGASTER; COMPLEX; ISWI; HISTONES AB Heterochromatin protein 2 (HP2) is a nonhistone chromosomal protein from Drosophila melanogaster that binds to heterochromatin protein 1 (HP1) and has been implicated in heterochromatin-induced gene silencing. Heretofore, HP1 has been the only known binding partner of HP2, a large protein devoid of sequence motifs other than a pair of AT hooks. In an effort to identify proteins that interact with HP2 and assign functions to its various domains, nuclear proteins were fractionated under nondenaturing conditions. On separation of nuclear proteins, nucleosome assembly protein 1 (Nap-1) has an overlapping elution profile with HP2 ( assayed by Western blot) and has been identified by mass spectrometry in fractions with HP2. Upon probing fractions in which HP2 and Nap-1 are both present, we find that the nucleosome remodeling factor ( NURF), an ISWI-dependent chromatin remodeling complex, is also present. Results from coimmunoprecipitation experiments suggest that HP2 interacts with Nap-1 as well as with NURF; NURF appears to interact directly with both HP2 and Nap-1. Three distinct domains within HP2 mediate the interaction with NURF, allowing us to assign NURF binding domains in addition to the AT hooks and HP1 binding domains already mapped in HP2. Mutations in Nap-1 are shown to suppress position effect variegation, suggesting that Nap-1 functions to help to assemble chromatin into a closed form, as does HP2. On the basis of these interactions, we speculate that HP2 may cooperate with these factors in the remodeling of chromatin for silencing. C1 Washington Univ, Dept Biol, St Louis, MO 63130 USA. NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Inst Zool, D-69120 Heidelberg, Germany. RP Elgin, SCR (reprint author), Washington Univ, Dept Biol, CB-1229, St Louis, MO 63130 USA. EM selgin@biology.wustl.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM068388, R01 GM068388-18, T32 GM007067, T32 GM07067, GM068388] NR 41 TC 12 Z9 12 U1 0 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 DEC 19 PY 2006 VL 45 IS 50 BP 14990 EP 14999 DI 10.1021/bi060983y PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115YZ UT WOS:000242771000012 PM 17154536 ER PT J AU Postnikov, YV Belova, GI Lim, JH Bustin, M AF Postnikov, Yuri V. Belova, Galina I. Lim, Jae-Hwan Bustin, Michael TI Chromosomal protein HMGN1 modulates the phosphorylation of serine 1 in histone H2A SO BIOCHEMISTRY LA English DT Article ID HIGH-MOBILITY; MITOTIC PHOSPHORYLATION; H3 PHOSPHORYLATION; CHROMATIN; ACETYLATION; BINDING; DOMAIN; LOCALIZATION; ENHANCEMENT; NUCLEOSOME AB Here we demonstrate that HMGN1, a nuclear protein that binds specifically to nucleosomes, modulates the level of histone H2A phosphorylation. In Hmgn1(-/-) cells, loss of HMGN1 elevates the steady-state levels of H2AS1ph throughout the cell cycle. In vitro, HMGN1 reduces the rate of Rsk2- and Msk1-mediated phosphorylation of nucleosomal, but not free, histone H2A. HMGN1 inhibits H2A phosphorylation by binding to nucleosomes since an HMGN mutant, which cannot bind to chromatin, does not inhibit the Rsk2- mediated H2A phosphorylation. HMGN2 also inhibits H2A phosphorylation, suggesting that the inhibition of H2A phosphorylation is not specific to only one member of this protein family. Thus, the present data add modifications of histone H2A to the list of histone modifications affected by HMGN proteins. It supports the suggestion that structural chromatin binding proteins can modify the whole profile of post-translational modifications of core histones. C1 NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. Andong Natl Univ, Dept Biol Sci, Andong 760749, Kyungsangbuk Do, South Korea. RP Postnikov, YV (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bldg 37,Room 3122, Bethesda, MD 20892 USA. EM yupo@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Intramural NIH HHS [Z01 BC004496-30] NR 26 TC 16 Z9 16 U1 0 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 DEC 19 PY 2006 VL 45 IS 50 BP 15092 EP 15099 DI 10.1021/bi0613271 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115YZ UT WOS:000242771000023 PM 17154547 ER PT J AU Lizunov, V Zimmerberg, J AF Lizunov, Vladimir Zimmerberg, Joshua TI Cellular biophysics: Bacterial endospore, membranes and random fluctuation SO CURRENT BIOLOGY LA English DT Editorial Material ID BACILLUS-SUBTILIS; ENGULFMENT; FORESPORE; PHYSICS; RATCHET; MOTORS AB Purposeful motion of biological processes can be driven by Brownian motion of macromolecular complexes with one-sided binding biasing movement in one direction: a Brownian ratchet, now proposed to explain membrane motion during a phagocytosis-like process in bacteria. C1 NICHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. RP Lizunov, V (reprint author), NICHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov NR 16 TC 5 Z9 5 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 19 PY 2006 VL 16 IS 24 BP R1025 EP R1028 DI 10.1016/j.cub.2006.11.010 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119UP UT WOS:000243039800013 PM 17174907 ER PT J AU Chu, PH Huang, TY Williams, J Stafford, DW AF Chu, Pei-Hsuan Huang, Teng-Yi Williams, Jason Stafford, D. W. TI Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE purification; reconstitution; membrane protein ID GAMMA-CARBOXYLATION SYSTEM; ACTIVE-SITE; FACTOR-IX; 2,3-EPOXIDE REDUCTASE; WARFARIN; IDENTIFICATION; INHIBITION; MECHANISM; MEMBRANE; VKORC1 AB More than 21 million prescriptions for warfarin are written yearly in the U.S. Despite its importance, warfarin's target, vitamin K epoxide reductase (VKOR), has resisted purification since its identification in 1972. Here, we report its purification and reconstitution. HPC4, a calcium-specific antibody that recognizes a 12-aa tag, was used to purify and identify VKOR. Partial reconstitution is achieved on the column by washing with 0.4% dioleoylphosphatidylcholine/0.4% deoxycholate. Activity is completely recovered by dialysis against a buffer containing a reducing agent but lacking dioleoylphosphatidylcholine/deoxycholate. Removal of detergent from the eluted proteins apparently facilitates liposome formation. Purified recombinant VKOR with tag is approximate to 21 kDa, as expected; fully active; and > 93% pure. The concentration of warfarin for 50% inhibition is the same for purified protein and microsomes. It has been reported that VKOR is a multisubunit enzyme. Our results, however, suggest that a single peptide can accomplish both the conversion of vitamin K epoxide to vitamin K and vitamin K to reduced vitamin K. This purification will allow further characterization of VKOR in relation to other components of the vitamin K cycle and should facilitate its structural determination. C1 Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Stafford, DW (reprint author), Univ N Carolina, Dept Biol, CB 3280, Chapel Hill, NC 27599 USA. EM dws@email.unc.edu FU NHLBI NIH HHS [R01 HL077740, 5-R01-HL077740-01] NR 25 TC 62 Z9 65 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19308 EP 19313 DI 10.1073/pnas.0609401103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600018 PM 17164330 ER PT J AU Eanes, WF Merritt, TJS Flowers, JM Kumagai, S Sezgin, E Zhu, CT AF Eanes, Walter F. Merritt, Thomas J. S. Flowers, Jonathan M. Kumagai, Seiji Sezgin, Efe Zhu, Chen-Tseh TI Flux control and excess capacity in the enzymes of glycolysis and their relationship to flight metabolism in Drosophila melanogaster SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID QUANTITATIVE EVOLUTIONARY DESIGN; INSECT FLIGHT; PHOSPHOGLUCOSE ISOMERASE; ENERGY-METABOLISM; GENETIC-VARIABILITY; WORKING MUSCLE; POWER OUTPUT; ORCHID BEES; PGM LOCUS; RATES AB An important question in evolutionary and physiological genetics is how the control of flux-base phenotypes is distributed across the enzymes in a pathway. This control is often related to enzyme-specific levels of activity that are reported to be in excess of that required for demand. In glycolysis, metabolic control is frequently considered vested in classical regulatory enzymes, each strongly displaced from equilibrium. Yet the contribution of individual steps to control is unclear. To assess enzyme-specific control in the glycolytic pathway, we used P-element excision-derived mutagenesis in Drosophila melanogaster to generate full and partial knockouts of seven metabolic genes and to measure tethered flight performance. For most enzymes, we find that reduction to half of the normal activity has no measurable impact on wing beat frequency. The enzymes catalyzing near-equilibrium reactions, phosphoglucose isomerase, phosphoglucomutase, and triosephosphate isomerase fail to show any decline in flight performance even when activity levels are reduced to 17% or less. At reduced activities, the classic regulatory enzymes, hexokinase and glycogen phosphorylase, show significant drops in flight performance and are nearer to saturation. Our results show that flight performance is canalized or robust to the activity variation found in natural populations. Furthermore, enzymes catalyzing near-equilibrium reactions show strong genetic dominance down to low levels of activity. This implies considerable excess enzyme capacity for these enzymes. C1 SUNY Stony Brook, Dept Ecol & Evolut, Stony Brook, NY 11794 USA. RP Eanes, WF (reprint author), NCI, Lab Genom Divers, NIH, Bldg 560,Room 2142, Frederick, MD 21702 USA. EM walter@life.bio.sunysb.edu RI Zhu, Chen-Tseh (Lei)/A-9761-2014; Sezgin, Efe/B-8418-2012 OI Sezgin, Efe/0000-0002-8000-7485 FU NIGMS NIH HHS [R01 GM045247, GM-45247] NR 58 TC 36 Z9 37 U1 3 U2 25 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19413 EP 19418 DI 10.1073/pnas.0607095104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600036 PM 17159148 ER PT J AU Ho, J Moir, S Malaspina, A Howell, ML Wang, W DiPoto, AC O'Shea, MA Roby, GA Kwan, R Mican, JM Chun, TW Fauci, AS AF Ho, Jason Moir, Susan Malaspina, Angela Howell, Melissa L. Wang, Wei DiPoto, Angela C. O'Shea, Marie A. Roby, Gregg A. Kwan, Richard Mican, JoAnn M. Chun, Tae-Wook Fauci, Anthony S. TI Two overrepresented B cell populations in HIV-infected individuals undergo apoptosis by different mechanisms SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunopathogenesis; Bcl-2; CD95 ID BONE-MARROW; CYTOCHROME-C; LYMPHOCYTE DYSFUNCTIONS; ANTIRETROVIRAL THERAPY; REGULATED EXPRESSION; ACTIVATION; HOMEOSTASIS; IMMUNODEFICIENCY; CASPASE-8; DEATH AB Perturbations of B cells in HIV-infected individuals are associated with the overrepresentation of distinct B cell populations. Here we describe high extrinsic CD95 ligand (CD95L)-mediated apoptosis in CD10(-)/CD21(lo) mature/activated B cells that likely arise from HIV-induced immune activation. In addition, high intrinsic apoptosis was observed in CD10(+) immature/transitional B cells that likely arise as a result of HIV-induced lymphopenia. CD10(+) B cells expressed low levels of Bcl-2 and Bcl-xL, consistent with their high susceptibility to intrinsic apoptosis. Higher levels of activated Bax and Bak were induced in CD10(+) B cells compared with CD95L-treated CD10(-) B cells, consistent with the greater involvement of mitochondria in intrinsic vs. extrinsic apoptosis. Of interest, both extrinsic apoptosis in CD95L-treated CD10(-) B cells and intrinsic apoptosis in CD10(+) B cells were associated with caspase-8 activation. Our data suggest that two distinct mechanisms of apoptosis are associated with B cells of HIV-infected individuals, and both may contribute to the depletion and dysfunction of B cells in these individuals. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov; afauci@niaid.nih.gov FU Intramural NIH HHS NR 40 TC 48 Z9 52 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19436 EP 19441 DI 10.1073/pnas.0609515103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600040 PM 17158796 ER PT J AU Messaoudi, I Warner, J Fischer, M Park, B Hill, B Mattison, J Lane, MA Roth, GS Ingram, DK Picker, LJ Douek, DC Mori, M Nikolich-Zugich, J AF Messaoudi, Ilhem Warner, Jessica Fischer, Miranda Park, Buyng Hill, Brenna Mattison, Julie Lane, Mark A. Roth, George S. Ingram, Donald K. Picker, Louis J. Douek, Daniel C. Mori, Motomi Nikolich-Zugich, Janko TI Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; immunity; T cell subsets; nutrition ID GENETICALLY HETEROGENEOUS MICE; DIETARY RESTRICTION; RHESUS-MONKEYS; CLONAL EXPANSIONS; REPLICATIVE SENESCENCE; PERIPHERAL-BLOOD; IMMUNE FUNCTION; MACACA-MULATTA; LIFE-SPAN; HUMANS AB Caloric restriction (CR) has long been known to increase median and maximal lifespans and to decreases mortality and morbidity in short-lived animal models, likely by altering fundamental biological processes that regulate aging and longevity. in rodents, CR was reported to delay the aging of the immune system (immune senescence), which is believed to be largely responsible for a dramatic increase in age-related susceptibility to infectious diseases. However, it is unclear whether CR can exert similar effects in long-lived organisms. Previous studies involving 2- to 4-year CR treatment of long-lived primates failed to find a CR effect or reported effects on the immune system opposite to those seen in CR-treated rodents. Here we show that long-term CR delays the adverse effects of aging on nonhuman primate T cells. CR effected a marked improvement in the maintenance and/or production of naive T cells and the consequent preservation of T cell receptor repertoire diversity. Furthermore, CR also improved T cell function and reduced production of inflammatory cytokines by memory T cells. Our results provide evidence that CR can delay immune senescence in nonhuman primates, potentially contributing to an extended lifespan by reducing susceptibility to infectious disease. C1 Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Inst Canc, Biostat Shared Resource, Portland, OR 97201 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. GeroSci Inc, Pylesville, MD 21132 USA. RP Nikolich-Zugich, J (reprint author), Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, W Campus,505 NW 185th Ave, Beaverton, OR 97006 USA. EM nikolich@ohsu.edu OI Nikolich-Zugich, Janko/0000-0001-5830-5323; /0000-0003-3516-7516 FU Intramural NIH HHS; NCRR NIH HHS [K01 RR000163, P51 RR000163, RR0163]; NIA NIH HHS [AG21384, U01 AG021384]; NIAID NIH HHS [5T32 AI0077472-10, T32 AI007472] NR 52 TC 112 Z9 114 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19448 EP 19453 DI 10.1073/pnas.0606661103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600042 PM 17159149 ER PT J AU Husain, M Weisberg, AS Moss, B AF Husain, Matloob Weisberg, Andrea S. Moss, Bernard TI Existence of an operative pathway from the endoplasmic reticulum to the immature poxvirus membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membrane protein trafficking; vaccinia virus; virus assembly ID GOLGI INTERMEDIATE COMPARTMENT; VACCINIA VIRUS MORPHOGENESIS; VIRION MORPHOGENESIS; ENVELOPE PROTEIN; INITIATE MORPHOGENESIS; ESSENTIAL COMPONENT; A14 PHOSPHOPROTEIN; F10 KINASE; SIGNAL; GENE AB In thin sections of cells infected with vaccinia virus or other poxviruses, the viral membrane is first discerned as a crescent or circle lacking obvious continuity with a cellular organelle, presenting an appearance of de novo membrane biogenesis. This notion, which many consider heretical, is nevertheless consistent with the absence of a signature of endoplasmic reticulum (ER) trafficking, such as signal peptide cleavage or glycosylation, in any of the numerous viral membrane proteins. The purpose of this study was to determine whether an operative pathway exists between the ER and the immature virion membrane. We showed that the highly conserved A9 viral membrane protein was inserted into the ER of uninfected cells with the same topology as in viral membranes. Next, we found that replacement of the nonessential cytoplasmic tail of A9 with one containing COPII-binding sites reduced incorporation of the modified A9 into viral membranes and led to its accumulation in the Golgi apparatus, implying that A9 was inserted into the ER and then diverted from its natural path. Most importantly, we demonstrated cleavage of a heterologous signal peptide fused to the N-terminal region of A9 and localized the truncated protein in immature and mature virions. Additionally, immuno-electron micrographs showed A9 in tubules containing protein disulfide isomerase, an ER lumenal protein, near immature viral membranes. The present data provide strong evidence for an operative pathway from ER domains within the virus factory to the viral membrane. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 43 TC 34 Z9 34 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19506 EP 19511 DI 10.1073/pnas.0609406103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600052 PM 17146047 ER PT J AU Bassettt, DS Meyer-Lindenberg, A Achard, S Duke, T Bullmore, ET AF Bassettt, Danielle S. Meyer-Lindenberg, Andreas Achard, Sophie Duke, Thomas Bullmore, Edward T. TI Adaptive reconfiguration of fractal small-world human brain functional networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE magnetoencephalography; wavelet; graph theory; connectivity; binding ID MAGNETIC-RESONANCE IMAGES; COMPLEX NETWORKS; CEREBRAL-CORTEX; NEURAL SYSTEMS; CONNECTIVITY; ORGANIZATION; SYNCHRONIZATION; OSCILLATIONS; TRANSITIONS; FREQUENCY AB Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a finger-tapping task, whereas the other half were studied at rest. We found that brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical delta (low and high), theta, alpha, beta, and gamma frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2-37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency gamma network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both beta and gamma networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding. Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters. C1 NIMH, Unit Syst Neurosci Psychiat Genes Cognit, NIH, Bethesda, MD 20892 USA. NIMH, Psychosis Program, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Brain Mappin Unit, Cambridge CB2 2QQ, England. Univ Cambridge, Cavendish Lab, Dept Phys, Cambridge CB3 0HE, England. RP Meyer-Lindenberg, A (reprint author), NIMH, Unit Syst Neurosci Psychiat Genes Cognit, NIH, Bethesda, MD 20892 USA. EM andreasm@mail.nih.gov; etb23@cam.ac.uk RI Achard, Sophie/L-5231-2014; Bullmore, Edward/C-1706-2012; Meyer-Lindenberg, Andreas/H-1076-2011 OI Bullmore, Edward/0000-0002-8955-8283; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS; Medical Research Council [G0001354] NR 64 TC 362 Z9 372 U1 13 U2 53 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 19 PY 2006 VL 103 IS 51 BP 19518 EP 19523 DI 10.1073/pnas.0606005103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121OJ UT WOS:000243166600054 PM 17159150 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases SO BIOLOGY DIRECT LA English DT Article ID DEOXYRIBONUCLEIC ACID SYNTHESIS; UNIVERSAL COMMON ANCESTOR; ESCHERICHIA-COLI PRIMASE; CRYSTAL-STRUCTURE; CATALYTIC PROPERTIES; FREE EXTRACTS; PSI-BLAST; VIRUSES; PROTEINS; ORIGIN AB Background: The core enzymes of the DNA replication systems show striking diversity among cellular life forms and more so among viruses. In particular, and counter-intuitively, given the central role of DNA in all cells and the mechanistic uniformity of replication, the core enzymes of the replication systems of bacteria and archaea ( as well as eukaryotes) are unrelated or extremely distantly related. Viruses and plasmids, in addition, possess at least two unique DNA replication systems, namely, the protein-primed and rolling circle modalities of replication. This unexpected diversity makes the origin and evolution of DNA replication systems a particularly challenging and intriguing problem in evolutionary biology. Results: I propose a specific succession for the emergence of different DNA replication systems, drawing argument from the differences in their representation among viruses and other selfish replicating elements. In a striking pattern, the DNA replication systems of viruses infecting bacteria and eukaryotes are dominated by the archaeal-type B-family DNA polymerase ( PolB) whereas the bacterial replicative DNA polymerase (PolC) is present only in a handful of bacteriophage genomes. There is no apparent mechanistic impediment to the involvement of the bacterial-type replication machinery in viral DNA replication. Therefore, I hypothesize that the observed, markedly unequal distribution of the replicative DNA polymerases among the known cellular and viral replication systems has a historical explanation. I propose that, among the two types of DNA replication machineries that are found in extant life forms, the archaeal-type, PolB-based system evolved first and had already given rise to a variety of diverse viruses and other selfish elements before the advent of the bacterial, PolC-based machinery. Conceivably, at that stage of evolution, the niches for DNA-viral reproduction have been already filled with viruses replicating with the help of the archaeal system, and viruses with the bacterial system never took off. I further suggest that the two other systems of DNA replication, the rolling circle mechanism and the protein-primed mechanism, which are represented in diverse selfish elements, also evolved prior to the emergence of the bacterial replication system. This hypothesis is compatible with the distinct structural affinities of PolB, which has the palm-domain fold shared with reverse transcriptases and RNA-dependent RNA polymerases, and PolC that has a distinct, unrelated nucleotidyltransferase fold. I propose that PolB is a descendant of polymerases that were involved in the replication of genetic elements in the RNA-protein world, prior to the emergence of DNA replication. By contrast, PolC might have evolved from an ancient non-templated polymerase, e. g., polyA polymerase. The proposed temporal succession of the evolving DNA replication systems does not depend on the specific scenario adopted for the evolution of cells and viruses, i.e., whether viruses are derived from cells or virus-like elements are thought to originate from a primordial gene pool. However, arguments are presented in favor of the latter scenario as the most parsimonious explanation of the evolution of DNA replication systems. Conclusion: Comparative analysis of the diversity of genomic strategies and organizations of viruses and cellular life forms has the potential to open windows into the deep past of life's evolution, especially, with the regard to the origin of genome replication systems. When complemented with information on the evolution of the relevant protein folds, this comparative approach can yield credible scenarios for very early steps of evolution that otherwise appear to be out of reach. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 58 TC 28 Z9 29 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD DEC 18 PY 2006 VL 1 AR 39 DI 10.1186/1745-6150-1-39 PG 18 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TW UT WOS:000244037400001 PM 17176463 ER PT J AU Szabadkai, G Bianchi, K Varnai, P De Stefani, D Wieckowski, MR Cavagna, D Nagy, AI Balla, T Rizzuto, R AF Szabadkai, Gyorgy Bianchi, Katiuscia Varnai, Peter De Stefani, Diego Wieckowski, Mariusz R. Cavagna, Dario Nagy, Aniko I. Balla, Tamas Rizzuto, Rosario TI Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DEPENDENT ANION CHANNEL; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; RAT-LIVER MITOCHONDRIA; CALCIUM-BINDING; HSP70 FAMILY; PERMEABILITY TRANSITION; MOLECULAR-INTERACTIONS; REGULATORY MECHANISM; ELECTRON TOMOGRAPHY; SIGNAL PROPAGATION AB The voltage-dependent anion channel ( VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca2+, and cell death signaling between the endoplasmic reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca2+-release channel inositol 1,4,5-trisphosphate receptor (IP3R) through the molecular chaperone glucose-regulated protein 75 (grp75). Functional interaction between the channels was shown by the recombinant expression of the ligand-binding domain of the IP3R on the ER or mitochondrial surface, which directly enhanced Ca2+ accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP3R and the mitochondrial Ca2+ uptake machinery. Because organelle Ca2+ homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis. C1 Univ Ferrara, Dept Expt & Diagnost Med, Sect Gen Pathol, Interdisciplinary Ctr Study Inflammat,Emilia Rama, I-44100 Ferrara, Italy. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Physiol, Fac Med, H-1081 Budapest, Hungary. Polish Acad Sci, Dept Cellular Biochem, M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. RP Rizzuto, R (reprint author), Univ Ferrara, Dept Expt & Diagnost Med, Sect Gen Pathol, Interdisciplinary Ctr Study Inflammat,Emilia Rama, I-44100 Ferrara, Italy. EM rzr@unife.it RI De Stefani, Diego/I-7715-2015; OI De Stefani, Diego/0000-0003-3796-8907; Balla, Tamas/0000-0002-9077-3335 FU Telethon [GGP05284] NR 63 TC 375 Z9 384 U1 4 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 18 PY 2006 VL 175 IS 6 BP 901 EP 911 DI 10.1083/jcb.200608073 PG 11 WC Cell Biology SC Cell Biology GA 120QL UT WOS:000243099800008 PM 17178908 ER PT J AU Je, HS Yang, F Zhou, JZ Lu, B AF Je, Hyun-Soo Yang, Feng Zhou, Jiangzheng Lu, Bai TI Neurotrophin 3 induces structural and functional modification of synapses through distinct molecular mechanisms SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; LONG-TERM-MEMORY; NERVE GROWTH-FACTOR; REGULATED KINASE ACTIVATION; SYNAPTIC PLASTICITY; TRANSCRIPTION FACTORS; CREB PHOSPHORYLATION; GENETIC DISSECTION; NEUROTRANSMITTER RELEASE; DEPENDENT TRANSCRIPTION AB The mechanisms by which neurotrophins elicit long-term structural and functional changes of synapses are not known. We report the mechanistic separation of functional and structural synaptic regulation by neurotrophin 3 (NT-3), using the neuromuscular synapse as a model. Inhibition of cAMP response element (CRE) binding protein (CREB)-mediated transcription blocks the enhancement of transmitter release elicited by NT-3, without affecting the synaptic varicosity of the presynaptic terminals. Further analysis indicates that CREB is activated through Ca2+/calmodulin-dependent kinase IV (CaMKIV) pathway, rather than the mitogen-activated protein kinase ( MAPK) or cAMP pathway. In contrast, inhibition of MAPK prevents the NT-3-induced structural, but not functional, changes. Genetic and imaging experiments indicate that the small GTPase Rap1, but not Ras, acts upstream of MAPK activation by NT-3. Thus, NT-3 initiates parallel structural and functional modi. cations of synapses through the Rap1-MAPK and CaMKIV-CREB pathways, respectively. These findings may have implications in the general mechanisms of long-term synaptic modulation by neurotrophins. C1 NICHHD, Sect Neural Dev & Plastic, NIH, Bethesda, MD 20892 USA. NIMH, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plastic, NIH, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; OI Je, hyunsoo/0000-0002-2924-5621 FU Intramural NIH HHS NR 76 TC 22 Z9 22 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 DEC 18 PY 2006 VL 175 IS 6 BP 1029 EP 1042 DI 10.1083/jcb.200603061 PG 14 WC Cell Biology SC Cell Biology GA 120QL UT WOS:000243099800019 PM 17178914 ER PT J AU MacArthur, RD Novak, RM Peng, G Chen, L Xiang, Y Hullsiek, KH Kozal, MJ van den Berg-Wolf, M Henely, C Schmetter, B Dehlinger, M AF MacArthur, Rodger D. Novak, Richard M. Peng, Grace Chen, Li Xiang, Ying Hullsiek, Katherine Huppler Kozal, Michael J. van den Berg-Wolf, Mary Henely, Christopher Schmetter, Barry Dehlinger, Marjorie CA CPCRA 058 Study Team Terry Beirn Community Programs TI A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial SO LANCET LA English DT Article ID COMBINATION THERAPY; HIV-INFECTION; RNA; NELFINAVIR; LAMIVUDINE; APOPTOSIS; REGIMENS; COHORT; DRUGS; COUNT AB Background Long-term data from randomised trials on the consequences of treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST trial, which compared initial treatment strategies for clinical, immunological, and virological outcomes. Methods Between 1999 and 2002, 1397 antiretroviral-treatment-naive patients, presenting at 18 clinical trial units with 80 research sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI; n=464). Primary endpoints were a composite of an AIDS-defining event, death, or CD4 cell count decline to less than 200 cells per mm(3) for the PI versus NNRTI comparison, and average change in CD4 cell count at or after 32 months for the three-class versus combined two-class comparison. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00000922. Findings 1397 patients were assessed for the composite endpoint. A total of 388 participants developed the composite endpoint, 302 developed AIDS or died, and 188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for AIDS or death, for death, and for virological failure were 1.02 (95% Cl 0.79-1.31), 1.07 (0.80-1.41), 0.95 (0.66-1.37), and 0.66 (0.56-0.78), respectively. 1196 patients were assessed for the three-class versus combined two-class primary endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per mm(3) and +227 cells per mm(3) for the three-class and the combined two-class strategies (p=0.62), respectively. HRs (three-class vs combined two-class) for AIDS or death and virological failure were 1.15 (0.91-1.45) and 0.87 (0.75-1.00), respectively. HRs (three-class vs combined two-class) for AIDS or death were similar for participants with baseline CD4 cell counts of 200 cells per mm3 or less and of more than 200 cells per mm(3) (p=0.38 for interaction), and for participants with baseline HIV RNA concentrations less than 100000 copies per ml, and 100000 copies per mL or more (p=0.26 for interaction). Participants assigned the three-class strategy were significantly more likely to discontinue treatment because of toxic effects than were those assigned to the two-class strategies (HR 1.58; p<0.0001). Interpretation Initial treatment with either an NNRTI-based regimen or a PI-based regimen, but not both together, is a good strategy for long-term antiretroviral management in treatment-naive patients with HIV. C1 Wayne State Univ, Detroit, MI USA. Univ Illinois, Chicago, IL USA. Univ Minnesota, Minneapolis, MN USA. Yale Univ, New Haven, CT USA. Temple Univ, Philadelphia, PA 19122 USA. Meridian Hlth Syst, Neptune, NJ USA. Social & Sci Syst, Silver Spring, MD USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. RP MacArthur, RD (reprint author), Div Infect Dis, UHC 7D,4201 St Antoine, Detroit, MI 48201 USA. EM rdmacarthur@mac.com FU NIAID NIH HHS [5U01AI042170-10, 5U01AI046362-03] NR 24 TC 97 Z9 102 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 16 PY 2006 VL 368 IS 9553 BP 2125 EP 2135 DI 10.1016/S0140-6736(06)69861-9 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 117EZ UT WOS:000242856900020 PM 17174704 ER PT J AU Odden, MC Chertow, GM Fried, LF Newman, AB Connelly, S Angleman, S Harris, TB Simonsick, EM Shlipak, MG AF Odden, Michelle C. Chertow, Glenn M. Fried, Linda F. Newman, Anne B. Connelly, Stephanie Angleman, Sara Harris, Tamara B. Simonsick, Eleanor M. Shlipak, Michael G. CA HABC Study TI Cystatin C and measures of physical function in elderly adults - The health, aging, and body composition (HABC) study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; cystatin C; exercise tolerance; kidney diseases; muscle weakness; walking ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; EXERCISE CAPACITY; HEMODIALYSIS-PATIENTS; SERUM CREATININE; OLDER-ADULTS; DIALYSIS; RISK AB Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m(2). In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function. C1 Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Nephrol, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Odden, MC (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL073208-01]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [R01 DK 066488] NR 42 TC 56 Z9 57 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2006 VL 164 IS 12 BP 1180 EP 1189 DI 10.1093/aje/kwj333 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 115DK UT WOS:000242714800006 PM 17035344 ER PT J AU Jaradat, M Stapleton, C Tilley, SL Dixon, D Erikson, CJ McCaskill, JG Kang, HS Angers, M Liao, G Collins, J Grissom, S Jetten, AM AF Jaradat, Maisa Stapleton, Cliona Tilley, Stephen L. Dixon, Darlene Erikson, Christopher J. McCaskill, Joshua G. Kang, Hong Soon Angers, Martin Liao, Grace Collins, Jennifer Grissom, Sherry Jetten, Anton M. TI Modulatory role for retinoid-related orphan receptor alpha in allergen-induced lung inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE asthma; inflammation; lung; nuclear receptor ID EOSINOPHILIC AIRWAY INFLAMMATION; ROR-ALPHA; PPAR-GAMMA; KAPPA-B; BRONCHOALVEOLAR LAVAGE; NUCLEAR RECEPTORS; EPITHELIAL-CELLS; DEFICIENT MICE; MURINE MODEL; IN-VITRO AB Rationale: Nuclear receptors play a critical role in the regulation of inflammation, thus representing attractive targets for the treatment of asthma. Objective: In this study, we assess the potential regulatory function of retinoid-related orphan receptor alpha (ROR alpha) in the adaptive immune response using ovalbumin (OVA)-induced airway inflammation as a model. Methods: Allergen-induced inflammation was compared between wild-type (WT) and staggerer (ROR alpha(sg/sg)) mice, a natural mutant strain that is deficient in ROR alpha expression. Measurements and Main Results: Despite robust increases in OVA-specific IgE, ROR alpha(sg/sg) mice developed significantly less pulmonary inflammation, mucous cell hyperplasia, and eosinophilia compared with similarly treated WT animals. Induction of Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, was also significantly less in ROR alpha(sg/sg) mice. Microarray analysis using lung RNA showed increased expression of many genes, previously implicated in inflammation, in OVA-treated WT mice. These include mucin Muc5b, the chloride channel calcium-activated 3 (Clca3), macrophage inflammatory protein (MIP) 1 alpha and 1 beta, eotaxin-2, serum amyloid A3 (Saa3), and insulin-like growth factor 1 (Igf1). These genes were induced to a greater extent in OVA-treated WT mice relative to ROR alpha(sg/sg) mice. Conclusions: Our study demonstrates that mice deficient in ROR alpha exhibit an attenuated allergic inflammatory response, indicating that ROR alpha plays a critical role in the development of Th2-driven allergic lung inflammation in mice, and suggests that this nuclear receptor should be further evaluated as a potential asthma target. C1 NIEHS, Cell Biol Sect, Lab Resp Biol, Div Intramural Res,NIH, Chapel Hill, NC 27599 USA. NIEHS, Microarray Grp, Lab Expt Pathol, Div Intramural Res,NIH, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Div Pulm & Crit Care Med, Pulm Immunobiol Lab, Chapel Hill, NC 27515 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Lab Resp Biol, Div Intramural Res,NIH, 111 TW Alexander Dr, Chapel Hill, NC 27599 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS; NHLBI NIH HHS [HL071802] NR 66 TC 38 Z9 39 U1 0 U2 5 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 DEC 15 PY 2006 VL 174 IS 12 BP 1299 EP 1309 DI 10.1164/rccm.200510-1672OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 117RA UT WOS:000242889400006 PM 16973978 ER PT J AU Basso, F Amar, MJ Wagner, EM Vaisman, B Paigen, B Santamarina-Fojo, S Remaley, AT AF Basso, Federica Amar, Marcelo J. Wagner, Elke M. Vaisman, Boris Paigen, Beverly Santamarina-Fojo, Silvia Remaley, Alan T. TI Enhanced ABCG1 expression increases atherosclerosis in LDLr-KO mice on a western diet SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE ABCG1; cholesterol efflux; atherosclerosis; cytokines ID BINDING CASSETTE TRANSPORTERS; DENSITY-LIPOPROTEIN; CHOLESTEROL EFFLUX; ABCA1 TRANSPORTER; GENE; MACROPHAGES; HDL; ACCUMULATION; APOPTOSIS; LESIONS AB ABCG1 promotes cholesterol efflux from cells, but ABCG1(-/-) bone marrow transplant into ApoE(-/-) and LDLr-/- mice reduces atherosclerosis. To further investigate the role of ABCG1 in atherosclerosis, ABCG1 transgenic mice were crossed with LDLr-KO mice and placed on a high-fat western diet. Increased expression of ABCG1 mRNA was detected in liver (1.8-fold) and macrophages (2.7-fold), and cholesterol efflux from macrophages to HDL was also increased (1.4-fold) in ABCG1xLDLr-KO vs. LDLr-KO mice. No major differences were observed in total plasma lipids. However, cholesterol in the IDL-LDL size range was increased by approximately 50% in ABCG1 x LDLr-KO mice compared to LDLr-KO mice. Atherosclerosis increased by 39% (10.1 +/- 0.8 vs 6.1 +/- 0.9% lesion area, p = 0.02), as measured by en face analysis, and by 53% (221 +/- 98 vs 104 +/- 58 x 10(3) mu m(2), P = 0.01), as measured by cross-sectional analysis in ABCG1 x LDLr-KO mice. Plasma levels for MCP-1 (1.5-fold) and TNF-alpha (1.2-fold) were also increased in ABCG1 x LDLr-KO mice. In summary, these findings suggest that enhanced expression of ABCG1 increases atherosclerosis in LDLr-KO mice, despite its role in promoting cholesterol efflux from cells. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Amar, MJ (reprint author), NHLBI, Lipoprot Metab Sect, NIH, 10 Ctr Dr,7N102, Bethesda, MD 20892 USA. EM mamar@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 25 TC 35 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 2006 VL 351 IS 2 BP 398 EP 404 DI 10.1016/j.bbrc.2006.10.044 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 106RT UT WOS:000242119200014 PM 17070501 ER PT J AU Ramos, C Rafikova, ER Melikov, K Chernomordik, LV AF Ramos, Corinne Rafikova, Elvira R. Melikov, Kamran Chernomordik, Leonid V. TI Transmembrane proteins are not required for early stages of nuclear envelope assembly SO BIOCHEMICAL JOURNAL LA English DT Article DE liposome; membrane-chromatin binding; membrane fusion; nuclear envelope assembly; Ran GTPase ID MEDIATED MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; CA2+-TRIGGERED EXOCYTOSIS; HEMIFUSION INTERMEDIATE; MITOTIC CHROMOSOMES; DNA-REPLICATION; GTP HYDROLYSIS; IMPORTIN-BETA; LAMIN-A; PORE AB All identified membrane fusion proteins are transmembrane proteins. In the present study, we explored the post-mitotic reassembly of the NE (nuclear envelope). The proteins that drive membrane rearrangements in NE assembly remain unknown. To determine whether transmembrane proteins are prerequisite components of this fusion machinery, we have focused on nuclear reconstitution in a cell-free system. Mixing of soluble interphase cytosolic extract and MV (membrane vesicles) from amphibian eggs with chromatin results in the formation of functional nuclei. We replaced MV and cytosol with protein-free phosphatidylcholine LS (liposomes) that were pre-incubated with interphase cytosol. While later stages of NE assembly yielding functional nucleus did not proceed without integral proteins of MV LS-associated cytosolic proteins were sufficient to reconstitute membrane targeting to the chromatin and GTP-dependent lipid mixing. Binding involved LS-associated A-type lamin, and fusion involved Ran GTPase. Thus in contrast with post-fusion stages, fusion initiation in NE assembly, like membrane remodelling in budding and fission, does not require transmembrane proteins. C1 NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov RI Melikov, Kamran/A-6604-2009 FU Intramural NIH HHS NR 47 TC 7 Z9 7 U1 1 U2 2 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 DEC 15 PY 2006 VL 400 BP 393 EP 400 DI 10.1042/BJ20061218 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118ZY UT WOS:000242983200002 PM 16953799 ER PT J AU Calvert, RJ Tepper, S Kammouni, W Anderson, LM Kritchevsky, D AF Calvert, Richard J. Tepper, Shirley Kammouni, Wafa Anderson, Lucy M. Kritchevsky, David TI Elevated K-ras activity with cholestyramine and lovastatin, but not konjac mannan or niacin in lung - Importance of mouse strain SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE lung; mice; cholestyramine; lovastatin; konjac mannan; niacin; K-ras activity; cholesterol ID CORONARY ATHEROSCLEROSIS PREVENTION; SCANDINAVIAN SIMVASTATIN SURVIVAL; LONG-TERM TREATMENT; DIETARY FIBER; COLORECTAL-CANCER; CONTROLLED TRIAL; CLINICAL-TRIALS; BREAST-CANCER; STATIN USE; FOLLOW-UP AB Our previous work established that hypocholesterolemic agents altered K-ras intracellular localization in lung. Here, we examined K-ras activity to define further its potential importance in lung carcinogenesis. K-ras activity in lungs from male A/J, Swiss and CS7BL/6 mice was examined. For 3 weeks, mice consumed either 2 or 4% cholestyramine (CS), 1% niacin, 5% konjac marman (KM), or were injected with lovastatin 25 mg/kg three or five times weekly (Lov-3X and Lov-5X). A pair-fed (PF) group was fed the same quantity of diet consumed by the Lov-5X mice to control for lower body weights in Lov-5X mice. After 3 weeks, serum cholesterol was assayed with a commercial kit. Activated K-ras protein from lung was affinity precipitated with a Raf-1 ras binding domain- glutathione-S-transferase fusion protein bound to glutathione-agarose beads, followed by Western blotting, K-ras antibody treatment, and chemilumines cent detection. Only KM reduced serum cholesterol (in two of three mouse strains). In C56BL/6 mice treated with Lov-3X, lung K-ras activity increased 1.8-fold versus control (p = 0.009). In normal lung with wild-type K-ras, this would be expected to be associated with maintenance of differentiation. In A/J mice fed 4% CS, K-ras activity increased 2.1-fold (p = 0.02), which might be responsible for the reported enhancement of carcinogenesis in carcinogen-treated rats fed CS. KM feeding and PF treatment had no significant effects on K-ras activity. These data are consistent with the concept that K-ras in lung has an oncogenic function when mutated, but may act as a tumor suppressor when wild-type. Published by Elsevier Inc. C1 US FDA, Div Res & Appl Technol, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. RP Calvert, RJ (reprint author), US FDA, Div Res & Appl Technol, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM calvert@mail.ncifcrf.gov FU NHLBI NIH HHS [K06 HL000734-45]; PHS HHS [00734, 03299] NR 34 TC 5 Z9 5 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 15 PY 2006 VL 72 IS 12 BP 1749 EP 1755 DI 10.1016/j.bcp.2006.08.026 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 118FT UT WOS:000242928500013 PM 17005160 ER PT J AU Krishnamoorthy, S Bei, T Zoumakis, E Chrousos, GP Iliadis, AA AF Krishnamoorthy, Soumya Bei, Thaleia Zoumakis, Emmanouil Chrousos, George P. Iliadis, Agis A. TI Morphological and binding properties of interleukin-6 on thin ZnO films grown on (100) silicon substrates for biosensor applications SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE ZnO biosensors; interleukin-6; ELISA; protein immobilization; silicon ID AFFINITY-CHROMATOGRAPHY; PROTEIN; IMMOBILIZATION; SENSORS AB To develop effective protein immobilization technology with minimal amounts of protein for high sensitivity surface acoustic wave biosensors, we determined the binding properties, and morphological characteristics of human interleukin-6 (IL-6), a pro-inflammatory cytokine, on the surface of ZnO, and SiO2 films grown onto (10 0) Si substrates, for the first time. Interleukin-6 was immobilized in the range of 0.276-10 pg/ml on the surface of ZnO and SiO2, and visualized at each stage, while protein-protein interactions were measured with the antigen/antibody immunoassay of solid-phase ELISA, which we modified for these types of substrates. A relative mass value was determined in each case. ELISA detected upward of I and 6 ng/ml of protein applied on ZnO and SiO2, respectively. It is concluded that the more reactive ZnO surface is a new and more effective template for protein immobilization. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. NICHHD, Dev Endocrinol Branch, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-10679 Athens, Greece. RP Iliadis, AA (reprint author), Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA. EM agismd@yahoo.com NR 22 TC 35 Z9 37 U1 3 U2 14 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD DEC 15 PY 2006 VL 22 IS 5 BP 707 EP 714 DI 10.1016/j.bios.2006.02.020 PG 8 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 108HL UT WOS:000242230800020 PM 16581242 ER PT J AU Ge, Y Montano, I Rustici, G Freebern, WJ Haggerty, CM Cui, WW Ponciano-Jackson, D Chandramouli, GVR Gardner, ER Figg, WD Abu-Asab, M Tsokos, M Jackson, SH Gardner, K AF Ge, Yun Montano, Idalia Rustici, Gabriella Freebern, Wendy J. Haggerty, Cynthia M. Cui, Wenwu Ponciano-Jackson, Damaris Chandramouli, G. V. R. Gardner, Erin R. Figg, William D. Abu-Asab, Mones Tsokos, Maria Jackson, Sharon H. Gardner, Kevin TI Selective leukemic-cell killing by a novel functional class of thalidomide analogs SO BLOOD LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; CHRONIC LYMPHOCYTIC-LEUKEMIA; NECROSIS-FACTOR-ALPHA; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; THERAPEUTIC IMPLICATIONS; SESQUITERPENE LACTONE; SIGNALING PATHWAY; ANTICANCER AGENTS; CANCER-CELLS AB Using a novel cell-based assay to profile transcriptional pathway targeting, we have identified a new functional class of thalidomide analogs with distinct and selective antileukemic activity. These agents activate nuclear factor of activated T cells (NFAT) transcriptional pathways while simultaneously repressing nuclear factor-KB (NF-KB) via a rapid intracellular amplification of reactive oxygen species (ROS). The elevated ROS is associated with increased intracellular free calcium, rapid dissipation of the mitochondrial membrane potential, disrupted mitochondrial structure, and caspase-independent cell death. This cytotoxicity is highly selective for transformed lymphoid cells, is reversed by free radical scavengers, synergizes with the antileukemic activity of other redox-directed compounds, and preferentially targets cells in the S phase of the cell cycle. Live-cell imaging reveals a rapid drug-induced burst of ROS originating in the endoplasmic reticulum and associated mitochondria just prior to spreading throughout the cell. As members; of a novel functional class of "redox-reactive" thalidomides, these compounds provide a new tool through which selective cellular properties of redox status and intracellular bioactivation can be leveraged by rational combinatorial therapeutic strategies and appropriate drug design to exploit cell-specific vulnerabilities for maximum drug efficacy. (Blood. 2006;108:4126-4135) (c) 2006 by The American Society of Hematology. C1 NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Expres, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Clin Pharmacol Res Core, Frederick, MD 21701 USA. NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Gardner, K (reprint author), NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Expres, NIH, Bethesda, MD 20892 USA. EM sjackson@niaid.nih.gov; gardnerk@mail.nih.gov RI Figg Sr, William/M-2411-2016; OI Rustici, Gabriella/0000-0003-3085-1271; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [, NIH0011335962]; NCI NIH HHS [N01-CO-12400, N01CO12400]; PHS HHS [NIH0011335962] NR 55 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2006 VL 108 IS 13 BP 4126 EP 4135 DI 10.1182/blood-2006-04-017046 PG 10 WC Hematology SC Hematology GA 114OK UT WOS:000242675300032 PM 16940421 ER PT J AU Savani, BN Kozanas, E Shenoy, A Barren, AJ AF Savani, Bipin N. Kozanas, Eleftheria Shenoy, Aarthi Barren, A. John TI Recovery of spermatogenesis after total-body irradiation SO BLOOD LA English DT Letter C1 NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barren, AJ (reprint author), NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Rm 3-5330,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 4 TC 11 Z9 11 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 DEC 15 PY 2006 VL 108 IS 13 BP 4292 EP 4293 DI 10.1182/blood-2006-08-044289 PG 2 WC Hematology SC Hematology GA 114OK UT WOS:000242675300057 PM 17148595 ER PT J AU Thangaraju, M Gopal, E Martin, PM Ananth, S Smith, SB Prasad, PD Sterneck, E Ganapathy, V AF Thangaraju, Muthusamy Gopal, Elangovan Martin, Pamela M. Ananth, Sudha Smith, Sylvia B. Prasad, Puttur D. Sterneck, Esta Ganapathy, Vadivel TI SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of histone deacetylases SO CANCER RESEARCH LA English DT Article ID NA+-COUPLED TRANSPORTER; COLON-CANCER; SUPPRESSOR; LACTATE; COTRANSPORTER; EXPRESSION; PATHWAY; KIDNEY AB Tumor cells up-regulate glycolysis but convert pyruvate into lactate instead of oxidizing it. Here, we show that pyruvate, but not lactate, is an inhibitor of histone deacetylases (HDAC) and an inducer of apoptosis in tumor cells and that SLC5A8, a Na+/monocarboxylate cotransporter, is obligatory for this process. We found that SLC5A8 is expressed in nontransformed breast epithelial cell lines but silenced by DNA methylation in tumor cell lines. The down-regulation of the gene is also evident in primary breast tumors. When MCF7 breast tumor cells are transfected with SLC5A8 cDNA, the cells undergo pyruvate-dependent apoptosis. Butyrate and propionate also induce apoptosis in SLC5A8-expressing cells, whereas lactate does not. The differential ability of these monocarboxylates to cause apoptosis in SLC5A8-expressing MCF7 cells correlates with their ability to inhibit HDACs. Apoptosis induced by SLC5A8/pyruvate in MCF7 cells is associated with up-regulation of p53, Bax, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptor (TRAILR) I, and TRAILR2 and down-regulation of Bcl2 and survivin. Lactate dehydrogenase isozymes are differentially expressed in nontransformed cells and tumor cells such that the latter convert pyruvate into lactate. Silencing of SLC5A8 coupled with conversion of pyruvate into lactate in tumor cells correlates with increased HDAC activity in these cells compared with nontransformed cells. Our studies thus identify pyruvate as a HDAC inhibitor and indicate that the Na+-coupled pyruvate transport underlies the tumor-suppressive role of SLC5A8. We propose that tumor cells silence SLC5A8 and convert pyruvate into lactate as complementary mechanisms to avoid pyruvate-induced cell death. C1 Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21701 USA. RP Ganapathy, V (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. EM vganapat@mail.mcg.edu NR 20 TC 65 Z9 69 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 11560 EP 11564 DI 10.1158/0008-5472.CAN-06-1950 PG 5 WC Oncology SC Oncology GA 118AY UT WOS:000242915600005 PM 17178845 ER PT J AU Horvath, A Giatzakis, C Robinson-White, A Boikos, S Levine, E Griffin, K Stein, E Kamvissi, V Soni, P Bossis, I de Herder, W Carney, JA Bertherat, J Gregersen, PK Remmers, EF Stratakis, CA AF Horvath, Anelia Giatzakis, Christoforos Robinson-White, Audrey Boikos, Sosipatros Levine, Elizabeth Griffin, Kurt Stein, Erica Kamvissi, Virginia Soni, Payal Bossis, Ioannis de Herder, Wouter Carney, J. Aidan Bertherat, Jerome Gregersen, Peter K. Remmers, Elaine F. Stratakis, Constantine A. TI Adrenal hyperplasia and adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent in the population SO CANCER RESEARCH LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; CARNEY COMPLEX; GENOMIC ORGANIZATION; CUSHING-SYNDROME; HUMAN TISSUES; PRKAR1A GENE; MUTATIONS; EXPRESSION; LOCALIZATION AB Several types of adrenocortical tumors that lead to Cushing syndrome may be caused by aberrant cyclic AMP (cAMP) signaling. We recently identified patients with micronodular adrenocortical hyperplasia who were carriers of inactivating mutations in the 2q-located phosphodiesterase 11A (PDE11A) gene. We now studied the frequency of two missense substitutions, R804H and R867G, in conserved regions of the enzyme in several sets of normal controls, including 745 individuals enrolled in a longitudinal cohort study, the New York Cancer Project. In the latter, we also screened for the presence of the previously identified PDE11A nonsense mutations. R804H and R867G were frequent among patients with adrenocortical tumors; although statistical significance was not reached, these variants affected significantly enzymatic function in vitro with variable increases in cAMP and/or cyclic guanosine 3',5'-monophosphate levels in HeLa and HEK293 cells. Adrenocortical tissues carrying the R804H mutation showed 2q allelic losses and higher cyclic nucleotide levels and cAMP-responsive element binding protein phosphorylation. We conclude that missense mutations of the PDE11A gene that affect enzymatic activity in vitro are present in the general population; protein-truncating PDE11A mutations may also contribute to a predisposition to other tumors, in addition to their association with adrenocortical hyperplasia. We speculate that PDE11A genetic defects may be associated with adrenal pathology in a wider than previously suspected clinical spectrum that includes asymptomatic individuals. C1 NICHHD, Sect Endocrinol & Genet, Pediat Endocrinol Training Program, DEB,NIH, Bethesda, MD 20892 USA. NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Inst Cochin, INSERM U567, Dept Endocrinol Metab & Canc, Genet Mol, F-75014 Paris, France. Univ Paris 05, CNRS, UMR 8104, Paris, France. Univ Paris 05, Ctr Reference Malad Rares Surrenale, Serv Endocrinol, Hop Cochin, Paris, France. N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Pediat Endocrinol Training Program, DEB,NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov OI Stein, Erica/0000-0001-8778-8846; Soni, Payal/0000-0001-8166-6442 FU Intramural NIH HHS; NICHD NIH HHS [Z01-HD-000642-04] NR 17 TC 66 Z9 69 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 11571 EP 11575 DI 10.1158/0008-5472.CAN-06-2914 PG 5 WC Oncology SC Oncology GA 118AY UT WOS:000242915600007 PM 17178847 ER PT J AU Thomas, DD Espey, MG Pociask, DA Ridnour, LA Donzelli, S Wink, DA AF Thomas, Douglas D. Espey, Michael G. Pociask, Derek A. Ridnour, Lisa A. Donzelli, Sonia Wink, David A. TI Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite SO CANCER RESEARCH LA English DT Article ID MALIGNANT MESOTHELIOMA; ALVEOLAR MACROPHAGES; REGULATED KINASE; GENE-EXPRESSION; INHALATION; PLEURA; LUNG; RAT; ACTIVATION; MECHANISMS AB Asbestos exposure is strongly associated with the development of malignant mesothelioma, yet the mechanistic! basis of this observation has not been resolved. Carcinogenic transformation or tumor progression mediated by asbestos may be related to the generation of free radical species and perturbation of cell signaling and transcription factors. We report here that exposure of human mesothelioma or lung carcinoma cells to nitric oxide (NO) in the presence of crocidolite asbestos resulted in a marked decrease in intracellular nitrosation and diminished NO-induced post-translational modifications of tumor-associated proteins (hypoxia-inducible factor-1 alpha and p53). Crocidolite rapidly scavenged NO with concomitant conversion to nitrite (NO2-). Crocidolite also catalyzed the nitration of cellular proteins in the presence of NO2- and hydrogen peroxide. Nitrated protein adducts are a prominent feature of asbestos-induced lung injury. These data highlight the ability of asbestos to induce phenotypic cellular changes through two processes: (a) by directly reducing bioactive NO levels and preventing its subsequent interaction with target molecules and (b) by increasing oxidative damage and protein modifications through NO2 production and 3-nitrotyrosine formation. C1 NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. Tulane Univ Med Ctr Hosp & Clin, Lung Biol Program, New Orleans, LA USA. RP Thomas, DD (reprint author), NCI, Radiat Biol Branch, Tumor Biol Sect, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM thomasdo@mail.nih.gov NR 20 TC 6 Z9 6 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 11600 EP 11604 DI 10.1158/0008-5472.CAN-06-1140 PG 5 WC Oncology SC Oncology GA 118AY UT WOS:000242915600013 PM 17178853 ER PT J AU Kim, HT Kong, G DeNardo, D Li, YX Uray, I Pal, S Mohsin, S Hilsenbeck, SG Bissonnette, R Lamph, WW Johnson, K Brown, PH AF Kim, Hee-Tae Kong, Gu DeNardo, David Li, Yuxin Uray, Ivan Pal, Sunita Mohsin, Syed Hilsenbeck, Susan G. Bissonnette, Reid Lamph, William W. Johnson, Karen Brown, Powel H. TI Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays SO CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR MODULATOR; INDUCED GROWTH ARREST; 9-CIS RETINOIC ACID; X-RECEPTOR; TRANSGENIC MICE; CYCLOOXYGENASE-2 EXPRESSION; CANCER CELLS; MAMMARY TUMORIGENESIS; 9-CIS-RETINOIC ACID; SELECTIVE LIGAND AB Retinoids have been found to be promising chemopreventive agents that play an important role in regulating cell growth, differentiation, and apoptosis. The action of retinoids is mediated by retinoid receptors (retinoic acid receptors and retinoid X receptors), which are nuclear transcription factors that, when bound to retinoids, regulate gene expression. LGD1069 is a highly selective RXR agonist that has reduced toxicity compared with retinoids. Our previous studies have shown that RXR-selective ligands (or "rexinoids"), including LGD1069, can inhibit the growth of normal and malignant breast cells and can suppress the development of breast cancer in transgenic mice. For the current study, we attempted to identify biomarkers of the chemopreventive effect of the RXR-selective retinoid LGD1069. In these experiments, we used Affymetrix microarrays to identify target genes that were modulated by LGD1069,in normal human breast cells. Affyntetrix and dChip analysis identified more than 100 genes that were up-regulated or down-regulated by LGD1069 treatment. We then tested 16 of these genes in validation experiments using quantitative reverse transcription-PCR and Western blotting of independently prepared samples, and found that 15 of 16 genes were modulated in a similar manner in these validation experiments as in the microarray experiments. Genes found to be regulated include known retinoid-regulated genes, growth regulatory genes, transcription factors, and differentiation markers. We then showed that the expression of several of these rexinoid-regulated biomarkers is modulated in vivo in mammary glands from mice treated with LGD1069. These critical growth-regulating proteins will be promising targets of future agents for the prevention and treatment of breast cancer. C1 Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Ligand Pharmaceut Inc, Dept Retinoid Res, San Diego, CA USA. NCI, NIH, Bethesda, MD USA. RP Brown, PH (reprint author), Baylor Coll Med, Breast Ctr, 1 Baylor Pl MS 600, Houston, TX 77030 USA. EM pbrown@bcm.tmc.edu FU NCI NIH HHS [R01 CA078480, R01 CA101211, U19 CA086809] NR 50 TC 33 Z9 35 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2006 VL 66 IS 24 BP 12009 EP 12018 DI 10.1158/0008-5472.CAN-05-2515 PG 10 WC Oncology SC Oncology GA 118AY UT WOS:000242915600060 PM 17178900 ER PT J AU Peruzzi, B Bottaro, DP AF Peruzzi, Benedetta Bottaro, Donald P. TI beta-Catenin signaling - Linking renal cell carcinoma and polycystic kidney disease SO CELL CYCLE LA English DT Article DE beta-catenin; renal cell carcinoma; hepatocyte growth factor; VHL; oncogenesis; PKD ID TUMOR-SUPPRESSOR GENE; HEPATOCYTE GROWTH-FACTOR; BRANCHING MORPHOGENESIS; INVASIVE GROWTH; PRIMARY CILIUM; EXPRESSION; EPITHELIUM; MET; IDENTIFICATION; THERAPEUTICS AB Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. The VHL gene product, pVHL, is part of an E3 ubiquitin ligase complex that targets hypoxia inducible factors for polyubiquitination and proteosomal degradation, implicating hypoxia response genes in RCC oncogenesis. VHL loss also allows robust RCC cell invasiveness and morphogenesis in response to hepatocyte growth factor (HGF), an important regulator of kidney development and renal homeostasis. Recent elucidation of the mechanism by which pVHL represses developmental HGF responses in adult kidney has identified another oncogenically relevant E3 ligase target: beta-catenin. This discovery also further unifies recent insights into the molecular pathogenesis of polycystic kidney disease, where the identification of disease genes has revealed the integration of signaling pathways associated with primary cilia function and the regulation of cell growth and differentiation. C1 NCI, Urol Oncol Branch, CCR, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, CCR, Bldg 10,CRC,Rm 1-3961,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU Intramural NIH HHS NR 34 TC 12 Z9 12 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2006 VL 5 IS 24 BP 2839 EP 2841 DI 10.4161/cc.5.24.3581 PG 3 WC Cell Biology SC Cell Biology GA 117UF UT WOS:000242898100003 PM 17218789 ER PT J AU Sedelnikova, OA Bonner, WM AF Sedelnikova, Olga A. Bonner, William M. TI gamma H2AX in cancer cells SO CELL CYCLE LA English DT Article DE DNA damage; gamma H2AX; genome instability; tumor progression; cancer biomarker ID DOUBLE-STRAND BREAKS; PHOSPHORYLATED HISTONE H2AX; DNA-DAMAGE CHECKPOINT; GENOMIC INSTABILITY; THERAPEUTIC TARGET; IN-VIVO; REPAIR; MARKERS; SENESCENCE; EPIGENETICS AB Current advances in cancer biology have identified major pathways involved in tumorigenesis. The association of DNA damage with premalignant stages of tumor progression, genome instability and further oncogenic transformation opens the possibility of using common DNA damage markers for early cancer detection, prediction, prognosis, therapeutics and possibly for cancer prevention. Perhaps the most sensitive DNA damage marker is gamma H2AX formation in the chromatin flanking the free DNA double-stranded ends in double-strand breaks (DSBs) and eroded telomeres, both present during oncogenic transformation. Our group and others found elevated endogenous levels of gamma H2AX in various human cancer cell lines, premalignant lesions and solid tumors. These data suggest that increased DNA damage is a general characteristic of cancer development gamma H2AX-based assay can be applied to human biopsies, aspirates and, possibly, to mononuclear cells of the peripheral blood. We propose that detection of gamma H2AX could benefit for the early cancer screening and to ascertain the efficiency of clinical treatment involving chemo- and radiotherapeutic protocols. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sedelnikova, OA (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37 Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sedelnio@mail.nih.gov FU Intramural NIH HHS NR 40 TC 94 Z9 97 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2006 VL 5 IS 24 BP 2909 EP 2913 DI 10.4161/cc.5.24.3569 PG 5 WC Cell Biology SC Cell Biology GA 117UF UT WOS:000242898100017 PM 17172873 ER PT J AU Abi-Habib, RJ Singh, R Leppla, SH Greene, JJ Ding, Y Berghuis, B Duesbery, NS Frankel, AE AF Abi-Habib, Ralph J. Singh, Ravibhushan Leppla, Stephen H. Greene, John J. Ding, Yan Berghuis, Bree Duesbery, Nicholas S. Frankel, Arthur E. TI Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice SO CLINICAL CANCER RESEARCH LA English DT Article ID KINASE-KINASE; BRAF; RECEPTOR; GROWTH; INACTIVATION; B-V599E-RAF; SENSITIVITY; MUTATIONS; CANCER AB Purpose: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor catalytically cleaves mitogen-activated, protein kinase (MAPK) kinases and inhibits the MAPK. signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation,, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic, to BRAF mutant melanoma cell lines in vitro, whereas most normal cells are resistant to this toxin. In this study, we determine the in vivo potency and safety of systemically administered LeTx. Experimental Design: A s.c. xenograft melanoma model in athymic nude mice was treated with different i.p. doses. of LeTx. Results: In this study, we show that in vivo systemic LeTx treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial and complete tumor regressions with minor toxicity to mice. When animal toxicity was observed, we did not find any histologic evidence of tissue damage Conclusions: LeTx is one of the rare targeted agents to produce complete remissions of human melanomas in an animal model and thus warrants further preclinical development. C1 Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76502 USA. Scott & White Mem Hosp & Clin, Dept Pathol, Temple, TX 76502 USA. NIAID, Bacterial Toxins & Therapeut Sect, Bethesda, MD 20892 USA. Van Andel Res Inst, Grand Rapids, MI USA. RP Frankel, AE (reprint author), Scott & White Mem Hosp & Clin, Canc Res Inst, 5701 S Airport Rd, Temple, TX 76502 USA. EM afrankel@swmail.sw.org OI DUESBERY, NICK/0000-0002-4258-5655 NR 28 TC 24 Z9 24 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2006 VL 12 IS 24 BP 7437 EP 7443 DI 10.1158/1078-0432.CCR-06-2019 PG 7 WC Oncology SC Oncology GA 121NT UT WOS:000243165000032 PM 17189417 ER PT J AU Beumer, JH Eiseman, JL Parise, RA Joseph, E Holleran, JL Covey, JM Egorin, MJ AF Beumer, Jan H. Eiseman, Julie L. Parise, Robert A. Joseph, Erin Holleran, Julianne L. Covey, Joseph M. Egorin, Merrill J. TI Pharmacokinetics, metabolism, and oral bioavailability of the DNA methyltransferase inhibitor 5-fluoro-2 '-deoxycytidine in mice SO CLINICAL CANCER RESEARCH LA English DT Article ID TARGET-DIRECTED THERAPIES; EXPLOIT HIGH-LEVELS; CYTIDINE DEAMINASE; DEOXYCYTIDYLATE DEAMINASE; CYTOSINE-ARABINOSIDE; THYMIDYLATE SYNTHASE; RHESUS-MONKEYS; ACHIEVE DNA; TETRAHYDROURIDINE; CANCER AB Purpose: In vivo, 5-fluoro-2'-deoxycytidine (FdCyd) is rapidly and sequentially converted to 5-fluoro-2'-deoxyuridine, 5-fluorouracil, and 5-fluorouridine. The i.v. combination of FdCyd and 3,4,5,6-tetrahydrouridine (THU), a cytidine deaminase (CD) inhibitor that blocks the first metabolic step in FdCyd catabolism, is being investigated clinically for its ability to inhibit DNA methyltransferase. However, the full effects of THU on FdCyd metabolism and pharmacokinetics are unknown. We aimed to characterize the pharmacokinetics, metabolism, and bioavailability of FdCyd with and without THU in mice. Experimental Design: We developed a sensitive high-performance liquid chromatography tandem mass spectrometry assay to quantitate FdCyd and metabolites in mouse plasma. Mice were dosed i.v. or p.o. with 25 mg/kg FdCyd with or without coadministration of 100 mg/kg THU p.o. or i.v. Results: The oral bioavailability of FdCyd alone was similar to 4%. Coadministration with THU increased exposure to FdCyd and decreased exposure to its metabolites; i.v. and p.o. coadministration of THU increased exposure to p.o. FdCyd by 87- and 58-fold, respectively. FdCyd exposure after p.o. FdCyd with p.o. THU was as much as 54% that of i.v. FdCyd with i.v. THU. Conclusions: FdCyd is well absorbed but undergoes substantial first-pass catabolism by CD to potentially toxic metabolites that do not inhibit DNA methyltransferase. THU is sufficiently bioavailable to reduce the first-pass effect of CD on FdCyd. Oral coadministration of THU and FdCyd is a promising approach that warrants clinical testing because it may allow maintaining effective FdCyd concentrations on a chronic basis, which would be an advantage over other DNA methyltransferase inhibitors that are currently approved or in development. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Toxicol & Pharmacol Branch, Bethesda, MD 20892 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G-28,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [N01-CM-52202] NR 41 TC 40 Z9 41 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2006 VL 12 IS 24 BP 7483 EP 7491 DI 10.1158/1078-0432.CCR-06-1250 PG 9 WC Oncology SC Oncology GA 121NT UT WOS:000243165000037 PM 17138702 ER PT J AU Khalsa, J Vocci, F Altice, F Fiellin, D Miller, V AF Khalsa, Jag Vocci, Francis Altice, Frederick Fiellin, David Miller, Veronica TI Buprenorphine and HIV primary care: New opportunities for integrated treatment - Introduction SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material AB Drug abuse and infection with human immunodeficiency virus (HIV) are associated with high rates of morbidity and mortality, but, because of medical, social, and legal factors, opiate addiction/dependence is a major obstacle to successful treatment of disease-for example, treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy. In an effort to improve the opportunity for treatment of drug abuse and HIV infection, the Forum for Collaborative HIV Research, in collaboration with the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and other agencies, presented a workshop entitled "Buprenorphine in the Primary HIV Care Setting." Participants reviewed and discussed current issues, such as the introduction of and sources for the provision of buprenorphine in HIV primary care settings and strategies for integrating treatment of HIV-infected drug abusers, all of which are covered in this supplement. C1 NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. George Washington Univ, Washington, DC 20052 USA. RP Khalsa, J (reprint author), NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Rm 4137, Bethesda, MD 20892 USA. EM jk98p@nih.gov FU NIDA NIH HHS [K24 DA017072] NR 15 TC 3 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2006 VL 43 SU 4 BP S169 EP S172 DI 10.1086/508179 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 106UB UT WOS:000242126100001 PM 17109302 ER PT J AU Parker, L Ellis, JE Nguyen, MQ Arora, K AF Parker, Louise Ellis, Jeremy E. Nguyen, Minh Q. Arora, Kavita TI The divergent TGF-beta ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila SO DEVELOPMENT LA English DT Article DE Drosophila; TGF-beta; Alp23B; activin; baboon; Smad2(Smox); motoneuron; axon pathfinding; neuromuscular system; glia ID RECEPTOR TYROSINE PHOSPHATASES; GROWTH CONE GUIDANCE; II-RECEPTOR; WISHFUL-THINKING; GENETIC-ANALYSIS; MOTOR AXONS; SYNAPTIC DEVELOPMENT; SIGNALING PATHWAYS; COMMISSURAL AXONS; BMP RECEPTOR AB Axon guidance is regulated by intrinsic factors and extrinsic cues provided by other neurons, glia and target muscles. Dawdle (Daw), a divergent TGF-beta superfamily ligand expressed in glia and mesoderm, is required for embryonic motoneuron pathfinding in Drosophila. In daw mutants, ISNb and SNa axons fail to extend completely and are unable to innervate their targets. We find that Daw initiates an activin signaling pathway via the receptors Punt and Baboon (Babo) and the signal-transducer Smad2. Furthermore, mutations in these signaling components display similar axon guidance defects. Cell-autonomous disruption of receptor signaling suggests that Babo is required in motoneurons rather than in muscles or glia. Ectopic ligand expression can rescue the daw phenotype, but has no deleterious effects. Our results indicate that Daw functions in a permissive manner to modulate or enable the growth cone response to other restricted guidance cues, and support a novel role for activin signaling in axon guidance. C1 Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. NIDCR, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Arora, K (reprint author), Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. EM karora@uci.edu FU NICHD NIH HHS [HD-38761]; NIGMS NIH HHS [GM-55442] NR 69 TC 44 Z9 45 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 15 PY 2006 VL 133 IS 24 BP 4981 EP 4991 DI 10.1242/dev.02673 PG 11 WC Developmental Biology SC Developmental Biology GA 108BN UT WOS:000242215100017 PM 17119022 ER PT J AU Zorad, S Dou, JT Benicky, J Hutanu, D Tybitanclova, K Zhou, J Saavedra, JM AF Zorad, Stefan Dou, Jing-tao Benicky, Julius Hutanu, Daniel Tybitanclova, Katarina Zhou, Jin Saavedra, Juan M. TI Long-term angiotensin II AT(1) receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPAR-gamma SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE renin-angiotensin system; candesartan cilexetil; adipokines; adipocytes ID SPONTANEOUSLY HYPERTENSIVE-RATS; ACTIVATED RECEPTOR-GAMMA; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; HUMAN ADIPOCYTES; GENE-EXPRESSION; RENIN/PRORENIN-RECEPTOR; TRIGLYCERIDE PRODUCTION; INDUCED OBESITY; TNF-ALPHA AB To clarify the mechanism of the effects of angiotensin II AT(1) receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT(1) receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum leptin levels and epididymal leptin mRNA, increased serum adiponectin levels and epididymal adiponectin mRNA, decreased epididymal tumor necrosis factor alpha (TNF alpha) mRNA, and increased fatty acid synthase mRNA. Considered free of peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist activity, Candesartan cilexetil increased epididymal expression of PPAR gamma mRNA. The effects of Candesartan cilexetil on adipokine production and release may be attributable to PPAR gamma activation and/or decrease in adipocyte cell size. In addition, Candesartan cilexetil treatment increased the expression of epididymal angiotensin II AT(2) receptor mRNA and protein and decreased the expression of renin receptor mRNA. These results suggest that Candesartan cilexetil influences lipid metabolism in adipose tissue by promoting adipose tissue rearrangement and modulating adipokine expression and release. These effects are probably consequences of local angiotensin II AT(1) receptor inhibition, angiotensin II AT(2) receptor stimulation, and perhaps additional angiotensin II-independent mechanisms. Our results indicate that the activity of local renin-angiotensin system plays an important role in adipose tissue metabolism. The decrease in the pro-inflammatory cytokine TNF alpha and the increase in the anti-inflammatory adipokine adiponectin indicate that Candesartan cilexetil may exert significant anti-inflammatory properties. Published by Elsevier B.V. C1 NIMH, DIRP, NIH,Dept Hlth & Human Serv, DHHS,Sect Pharmacol, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 80936, Slovakia. RP Benicky, J (reprint author), NIMH, DIRP, NIH,Dept Hlth & Human Serv, DHHS,Sect Pharmacol, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM Benickyj@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 62 TC 95 Z9 98 U1 0 U2 6 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 DEC 15 PY 2006 VL 552 IS 1-3 BP 112 EP 122 DI 10.1016/j.ejphar.2006.08.062 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 111LG UT WOS:000242452500015 PM 17064684 ER PT J AU Dias-Junior, CAC Gladwin, MT Tanus-Santos, JE AF Dias-Junior, Carlos A. C. Gladwin, Mark T. Tanus-Santos, Jose E. TI Low-dose intravenous nitrite improves hemodynamics in a canine model of acute pulmonary thromboembolism SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE acute pulmonary embolism; embolism; nitric oxide; nitrite; pulmonary embolism; pulmonary hypertension; thromboembolism ID ENDOTHELIN-RECEPTOR ANTAGONISM; INDUCED OXIDATIVE STRESS; OXIDE SYNTHASE ACTIVITY; VENOUS AIR INFUSION; RED-BLOOD-CELLS; HYPOXIC VASODILATION; ISCHEMIA-REPERFUSION; EMERGING BIOLOGY; S-NITROSOTHIOLS; L-ARGININE AB Acute pulmonary thomboembolism (APT)-induced pulmonary hypertension can be counteracted by activating the nitric oxide (NO)-cGMP pathway. Recent studies have demonstrated that the naturally occurring anion nitrite (NO(2)(-)) is a bioactive storage reservoir for NO, and is reduced to NO under conditions of hypoxia and acidosis. We hypothesized that nitrite infused intravenously could attenuate the hemodynamic changes associated with APT. APT was induced with autologous blood clots injected into the right atrium in mongrel dogs. After APT (or saline), the dogs received an intravenous nitrite (or saline) infusion (6.75 mu mol/kg over 15 min and then 0.28 mu mol/kg/min) and hemodynamic evaluations were carried out for 2 h. Plasma nitrite concentrations were measured using ozone-based reductive chemiluminescence methodologies. APT decreased cardiac index (CI) and increased pulmonary vascular resistance index (PVRI); these effects were improved during infusions of sodium nitrite. Accordingly, nitrite infusion increased cardiac index by 28%, reduced the PVRI by 48%, and the systemic vascular resistance index (SVRI) by 21% in embolized dogs, suggesting a greater effect on the ischemic embolized vascular system than the systemic circulation following embolization. Interestingly, in nonembolized control dogs the same nitrite infusion decreased MAP and CI (all P < 0.05). The nitrite infusion increased plasma nitrite concentrations by approximately 2 mu M, and produced dose-dependent effects on PVRI, MAP, and SVRI. Remarkably, blood levels of nitrite as low as 500 nM decreased PVRI and SVRI in this model, suggesting a potential role of nitrite in physiological blood flow regulation. These results suggest that a low-dose nitrite infusion produces beneficial hemodynamic effects in a dog model of APT. These findings suggest a new therapeutic application for nitrite and support emerging evidence for a surprisingly potent and potentially physiological vasoactivity of nitrite. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP, Brazil. NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Tanus-Santos, JE (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, Av Bandeirantes,3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM tanus@fmrp.usp.br RI Dias-Junior, Carlos Alan/D-8627-2012; Tanus-Santos, Jose/A-4451-2008 FU Intramural NIH HHS NR 49 TC 52 Z9 57 U1 0 U2 3 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 DEC 15 PY 2006 VL 41 IS 12 BP 1764 EP 1770 DI 10.1016/j.freeradbiomed.2006.08.022 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 119KV UT WOS:000243012100005 PM 17157179 ER PT J AU Fukushige, T Brodigan, TM Schriefer, LA Waterston, RH Krause, M AF Fukushige, Tetsunari Brodigan, Thomas M. Schriefer, Lawrence A. Waterston, Robert H. Krause, Michael TI Defining the transcriptional redundancy of early bodywall muscle development in C-elegans: evidence for a unified theory of animal muscle development SO GENES & DEVELOPMENT LA English DT Article DE Myogenesis; MyoD; SRF; HAND ID NEURAL CREST DERIVATIVES; SERUM RESPONSE FACTOR; MYOD HOMOLOG HLH-1; CAENORHABDITIS-ELEGANS; WALL MUSCLE; CIONA-INTESTINALIS; VERTEBRATE HEART; GENE-EXPRESSION; SMOOTH-MUSCLE; GATA-FACTOR AB Myogenic regulatory factors (MRFs) are required for mammalian skeletal myogenesis. In contrast, bodywall muscle is readily detectable in Caenorhabditis elegans embryos lacking activity of the lone MRF ortholog HLH-1, indicating that additional myogenic factors must function in the nematode. We find that two additional C. elegans proteins, UNC-120/SRF and HND-1/HAND, can convert naive blastomeres to muscle when overproduced ectopically in the embryo. In addition, we have used genetic null mutants to demonstrate that both of these factors act in concert with HLH-1 to regulate myogenesis. Loss of all three factors results in embryos that lack detectable bodywall muscle differentiation, identifying this trio as a set that is both necessary and sufficient for bodywall myogenesis in C. elegans. In mammals, SRF and HAND play prominent roles in regulating smooth and cardiac muscle development. That C. elegans bodywall muscle development is dependent on transcription factors that are associated with all three types of mammalian muscle supports a theory that all animal muscle types are derived from a common ancestral contractile cell type. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Washington Univ, Dept Genet, St Louis, MO 63108 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Krause, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM mwkrause@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 FU Intramural NIH HHS NR 52 TC 63 Z9 72 U1 0 U2 3 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 DEC 15 PY 2006 VL 20 IS 24 BP 3395 EP 3406 DI 10.1101/gad.1481706 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 119EU UT WOS:000242996100007 PM 17142668 ER PT J AU Matesic, LE Haines, DC Copeland, NG Jenkins, NA AF Matesic, Lydia E. Haines, Diana C. Copeland, Neal G. Jenkins, Nancy A. TI Itch genetically interacts with Notch1 in a mouse autoimmune disease model SO HUMAN MOLECULAR GENETICS LA English DT Article ID T-CELL DEVELOPMENT; FAMILY-MEMBER BIM; PROTEIN-KINASE-B; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; RECEPTOR NUR77; IN-VIVO; APOPTOSIS; CD4; UBIQUITIN AB Homozygous itchy mice develop a fatal, late-onset autoimmune-like disease due to a loss of function mutation in an ubiquitin protein ligase. Phylogenetic and in vitro analyses suggest that Itch is a negative regulator of Notch signaling. Since Notch proteins have many important functions in the immune system, we determined whether Itch regulates Notch signaling in vivo. This was accomplished by breeding homozygous itch mice to mice carrying an activated Notch1 transgene that was specifically overexpressed in developing thymocytes. Interestingly, all itch mice carrying this transgene were smaller than their littermates and died by 12 weeks of age. These mice had a similar autoimmune disease to that seen in itch animals. However, the lesions were more severe with a much earlier age of onset, supporting the assertion that these mutations genetically interact. In addition, the combination of these mutations produced novel phenotypes including a perturbation in T cell development, with a reduction in the number of double-positive (DP) and an increase in the number of double-negative and single-positive T cells. TUNEL staining showed reduced apoptosis in the thymus of itch animals that carry the Notch1 transgene. Antibody staining displayed increased levels of full-length Notch1 and phospho-AKT specifically in DP thymocytes but no change in other signaling pathways including MAPK, p38 and JNK. These results provide the first direct demonstration that increased AKT-mediated Notch1 signaling results in autoimmunity and may provide insight into the treatment of a group of diseases that affect a significant proportion of the population. C1 NCI, Canc Res Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. SAIC Frederick, Pathol Histotechnol Lab, Frederick, MD 21702 USA. RP Matesic, LE (reprint author), Univ S Carolina, Dept Biol Sci, CLS 703, Columbia, SC 29208 USA. EM lmatesic@biol.sc.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 49 TC 23 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2006 VL 15 IS 24 BP 3485 EP 3497 DI 10.1093/hmg/ddl425 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 115DY UT WOS:000242716200001 PM 17095521 ER PT J AU Yau, WL Lung, HL Zabarovsky, ER Lerman, MI Sham, JST Chua, DTT Tsao, SW Stanbridge, EJ Lung, ML AF Yau, Wing Lung Lung, Hong Lok Zabarovsky, Eugene R. Lerman, Michael I. Sham, Jonathan Shun-tong Chua, Daniel Tsin-tien Tsao, Sai Wah Stanbridge, Eric J. Lung, Maria Li TI Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE BLU/ZMYND10; tumor suppressor gene; chromosome 3p21.3; nasopharyngeal carcinoma ID COMPARATIVE GENOMIC HYBRIDIZATION; CELL LUNG-CANCER; EPIGENETIC INACTIVATION; REGION; BLU; RASSF1A; HETEROZYGOSITY; EXPRESSION; GROWTH; 3P AB Chromosome 3p plays an important role in tumorigenesis in many cancers, including nasopharyngeal carcinoma (NPC). We have previously shown chromosome 3p can suppress tumor growth in vivo by using the monochromosome transfer approach, which indicated the chromosome 3p21.3 region was critical for tumor suppression. BLUIZMYND10 is one of the candidate tumor suppressor genes mapping in the 3p21.3 critical region and is a candidate TSG for NPC. By quantitative RT-PCR, it is frequently downregulated in NPC cell lines (83%) and NPC biopsies (80%). However, no functional studies have yet verified the functional role of BLU/ZMYND10 as a tumor suppressor gene. In the current study, a gene inactivation test (GIT) utilizing a tetracycline regulation system was used to study the functional role of BLU/ZMYND10. When BLU/ZMYND10 is expressed in the absence of doxycycline, the stable transfectants were able to induce tumor suppression in nude mice. In contrast, downregulation of BLU/ZMYND10 in these tumor suppressive clones by doxycycline treatment restored the tumor formation ability. This study provides the first significant evidence to demonstrate BLUIZMYNDIO can functionally suppress tumor formation in vivo and is, therefore, likely to be one of the candidate tumor suppressor genes involved in NPC. Published 2006 Wiley-Liss, Inc. C1 Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Ctr Canc Res, Hong Kong, Hong Kong, Peoples R China. Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden. NCI, Immunobiol Lab, Canc Res Ctr, Frederick, MD 21701 USA. Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. RP Lung, ML (reprint author), Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China. EM bomaria@ust.hk RI Lung, Hong Lok/C-4494-2009; Zabarovsky, Eugene/A-6645-2010 FU Intramural NIH HHS NR 31 TC 35 Z9 37 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2006 VL 119 IS 12 BP 2821 EP 2826 DI 10.1002/ijc.22232 PG 6 WC Oncology SC Oncology GA 109KV UT WOS:000242307800013 PM 16929489 ER PT J AU Toro, JR Travis, LB Wu, HJ Zhu, K Fletcher, CDM Devesa, SS AF Toro, Jorge R. Travis, Lois B. Wu, Hongyu Julian Zhu, Kangmin Fletcher, Christopher D. M. Devesa, Susan S. TI Incidence patterns of soft tissue sarcomas, regardless of primary site, in the Surveillance, Epidemiology and End Results program, 1978-2001: an analysis of 26,758 cases SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE soft tissue sarcomas; SEER; incidence; leiomyosarcoma; WHO; dermatofibrosarcoma; liposarcoma; rhabdomyosarcoma; angiosarcoma; malignant fibrous histiocytoma ID UNITED-STATES; PLEOMORPHIC RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; UTERINE LEIOMYOMAS; HYSTERECTOMY; TRENDS; CANCER; TUMORS; LIPOSARCOMAS; ASSOCIATION AB Soft tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that show a broad range of differentiation that may reflect etiologic distinction. Routine tabulations of STS are not morphology-specific. Further, the lack of inclusion of sarcomas arising in all organs in most standard evaluations underestimates the true rates. We analyzed the 1978-2001 Surveillance, Epidemiology and End Results program incidence rates of STS regardless of primary site, except bones and joints, using the 2002 criteria of the WHO classification. There were 26,758 cases available for analysis. Leiomyosarcomas accounted for 23.9%, malignant fibrous histiocytomas 17.1%, liposarcomas 11.5%, dermatofibrosarcomas 10.5%, rhabdomyosarcomas 4.6% and angiosarcomas 4.1%. Almost half (47.9%) of the sarcomas arose in the soft tissues, 14.0% in the skin and 7.0% in the uterus. Overall, incidence rates were highest among black women (6.26/100,000 woman years) and the lowest among white women (4.60/100,000). Age-adjusted rates increased at 1.2% and 0.8% per year among white males and females, respectively, both trends statistically significant, while rates among blacks declined slightly. About 40% of leiomyosarcomas among women were uterine in origin, with a black/white rate ratio of 1.7. This rate ratio increased to 2.0 when we accounted for the lower prevalence of intact uteri among black compared to white women. Total STS rates rose exponentially with age. Rates for both uterine leiomyosarcoma and dermatofibrosarcoma increased rapidly during the childbearing years, peaking at about age 40 and 50, respectively. Incidence patterns of STS varied markedly by histologic type, supporting the notion that these tumors may be etiologically distinct. (c) 2006 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. US Mil Canc Inst, Walter Reed Army Med Ctr, Washington, DC USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,Execut Pl S,Room 7012, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov FU Intramural NIH HHS NR 59 TC 156 Z9 166 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2006 VL 119 IS 12 BP 2922 EP 2930 DI 10.1002/ijc.22239 PG 9 WC Oncology SC Oncology GA 109KV UT WOS:000242307800026 PM 17013893 ER PT J AU Kirby, TW Harvey, S DeRose, EF Chalov, S Chikova, AK Perrino, FW Schaaper, RM London, RE Pedersen, LC AF Kirby, Thomas W. Harvey, Scott DeRose, Eugene F. Chalov, Sergey Chikova, Anna K. Perrino, Fred W. Schaaper, Roel M. London, Robert E. Pedersen, Lars C. TI Structure of the Escherichia coli DNA polymerase III epsilon-HOT proofreading complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TORSION ANGLE DYNAMICS; THETA-SUBUNIT; PROTEIN; PROGRAM; DOMAIN; CRYSTALLOGRAPHY; REPLICATION; EXONUCLEASE; MUTANTS; SYSTEM AB The epsilon subunit of Escherichia coli DNA polymerase III possesses 3'-exonucleolytic proofreading activity. Within the Pol III core, epsilon is tightly bound between the alpha subunit ( DNA polymerase) and theta subunit. Here, we present the crystal structure of epsilon in complex with HOT, the bacteriophage P1-encoded homolog of theta, at 2.1 angstrom resolution. The epsilon-HOT interface is defined by two areas of contact: an interaction of the previously unstructured N terminus of HOT with an edge of the epsilon central beta-sheet as well as interactions between HOT and the catalytically important helix alpha 1-loop-helix alpha 2 motif of epsilon. This structure provides insight into how HOT and, by implication, theta may stabilize the epsilon subunit, thus promoting efficient proofreading during chromosomal replication. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, MR 01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov RI Chalov, Sergey/K-1847-2012 OI Chalov, Sergey/0000-0002-6937-7020 FU NIGMS NIH HHS [GM 069962, R01 GM069962] NR 33 TC 21 Z9 21 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 2006 VL 281 IS 50 BP 38466 EP 38471 DI 10.1074/jbc.M606917200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115BL UT WOS:000242709500040 PM 16973612 ER PT J AU Otterlei, M Bruheim, P Ahn, B Bussen, W Karmakar, P Baynton, K Bohr, VA AF Otterlei, Marit Bruheim, Per Ahn, Byungchan Bussen, Wendy Karmakar, Parimal Baynton, Kathy Bohr, Vilhelm A. TI Werner syndrome protein participates in a complex with RAD51, RAD54, RAD54B and ATR in response to ICL-induced replication arrest SO JOURNAL OF CELL SCIENCE LA English DT Article DE WRN; ICL; RAD51; RAD54B; ATR; DNA repair ID INTERSTRAND CROSS-LINKS; NUCLEOTIDE EXCISION-REPAIR; DNA-DEPENDENT ATPASE; MAMMALIAN-CELLS; S-PHASE; HOMOLOGOUS RECOMBINATION; FUNCTIONAL INTERACTION; IONIZING-RADIATION; MRE11 COMPLEX; NUCLEAR FOCI AB Werner syndrome (WS) is a rare genetic disorder characterized by genomic instability caused by defects in the WRN gene encoding a member of the human RecQ helicase family. RecQ helicases are involved in several DNA metabolic pathways including homologous recombination (HR) processes during repair of stalled replication forks. Following introduction of interstrand DNA crosslinks (ICL), WRN relocated from nucleoli to arrested replication forks in the nucleoplasm where it interacted with the HR protein RAD52. In this study, we use fluorescence resonance energy transfer ( FRET) and immune-precipitation experiments to demonstrate that WRN participates in a multiprotein complex including RAD51, RAD54, RAD54B and ATR in cells where replication has been arrested by ICL. We verify the WRN-RAD51 and WRN-RAD54B direct interaction in vitro. Our data support a role for WRN also in the recombination step of ICL repair. C1 NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Lab Ctr, Fac Med, N-7006 Trondheim, Norway. Norwegian Univ Sci & Technol, Dept Biotechnol, N-7491 Trondheim, Norway. Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06515 USA. Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, W Bengal, India. Hop St Justine, Res Ctr, Montreal, PQ H3T 1C5, Canada. RP Otterlei, M (reprint author), NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM marit.otterlei@ntnu.no NR 76 TC 56 Z9 57 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2006 VL 119 IS 24 BP 5137 EP 5146 DI 10.1242/jcs.03291 PG 10 WC Cell Biology SC Cell Biology GA 119ET UT WOS:000242995900014 PM 17118963 ER PT J AU Teleshova, N Kenney, J Van Nest, G Marshall, J Lifson, JD Sivin, I Dufour, J Bohm, R Gettie, A Robbiani, M AF Teleshova, Natalia Kenney, Jessica Van Nest, Gary Marshall, Jason Lifson, Jeffrey D. Sivin, Irving Dufour, Jason Bohm, Rudolf Gettie, Agegnehu Robbiani, Melissa TI Local and systemic effects of intranodally injected CpG-C immunostimulatory-oligodeoxyribonucleotides in macaques SO JOURNAL OF IMMUNOLOGY LA English DT Review ID PLASMACYTOID DENDRITIC CELLS; SIMIAN IMMUNODEFICIENCY VIRUS; IMMUNE-DEFICIENCY-SYNDROME; INTERFERON-PRODUCING CELLS; HUMAN B-CELLS; HIV-INFECTED INDIVIDUALS; IN-VIVO; RHESUS MACAQUES; LYMPHOID-TISSUE; OPPORTUNISTIC INFECTIONS AB Immunostimulatory CpG-C oligodeoxyribonucleotides (ISS-ODNs) represent a promising strategy to enhance vaccine efficacy. We have shown that the CpG-C ISS-ODN C274 stimulates macaque blood dendritic cells (DCs) and B cells and augments SIV-specific IFN-gamma responses in vitro. To further explore the potential of C274 for future vaccine studies, we assessed the in vivo effects of locally administered C274 (in naive and healthy infected macaques). Costimulatory molecules were marginally increased on DCs and B cells within cells isolated from C274-injected lymph nodes (LNs). However, cells from C274-injected LNs exhibited heightened responsiveness to in vitro culture. This was particularly apparent at the level of CD80 (less so CD86) expression by CD123(+) plasmacytoid DCs and was further boosted in the presence of additional C274 in vitro. Notably, cells from C274-injected LNs secreted significantly elevated levels of several cytokines and chemokines upon in vitro culture. This was more pronounced when cells were exposed to additional stimuli in vitro, producing IFN-alpha, IL-3, IL-6, IL-12, TNF-alpha, CCL2, CCU, CCL5, and CXCL8. Following C274 administration in the absence of additional SIV Ag, endogenous IFN-gamma secretion was elevated in LN cells of infected animals, but SIV-specific responses were unchanged. Endogenous and SIV-specific responses decreased in blood, before the SIV-specific responses rebounded by 2 wk after C274 treatment. Elevated IFN-alpha, CCL2, and CCL5 were also detected in the plasma after C274 injection. Thus, locally administered C274 has local and systemic activities, supporting the potential for CpG-C ISS-ODNs to boost immune function to enhance anti-HIV vaccine immunogenicity. C1 Populat Council, Ctr Biomed Res, New York, NY 10021 USA. Dynavax Technol, Berkeley, CA 94710 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Robbiani, M (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA. EM mrobbiani@popcouncil.org FU NCI NIH HHS [N01 CO 12400]; NCRR NIH HHS [RR 00164]; NIAID NIH HHS [R01 AI 040877, R21 AI 060405]; NIDCR NIH HHS [R01 DE 016256] NR 106 TC 14 Z9 15 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2006 VL 177 IS 12 BP 8531 EP 8541 PG 11 WC Immunology SC Immunology GA 125BP UT WOS:000243416800030 PM 17142751 ER PT J AU Onda, M Nagata, S FitzGerald, DJ Beers, R Fisher, RJ Vincent, JJ Lee, B Nakamura, M Hwang, JL Kreitman, RJ Hassan, R Pastan, I AF Onda, Masanori Nagata, Satoshi FitzGerald, David J. Beers, Richard Fisher, Robert J. Vincent, James J. Lee, Byungkook Nakamura, Michihiro Hwang, Jaulang Kreitman, Robert J. Hassan, Raffit Pastan, Ira TI Characterization of the B cell epitopes associated with a truncated form of Pseudomonas exotoxin (PE38) used to make immunotoxins for the treatment of cancer patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALANINE-SCANNING MUTAGENESIS; ANTIBODY-BINDING REGIONS; PHASE-I TRIAL; MONOCLONAL-ANTIBODIES; RECOMBINANT IMMUNOTOXIN; THERAPEUTIC PROTEINS; AERUGINOSA EXOTOXIN; ANTITOXIN ANTIBODIES; ANTIGENIC STRUCTURE; ANTITUMOR-ACTIVITY AB Recombinant immunotoxins composed of an Ab Fv fragment joined to a truncated portion of Pseudomonas exotoxin A (termed PE38) have been evaluated in clinical trials for the treatment of various human cancers. Immunotoxin therapy is very effective in hairy cell leukemia and also has activity in other hemological malignancies; however, a neutralizing Ab response to PE38 in patients with solid tumors prevents repeated treatments to maximize the benefit. In this study, we analyze the murine Ab response as a model to study the B cell epitopes associated with PE38. Sixty distinct mAbs to PE38 were characterized. Mutual competitive binding of the mAbs indicated the presence of 7 major epitope groups and 13 subgroups. The competition pattern indicated that the epitopes are discrete and could not be reproduced using a computer simulation program that created epitopes out of random surface residues on PE38. Using sera from immunotoxin-treated patients, the formation of human Abs to each of the topographical epitopes was demonstrated. One epitope Subgroup, E1a, was identified as the principal neutralizing epitope. The location of each epitope on PE38 was determined by preparing 41 mutants of PE38 in which bulky surface residues were mutated to either alanine or glycine. All 7 major epitope groups and 9 of 13 epitope subgroups were identified by 14 different mutants and these retained high cytotoxic activity. Our results indicate that a relatively small number of discrete immunogenic sites are associated with PE38, most of which can be eliminated by point mutations. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Prot Chem Lab, Res Technol Program, NCI, Frederick, MD 21702 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01 CO 12400] NR 87 TC 63 Z9 63 U1 2 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2006 VL 177 IS 12 BP 8822 EP 8834 PG 13 WC Immunology SC Immunology GA 125BP UT WOS:000243416800064 PM 17142785 ER PT J AU Kochenderfer, JN Chien, CD Simpson, JL Gress, RE AF Kochenderfer, James N. Chien, Christopher D. Simpson, Jessica L. Gress, Ronald E. TI Synergism between CpG-containing oligodeoxynucleotides and IL-2 causes dramatic enhancement of vaccine-elicited CD8(+) T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MELANOMA PEPTIDE VACCINE; DENDRITIC CELLS; TUMOR-ANTIGEN; B16 MELANOMA; IN-VIVO; ESTABLISHED TUMORS; ANTITUMOR IMMUNITY; CTLA-4 BLOCKADE; INTERLEUKIN-2; AUTOIMMUNITY AB Novel anticancer vaccination regimens that can elicit large numbers of Ag-specific T cells are needed. When we administered therapeutic vaccines containing the MHC class I-presented self-peptide tyrosinase-related protein (TRP)-2(180-188) and CpG-containing oligodeoxynucleotides (CpG ODN) to mice, growth of the TRP-2-expressing B16F1 melanoma was not inhibited compared with growth in mice that received control vaccinations. When we added systemic IL-2 to the TRP-2(180-188) plus CpG ODN vaccines, growth of B16F1 was inhibited in a CD8-dependent, epitope-specific manner. Vaccines containing TRP-2(180-188) without CpG ODN did not cause epitope-specific tumor growth inhibition when administered with IL-2. The antitumor efficacy of the different regimens correlated with their ability to elicit TRP-2(180-188)-specific CD8(+) T cell responses. When we administered TRP-2180-188 plus CpG ODN-containing vaccines with systemic IL-2, 18.2% of CD8(+) T cells were specific for TRP-2(180-188). Identical TRP2(180-188) plus CpG ODN vaccines given without IL-2 elicited a TRP-2(180-188)-specific CD8(+) T cell response of only 1.1% of CD8' T cells. Vaccines containing TRP-2(180-188) without CpG ODN elicited TRP-2(180-188)-specific responses of 2.8% of CD8(+) T cells when administered with IL-2. There was up to a 221-fold increase in the absolute number of TRP-2(180-188)-specific CD8' T cells when IL-2 was added to TRP-2180-188 plus CpG ODN-containing vaccines. Peptide plus CpG ODN vaccines administered with IL-2 generated epitope-specific CD8' T cells by a mechanism that depended on endogenous IL-6. This is the first report of synergism between CpG ODN and IL-2. This synergism caused a striking increase in vaccine-elicited CD8(+) T cells and led to epitope-specific antitumor immunity. C1 NCI, NIH, Clin Res Ctr 3 3288, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Kochenderfer, JN (reprint author), NCI, NIH, Clin Res Ctr 3 3288, Expt Transplantat & Immunol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kochendj@mail.nih.gov FU Intramural NIH HHS NR 41 TC 18 Z9 20 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2006 VL 177 IS 12 BP 8860 EP 8873 PG 14 WC Immunology SC Immunology GA 125BP UT WOS:000243416800068 PM 17142789 ER PT J AU Catanzaro, AT Koup, RA Roederer, M Bailer, RT Enama, ME Moodie, Z Gu, L Martin, JE Novik, L Chakrabarti, BK Butman, BT Gall, JGD King, CR Andrews, CA Sheets, R Gomez, PL Mascola, JR Nabel, GJ Graham, BS AF Catanzaro, Andrew T. Koup, Richard A. Roederer, Mario Bailer, Robert T. Enama, Mary E. Moodie, Zoe Gu, Lin Martin, Julie E. Novik, Laura Chakrabarti, Bimal K. Butman, Bryan T. Gall, Jason G. D. King, C. Richter Andrews, Charla A. Sheets, Rebecca Gomez, Phillip L. Mascola, John R. Nabel, Gary J. Graham, Barney S. CA Vaccine Research Ctr 006 TI Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING ANTIBODIES; GENETIC IMMUNIZATION; CELL RESPONSES; RHESUS-MONKEYS; GAG GENE; INFECTION; IMMUNITY; VIREMIA AB Background. The development of an effective human immunodeficiency virus (HIV) vaccine is a high global priority. Here, we report the safety, tolerability, and immunogenicity of a replication-defective recombinant adenovirus serotype 5 (rAd5) vector HIV-1 candidate vaccine. Methods. The vaccine is a mixture of 4 rAd5 vectors that express HIV-1 subtype B Gag-Pol fusion protein and envelope (Env) from subtypes A, B, and C. Healthy, uninfected adults were randomized to receive 1 intramuscular injection of placebo (n = 6) or vaccine at dose levels of 10(9) (n = 6), 10(10) (n = 10), or 10(11) (n = 10) particle units and were followed for 24 weeks to assess immunogenicity and safety. Results. The vaccine was well tolerated but was associated with more reactogenicity at the highest dose. At week 4, vaccine antigen-specific T cell responses were detected in 28 (93.3%) and 18 (60%) of 30 vaccine recipients for CD4(+) and CD8(+) T cells, respectively, by intracellular cytokine staining assay and in 22 (73%) of 30 vaccine recipients by enzyme-linked immunospot assay. Env-specific antibody responses were detected in 15 (50%) of 30 vaccine recipients by enzyme-linked immunosorbant assay and in 28 (93.3%) of 30 vaccine recipients by immunoprecipitation followed by Western blotting. No neutralizing antibody was detected. Conclusions. A single injection induced HIV-1 antigen-specific CD4(+) T cell, CD8(+) T cell, and antibody responses in the majority of vaccine recipients. This multiclade rAd5 HIV-1 vaccine is now being evaluated in combination with a multiclade HIV-1 DNA plasmid vaccine. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. GenVec Inc, Gaithersburg, MD USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC-3017,Bldg 40,Rm 2502, Bethesda, MD 20892 USA. EM bgraham@mail.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS [Z99 AI999999] NR 40 TC 217 Z9 220 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1638 EP 1649 DI 10.1086/509258 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000005 PM 17109335 ER PT J AU Graham, BS Koup, RA Roederer, M Bailer, RT Enama, ME Moodie, Z Martin, JE McCluskey, MM Chakrabarti, BK Lamoreaux, L Andrews, CA Gomez, PL Mascola, JR Nabel, GJ AF Graham, Barney S. Koup, Richard A. Roederer, Mario Bailer, Robert T. Enama, Mary E. Moodie, Zoe Martin, Julie E. McCluskey, Margaret M. Chakrabarti, Bimal K. Lamoreaux, Laurie Andrews, Charla A. Gomez, Phillip L. Mascola, John R. Nabel, Gary J. CA Vaccine Research Str 004 TI Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; DIFFERING PLASMID BACKBONES; ACUTE-RESPIRATORY-SYNDROME; VIRUS TYPE-1 INFECTION; WEST-NILE-VIRUS; IMMUNE-RESPONSES; GENETIC IMMUNIZATION; RHESUS-MONKEYS; CELLS; VIREMIA AB Background. Gene-based vaccine delivery is an important strategy in the development of a preventive vaccine for acquired immunodeficiency syndrome (AIDS). Vaccine Research Center (VRC) 004 is the first phase 1 dose-escalation study of a multiclade HIV-1 DNA vaccine. Methods. VRC-HIVDNA009-00-VP is a 4-plasmid mixture encoding subtype B Gag-Pol-Nef fusion protein and modified envelope (Env) constructs from subtypes A, B, and C. Fifty healthy, uninfected adults were randomized to receive either placebo (n = 10) or study vaccine at 2 mg (n = 5), 4 mg (n = 20), or 8 mg (n = 15) by needle-free intramuscular injection. Humoral responses (measured by enzyme-linked immunosorbant assay, Western blotting, and neutralization assay) and T cell responses (measured by enzyme-linked immunospot assay and intracellular cytokine staining after stimulation with antigen-specific peptide pools) were measured. Results. The vaccine was well tolerated and induced cellular and humoral responses. The maximal CD4(+) and CD8(+) T cell responses occurred after 3 injections and were in response to Env peptide pools. The pattern of cytokine expression by vaccine-induced HIV-specific T cells evolved over time, with a diminished frequency of interferon-gamma-producing T cells and an increased frequency of interleukin-2-producing T cells at 1 year. Conclusions. DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC-3017,Bldg 40,Rm 2502, Bethesda, MD 20892 USA. EM bgraham@mail.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS [Z99 AI999999] NR 36 TC 155 Z9 158 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1650 EP 1660 DI 10.1086/509259 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000006 PM 17109336 ER PT J AU Kilby, JM Bucy, RP Mildvan, D Fischl, M Santana-Bagur, J Lennox, J Pilcher, C Zolopa, A Lawrence, J Pollard, RB El Habib, R Sahner, D Fox, L Aga, E Bosch, RJ Mitsuyasu, R AF Kilby, J. Michael Bucy, R. Pat Mildvan, Donna Fischl, Margaret Santana-Bagur, Jorge Lennox, Jeff Pilcher, Chris Zolopa, Andrew Lawrence, Jody Pollard, Richard B. El Habib, Raphaelle Sahner, David Fox, Lawrence Aga, Evgenia Bosch, Ronald J. Mitsuyasu, Ronald CA Adult AIDS Clin Trial Group TI A randomized, partially blinded phase 2 trial of antiretroviral therapy, HIV-specific immunizations, and interleukin-2 cycles to promote efficient control of viral replication (ACTG A5024) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CANARYPOX VACCINE; INFECTED PATIENTS; TYPE-1 INFECTION; DISCONTINUATION; INTERMITTENT; VIREMIA AB Strategies to limit life-long dependence on antiretroviral therapy (ART) are needed. We randomized 81 human immunodeficiency virus (HIV)-infected subjects to 4 interventional arms involving continued ART plus ALVAC vCP1452 (or placebo) with or without interleukin (IL)-2 infusions. Viral load rebound 12 weeks after ART interruption was then analyzed to assess immune control. Fifty-two subjects reached the study end point. ALVAC recipients had 0.5 log(10) lower virologic rebounds (P = .033). IL-2 plus vaccine boosted CD4(+) T cell counts (P < .001) but did not diminish viral rebound. Significant changes were not detected for HIV-specific lymphoproliferative responses in any arm. This exploratory protocol provides useful clinical data for future therapeutic immunization trial design. C1 Univ Alabama, Birmingham, AL 35294 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Univ Miami, Miami, FL 33152 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Emory Univ, Atlanta, GA 30322 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Chiron Corp, Emeryville, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Sanofi Pasteur, Paris, France. RP Kilby, JM (reprint author), Univ Alabama, Birmingham, AL 35294 USA. EM mkilby@uab.edu RI Lennox, Jeffrey/D-1654-2014; OI Lennox, Jeffrey/0000-0002-2064-5565; Kilby, J. Michael/0000-0003-3222-1003 FU NCRR NIH HHS [M01 RR-00032]; NIAID NIH HHS [AI 25915, AI 25859, AI 25868, AI 27660, AI 27666, AI 27673, AI 27675, AI 32770, AI 32783, AI 34853, AI 38855, AI 46339, AI 27658, AI 27661, AI 27663, AI 32775, AI 32782, AI 34832, AI 38858, AI 46370] NR 15 TC 41 Z9 41 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1672 EP 1676 DI 10.1086/509508 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000008 PM 17109338 ER PT J AU Castle, PE Schiffman, M Glass, AG Rush, BB Scott, DR Wacholder, S Dunn, A Burk, RD AF Castle, Philip E. Schiffman, Mark Glass, Andrew G. Rush, Brenda B. Scott, David R. Wacholder, Sholom Dunn, Anne Burk, Robert D. TI Human papillomavirus prevalence in women who have and have not undergone hysterectomies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL-CANCER; INFECTION AB We compared human papillomavirus (HPV) prevalence in an age-stratified random sample of women who have undergone a hysterectomy (WH) (n = 573) with the HPV prevalence in age-matched women with intact cervices (women who have not undergone a hysterectomy [WNH]) (n = 581) participating in a study at Kaiser Permanente in Portland, Oregon. Testing cervicovaginal lavage fluids for > 40 HPV genotypes using an MY09/11 L1 consensus primer polymerase chain reaction method, we found no statistical differences in the prevalence of HPV (16% for WNH vs. 13.9% for WH) or carcinogenic HPV (6.5% for WNH vs. 4.5% for WH) between the 2 groups of women. Although WH have a similar prevalence of carcinogenic HPV infection, compared with WNH without a cervix, they have minimal risk of HPV-induced cancer and are unlikely to benefit from HPV testing. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Rm 7074,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU Intramural NIH HHS NR 12 TC 18 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1702 EP 1705 DI 10.1086/509511 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000012 PM 17109342 ER PT J AU Saikh, KU Kissner, TL Dyas, B Tropea, JE Waugh, DS Ulrich, RG AF Saikh, Kamal U. Kissner, Teri L. Dyas, Beverly Tropea, Joseph E. Waugh, David S. Ulrich, Robert G. TI Human cytolytic T cell recognition of Yersinia pestis virulence proteins that target innate immune responses SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID V-ANTIGEN; PNEUMONIC PLAGUE; SECRETION SYSTEM; DENDRITIC CELLS; OUTER PROTEINS; YOP EFFECTORS; III SECRETION; INFECTION; MICE; PSEUDOTUBERCULOSIS AB Cell contact by the plague bacterium Yersinia pestis initiates the injection of several virulence factors that target biochemical pathways critical for host clearance of bacteria. Despite this impairment of innate immunity, it is unclear whether antigen recognition by T cells is equally affected. We present evidence that human cytolytic T cells respond to Y. pestis virulence proteins presented by infected monocytes and dendritic cells. These T cell antigens consisted of a panel of proteins encoded by pCD1, a 70-kDa plasmid that harbors virulence factors and transport proteins of the cell contact-dependent, type III secretion system. Infected cells retained the ability to process and present tetanus toxoid to T cells, which indicates that responses to unrelated antigens were also maintained. Our results indicate that T cell immunity remains functional during Y. pestis infection, which thus suggests the potential benefits of therapeutic vaccination and strategies that emphasize the inclusion of cytotoxic T lymphocyte responses. C1 USA, Med Res Inst Infect Dis, Dept Immunol, Div Toxicol, Frederick, MD 21701 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Saikh, KU (reprint author), USA, Med Res Inst Infect Dis, Dept Immunol, Div Toxicol, 1425 Porter St, Frederick, MD 21701 USA. EM kamal.saikh@det.amedd.army.mil; ulrich@ncifcrf.gov NR 45 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1753 EP 1760 DI 10.1086/509507 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000019 PM 17109349 ER PT J AU Voyich, JM Otto, M Mathema, B Braughton, KR Whitney, AR Welty, D Long, RD Dorward, DW Gardner, DJ Lina, G Kreiswirth, BN DeLeo, FR AF Voyich, Jovanka M. Otto, Michael Mathema, Barun Braughton, Kevin R. Whitney, Adeline R. Welty, Diane Long, R. Daniel Dorward, David W. Gardner, Donald J. Lina, Gerard Kreiswirth, Barry N. DeLeo, Frank R. TI Is panton-valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN NEUTROPHILS; UNITED-STATES; STRAINS; INFECTIONS; GENES; CLONE; LEUCOCIDIN; PNEUMONIA; GENOME; SKIN AB Methicillin-resistant Staphylococcus aureus (MRSA) remains a major problem in hospitals, and it is now spreading in the community. A single toxin, Panton-Valentine leukocidin (PVL), has been linked by epidemiological studies to community-associated MRSA (CA-MRSA) disease. However, the role that PVL plays in the pathogenesis of CA-MRSA has not been tested directly. To that end, we used mouse infection models to compare the virulence of PVL-positive with that of PVL-negative CA-MRSA representing the leading disease-causing strains. Unexpectedly, strains lacking PVL were as virulent in mouse sepsis and abscess models as those containing the leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of USA300 and USA400 were as lethal as wild-type strains in a sepsis model, and they caused comparable skin disease. Moreover, lysis of human neutrophils and pathogen survival after phagocytosis were similar between wild-type and mutant strains. Although the toxin may be a highly linked epidemiological marker for CA-MRSA strains, we conclude that PVL is not the major virulence determinant of CA-MRSA. C1 NIAAA, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAAA, Rocky Mt Vet Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. NIAAA, RTB Res Technol Sect, Rocky Mt Labs, Microscopy Unit, Hamilton, MT 59840 USA. Int Ctr Publ Hlth, Publ Hlth Res Inst, TB Ctr, Newark, NJ USA. Univ Lyon 1, Fac Med Laennec, Inst Fed Rech 62, INSERM,E230, F-69365 Lyon, France. RP DeLeo, FR (reprint author), NIAAA, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov RI Lina, Gerard/L-9352-2014; OI Otto, Michael/0000-0002-2222-4115; DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 26 TC 398 Z9 405 U1 4 U2 22 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1761 EP 1770 DI 10.1086/509506 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000020 PM 17109350 ER PT J AU Rothman, KJ Arellano, FM Yinong, YX Simonsen, L AF Rothman, Kenneth J. Arellano, Felix M. Yinong Young-Xu Simonsen, Lone TI Is there a safe age for vaccinating infants with tetravalent rhesus-human reassortant rotavirus vaccine? Reply to Gargiullo et al. SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID INTUSSUSCEPTION; ROTASHIELD C1 Res Triangle Inst, Hlth Solut, Res Triangle Pk, NC 27709 USA. Risk Management Resources, Bridgewater, NJ USA. NIAID, Bethesda, MD 20892 USA. RP Rothman, KJ (reprint author), Res Triangle Inst, Hlth Solut, 200 Pk Off,Hyw 54, Res Triangle Pk, NC 27709 USA. EM Krothman@rti.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2006 VL 194 IS 12 BP 1794 EP 1795 DI 10.1086/509265 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 114GZ UT WOS:000242656000027 ER PT J AU Origlia, N Kuczewski, N Aztiria, E Gautam, D Wess, J Domenici, L AF Origlia, Nicola Kuczewski, Nicola Aztiria, Eugenio Gautam, Dinesh Wess, Jurgen Domenici, Luciano TI Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LONG-TERM POTENTIATION; FOREBRAIN CHOLINERGIC SYSTEM; BASAL FOREBRAIN; NMDA RECEPTORS; CORTICAL PLASTICITY; PYRAMIDAL NEURONS; PHOSPHOLIPASE-C; PROTEIN-KINASE; RAT; ACTIVATION AB In the present report, we focused our attention on the role played by the muscarinic acetylcholine receptors (mAChRs) in different forms of long-term synaptic plasticity. Specifically, we investigated long-term potentiation (LTP) and long-term depression (LTD) expression elicited by theta-burst stimulation (TBS) and low-frequency stimulation (LFS), respectively, in visual cortical slices obtained from different mAChR knockout (KO) mice. A normal LTP was evoked in M-1/M-3 double KO mice, while LTP was impaired in the M-2/M-4 double KO animals. On the other hand, LFS induced LTD in M-2/M-4 double KO mice, but failed to do so in M-1/M-3 KO mice. Interestingly, LFS produced LTP instead of LTD in M-1/M-3 KO mice. Analysis of mAChR single KO mice revealed that LTP was affected only by the simultaneous absence of both M-2 and M-4 receptors. A LFS-dependent shift from LTD to LTP was also observed in slices from M-1 KO mice, while LTD was simply abolished in slices from M-3 KO mice. Using pharmacological tools, we showed that LTP in control mice was blocked by pertussis toxin, an inhibitor of G(i/o) proteins, but not by raising intracellular cAMP levels. In addition, the inhibition of phospholipase C by U73122 induced the same shift from LTD to LTP after LFS observed in M-1 single KO and M-1/M-3 double KO mice. Our results indicate that different mAChR subtypes regulate different forms of long-term synaptic plasticity in the mouse visual cortex, activating specific G proteins and downstream intracellular mechanisms. C1 CNR, Inst Neurosci, I-56100 Pisa, Italy. SISSA, Int Sch Adv Studies, I-34014 Trieste, Italy. NIDDK, Mol Signalling Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Sci & Tecnol Biomed, I-67010 Coppito, Italy. RP Domenici, L (reprint author), CNR, Inst Neurosci, I-56100 Pisa, Italy. EM domenici@in.cnr.it OI Domenici, Luciano/0000-0003-2923-9421 NR 55 TC 31 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2006 VL 577 IS 3 BP 829 EP 840 DI 10.1113/jphysiol.2006.117119 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 117JW UT WOS:000242870400008 PM 17023506 ER PT J AU Horkay, F Hecht, AM Geissler, E AF Horkay, Ferenc Hecht, Anne-Marie Geissler, Erik TI Similarities between polyelectrolyte gels and biopolymer solutions SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS LA English DT Article DE biopolymers; gels; neutron scattering; osmotic modulus; swelling pressure ID PHYSIOLOGICAL SALT-SOLUTIONS; POLYACRYLATE HYDROGELS; OSMOTIC OBSERVATIONS; DNA; SCATTERING; CONDENSATION; NETWORKS; EXCHANGE; SWOLLEN; LENGTH AB Small angle neutron scattering (SANS) measurements and osmotic swelling pressure measurements are reported for polyelectrolyte gels and solutions under nearly physiological conditions. A synthetic polymer (sodium-polyacrylate) and three biopolymers (DNA, hyaluronic acid, and polyaspartic acid) are studied. The neutron scattering response of these anionic polyelectrolytes is closely similar, indicating that at larger length scales the organization of the polymer molecules is not significantly affected by the fine details of the molecular architecture (e.g., size and chemical structure of the monomer unit, type of polymer backbone). The results suggest that specific interactions between the polyelectrolyte chains and the surrounding monovalent cations are negligible. It is found that the osmotic compression modulus of these biopolymer solutions determined from the analysis of the SANS response decreases with increasing chain persistence length. (c) 2006 Wiley Periodicals, Inc. C1 NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS UMR 5588, Spectrometrie Phys Lab, FR-38402 St Martin Dheres, France. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov NR 37 TC 12 Z9 12 U1 3 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-6266 J9 J POLYM SCI POL PHYS JI J. Polym. Sci. Pt. B-Polym. Phys. PD DEC 15 PY 2006 VL 44 IS 24 BP 3679 EP 3686 DI 10.1002/polb.21008 PG 8 WC Polymer Science SC Polymer Science GA 111PY UT WOS:000242467100029 ER PT J AU Dellago, C Hummer, G AF Dellago, Christoph Hummer, Gerhard TI Kinetics and mechanism of proton transport across membrane nanopores SO PHYSICAL REVIEW LETTERS LA English DT Article ID VALENCE-BOND MODEL; MOLECULAR-DYNAMICS; CARBON NANOTUBES; TRANSITION PATHS; H+ CONDUCTION; WATER; CHANNEL; SIMULATIONS; INTERFACE; RATES AB We use computer simulations to study the kinetics and mechanism of proton passage through a narrow-pore carbon-nanotube membrane separating reservoirs of liquid water. Free energy and rate constant calculations show that protons move across the membrane diffusively along single-file chains of hydrogen-bonded water molecules. Proton passage through the membrane is opposed by a high barrier in the effective potential, reflecting the large electrostatic penalty for desolvation and reminiscent of charge exclusion in biological water channels. At neutral pH, we estimate a translocation rate of about 1 proton per hour and tube. C1 Univ Vienna, Fac Phys, A-1090 Vienna, Austria. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Dellago, C (reprint author), Univ Vienna, Fac Phys, Boltzmanngasse 5, A-1090 Vienna, Austria. RI Dellago, Christoph/E-1625-2011; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 33 TC 54 Z9 55 U1 1 U2 19 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD DEC 15 PY 2006 VL 97 IS 24 AR 245901 DI 10.1103/PhysRevLett.97.245901 PG 4 WC Physics, Multidisciplinary SC Physics GA 117QT UT WOS:000242888700045 PM 17280300 ER PT J AU Taylor, S Barragan, A Su, C Fux, B Fentress, SJ Tang, K Beatty, WL El Hajj, H Jerome, M Behnke, MS White, M Wootton, JC Sibley, LD AF Taylor, S. Barragan, A. Su, C. Fux, B. Fentress, S. J. Tang, K. Beatty, W. L. El Hajj, H. Jerome, M. Behnke, M. S. White, M. Wootton, J. C. Sibley, L. D. TI A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii SO SCIENCE LA English DT Article ID PARASITOPHOROUS VACUOLE; INTRACELLULAR PARASITE; STRAINS; INFECTION; REVEALS; OVERPRODUCTION; RECOMBINATION; TRANSMISSION; APOPTOSIS; LINEAGES AB Toxoplasma gondii strains differ dramatically in virulence despite being genetically very similar. Genetic mapping revealed two closely adjacent quantitative trait loci on parasite chromosome VIIa that control the extreme virulence of the type I lineage. Positional cloning identified the candidate virulence gene ROP18, a highly polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion. Transfection of the virulent ROP18 allele into a nonpathogenic type III strain increased growth and enhanced mortality by 4 to 5 logs. These attributes of ROP18 required kinase activity, which revealed that secretion of effectors is a major component of parasite virulence. C1 Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA. Karolinska Inst, Swedish Inst Infect Dis Control, Dept Med, S-14186 Stockholm, Sweden. Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden. Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. Univ Montpellier 2, UMR 5539, CNRS, F-34095 Montpellier 5, France. Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Sibley, LD (reprint author), Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63130 USA. EM sibley@borcim.wustl.edu RI Sibley, L. David/C-4616-2008; White, Michael/A-4978-2012; Su, Chunlei/M-1892-2013; Barragan, Antonio/P-6278-2015; Behnke, Michael/R-8839-2016 OI Su, Chunlei/0000-0001-8392-7108; Barragan, Antonio/0000-0001-7746-9964; Behnke, Michael/0000-0002-4668-8109 FU Intramural NIH HHS; NCRR NIH HHS [P20 RR-020185]; NIAID NIH HHS [AI44600, AI059176, AI36629] NR 29 TC 275 Z9 303 U1 2 U2 21 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 DEC 15 PY 2006 VL 314 IS 5806 BP 1776 EP 1780 DI 10.1126/science.1133643 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116WD UT WOS:000242833600059 PM 17170305 ER PT J AU Ota, E Nagashima, Y Shiomi, K Sakurai, T Kojima, C Waalkes, MP Himeno, S AF Ota, Eiji Nagashima, Yuji Shiomi, Kazuo Sakurai, Teruaki Kojima, Chikara Waalkes, Michael P. Himeno, Seiichiro TI Caspase-independent apoptosis induced in rat liver cells by plancitoxin I, the major lethal factor from the crown-of-thorns starfish Acanthaster planci venom SO TOXICON LA English DT Article DE Acanthaster planci; apoptosis; crown-of-thorns starfish; DNase activity; hepatotoxicity; plancitoxin I ID CYTOLETHAL DISTENDING TOXIN; DIMETHYLARSINIC ACID; BACTERIAL GENOTOXIN; PURIFICATION; GLUTATHIONE; PROTEIN; CDTB; DNA AB Plancitoxin I, the major lethal factor from the crown-of-thorns starfish Acanthaster planci venom, is quite unique not only in exhibiting potent hepatotoxicity but also in sharing high sequence homology with mammalian deoxyribonulease II. In this study, morphological and biochemical changes in rat liver epithelial cells (TRL 1215 cells) treated with the toxin were examined to understand the mechanism by which plancitoxin I displays hepatotoxicity. AlamarBlue assay established that plancitoxin I is cytolethal to TRL 1215 cells. This cytolethalithy was ascribable to apoptotic cell death. Nuclear fragmentation evidenced by either Diff-Quick or Hoechst 33258 staining, DNA fragmentation by TUNEL assay and electrophoretic analysis on agarose gel and phosphatidylserine externalization by flow cytometric analysis of annexin V-FITC stained cells were all characteristics of apoptosis. The observed apoptosis was shown to be independent of the caspase 3 cascade that is generally accepted as the effector of the apoptotic process. Very interestingly, experiments using FITC-labeled plancitoxin I proved that the toxin can enter the nucleus of TRL 1215 cells. Our results suggested that plancitoxin I induces apoptosis of TRL 1215 cells through the following procedure: binding to a specific receptor in the cytoplasmic membrane, entering the cell, entering the nucleus and degrading DNA. (c) 2006 Elsevier Ltd. All rights reserved. C1 Tokyo Univ Marine Sci & Technol, Dept Food Sci & Technol, Minato Ku, Tokyo 1088477, Japan. Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Tokushima 7708514, Japan. NIEHS, Comparat Carcinogenesis Lab, NCI, NIH, Res Triangle Pk, NC 27709 USA. RP Shiomi, K (reprint author), Tokyo Univ Marine Sci & Technol, Dept Food Sci & Technol, Minato Ku, Konan 4, Tokyo 1088477, Japan. EM shiomi@s.kaiyodai.ac.jp RI NAGASHIMA, yuji/O-1968-2014 NR 25 TC 12 Z9 15 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC 15 PY 2006 VL 48 IS 8 BP 1002 EP 1010 DI 10.1016/j.toxicon.2006.08.005 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 119BR UT WOS:000242987700007 PM 16973201 ER PT J AU Benson, JM Gomez, AP Statom, GL Tibbetts, BM Fleming, LE Backer, LC Reich, A Baden, DG AF Benson, Janet M. Gomez, Andrea P. Statom, Gloria L. Tibbetts, Brad M. Fleming, Lora E. Backer, Lorraine C. Reich, Andrew Baden, Daniel G. TI Placental transport of brevetoxin-3 in CD-1 mice SO TOXICON LA English DT Article DE brevetoxin-3; placental transport; intratracheal instillation; mice ID RED TIDE TOXINS; AEROSOLIZED BREVETOXINS; INHALATION TOXICITY; GYMNODINIUM-BREVE; FLORIDA; RAT; EXPOSURE; FETAL; ELIMINATION; METABOLITES AB The purpose of this study was to examine the distribution of brevetoxin-3 administered to pregnant dams and to determine the extent of placental transport to fetuses. Twenty-nine pregnant CD-1 mice were administered H-3-brevetoxin-3 (similar to 1.3 mu Ci/animal; similar to 2.8 mu g compound/kg) by intratracheal instillation on one of gestational days 15-18. Groups of four or five dams were killed at selected times through 48 h post-dosing. Four pregnant dams were administered H-3-brevetoxin-3 on gestational day 15 or 16 via osmotic minipump to provide continuous delivery of compound (similar to 0.13 mu Ci, 7.5ng compound/day) over a 72-h period. Then the dams and fetuses were killed. Brevetoxin-associated radioactivity was detected in placentas and fetuses within 0.5 h of intratracheal administration. Concentrations of brevetoxin equivalents in fetuses were approximately 0.3 ng/g throughout the 48-h post-dosing, resulting in a calculated dose to fetuses of 19 ng/g h. Following brevetoxin infusion, concentration of brevetoxin equivalents in fetuses was 0.1 ng/g, lower than that present in most maternal tissues. Results demonstrated placental transport of brevetoxin or its metabolites following maternal acute exposure and repeated low-dose exposure. The consequences of these findings for pregnant women exposed to brevetoxins by inhalation or ingestion remain to be determined. (c) 2006 Elsevier Ltd. All rights reserved. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Florida Dept Hlth, Tallahassee, FL 32399 USA. Univ N Carolina, Marine Sci Res Ctr, Wilmington, NC 28409 USA. RP Benson, JM (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM jbenson@LRRI.org FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-05, P01 ES10594] NR 37 TC 12 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC 15 PY 2006 VL 48 IS 8 BP 1018 EP 1026 DI 10.1016/j.toxicon.2006.08.008 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 119BR UT WOS:000242987700009 PM 17011606 ER PT J AU Cosyn, L Palaniappan, KK Kim, SK Duong, HT Gao, ZG Jacobson, KA Van Calenbergh, S AF Cosyn, Liesbet Palaniappan, Krishnan K. Kim, Soo-Kyung Duong, Heng T. Gao, Zhan-Guo Jacobson, Kenneth A. Van Calenbergh, Serge TI 2-Triazole-substituted adenosines: A new class of selective A(3) adenosine receptor agonists, partial agonists, and antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID STRUCTURAL DETERMINANTS; BIOLOGICAL-ACTIVITY; SPECIES-DIFFERENCES; IN-SITU; DERIVATIVES; LIGANDS; POTENT; NUCLEOSIDES; EFFICACY; PHARMACOLOGY AB ''Click chemistry" was explored to synthesize two series of 2-(1,2,3-triazolyl) adenosine derivatives (1-14). Binding affinity at the human A(1), A(2A), and A(3)ARs (adenosine receptors) and relative efficacy at the A(3)AR were determined. Some triazol-1-yl analogues showed A(3)AR affinity in the low nanomolar range, a high ratio of A(3)/A(2A) selectivity, and a moderate-to-high A(3)/A(1) ratio. The 1,2,3-triazol-4-yl regiomers typically showed decreased A(3)AR affinity. Sterically demanding groups at the adenine C2 position tended to reduce relative A(3)AR efficacy. Thus, several 5'-OH derivatives appeared to be selective A(3)AR antagonists, i.e., 10, with 260-fold binding selectivity in comparison to the A(1)AR and displaying a characteristic docking mode in an A(3)AR model. The corresponding 5'-ethyluronamide analogues generally showed increased A(3)AR affinity and behaved as full antagonists, i.e., 17, with 910-fold A(3)/A(1) selectivity. Thus, N-6-substituted 2-( 1,2,3-triazolyl)-adenosine analogues constitute a novel class of highly potent and selective nucleoside-based A(3)AR antagonists, partial agonists, and agonists. C1 Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, FFW, B-9000 Ghent, Belgium. NIDDK, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, FFW, Harelbeckstr 72, B-9000 Ghent, Belgium. EM kajacobs@helix.nih.gov; serge.vancalenbergh@ugent.be RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009 OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 50 TC 60 Z9 60 U1 0 U2 8 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 DEC 14 PY 2006 VL 49 IS 25 BP 7373 EP 7383 DI 10.1021/jm0608208 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 113VJ UT WOS:000242625800013 PM 17149867 ER PT J AU Momeni, P Schymick, J Jain, S Cookson, MR Cairns, NJ Greggio, E Greenway, MJ Berger, S Pickering-Brown, S Chio, A Fung, HC Holtzman, DM Huey, ED Wassermann, EM Adamson, J Hutton, ML Rogaeva, E St George-Hyslop, P Rothstein, JD Hardiman, O Grafman, J Singleton, A Hardy, J Traynor, BJ AF Momeni, Parastoo Schymick, Jennifer Jain, Shushant Cookson, Mark R. Cairns, Nigel J. Greggio, Elisa Greenway, Matthew J. Berger, Stephen Pickering-Brown, Stuart Chio, Adriano Fung, Hon Chung Holtzman, David M. Huey, Edward D. Wassermann, Eric M. Adamson, Jennifer Hutton, Michael L. Rogaeva, Ekaterina St George-Hyslop, Peter Rothstein, Jeffrey D. Hardiman, Orla Grafman, Jordan Singleton, Andrew Hardy, John Traynor, Bryan J. TI Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD SO BMC NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL DEMENTIA; DCTN1 GENE; MUTATIONS; LOCUS; ASSOCIATION; PROTEIN; FAMILY; FORM; TAU AB Background: A new locus for amyotrophic lateral sclerosis - frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p. Methods: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus. Results: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 ( F476), but no mutation was detected within IFT74 in family 2 ( F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 ( predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases ( n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. Conclusion: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Royal Coll Surgeons Ireland, Dept Clin Neurol, Dublin 2, Ireland. Univ Manchester, Hope Hosp, Greater Manchester Neurosci Ctr, Ctr Clin Neurosci, Salford M6 8HD, Lancs, England. Dept Neurosci, I-10126 Turin, Italy. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. Univ Toronto, Dept Med & Physiol, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. Johns Hopkins Univ, Dept Neurol & Neurosci, Baltimore, MD USA. Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. NIMH, SDGE, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. EM momeni@mail.nih.gov; schymickj@mail.nih.gov; jains@mail.nih.gov; cookson@mail.nih.gov; cairns@wustl.edu; greggio@mail.nih.gov; greenwaymatt@yahoo.co.uk; bergerst@mail.nih.gov; spb@manchester.ac.uk; achio@usa.net; fungp@mail.nih.gov; holtzman@neuro.wustl.edu; hueye@mail.nih.gov; wassermanne@mail.nih.gov; adamson.jennifer@mayo.edu; hutton.michael@mayo.edu; ekaterina.rogaeva@utoronto.ca; p.hyslop@utoronto.ca; jrothste@jhmi.edu; ohard@iol.ie; grafmanj@ninds.nih.gov; singleta@mail.nih.gov; hardyj@mail.nih.gov; traynorb@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Pickering-Brown, Stuart/D-4008-2009; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; rothstein, jeffrey/C-9470-2013; Greggio, Elisa/H-6119-2013; OI Pickering-Brown, Stuart/0000-0003-1561-6054; Greggio, Elisa/0000-0002-8172-3598; Grafman, Jordan H./0000-0001-8645-4457; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291 FU Intramural NIH HHS; Medical Research Council [G0400356, G0701075]; NIA NIH HHS [P50 AG005681, P50 AG008702, P50 AG05681, P50 AG08702] NR 31 TC 60 Z9 62 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD DEC 13 PY 2006 VL 6 AR 44 DI 10.1186/1471-2377-6-44 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 128SL UT WOS:000243678700001 PM 17166276 ER PT J AU Nakamura, K Hikosaka, O AF Nakamura, Kae Hikosaka, Okihide TI Facilitation of saccadic eye movements by postsaccadic electrical stimulation in the primate caudate SO JOURNAL OF NEUROSCIENCE LA English DT Article DE basal ganglia; caudate; saccade; primate; reinforcement learning; electrical stimulation ID INTRACRANIAL SELF-STIMULATION; ACTIVITY-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; SUBSTANTIA-NIGRA; BASAL GANGLIA; IN-VIVO; CORTICOSTRIATAL SYNAPSES; FUNCTIONAL-PROPERTIES; DOPAMINERGIC-NEURONS; PARS RETICULATA AB Sensorimotor experience followed by positive feedback leads to motor learning. Although the striatum, an input channel of the basal ganglia, has been implicated to play a key role in motor learning, little is known about how reward information modulates the neuronal processes in the striatum that causes behavioral changes. Here, we report that direct manipulation of the neuronal signal in the primate caudate yields behavioral changes comparable with those induced by natural reward. Electrical stimulation in the oculomotor region of the caudate immediately after saccades to a fixed direction led to selective facilitation of saccades in that direction. The facilitation remained even after stimulation was stopped, indicating a plastic change. These effects were observed when stimulation was applied after, not before, saccades. We propose that the caudate plays a causal role in behavioral changes by integrating selective sensorimotor and reward information in a temporally specific manner. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nakamura, K (reprint author), Univ Wisconsin, Dept Physiol, 127 Serv Mem Inst,1300 Univ Ave, Madison, WI 53706 USA. EM kae@physiology.wisc.edu FU Intramural NIH HHS NR 71 TC 21 Z9 22 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 13 PY 2006 VL 26 IS 50 BP 12885 EP 12895 DI 10.1523/JNEUROSCI.3688-06.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 119EV UT WOS:000242996200005 PM 17167079 ER PT J AU Rai, V Gaur, M Shukla, S Shukla, S Ambudkar, SV Komath, SS Prasad, R AF Rai, Versha Gaur, Manisha Shukla, Sudhanshu Shukla, Suneet Ambudkar, Suresh V. Komath, Sneha Sudha Prasad, Rajendra TI Conserved Asp327 of Walker B motif in the N-terminal nucleotide binding domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis SO BIOCHEMISTRY LA English DT Article ID ABC DRUG TRANSPORTER; CONFERS MULTIDRUG-RESISTANCE; HUMAN P-GLYCOPROTEIN; FUNCTIONAL-CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; CASSETTE TRANSPORTERS; MUTATIONAL ANALYSIS; MAJOR FACILITATOR; CRYSTAL-STRUCTURE; CATALYTIC CYCLE AB The Walker A and B motifs of nucleotide binding domains (NBDs) of Cdr1p though almost identical to all ABC transporters, has unique substitutions. We have shown in the past that Trp326 of Walker B and Cys193 of Walker A motifs of N-terminal NBD of Cdr1p have distinct roles in ATP binding and hydrolysis, respectively. In the present study, we have examined the role of a well conserved Asp327 in the Walker B motif of the N-terminal NBD, which is preceded (Trp326) and followed (Asn328) by atypical amino acid substitutions and compared it with its equivalent well conserved Asp1026 of the C-terminal NBD of Cdr1p. We observed that the removal of the negative charge by D327N, D327A, D1026N, D1026A, and D327N/D1026N substitutions, resulted in Cdr1p mutant variants that were severely impaired in ATPase activity and drug efflux. Importantly, all of the mutant variants showed characteristics similar to those of the wild type with respect to cell surface expression and photoaffinity drug analogue [I-125] IAAP and [H-3] azidopine labeling. Although the Cdr1p D327N mutant variant showed comparable binding with [alpha-P-32] 8-azido ATP, Cdr1p D1026N and Cdr1p D327N/D1026N mutant variants were crippled in nucleotide binding. That the two conserved carboxylate residues Asp327 and Asp1026 are functionally different was further evident from the pH profile of ATPase activity. The Cdr1p D327N mutant variant showed similar to 40% enhancement of its residual ATPase activity at acidic pH, whereas no such pH effect was seen with the Cdr1p D1026N mutant variant. Our experimental data suggest that Asp327 of N-terminal NBD has acquired a new role to act as a catalytic base in ATP hydrolysis, a role normally conserved for Glu present adjacent to the conserved Asp in the Walker B motif of all the non-fungal transporters. C1 Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. Jawaharlal Nehru Univ, Sch Life Sci, Biophys Chem Lab, New Delhi 110067, India. NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Prasad, R (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. EM rp47@hotmail.com RI shukla, suneet/B-4626-2012; OI Shukla, Sudhanshu/0000-0002-7091-7215 FU Intramural NIH HHS [Z01 BC010030-12] NR 49 TC 17 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 12 PY 2006 VL 45 IS 49 BP 14726 EP 14739 DI 10.1021/bi061535t PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112HI UT WOS:000242516100017 PM 17144665 ER PT J AU O'Meara, WP Barcus, M Wongsrichanalai, C Muth, S Maguire, JD Jordan, RG Prescott, WR McKenzie, FE AF O'Meara, Wendy Prudhomme Barcus, Mazie Wongsrichanalai, Chansuda Muth, Sinuon Maguire, Jason D. Jordan, Robert G. Prescott, William R. McKenzie, F. Ellis TI Reader technique as a source of variability in determining malaria parasite density by microscopy SO MALARIA JOURNAL LA English DT Article ID DIAGNOSIS; CHILDREN; VACCINE; TRIAL; THICK AB Background: Accurate identification and quantification of malaria parasites are critical for measuring clinical trial outcomes. Positive and negative diagnosis is usually sufficient for the assessment of therapeutic outcome, but vaccine or prophylactic drug trials require measuring density of infection as a primary endpoint. Microscopy is the most established and widely-used technique for quantifying parasite densities in the blood. Methods: Results obtained by 24 - 27 expert malaria microscopists, who had independently read 895 slides from 35 donors, were analysed to understand how reader technique contributes to discrepancy in measurements of parasite density over a wide range of densities. Results: Among these 35 donations, standard deviations ranged from 30% to 250% of the mean parasite density and the percent discrepancy was inversely correlated with the mean parasite density. The number of white blood cells indexed and whether parasites were counted in the thick film or thin film were shown to significantly contribute to discrepancy amongst microscopists. Conclusion: Errors in microscopy measurements are not widely appreciated or addressed but have serious consequences for efficacy trials, including possibly abandoning promising vaccine candidates. C1 NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. Hydas World Hlth, Hershey, PA USA. USN, Med Res Unit 2, Jakarta, Indonesia. Minist Hlth, Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. RP O'Meara, WP (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov; mazie_barcus@yahoo.com; dr.chansuda@gmail.com; sinuonm@cnm.gov.kh; jdmaguire@mar.med.navy.mil; Robert.Jordon@hydasworldhealth.org; roy@hydas.com; mckenzel@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999]; NIAID NIH HHS [N01-AI-85355]; NIDA NIH HHS [N01AI85355] NR 16 TC 30 Z9 30 U1 1 U2 3 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 DEC 12 PY 2006 VL 5 AR 118 DI 10.1186/1475-2875-5-118 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 119CZ UT WOS:000242991100001 PM 17164007 ER PT J AU Kaneski, CR Moore, DF Ries, M Zirzow, GC Schiffmann, R AF Kaneski, C. R. Moore, D. F. Ries, M. Zirzow, G. C. Schiffmann, R. TI Myeloperoxidase predicts risk of vasculopathic events in hemizgygous males with Fabry disease SO NEUROLOGY LA English DT Article ID CEREBRAL HYPERPERFUSION; ENZYME REPLACEMENT; THERAPY; ALPHA AB Fabry disease results in a global vasculopathy leading to earlyonset stroke and renal and cardiac failure. We found that random myeloperoxidase in serum and plasma was significantly elevated in 73 consecutive male patients with Fabry disease. Random serum myeloperoxidase level in men predicted the risk of a Fabry vasculopathy-related event in subsequent years. Long-term enzyme replacement therapy did not reduce myeloperoxidase level or eliminate the risk of vasculopathic events. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Internal Med, Neurol Sect, Winnipeg, MB, Canada. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Kaneski, Christine/0000-0003-1453-2502 FU Intramural NIH HHS [Z01 NS002984-09] NR 10 TC 27 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 12 PY 2006 VL 67 IS 11 BP 2045 EP 2047 DI 10.1212/01.wnl.0000247278.88077.09 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000242750900028 PM 17159117 ER PT J AU Timmons, M Tsokos, M Abu Asab, M Seminara, SB Zirzow, GC Kaneski, CR Heiss, JD van der Knaap, MS Vanier, MT Schiffmann, R Wong, K AF Timmons, M. Tsokos, M. Abu Asab, M. Seminara, S. B. Zirzow, G. C. Kaneski, C. R. Heiss, J. D. van der Knaap, M. S. Vanier, M. T. Schiffmann, R. Wong, K. TI Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia SO NEUROLOGY LA English DT Article ID SCHWANN-CELLS; ATAXIA AB We identified four unrelated patients (three female, one male) aged 20 to 30 years with hypomyelination, pituitary hypogonadotropic hypogonadism, and hypodontia. Electron microscopy and myelin protein immunohistochemistry of sural nerves showed granular debris-lined clefts, expanded abaxonal space, outpocketing with vacuolar disruption, and loss of normal myelin periodicity. Reduced galactocerebroside, sphingomyelin, and GM1-N-acetylglucosamine and increased esterified cholesterol were found. This is a clinically homogeneous progressive hypomyelinating disorder. The term 4H syndrome is suggested. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vrije Univ Amsterdam, Dept Child Neurol, Med Ctr, NL-1081 HV Amsterdam, Netherlands. Lyon Sud Univ Hosp, Lyon Sud Med Sch, Pierre Benite, France. Lyon Sud Univ Hosp, Fdn Gillet Merieux, Pierre Benite, France. Wilford Hall USAF Med Ctr, Div Neuropathol, San Antonio, TX 78236 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rs4e@nih.gov OI Kaneski, Christine/0000-0003-1453-2502 FU Intramural NIH HHS [Z01 NS002984-09]; NICHD NIH HHS [R01 HD043341]; NINDS NIH HHS [Z01 NS002984] NR 10 TC 45 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 12 PY 2006 VL 67 IS 11 BP 2066 EP 2069 DI 10.1212/01.wnl.0000247666.28904.35 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 115RG UT WOS:000242750900035 PM 17159124 ER PT J AU Harris, A Cardone, G Winkler, DC Heymann, JB Brecher, M White, JM Steven, AC AF Harris, Audray Cardone, Giovanni Winkler, Dennis C. Heymann, J. Bernard Brecher, Matthew White, Judith M. Steven, Alasclair C. TI Influenza virus pleiomorphy characterized by cryoelectron tomography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE envelope glycoproteins; matrix protein; ribonucleoprotein particles; virus assembly; virus structure ID ELECTRON-MICROSCOPY; 3-DIMENSIONAL STRUCTURE; PARTICLES; PROTEIN; RIBONUCLEOPROTEIN; NEURAMINIDASE; LOCALIZATION; POLYMERASE; RESOLUTION; COMPLEX AB Influenza virus remains a global health threat, with millions of infections annually and the impending threat that a strain of avian influenza may develop into a human pandemic. Despite its importance as a pathogen, little is known about the virus structure, in part because of its intrinsic structural variability (pleiomorphy): the primary distinction is between spherical and elongated particles, but both vary in size. Pleiomorphy has thwarted structural analysis by image reconstruction of electron micrographs based on averaging many identical particles. In this study, we used cryoelectron tomography to visualize the 3D structures of 110 individual virions of the X-31 (H3N2) strain of influenza A. The tomograms distinguish two kinds of glycoprotein spikes [hemagglutinin (HA) and neuraminidase (NA)] in the viral envelope, resolve the matrix protein layer lining the envelope, and depict internal configurations of ribonucleoprotein (RNP) complexes. They also reveal the stems that link the glycoprotein ectodomains to the membrane and interactions among the glycoproteins, the matrix, and the RNPs that presumably control the budding of nascent virions from host cells. Five classes of virions, four spherical and one elongated, are distinguished by features of their matrix layer and RNP organization. Some virions have substantial gaps in their matrix layer ("molecular fontanels"), and others appear to lack a matrix layer entirely, suggesting the existence of an alternative budding pathway in which matrix protein is minimally involved. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 FU NIAID NIH HHS [5T32 AI 07047, R01 AI 22470, R01 AI022470, T32 AI007047, T32 AI055432] NR 35 TC 197 Z9 201 U1 5 U2 24 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 12 PY 2006 VL 103 IS 50 BP 19123 EP 19127 DI 10.1073/pnas.0607614103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117PC UT WOS:000242884200045 PM 17146053 ER PT J AU Ghil, S Choi, JM Kim, SS Lee, YD Liao, Y Birnbaumer, L Suh-Kim, H AF Ghil, Sungho Choi, Jung-Mi Kim, Sung-Soo Lee, Young-Don Liao, Yanhong Birnbaumer, Lutz Suh-Kim, Haeyoung TI Compartmentalization of protein kinase A signaling by the heterotrimeric G protein G(o) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-catenin; cAMP; Rap1; somatostatin; cAMP response element binding protein ID CYCLIC-AMP; NEURITE OUTGROWTH; ALPHA-SUBUNIT; HIGH-AFFINITY; BETA-CATENIN; RECEPTOR; ACTIVATION; CELLS; PHOSPHORYLATION; TRANSFORMATION AB G(o), a member of the G(o/i) family, is the most abundant heterotrimeric G protein in brain. Most functions of G(o) are mediated by the G(beta gamma) dimer; effector(s) for its beta-subunit have not been clearly defined. Here we report that G(o alpha) interacts directly with cAMP-dependent protein kinase (PKA) through its GTPase domain. This interaction did not inhibit the kinase function of PKA but interfered with nuclear translocation of PKA while sparing its cytosolic function. This regulatory mechanism by which G(o) bifurcates PKA signaling may provide insights into how G(o) regulates complex processes such as neuritogenesis, synaptic plasticity, and cell transformation. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Kyonggi Univ, Dept Biol, Suwon 442760, South Korea. Ajou Univ, Sch Med, Dept Anat, Suwon 443749, South Korea. Ajou Univ, Sch Med, Dept Mol Sci Technol, Suwon 443749, South Korea. Ajou Univ, Sch Med, Grad Program Neurosci, Suwon 443749, South Korea. Ajou Univ, Sch Med, Ctr Cell Death Regulating Biodrug, Suwon 443749, South Korea. Ajou Univ, Sch Med, Brain Dis Res Ctr, Suwon 443749, South Korea. RP Suh-Kim, H (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov; hysuh@ajou.ac.kr FU Intramural NIH HHS NR 28 TC 15 Z9 15 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 12 PY 2006 VL 103 IS 50 BP 19158 EP 19163 DI 10.1073/pnas.0609392103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117PC UT WOS:000242884200051 PM 17148597 ER PT J AU Foster, CB Aswath, K Chanock, SJ Mckay, HF Peters, U AF Foster, Charles B. Aswath, Kshama Chanock, Stephen J. Mckay, Heather F. Peters, Ulrike TI Polymorphism analysis of six selenoprotein genes: support for a selective sweep at the glutathione peroxidase I locus (3p2I) in Asian populations SO BMC GENETICS LA English DT Article ID CANCER PREVENTION TRIAL; BREAST-CANCER; PROSTATE-CANCER; HUMAN GENOME; SELENIUM SUPPLEMENTATION; PRO198LEU POLYMORPHISM; 3'-UNTRANSLATED REGION; ALPHA-DYSTROGLYCAN; STATISTICAL-METHOD; DNA POLYMORPHISM AB Background: There are at least 25 human selenoproteins, each characterized by the incorporation of selenium into the primary sequence as the amino acid selenocysteine. Since many selenoproteins have antioxidant properties, it is plausible that inter-individual differences in selenoprotein expression or activity could influence risk for a range of complex diseases, such as cancer, infectious diseases as well as deleterious responses to oxidative stressors like cigarette smoke. To capture the common genetic variants for 6 important selenoprotein genes (GPX1, GPX2, GPX3, GPX4, TXNRD1, and SEPP1) known to contribute to antioxidant host defenses, a re-sequence analysis was conducted across these genes with particular interest directed at the coding regions, intron-exon borders and flanking untranslated regions (UTR) for each gene in an 102 individual population representative of 4 major ethnic groups found within the United States. Results: For 5 of the genes there was no strong evidence for selection according to the expectations of the neutral equilibrium model of evolution; however, at the GPX1 locus (3p21) there was evidence for positive selection. Strong confirmatory evidence for recent positive selection at the genomic region 3p21 in Asian populations is provided by data from the International HapMap project. Conclusion: The SNPs and fine haplotype maps described in this report will be valuable resources for future functional studies, for population specific genetic studies designed to comprehensively explore the role of selenoprotein genetic variants in the etiology of various human diseases, and to define the forces responsible for a recent selective sweep in the vicinity of the GPX1 locus. C1 Childrens Hosp, Cleveland Clin, Div Pediat, Sect Pediat Infect Dis, Cleveland, OH 44195 USA. Johns Hopkins Univ, Div Pediat Infect Dis, Dept Pediat, Baltimore, MD 21287 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. RP Foster, CB (reprint author), Childrens Hosp, Cleveland Clin, Div Pediat, Sect Pediat Infect Dis, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM fosterc3@ccf.org; work7life@yahoo.com; chanocks@mail.nih.gov; heather.mckay@gmail.com; upeters@fhcrc.org FU Intramural NIH HHS; NCI NIH HHS [5K22CA096683, K22 CA096683] NR 70 TC 46 Z9 48 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 11 PY 2006 VL 7 AR 56 DI 10.1186/1471-2156-7-56 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 126KF UT WOS:000243511100001 PM 17156480 ER PT J AU Gobbini, MI Haxby, JV AF Gobbini, M. Ida Haxby, James V. TI Neural response to the visual familiarity of faces SO BRAIN RESEARCH BULLETIN LA English DT Article DE fMRI; face perception; familiarity; adaptation; precuneus ID MEMORY; RECOGNITION; PERCEPTION; SYSTEMS; BRAIN; PET; REPRESENTATION; ACTIVATION; MECHANISMS; EMOTION AB Recognizing personally familiar faces is the result of a spatially distributed process that involves visual perceptual areas and areas that play a role in other cognitive and social functions, such as the anterior paracingulate cortex, the precuneus and the amygdala [M.I. Gobbini, E. Leibenluft, N. Santiago, J.V Haxby, Social and emotional attachment in the neural representation of faces, Neuroimage 22 (2004) 1628-1635; M.I. Gobbini, JX Haxby, Neural systems for recognition of familiar faces, Neuropsychologia, in press; E. Leibenluft, M.I. Gobbini, T. Harrison, J.V. Haxby, Mothers' neural activation in response to pictures of their, and other, children, Biol. Psychiatry 56 (2004) 225-232]. In order to isolate the role of visual familiarity in face recognition, we used fMRI to measure the response to faces characterized by experimentally induced visual familiarity that carried no biographical information or emotional content. The fMRI results showed a stronger response in the precuneus to the visually familiar faces consistent with studies that implicate this region in the retrieval of information from long-term memory and imagery. Moreover, this finding supports the hypothesis of a key role for the precuneus in the acquisition of familiarity with faces [H. Kosaka, M. Omori, T. lidaka, T. Murata, T. Shimoyama, T. Okada, N. Sadato, Y. Yonckura, Y. Wada, Neural substrates participating in acquisition of facial familiarity: an fMRI study, Neuroimage 20 (2003) 1734-1742]. By contrast, the visually familiar faces evoked a weaker response in the fusiform gyrus, which may reflect the development of a sparser encoding or a reduced attentional load when processing stimuli that are familiar. The visually familiar faces also evoked a weaker response in the amygdala, supporting the proposed role of this structure in mediating the guarded attitude when meeting someone new. (c) 2006 Published by Elsevier Inc. C1 Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. Univ Bologna, Dept Psychol, I-40127 Bologna, Italy. Univ Bologna, Dept Psychol, I-40127 Bologna, Italy. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Gobbini, MI (reprint author), Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. EM mgobbini@princeton.edu NR 36 TC 83 Z9 84 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD DEC 11 PY 2006 VL 71 IS 1-3 BP 76 EP 82 DI 10.1016/j.brainresbull.2006.08.003 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 115LJ UT WOS:000242735500012 PM 17113931 ER PT J AU Reyes-Reyes, ME George, MD Roberts, JD Akiyama, SK AF Reyes-Reyes, Merit E. George, Margaret D. Roberts, John D. Akiyama, Steven K. TI P-selectin activates integrin-mediated colon carcinoma cell adhesion to fibronectin SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE integrins; P-selectin; cell adhesion ID MULTIPLE SIGNALING PATHWAYS; PROTEIN-KINASE-C; GROWTH-FACTOR; TUMOR-CELLS; COLORECTAL-CANCER; BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; ALPHA(5)BETA(1) INTEGRIN; EXTRACELLULAR-MATRIX AB During hematogenous cancer metastasis, tumor cells separate from a primary mass, enter the bloodstream, disperse throughout the body, migrate across vessel walls, and generate distant colonies. The later steps of metastasis superficially resemble leukocyte extravasation, a process initiated by selectin-mediated cell tethering to the blood vessel wall followed by integrin-mediated arrest and trans endothelial migration. Some cancer cells express P-selectin ligands and attach to immobilized P-selectin, suggesting that these cells can arrest in blood vessels using sequential selectin- and integrin-mediated adhesion, as do leukocytes. We hypothesize that selectin binding may regulate subsequent integrin-mediated steps in metastasis. Using a model system of cultured Colo 320 human colon adenocarcinoma cells incubated with soluble P-selectin-IgG chimeric protein, we have found that P-selectin can stimulate activation of the alpha(5)beta(1) integrin resulting in a specific increase of adhesion and spreading of these cells on fibronectin substrates. P-selectin binding also induced activation of p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase (PI3-K). PI3-K inhibitors blocked P-selectin-mediated integrin activation, cell attachment, and cell spreading. Inhibition of p38 MAPK activation blocked cell spreading, but not cell attachment. P-selectin binding also resulted in formation of a signaling complex containing PI3-K and p38 MAPK. These results suggest that P-selectin binding to tumor cells can activate alpha(5)beta(1) integrin via PI3-K and p38 MAPK signaling pathways leading to increased cell adhesion. We propose that P-selectin ligands are important tumor cell signaling molecules that modulate integrin-mediated cell adhesion in the metastatic process. Published by Elsevier Inc. C1 NIEHS, Lab Mol Carcinogenesis, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Akiyama, SK (reprint author), NIEHS, Lab Mol Carcinogenesis, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM akiyama@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES023025-08] NR 111 TC 16 Z9 20 U1 0 U2 1 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 DEC 10 PY 2006 VL 312 IS 20 BP 4056 EP 4069 DI 10.1016/j.yexcr.2006.09.008 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 116XW UT WOS:000242838100009 PM 17056038 ER PT J AU Yang, JC Childs, R AF Yang, James C. Childs, Richard TI Immunotherapy for renal cell cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID INTENSITY CONDITIONING REGIMEN; HIGH-DOSE INTERLEUKIN-2; REDUCED-INTENSITY; METASTATIC MELANOMA; DENDRITIC CELLS; SOLID TUMORS; PREPARATIVE REGIMEN; CLINICAL-RESPONSES; FOLLOW-UP; CARCINOMA AB For eligible patients, the value of immunotherapy for metastatic clear-cell renal cancer is its curative potential, as demonstrated by long-term follow-up after interleukin-2. Advances in cellular therapies, manipulation of activating and inhibitory receptors on T cells and modification of allotransplantation regimens have all produced new tumor regressions in patients who did not respond to conventional interleukin-2 regimens. It is clear that renal cancer remains one of the most immunoresponsive of human malignancies and that advances in immune modulation are again translating into clinical responses for patients with this disease. As the array of biologic therapies for renal cancer expands with the approval of tyrosine kinase inhibitors, immunotherapy, the only modality that can cure widespread renal cancer, must not be overlooked. C1 NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Ctr Canc Res, Room CCR-3-5952,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jamesyang@mail.nih.gov NR 49 TC 69 Z9 69 U1 0 U2 4 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 DEC 10 PY 2006 VL 24 IS 35 BP 5576 EP 5583 DI 10.1200/JCO.2006.08.3774 PG 8 WC Oncology SC Oncology GA 118AL UT WOS:000242914300012 PM 17158543 ER PT J AU Goldspiel, B Wiernikowski, J AF Goldspiel, Barry Wiernikowski, John TI Comment on ASCO-ESMO consensus statement on quality cancer care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. McMaster Childrens Hosp, Hamilton, ON, Canada. RP Goldspiel, B (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 DEC 10 PY 2006 VL 24 IS 35 BP 5613 EP 5614 DI 10.1200/JCO.2006.08.6181 PG 2 WC Oncology SC Oncology GA 118AL UT WOS:000242914300022 PM 17158550 ER PT J AU Woodard, GE Li, XH Rosado, JA AF Woodard, Geofirey E. Li, Xiaohong Rosado, Juan A. TI Renal atrial natriuretic peptide receptors binding properties and function are resistant to DOCA-salt-induced hypertension in rats SO REGULATORY PEPTIDES LA English DT Article DE NPR-A; NPR-C; renal glomeruli; hypertension; DOCA; cAMP ID ANP KNOCKOUT MICE; SENSITIVE HYPERTENSION; COMPUTERIZED APPROACH; KIDNEY; MECHANISMS; EXPRESSION; GLOMERULI; LACKING AB Atrial natriuretic peptide receptor types A (NPR-A) and C (NPR-C) binding properties and functional characteristics in renal glomeruli have been investigated in deoxycorticosterone acetate (DOCA)-treated hypertensive Wistar-Kyoto (WKY) rats and their respective controls. We found that DOCA administration had no significant effect on the maximum binding capacity or the affinity of renal NPR-A and NPR-C. NPR-C is involved in the regulation of cAMP production. Our results indicate that the cAMP production by NPR-C is not altered in DOCA-induced hypertension, since ANP(1-28), CNP1-22 and C-ANP, which specifically bind to NPR-C, show a similar inhibitory effect on cAMP production stimulated by the physiological agonist histamine in glomeruli from DOCA-treated rats and controls. Finally, we have found that DOCA-induced hypertension does not modify NPR-A or NPR-C expression in rat glomerular membranes. These findings indicate that NPR-A and NPR-C binding properties and NPR-C-mediated inhibition of cAMP generation remain unaltered in DOCA-treated rats. (c) 2006 Elsevier B.V All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIDDKD, NIH, Bldg 10,Rm 8C-208,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM GeoffreyW@intra.niddk.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 39 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 EI 1873-1686 J9 REGUL PEPTIDES JI Regul. Pept. PD DEC 10 PY 2006 VL 137 IS 3 BP 114 EP 120 DI 10.1016/j.regpep.2006.06.003 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 123QN UT WOS:000243310500003 ER PT J AU Das, A Wiederhold, L Leppard, JB Kedar, P Prasad, R Wang, HX Boldogh, I Karimi-Busheri, F Weinfeld, M Tomkinson, AE Wilson, SH Mitra, S Hazra, TK AF Das, Aditi Wiederhold, Lee Leppard, John B. Kedar, Padmini Prasad, Rajendra Wang, Huxian Boldogh, Istvan Karimi-Busheri, Feridoun Weinfeld, Michael Tomkinson, Alan E. Wilson, Samuel H. Mitra, Sankar Hazra, Tapas K. TI NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells SO DNA REPAIR LA English DT Article DE base excision repair; DNA glycosylase; oxidative DNA damage; NEIL2; PNK-dependent repair ID STRAND BREAK REPAIR; COLI ENDONUCLEASE-VIII; EXCISION-REPAIR; POLYNUCLEOTIDE KINASE; MAMMALIAN-CELLS; POLYMERASE-BETA; GLYCOSYLASES NEIL1; OXIDATIVE DAMAGE; IN-VITRO; IDENTIFICATION AB DNA glycosylases/AP lyases initiate repair of oxidized bases in the genomes of all organisms by excising these lesions and then cleaving the DNA strand at the resulting abasic (AP) sites and generate 3' phospho alpha, beta-unsaturated aldehyde (3' PUA) or 3' phosphate (3' P) terminus. In Escherichia coli, the AP-endonucleases (APEs) hydrolyze both 3' blocking groups (T PUA and 3' P) to generate the T-OH termini needed for repair synthesis. In mammalian cells, the previously characterized DNA glycosylases, NTH1 and OGG1, produce 3' PUA, which is removed by the only AP-endonuclease, APE1. However, APE1 is barely active in removing 3' phosphate generated by the recently discovered mammalian DNA glycosylases NEIL1 and NEIL2. We showed earlier that the 3' phosphate generated by NEIL1 is efficiently removed by polynucleotide kinase (PNK) and not APE1. Here we show that the NEIL2-initiated repair of 5-hydroxyuracil (5-OHU) similarly requires PNK. We have also observed stable interaction between NEIL2 and other BER proteins DNA polymerase beta (Pol beta), DNA ligase III alpha (Lig III alpha) and XRCC1. In spite of their limited sequence homology, NEIL1 and NEIL2 interact with the same domains of Pol p and Lig III alpha. Surprisingly, while the catalytically dispensable C-terminal region of NEIL1 is the common interacting domain, the essential N-terminal segment of NEIL2 is involved in analogous interaction. The BER proteins including NEIL2, PNK, Pol P, Lig III alpha and XRCC1 (but not APE1) could be isolated as a complex from human cells, competent for repair of 5-OHU in plasmid DNA. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Cross Canc Inst, Dept Expt Oncol, Edmonton, AB T6G 1Z2, Canada. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Dept Radiat Oncol, Baltimore, MD 21201 USA. RP Hazra, TK (reprint author), Univ Texas, Med Branch, Sealy Ctr Mol Sci, Dept Biochem & Mol Biol, 6-136 Med Res Bldg,Route 1079, Galveston, TX 77555 USA. EM tkhazra@utmb.edu FU Intramural NIH HHS [Z01 ES050159-11]; NCI NIH HHS [CA102271, R01 CA081063, P01 CA092584, R01 CA084461, CA81063, CA92584, R01 CA102271]; NIA NIH HHS [P01 AG021830]; NIEHS NIH HHS [ES012512, R01 ES012512, P30 ES006676, P01 ES06676] NR 41 TC 69 Z9 71 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 DEC 9 PY 2006 VL 5 IS 12 BP 1439 EP 1448 DI 10.1016/j.dnarep.2006.07.003 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 114KT UT WOS:000242665800004 PM 16982218 ER PT J AU Chen, CC Motegi, A Hasegawa, Y Myung, K Kolodner, R D'Andrea, A AF Chen, Clark C. Motegi, Akira Hasegawa, Yuko Myung, Kyungjae Kolodner, Richard D'Andrea, Alan TI Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164SUMOylation and ubiquitination SO DNA REPAIR LA English DT Article DE ionizing radiation; translesion synthesis; SUMOylation; ubiquitination; mutagenesis; PCNA; DNA repair; homologous recombination; non-homologous end joining; nuclotide excision repair; REV3; REV7; REV1; RAD30; polymerase zeta; polymerase eta; deoxycytidyl transferase ID CELL NUCLEAR ANTIGEN; GAMMA-RAY MUTAGENESIS; STRAND-BREAK REPAIR; NUCLEOTIDE EXCISION-REPAIR; ARRESTED YEAST-CELLS; DNA-POLYMERASE-ZETA; FRAMESHIFT MUTATIONS; CHROMOSOMAL REARRANGEMENTS; SEQUENCE-ANALYSIS; MISMATCH REPAIR AB Ionizing radiation-induced mutagenesis (IR-IM) underlies a basis for radiation associated carcinogenesis as well as resistance to radiation therapy. This process was examined in Saccharomyces cerevisiae using an array of isogenic DNA repair deficient mutants. Mutations inactivating homologous recombination (rad51, 52, 54) or nucleotide excision repair (rad1, radio, rad4) caused elevated IR-IM whereas inactivation of TransLesion Synthesis (TLS: rad6) caused severely defective IR-IM. Of the mutations inactivating TLS polymerases, rev3 and rev1 caused equally severe defects in IR-IM whereas rad30 did not significantly affect the process. The effects of the rev3, rev1, and rad6 mutations on IR-IM were epistatic, suggesting the requirement of both polymerase zeta and Rev1p in IR-IM related TLS. Although PCNA K164 SUMOylation/ubiquitination is a proposed prerequisite for TLS, the IR-IM defect of a rev3 or a rad6 mutant was worse than and epistatic to the pol30K164R mutant, a mutant in which the PCNA had been mutated to abolish such modifications. These results suggested that IR-IM related TLS occurs in the absence of PCNA K164 modification. Further analysis of a mutant simultaneously defective in SUMOylation and mono-ubiquitination (rad18 siz1) revealed that these modifications redundantly affected TLS as well as NHEJ. A genetic model based on these observations is proposed. (c) 2006 Elsevier B.V. All rights reserved. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP D'Andrea, A (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,Mayer 642, Boston, MA 02114 USA. EM alan-dandrea@dfci.harvard.edu RI Chen, Clark/C-8714-2013 OI Chen, Clark/0000-0001-6258-9277 FU Intramural NIH HHS; NHLBI NIH HHS [R01HL52725]; NIDDK NIH HHS [R01DK43889]; NIGMS NIH HHS [R01GM26017] NR 72 TC 16 Z9 16 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 DEC 9 PY 2006 VL 5 IS 12 BP 1475 EP 1488 DI 10.1016/j.dnarep.2006.07.007 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 114KT UT WOS:000242665800007 PM 16990054 ER PT J AU Miao, ZH Agama, K Sordet, O Povirk, L Kohn, KW Pommier, Y AF Miao, Ze-Hong Agama, Keli Sordet, Olivier Povirk, Lawrence Kohn, Kurt W. Pommier, Yves TI Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes SO DNA REPAIR LA English DT Article DE topoisomerase I cleavage complexes; tyrosyl-DNA phosphodiesterase; SCAN1; DNA repair ID DNA PHOSPHODIESTERASE TDP1; DOUBLE-STRAND BREAKS; SPINOCEREBELLAR ATAXIA; MAMMALIAN-CELLS; CAMPTOTHECIN; DAMAGE; INHIBITOR; MECHANISM; ENZYME; YEAST AB Hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1) is caused by an inactivating mutation (H493R) in the enzyme tyrosyl-DNA phosphodiesterase (Tdp1), which removes blocked T-termini at DNA strand breaks. Using SCAN1 cells treated with the specific topoisomerase 1 (Top1) inhibitor camptothecin, we find enhanced levels of Top1 cleavage complexes (Top1cc) and defective reversal of Top1cc in SCAN1 Tdp1-deficient cells, indicating a direct involvement of Tdp1 in the repair of Top1cc. Because the defective removal of Top1cc and the hypersensitivity of SCAN1 cells to camptothecin are not affected by aphidicolin, we propose that Tdp1 is involved in the repair of Top1cc associated with transcription damage in SCAN1 cells. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 FU NIA NIH HHS [AG023783] NR 30 TC 57 Z9 60 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 9 PY 2006 VL 5 IS 12 BP 1489 EP 1494 DI 10.1016/j.dnarep.2006.07.004 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 114KT UT WOS:000242665800008 PM 16935573 ER PT J AU Schubot, FD Tropea, JE Waugh, DS AF Schubot, Florian D. Tropea, Joseph E. Waugh, David S. TI Structure of the POZ domain of human LRF, a master regulator of oncogenesis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE POK; POZ; BTB; Kruppel; LRF; FBI-1; Pokemon; PLZF; BCL6; SMRT ID ACUTE PROMYELOCYTIC LEUKEMIA; BTB DOMAIN; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; BTB/POZ DOMAIN; RAR-ALPHA; PLZF; PROTEIN; BCL-6; PATHOGENESIS AB The proto-oncogenic properties of the POK family of transcriptional repressors BCL6, PLZF, and LRF have been well established. These proteins utilize their amino-terminal POZ domains for multimerization and the recruitment of co-repressors. Because LRF represses the production of the tumor suppressor p19(Arf) (ARF), it is regarded as an attractive therapeutic target for the treatment of many types of cancer. The crystal structure of the LRF POZ domain reveals a high degree of structural conservation with the corresponding domains of BCL6 and PLZF. However, striking differences between the electrostatic properties of the BCL6 and LRF POZ domains suggest that if, like BCL6, LRF interacts with the co-repressor SMRT, it almost certainly uses a different mechanism to do so. These differences may also explain why LRF interacts with BCL6 but not with PLZF. Finally, the conservation of crystal packing contacts suggests the probable location of the interface that mediates LRF/BCL6 complex formation. Published by Elsevier Inc. C1 Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), Natl Canc Inst, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov FU Intramural NIH HHS NR 33 TC 25 Z9 30 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 8 PY 2006 VL 351 IS 1 BP 1 EP 6 DI 10.1016/j.bbrc.2006.09.167 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 103VG UT WOS:000241914400001 PM 17052694 ER PT J AU Dewey, CN Rogozin, IB Koonin, EV AF Dewey, Colin N. Rogozin, Igor B. Koonin, Eugene V. TI Compensatory relationship between splice sites and exonic splicing signals depending on the length of vertebrate introns SO BMC GENOMICS LA English DT Article ID PRE-MESSENGER-RNA; HUMAN GENES; ENHANCERS; SEQUENCES; IDENTIFICATION; SELECTION; ELEMENTS; RECOGNITION; PROTEINS; INFORMATION AB Background: The signals that determine the specificity and efficiency of splicing are multiple and complex, and are not fully understood. Among other factors, the relative contributions of different mechanisms appear to depend on intron size inasmuch as long introns might hinder the activity of the spliceosome through interference with the proper positioning of the intron-exon junctions. Indeed, it has been shown that the information content of splice sites positively correlates with intron length in the nematode, Drosophila, and fungi. We explored the connections between the length of vertebrate introns, the strength of splice sites, exonic splicing signals, and evolution of flanking exons. Results: A compensatory relationship is shown to exist between different types of signals, namely, the splice sites and the exonic splicing enhancers ( ESEs). In the range of relatively short introns ( approximately, < 1.5 kilobases in length), the enhancement of the splicing signals for longer introns was manifest in the increased concentration of ESEs. In contrast, for longer introns, this effect was not detectable, and instead, an increase in the strength of the donor and acceptor splice sites was observed. Conceivably, accumulation of A-rich ESE motifs beyond a certain limit is incompatible with functional constraints operating at the level of protein sequence evolution, which leads to compensation in the form of evolution of the splice sites themselves toward greater strength. In addition, however, a correlation between sequence conservation in the exon ends and intron length, particularly, in synonymous positions, was observed throughout the entire length range of introns. Thus, splicing signals other than the currently defined ESEs, i.e., potential new classes of ESEs, might exist in exon sequences, particularly, those that flank long introns. Conclusion: Several weak but statistically significant correlations were observed between vertebrate intron length, splice site strength, and potential exonic splicing signals. Taken together, these findings attest to a compensatory relationship between splice sites and exonic splicing signals, depending on intron length. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM cdewey@biostat.wisc.edu; rogozin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 42 TC 41 Z9 42 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 8 PY 2006 VL 7 AR 311 DI 10.1186/1471-2164-7-311 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 118YI UT WOS:000242979000001 PM 17156453 ER PT J AU Quasnichka, H Slater, SC Beeching, CA Boehm, M Sala-Newby, GB George, SJ AF Quasnichka, Helen Slater, Sadie C. Beeching, Cressida A. Boehm, Manfred Sala-Newby, Graciela B. George, Sarah J. TI Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression SO CIRCULATION RESEARCH LA English DT Article DE smooth muscle; proliferation; cell cycle ID N-CADHERIN; GROWTH-FACTOR; IN-VITRO; TISSUE INHIBITOR; ARTERIAL INJURY; MIGRATION; PATHWAY; GENE; ACTIVATION; MOLECULES AB We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of beta-catenin. In this study we demonstrate directly that growth factors stimulate beta-catenin/T-cell factor (TCF) signaling in primary VSMCs. To determine whether beta-catenin/TCF signaling regulates VSMC proliferation via modulation of the beta-catenin/TCF responsive cell cycle genes, cyclin D1 and p21, we inhibited beta-catenin/TCF signaling by adenoviral-mediated over-expression of N-Cadherin, ICAT (an endogenous inhibitor of beta-catenin/TCF signaling), or a dominant negative (dn) mutant of TCF-4. N-cadherin, ICAT or dnTCF-4 over-expression significantly reduced proliferation of isolated human VSMCs by approximately 55%, 80%, and 45% respectively. Similar effects were observed in human saphenous vein medial segments where proliferation was reduced by approximately 55%. Transfection of dnTCF-4 in the ISS10 human VSMC line significantly lowered TCF and cyclin D1 reporter activity but significantly elevated p21 reporter activity, indicating regulation of these genes by beta-catenin/TCF signaling. In support of this, over-expression of N-cadherin, ICAT or dnTCF-4 in isolated human VSMCs significantly lowered levels of cyclin D1 mRNA and protein levels. In contrast, over-expression of N-Cadherin, ICAT or dnTCF4 significantly elevated p21 mRNA and protein levels. In summary, we have demonstrated that increasing N-cadherin and inhibiting beta-catenin/TCF signaling reduces VSMC proliferation, decreases the expression of cyclin D1 and increases levels of the cell cycle inhibitor, p21. We therefore suggest that the N-cadherin and beta-catenin/TCF signaling pathway is a key modulator of VSMC proliferation via regulation of these 2 beta-catenin/TCF responsive genes. C1 Bristol Royal Infirm & Gen Hosp, Inst Heart, Bristol BS2 8HW, Avon, England. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP George, SJ (reprint author), Bristol Royal Infirm & Gen Hosp, Inst Heart, Upper Maudlin St, Bristol BS2 8HW, Avon, England. EM s.j.george@bris.ac.uk NR 32 TC 83 Z9 83 U1 0 U2 2 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 DEC 8 PY 2006 VL 99 IS 12 BP 1329 EP 1337 DI 10.1161/01.RES.0000253533.65446.33 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 124XX UT WOS:000243407200008 PM 17122440 ER PT J AU Mukhopadhyay, I Sausville, EA Doroshow, JH Roy, KK AF Mukhopadhyay, Indranil Sausville, Edward A. Doroshow, James H. Roy, Krishnendu K. TI Molecular mechanism of adaphostin-mediated G(1) arrest in prostate cancer (PC-3) cells - Signaling events mediated by hepatocyte growth factor receptor, c-Met, and p38 MAPK pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LEUKEMIA-CELLS; BRCA1-BARD1 UBIQUITIN LIGASE; ACTIVATED PROTEIN-KINASE; TYROSINE KINASE; IN-VITRO; CENTROSOME DUPLICATION; INDUCED APOPTOSIS; MAMMALIAN-CELLS; CARCINOMA-CELLS; TUMOR-CELLS AB Adaphostin (NSC680410), a small molecule congener of tyrphostin AG957, has been demonstrated previously to have significant anti-proliferative effects in several leukemia models. However, this effect of adaphostin in adherent cells/solid tumor models has not been examined. In this study, we investigated the anti-proliferative effects of adaphostin in the human prostate cancer cell line PC-3. Specifically, we explored the potential molecular mechanism(s) by which adaphostin elicits its anti-proliferative effect(s). We demonstrate that adaphostin inhibits the proliferation of PC-3 cells by inducing a G(1) phase cell cycle arrest. This adaphostin-induced G(1) arrest was associated with an increase in the expression of p21 and p27 and a decrease in the expression of G(1)-specific cyclins (cyclin A, D1, and D3) and cyclin-dependent kinases 4 and 6. Consequently, a dramatic decrease in the phosphorylation of retinoblastoma protein was also observed. Additionally, we found that adaphostin treatment induced a decrease in the phosphorylation of nucleophosmin, a major nuclear phosphoprotein, and that this decreased phosphorylation was a result of the p21- and p27-mediated inactivation of cyclin E-cyclin-dependent kinase 2 complex kinase activity. Furthermore, we have determined that the adaphostin-mediated cell cycle arrest of PC-3 cells is dependent upon activation of the p38 MAPK. We also demonstrate that the hepatocyte growth factor receptor-c-Met is involved in the adaphostin-mediated signaling events that regulate p38 MAPK. Taken together, these results identify for the first time a signaling cascade of adaphostin-mediated G(1) phase-specific cell cycle arrest in PC-3 cells. These findings suggest that the tyrphostin member has a broader spectrum of activity than originally predicted. C1 NCI, Lab Clin Tials Unit, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Roy, KK (reprint author), NCI, Lab Clin Tials Unit, Div Canc Treatment & Diag, NIH, 37 Convent Dr,Bldg 37,Rm 1052, Bethesda, MD 20892 USA. EM kr91w@nih.gov NR 66 TC 19 Z9 21 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 DEC 8 PY 2006 VL 281 IS 49 BP 37330 EP 37344 DI 10.1074/jbc.M605569200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100010 PM 16956884 ER PT J AU Chan, SL Liu, D Kyriazis, GA Bagsiyao, P Ouyang, X Mattson, MP AF Chan, Sic. L. Liu, Dong Kyriazis, George A. Bagsiyao, Pamela Ouyang, Xin Mattson, Mark P. TI Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; INTRACELLULAR CA2+ STORES; PREVENTS NEURONAL DEATH; OXIDATIVE STRESS; T-LYMPHOCYTES; SH-SY5Y CELLS; ION-CHANNEL; EXPRESSION; GENE; ACTIVATION AB An increase in the cytoplasmic-free Ca2+ concentration mediates cellular responses to environmental signals that influence a range of processes, including gene expression, motility, secretion of hormones and neurotransmitters, changes in energy metabolism, and apoptosis. Mitochondria play important roles in cellular Ca2+ homeostasis and signaling, but the roles of specific mitochondrial proteins in these processes are unknown. Uncoupling proteins (UCPs) are a family of proteins located in the inner mitochondrial membrane that can dissociate oxidative phosphorylation from respiration, thereby promoting heat production and decreasing oxyradical production. Here we show that UCP4, a neuronal UCP, influences store-operated Ca2+ entry, a process in which depletion of endoplasmic reticulum Ca2+ stores triggers Ca2+ influx through plasma membrane "store-operated" channels. PC12 neural cells expressing human UCP4 exhibit reduced Ca2+ entry in response to thapsigargin-induced endoplasmic reticulum Ca2+ store depletion. The elevations of cytoplasmic and intramitochondrial Ca2+ concentrations and mitochondrial oxidative stress induced by thapsigargin were attenuated in cells expressing UCP4. The stabilization of Ca2+ homeostasis and preservation of mitochondrial function by UCP4 was correlated with reduced mitochondrial reactive oxygen species generation, oxidative stress, and Gadd153 up-regulation and increased resistance of the cells to death. Reduced Ca2+-dependent cytosolic phospholipase A2 activation and oxidative metabolism of arachidonic acid also contributed to the stabilization of mitochondrial function in cells expressing human UCP4. These findings demonstrate that UCP4 can regulate cellular Ca2+ homeostasis, suggesting that UCPs may play roles in modulating Ca2+ signaling in physiological and pathological conditions. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32816 USA. NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Chan, SL (reprint author), Univ Cent Florida, Biomol Sci Ctr, 4000 Cent Florida Blvd, Orlando, FL 32816 USA. EM schan@mail.ucf.edu RI Mattson, Mark/F-6038-2012 NR 62 TC 63 Z9 68 U1 1 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 DEC 8 PY 2006 VL 281 IS 49 BP 37391 EP 37403 DI 10.1074/jbc.M605552200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100016 PM 17035241 ER PT J AU Rostovtseva, TK Kazemi, N Weinrich, M Bezrukov, SM AF Rostovtseva, Tatiana K. Kazemi, Namdar Weinrich, Michael Bezrukov, Sergey M. TI Voltage gating of VDAC is regulated by nonlamellar lipids of mitochondrial membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANION-SELECTIVE CHANNEL; CYTOCHROME-C RELEASE; OUTER-MEMBRANE; NEUROSPORA-CRASSA; PHOSPHATIDYLSERINE BILAYERS; MECHANOSENSITIVE CHANNELS; TRANSMEMBRANE CHANNEL; GRAMICIDIN CHANNELS; YEAST MITOCHONDRIA; LATERAL PRESSURE AB Evidence is accumulating that lipids play important roles in permeabilization of the mitochondria outer membrane (MOM) at the early stage of apoptosis. Lamellar phosphatidylcholine (PC) and nonlamellar phosphatidylethanolamine (PE) lipids are the major membrane components of the MOM. Cardiolipin (CL), the characteristic lipid from the mitochondrial inner membrane, is another nonlamellar lipid recently shown to play a role in MOM permeabilization. We investigate the effect of these three key lipids on the gating properties of the voltage-dependent anion channel (VDAC), the major channel in MOM. We find that PE induces voltage asymmetry in VDAC current-voltage characteristics by promoting channel closure at cis negative applied potentials. Significant asymmetry is also induced by CL. The observed differences in VDAC behavior in PC and PE membranes cannot be explained by differences in the insertion orientation of VDAC in these membranes. Rather, it is clear that the two nonlamellar lipids affect VDAC gating. Using gramicidin A channels as a tool to probe bilayer mechanics, we show that VDAC channels are much more sensitive to the presence of CL than could be expected from the experiments with gramicidin channels. We suggest that this is due to the preferential insertion of VDAC into CL-rich domains. We propose that the specific lipid composition of the mitochondria outer membrane and/or of contact sites might influence MOM permeability by regulating VDAC gating. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NICHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Rostovtseva, TK (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E-106, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov FU Intramural NIH HHS NR 92 TC 63 Z9 63 U1 1 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 DEC 8 PY 2006 VL 281 IS 49 BP 37496 EP 37506 DI 10.1074/jbc.M602548200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100026 PM 16990283 ER PT J AU Hoffmann, KM Tapia, JA Berna, MJ Thill, M Braunschweig, T Mantey, SA Moody, TW Jensen, RT AF Hoffmann, K. Martin Tapia, Jose A. Berna, Marc J. Thill, Michelle Braunschweig, Till Mantey, Samuel A. Moody, Terry W. Jensen, Robert T. TI Gastrointestinal hormones cause rapid c-Met receptor down-regulation by a novel mechanism involving clathrin-mediated endocytosis and a lysosome-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; PANCREATIC ACINAR-CELLS; PROTEIN-KINASE-C; STIMULATED TYROSINE PHOSPHORYLATION; CHOLECYSTOKININ RECEPTORS; FEEDBACK-REGULATION; ACTIN CYTOSKELETON; COUPLED RECEPTORS; MET/HGF RECEPTOR; AMYLASE RELEASE AB The activated c-Met receptor has potent effects on normal tissues and tumors. c-Met levels are regulated by hepatocyte growth factor (HGF); however, it is unknown if they can be regulated by gastrointestinal (GI) hormones. c-Met is found in many GI tissues/tumors that possess GI hormone receptors. We studied the effect of GI hormones on c-Met in rat pancreatic acini, which possess both receptors. CCK-8, carbachol, and bombesin, but not VIP/secretin, decreased c-Met. CCK-8 caused rapid and potent c-Met down-regulation and abolished HGF-induced c-Met and Gab1 tyrosine phosphorylation, while stimulating c-Met serine phosphorylation. The effect of cholecystokinin (CCK) was also seen in intact acini using immunofluorescence, in a biotinylated fraction representing membrane proteins, in single acinar cells, in Panc-1 tumor cells, and in vivo in rats injected with CCK. CCK-8 did not decrease cell viability or overall responsiveness. GF109203X, thapsigargin, or their combination partially reversed the effect of CCK-8. In contrast to HGF-induced c-Met down-regulation, the effect of CCK was decreased by a lysosome inhibitor (concanamycin) but not the proteasome inhibitor lactacystin. Inhibitors of clathrin-mediated endocytosis blocked the effect of CCK. HGF but not CCK-8 caused c-Met ubiquitination. These results show CCK and other GI hormones can cause rapid c-Met down-regulation, which occurs by a novel mechanism. These results could be important for c-Met regulation in normal as well as in neoplastic tissue in the GI tract. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Extremadura, Dept Fisiol, Badajoz 10071, Spain. NEI, Natl Inst Hlth, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 FU Intramural NIH HHS NR 86 TC 8 Z9 8 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 DEC 8 PY 2006 VL 281 IS 49 BP 37705 EP 37719 DI 10.1074/jbc.M602583200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100048 PM 17035232 ER PT J AU Conrads, TP Tocci, GM Hood, BL Zhang, CO Guo, L Koch, KR Michejda, CJ Veenstra, TD Keay, SK AF Conrads, Thomas P. Tocci, Gillian M. Hood, Brian L. Zhang, Chen-Ou Guo, Li Koch, Kristopher R. Michejda, Christopher J. Veenstra, Timothy D. Keay, Susan K. TI CKAP4/p63 is a receptor for the frizzled-8 protein-related antiproliferative factor from interstitial cystitis patients SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLADDER EPITHELIAL-CELLS; EPIDERMAL GROWTH-FACTOR; ENDOPLASMIC-RETICULUM; URINE; P63; EXPRESSION; SIALOGLYCOPEPTIDE; MICROTUBULES; MARKERS; SURFACE AB Antiproliferative factor (APF) is a low molecular weight sialoglycopeptide that is secreted by bladder cells from interstitial cystitis patients and is a potent inhibitor of both normal bladder epithelial and bladder carcinoma cell proliferation. We hypothesized that APF may produce its antiproliferative effects by binding to a transmembrane receptor. This study demonstrates that cytoskeleton-associated protein 4/p63(CKAP4/p63), a type II transmembrane receptor, binds with high affinity to APF. The antiproliferative activity of APF is effectively inhibited by preincubation with anti-CKAP4/p63-specific antibodies, as well as by short interfering RNA knockdown of CKAP4/p63. Immunofluorescent confocal microscopy showed co-localization of antiCKAP4/p63 and rhodamine-labeled synthetic APF binding in both cell membrane and perinuclear areas. APF also inhibits the proliferation of HeLa cervical carcinoma cells that are known to express CKAP4/p63. These data indicate that CKAP4/p63 is an important epithelial cell receptor for APF. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, NIH, Ft Detrick, MD 21702 USA. NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, NIH, Ft Detrick, MD 21702 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Vet Affairs Maryland Hlth Care Syst, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. RP Keay, SK (reprint author), Vet Affairs Med Ctr, Rm 3B-184,10 N Greene St, Baltimore, MD 21201 USA. EM skeay@medicine.umaryland.edu FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK52596] NR 29 TC 45 Z9 47 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 DEC 8 PY 2006 VL 281 IS 49 BP 37836 EP 37843 DI 10.1074/jbc.M604581200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100061 PM 17030514 ER PT J AU Govin, J Caron, C Escoffier, E Ferro, M Kuhn, L Rousseaux, S Eddy, EM Garin, J Khochbin, S AF Govin, Jerome Caron, Cecile Escoffier, Emmanuelle Ferro, Myriam Kuhn, Lauriane Rousseaux, Sophie Eddy, Edward M. Garin, Jerome Khochbin, Saadi TI Post-meiotic shifts in HSPA2/HSP70.2 chaperone activity during mouse spermatogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHROMATIN; HSP70-2; HISTONES; SPERMATOCYTES; CELLS; SPERMIOGENESIS; MEIOSIS; PROTEIN AB HSPA2 (formerly HSP70.2) is a testis-specific member of the HSP70 family known to play a critical role in the completion of meiosis during male germ cell differentiation. Although abundantly present in post-meiotic cells, its function during spermiogenesis remained obscure. Here, using a global proteomic approach to identify genome-organizing proteins in condensing spermatids, we discovered an unexpected role for HSPA2, which acquires new functions and becomes tightly associated with major spermatid DNA-packaging proteins, transition proteins 1 and 2. Hence, HSPA2 is identified here as the first transition protein chaperone, and these data shed a new light on the yet totally unknown process of genome-condensing structure assembly in spermatids. C1 Inst Albert Bonniot, INSERM, U309, F-38706 La Tronche, France. Univ Grenoble 1, F-38700 Grenoble, France. Commissariat LEnergie Atom, DSV, DRDC, Lab Chim Prot, F-38054 Grenoble, France. INSERM, ERM0201, F-38054 Grenoble, France. NIEHS, Reprod & Dev Toxicol Lab, Gamete Biol Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Khochbin, S (reprint author), Inst Albert Bonniot, INSERM, U309, Domaine De La Merci, F-38706 La Tronche, France. EM khochbin@ujf-grenoble.fr RI Khochbin, Saadi/M-8090-2013; Govin, Jerome/B-2326-2014; Caron, Cecile/M-3485-2013; FERRO, Myriam/O-6588-2014; Rousseaux, Sophie/G-1697-2013 OI Govin, Jerome/0000-0001-5511-6965; FERRO, Myriam/0000-0002-4222-6847; FU NIEHS NIH HHS [Z01 ES070077-17] NR 20 TC 65 Z9 71 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 2006 VL 281 IS 49 BP 37888 EP 37892 DI 10.1074/jbc.M608147200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100067 PM 17035236 ER PT J AU Notari, L Baladron, V Aroca-Aguilar, JD Balko, N Heredia, R Meyer, C Notario, PM Saravanamuthu, S Nueda, ML Sanchez-Sanchez, F Escribano, J Laborda, J Becerra, SP AF Notari, Luigi Baladron, Victoriano Aroca-Aguilar, J. Daniel Balko, Natalia Heredia, Raul Meyer, Christina Notario, Patricia M. Saravanamuthu, Senthil Nueda, Maria-Luisa Sanchez-Sanchez, Francisco Escribano, Julio Laborda, Jorge Becerra, S. Patricia TI Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; CEREBELLAR GRANULE CELLS; MEDIATED GENE-TRANSFER; FACTOR PEDF; DOCOSAHEXAENOIC ACID; MOTOR-NEURONS; CHOROIDAL NEOVASCULARIZATION; INTERPHOTORECEPTOR MATRIX; NEUROTROPHIC ACTIVITY; NEUROPROTECTIN D1 AB Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells. This study was designed to reveal a receptor involved in the biological activities of PEDF. Using a yeast two-hybrid screening, we identified a novel gene from pigment epithelium of the human retina that codes for a PEDF-binding partner, which we term PEDF-R. The derived polypeptide has putative transmembrane, intracellular and extracellular regions, and a phospholipase domain. Recently, PEDF-R (TTS2.2/independent phospholipase A(2) (PLA(2))zeta and mouse desnutrin/ATGL) has been described in adipose cells as a member of the new calcium-independent PLA(2)/nutrin/patatin- like phospholipase domain-containing 2 (PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase activities. Here we describe the PEDF-R gene expression in the retina and its heterologous expression by bacterial and eukaryotic systems, and we demonstrate that its protein product has specific and high binding affinity for PEDF, has a potent phospholipase A(2) activity that liberates fatty acids, and is associated with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane protein with high affinity for PEDF, suggesting a molecular pathway by which ligand/receptor interaction on the cell surface could generate a cellular signal. C1 NEI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Castilla La Mancha, Sch Med, Ctr Reg Invest Biomed, Albacete 02071, Spain. RP Becerra, SP (reprint author), NEI, NIH, Bldg 7,Rm 304,7 Mem Dr,MSC 0706, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov RI Nueda, Maria-Luisa/L-3044-2014; Laborda, Jorge/L-5726-2014; Baladron, Victoriano/L-1758-2014; Aroca-Aguilar, J.Daniel/B-7842-2008; OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760; Aroca-Aguilar, J.Daniel/0000-0001-6487-1612; Escribano, Julio/0000-0002-8919-8134 FU Intramural NIH HHS NR 72 TC 161 Z9 170 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 DEC 8 PY 2006 VL 281 IS 49 BP 38022 EP 38037 DI 10.1074/jbc.M600353200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100081 PM 17032652 ER PT J AU Perry, JL Dembla-Rajpal, N Hall, LA Pritchard, JB AF Perry, Jennifer L. Dembla-Rajpal, Neetu Hall, Laura A. Pritchard, John B. TI A three-dimensional model of human organic anion transporter 1 - Aromatic amino acids required for substrate transport SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATION TRANSPORTERS; PROTEIN-STRUCTURE; LACTOSE PERMEASE; ESCHERICHIA-COLI; PROXIMAL TUBULE; BINDING REGION; RAT-KIDNEY; MEMBRANE; RESIDUES; MECHANISM AB Organic anion transporters (OATs) play a critical role in the handling of endogenous and exogenous organic anions by excretory and barrier tissues. Little is known about the OAT three-dimensional structure or substrate/protein interactions involved in transport. In this investigation, a theoretical three-dimensional model was generated for human OAT1 (hOAT1) based on fold recognition to the crystal structure of the glycerol 3-phosphate transporter (GlpT) from Escherichia coli. GlpT and hOAT1 share several sequence motifs as major facilitator superfamily members. The structural hOAT1 model shows that helices 5, 7, 8, 10, and 11 surround an electronegative putative active site (similar to 830 angstrom(3)). The site opens to the cytoplasm and is surrounded by three residues not previously examined for function (Tyr(230) (domain 5) and Lys(431) and Phe(438) (domain 10)). Effects of these residues on p-aminohippurate (PAH) and cidofovir transport were assessed by point mutations in a Xenopus oocyte expression system. Membrane protein expression was severely limited for the Y230A mutant. For the K431A and F438A mutants, [H-3] PAH uptake was less than 30% of wild-type hOAT1 uptake after protein expression correction. Reduced Vmax values for the F438A mutant confirmed lower protein expression. In addition, the F438A mutant exhibited an increased affinity for cidofovir but was not significantly different for PAH. Differences in handling of PAH and cidofovir were also observed for the Y230F mutant. Little uptake was determined for cidofovir, whereas PAH uptake was similar to wildtype hOAT1. Therefore, the hOAT1 structural model has identified two new residues, Tyr(230) and Phe(438), which are important for substrate/protein interactions. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), POB 12233,F1-03, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES080031-29, Z01 ES048014-06] NR 46 TC 44 Z9 46 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 DEC 8 PY 2006 VL 281 IS 49 BP 38071 EP 38079 DI 10.1074/jbc.M608834200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100085 PM 17038320 ER PT J AU Jiao, W Datta, J Lin, HM Dundr, M Rane, SG AF Jiao, Wan Datta, Jashodeep Lin, Huei-Min Dundr, Miroslav Rane, Sushil G. TI Nucleocytoplasmic shuttling of the retinoblastoma tumor suppressor protein via Cdk phosphorylation-dependent nuclear export SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RING-FINGER DOMAIN; GENE-PRODUCT; CELL-CYCLE; CANCER; E2F; P53; LOCALIZATION; PHO80-PHO85; EXPRESSION; PROLIFERATION AB The retinoblastoma (RB) tumor suppressor protein is a negative regulator of cell proliferation that is functionally inactivated in the majority of human tumors. Elevated Cdk activity via RB pathway mutations is observed in virtually every human cancer. Thus, Cdk inhibitors have tremendous promise as anticancer agents although detailed mechanistic knowledge of their effects on RB function is needed to harness their full potential. Here, we illustrate a novel function for Cdks in regulating the subcellular localization of RB. We present evidence of significant cytoplasmic mislocalization of ordinarily nuclear RB in cells harboring Cdk4 mutations. Ourfindings uncover a novel mechanism to circumvent RB-mediated growth suppression by altered nucleocytoplasmic trafficking via the Exportin1 pathway. Cytoplasmically mislocalized RB could be efficiently confined to the nucleus by inhibiting the Exportin1 pathway, reducing Cdk activity, or mutating the Cdk-dependent phosphorylation sites in RB that result in loss of RB-Exportin1 association. Thus RB-mediated tumor suppression can be subverted by phosphorylation-dependent enhancement of nuclear export. These results support the notion that tumor cells can modulate the protein transport machinery thereby making the protein transport process a viable therapeutic target. C1 NIDDK, Cell Cycle & Human Dis Grp, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Rosalind Franklin Univ Med & Sci, Dept Cell Biol, N Chicago, IL 60064 USA. RP Rane, SG (reprint author), NIDDK, Cell Cycle & Human Dis Grp, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM ranes@mail.nih.gov OI Datta, Jashodeep/0000-0003-2869-1571 NR 43 TC 37 Z9 37 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 8 PY 2006 VL 281 IS 49 BP 38098 EP 38108 DI 10.1074/jbc.M605271200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 111TH UT WOS:000242477100088 PM 17043357 ER PT J AU Fujii, M Lyakh, LA Bracken, CP Fukuoka, J Hayakawa, M Tsukiyama, T Soil, SJ Harris, M Rocha, S Roche, KC Tominaga, SI Jen, J Perkins, ND Lechleider, RJ Roberts, AB AF Fujii, Makiko Lyakh, Lyudmila A. Bracken, Cameron P. Fukuoka, Junya Hayakawa, Morisada Tsukiyama, Tadasuke Soil, Steven J. Harris, Melissa Rocha, Sonia Roche, Kevin C. Tominaga, Shin-ichi Jen, Jin Perkins, Neil D. Lechleider, Robert J. Roberts, Anita B. TI SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes SO MOLECULAR CELL LA English DT Article ID UBIQUITIN-MEDIATED PROTEOLYSIS; CELL-PROLIFERATION; EMBRYO FIBROBLASTS; PROTEIN STABILITY; DNA-BINDING; FHA DOMAIN; EXPRESSION; ACTIVATION; PHOSPHORYLATION; DEGRADATION AB Using a yeast two-hybrid screen, we found that SNIP1 (Smad nuclear-interacting protein 1) associates with c-Myc, a key regulator of cell proliferation and transformation. We demonstrate that SNIP1 functions as an important regulator of c-Myc activity, binding the N terminus of c-Myc through its own C terminus, and that SNIP1 enhances the transcriptional activity of c-Myc both by stabilizing it against proteosomal degradation and by bridging the c-Myc/p300 complex. These effects of SNIP1 on c-Myc likely contribute to synergistic effects of SNIP1, c-Myc, and H-Ras in inducing formation of foci in an in vitro transformation assay and also in supporting anchorage-independent growth. The significant association of SNIP1 and c-Myc staining in a non-small cell lung cancer tissue array is further evidence that their activities might be linked and suggests that SNIP1 might be an important modulator of c-Myc activity in carcinogenesis. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Univ Dundee, Div Gene Regulat & Express, Coll Life Sci, Dundee DD1 5EH, Scotland. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Jichi Med Univ, Dept Biochem, Minami Kawachi, Tochigi 3290498, Japan. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. NCI, Mol Oncol Res Unit, Bethesda, MD 20892 USA. RP Lechleider, RJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM fujiim@jichi.ac.jp; lechleiderr@mail.nih.gov RI Tsukiyama, Tadasuke/D-7589-2012; OI Rocha, Sonia/0000-0002-2413-4981; Hayakawa, Morisada/0000-0002-1869-2450 FU Intramural NIH HHS NR 45 TC 28 Z9 29 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 8 PY 2006 VL 24 IS 5 BP 771 EP 783 DI 10.1016/j.molcel.2006.11.006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 116OK UT WOS:000242812000013 PM 17157259 ER PT J AU Emanuel, EJ Wertheimer, A AF Emanuel, Ezekiel J. Wertheimer, Alan TI Deciding who should get the flu vaccine - Response SO SCIENCE LA English DT Letter C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 8 PY 2006 VL 314 IS 5805 BP 1539 EP 1540 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 113UX UT WOS:000242624600014 ER PT J AU Gertz, EM Yu, YK Agarwala, R Schaffer, AA Altschul, SF AF Gertz, E. Michael Yu, Yi-Kuo Agarwala, Richa Schaffer, Alejandro A. Altschul, Stephen F. TI Composition-based statistics and translated nucleotide searches: Improving the TBLASTN module of BLAST SO BMC BIOLOGY LA English DT Article ID ACID SUBSTITUTION MATRICES; PROTEIN-CODING REGIONS; SACCHAROMYCES-CEREVISIAE; DROSOPHILA TRACHEA; DATABASE SEARCHES; GENETIC-CODE; DNA-SEQUENCE; ALIGNMENT; MITOCHONDRIA; SIMILARITY AB Background: TBLASTN is a mode of operation for BLAST that aligns protein sequences to a nucleotide database translated in all six frames. We present the first description of the modern implementation of TBLASTN, focusing on new techniques that were used to implement composition-based statistics for translated nucleotide searches. Composition-based statistics use the composition of the sequences being aligned to generate more accurate E-values, which allows for a more accurate distinction between true and false matches. Until recently, composition-based statistics were available only for protein-protein searches. They are now available as a command line option for recent versions of TBLASTN and as an option for TBLASTN on the NCBI BLAST web server. Results: We evaluate the statistical and retrieval accuracy of the E-values reported by a baseline version of TBLASTN and by two variants that use different types of composition-based statistics. To test the statistical accuracy of TBLASTN, we ran 1000 searches using scrambled proteins from the mouse genome and a database of human chromosomes. To test retrieval accuracy, we modernize and adapt to translated searches a test set previously used to evaluate the retrieval accuracy of protein-protein searches. We show that composition-based statistics greatly improve the statistical accuracy of TBLASTN, at a small cost to the retrieval accuracy. Conclusion: TBLASTN is widely used, as it is common to wish to compare proteins to chromosomes or to libraries of mRNAs. Composition-based statistics improve the statistical accuracy, and therefore the reliability, of TBLASTN results. The algorithms used by TBLASTN are not widely known, and some of the most important are reported here. The data used to test TBLASTN are available for download and may be useful in other studies of translated search algorithms. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, US Dept HHS, NIH, Bethesda, MD 20894 USA. RP Gertz, EM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, US Dept HHS, NIH, Bethesda, MD 20894 USA. EM gertz@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov; richa@helix.nih.gov; schaffer@helix.nih.gov; altschul@ncbi.nlm.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 52 TC 18 Z9 18 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD DEC 7 PY 2006 VL 4 AR 4 DI 10.1186/1741-7007-4-41 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 128JY UT WOS:000243655200001 PM 17156431 ER PT J AU Hochman, JS Lamas, GA Buller, CE Dzavik, V Reynolds, HR Abramsky, SJ Forman, S Ruzyllo, W Maggioni, AP White, H Sadowski, Z Carvalho, AC Rankin, JM Renkin, JP Steg, PG Mascette, AM Sopko, G Pfisterer, ME Leor, J Fridrich, V Mark, DB Knatterud, GL AF Hochman, Judith S. Lamas, Gervasio A. Buller, Christopher E. Dzavik, Vladimir Reynolds, Harmony R. Abramsky, Staci J. Forman, Sandra Ruzyllo, Witold Maggioni, Aldo P. White, Harvey Sadowski, Zygmunt Carvalho, Antonio C. Rankin, Jamie M. Renkin, Jean P. Steg, P. Gabriel Mascette, Alice M. Sopko, George Pfisterer, Matthias E. Leor, Jonathan Fridrich, Viliam Mark, Daniel B. Knatterud, Genell L. CA Occluded Artery Trial Invest TI Coronary intervention for persistent occlusion after myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ST-SEGMENT-ELEVATION; LEFT-VENTRICULAR FUNCTION; RANDOMIZED CONTROLLED-TRIAL; REPERFUSION THERAPY; GLOBAL REGISTRY; EVENTS GRACE; BLOOD-FLOW; ARTERY; ANGIOPLASTY; RECANALIZATION AB BACKGROUND: It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events. METHODS: We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure. RESULTS: The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization). CONCLUSIONS: PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. C1 NYU, Sch Med, Cardiovasc Clin Res Ctr, Leon Charney Div Cardiol, New York, NY 10016 USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. Maryland Med Res Inst, Baltimore, MD USA. Natl Inst Cardiol, Warsaw, Poland. Italian Assoc Hosp Cardiologists Res Ctr, Florence, Italy. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. Hosp Sao Paulo, Sao Paulo, Brazil. Royal Perth Hosp, Perth, WA, Australia. Clin Univ St Luc, B-1200 Brussels, Belgium. Hop Bichat, F-75877 Paris, France. NHLBI, Bethesda, MD 20892 USA. Univ Hosp, Basel, Switzerland. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Slovak Inst Cardiovasc Dis, Bratislava, Slovakia. Duke Clin Res Inst, Durham, NC USA. RP Hochman, JS (reprint author), NYU, Sch Med, Cardiovasc Clin Res Ctr, Leon Charney Div Cardiol, 530 1st Ave,HCC 1173, New York, NY 10016 USA. RI Reynolds, Harmony/M-4818-2013; OI Mark, Daniel/0000-0001-6340-8087; Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [R01 HL067683, R01 HL67683, U01 HL062257, U01 HL062509, U01 HL062509-01A1, U01 HL062509-02, U01 HL062509-03, U01 HL062509-04, U01 HL062509-05, U01 HL062509-05S1, U01 HL062511] NR 41 TC 338 Z9 385 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 2006 VL 355 IS 23 BP 2395 EP 2407 DI 10.1056/NEJMoa066139 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400004 PM 17105759 ER PT J AU Druker, BJ Guilhot, F O'Brien, SG Gathmann, I Kantarjian, H Gattermann, N Deininger, MWN Silver, RT Goldman, JM Stone, RM Cervantes, F Hochhaus, A Powell, BL Gabrilove, JL Rousselot, P Reiffers, J Cornelissen, JJ Hughes, T Agis, H Fischer, T Verhoef, G Shepherd, J Saglio, G Gratwohl, A Nielsen, JL Radich, JP Simonsson, B Taylor, K Baccarani, M So, C Letvak, L Larson, RA AF Druker, Brian J. Guilhot, Francois O'Brien, Stephen G. Gathmann, Insa Kantarjian, Hagop Gattermann, Norbert Deininger, Michael W. N. Silver, Richard T. Goldman, John M. Stone, Richard M. Cervantes, Francisco Hochhaus, Andreas Powell, Bayard L. Gabrilove, Janice L. Rousselot, Philippe Reiffers, Josy Cornelissen, Jan J. Hughes, Timothy Agis, Hermine Fischer, Thomas Verhoef, Gregor Shepherd, John Saglio, Giuseppe Gratwohl, Alois Nielsen, Johan L. Radich, Jerald P. Simonsson, Bengt Taylor, Kerry Baccarani, Michele So, Charlene Letvak, Laurie Larson, Richard A. CA IRIS Investigators TI Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; COMPLETE CYTOGENETIC REMISSION; CHRONIC GRANULOCYTIC-LEUKEMIA; ALPHA PLUS CYTARABINE; PHILADELPHIA-CHROMOSOME; INTERFERON-ALPHA; CHRONIC-PHASE; BLAST CRISIS; CELLS AB BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97239 USA. CHU, Poitiers, France. Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. Novartis, Basel, Switzerland. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Univ Leipzig, D-7010 Leipzig, Germany. Weill Cornell Med Ctr, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Clin Barcelona, Barcelona, Spain. Univ Heidelberg, D-6800 Mannheim, Germany. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Mt Sinai Sch Med, New York, NY USA. Hop St Louis, Paris, France. CHU Bordeaux, Pessac, France. Erasmus MC, Rotterdam, Netherlands. Royal Adelaide Hosp, Adelaide, SA 5000, Australia. Univ Vienna, Innere Med Klin 1, Vienna, Austria. Univ Mainz, D-6500 Mainz, Germany. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Vancover Hosp, Vancouver, BC, Canada. Azienda Osped S Luigi Gonzaga, Orbassano, Italy. Univ Basel Hosp, CH-4031 Basel, Switzerland. Aarhus Kommune Hosp, DK-8000 Aarhus, Denmark. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Akad Sjukhuset, Uppsala, Sweden. Mater Hosp, Brisbane, Qld, Australia. Policlin O Orsola Malpighi, Bologna, Italy. Novarits, Florham Pk, NJ USA. Univ Chicago, Chicago, IL 60637 USA. RP Druker, BJ (reprint author), Oregon Hlth Sci Univ, Inst Canc, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM drukerb@ohsu.edu OI Hochhaus, Andreas/0000-0003-0626-0834; Larson, Richard/0000-0001-9168-3203 NR 36 TC 1847 Z9 1953 U1 14 U2 119 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 7 PY 2006 VL 355 IS 23 BP 2408 EP 2417 DI 10.1056/NEJMoa062867 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400005 PM 17151364 ER PT J AU Hoofnagle, JH Seeff, LB AF Hoofnagle, Jay H. Seeff, Leonard B. TI Peginterferon and ribavirin for chronic hepatitis C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALPHA-2B PLUS RIBAVIRIN; IMMUNODEFICIENCY-VIRUS INFECTION; PEGYLATED INTERFERON-ALPHA-2B; COMBINATION THERAPY; INITIAL TREATMENT; RANDOMIZED-TRIAL; HCV INFECTION; UNITED-STATES; GENOTYPE-2; MANAGEMENT C1 NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bldg 31,Rm 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nih.gov NR 51 TC 295 Z9 314 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 DEC 7 PY 2006 VL 355 IS 23 BP 2444 EP 2451 DI 10.1056/NEJMct061675 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 113EO UT WOS:000242581400008 PM 17151366 ER PT J AU Timofeeva, OA Plisov, S Evseev, AA Peng, S Jose-Kampfner, M Lovvorn, HN Dome, JS Perantoni, AO AF Timofeeva, O. A. Plisov, S. Evseev, A. A. Peng, S. Jose-Kampfner, M. Lovvorn, H. N. Dome, J. S. Perantoni, A. O. TI Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor pathogenesis SO ONCOGENE LA English DT Article DE serine 727; STAT1; protein kinase CK2; MCL-1; HSP27; Wilms' tumor ID PROTEIN-KINASE CK2; CHRONIC LYMPHOCYTIC-LEUKEMIA; TARGET GENE-EXPRESSION; SIGNAL TRANSDUCER; IFN-GAMMA; INTERFERON-GAMMA; INDUCED APOPTOSIS; CASEIN KINASE-2; CANCER-THERAPY; CELL LYMPHOMA AB Wilms' tumor (WT), one of the most common pediatric solid cancers, arises in the developing kidney as a result of genetic and epigenetic changes that lead to the abnormal proliferation and differentiation of the metanephric blastema. As activation of signal transducers and activators of transcription (STATs) plays an important role in the maintenance/growth and differentiation of the metanephric blastema, and constitutively activated STATs facilitate neoplastic behaviors of a variety of cancers, we hypothesized that dysregulation of STAT signaling may also contribute to WT pathogenesis. Accordingly, we evaluated STAT phosphorylation patterns in tumors and found that STAT1 was constitutively phosphorylated on serine 727 (S727) in 19 of 21 primary WT samples and two WT cell lines. An inactivating mutation of S727 to alanine reduced colony formation of WT cells in soft agar by more than 80% and induced apoptosis under conditions of growth stress. S727-phosphorylated STAT1 provided apoptotic resistance for WT cells via upregulation of expression of the heat-shock protein (HSP) 27 and antiapoptotic protein myeloid cell leukemia (MCL)-1. The kinase responsible for STAT1 S727 phosphorylation in WT cells was identified based upon the use of selective inhibitors as protein kinase CK2, not p38, MAP-kinase kinase (MEK)1/2, phosphatidylinositol 3'-kinase, protein kinase C or Ca/calmodulin-dependent protein kinase II (CaMKII). The inhibition of CK2 blocked the anchorage-independent growth of WT cells and induced apoptosis under conditions of growth stress. Our findings suggest that serine-phosphorylated STAT1, as a downstream target of protein kinase CK2, plays a critical role in the pathogenesis of WT and possibly other neoplasms with similar STAT1 phosphorylation patterns. C1 NCI, Lab Comparat Carcinogenesis, Canc Res Ctr, Frederick, MD 21702 USA. Vanderbilt Univ, Dept Pediat Surg, Nashville, TN USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. RP Perantoni, AO (reprint author), NCI, Lab Comparat Carcinogenesis, Canc Res Ctr, 1050 Boyless St,Bldg 538,R 205E, Frederick, MD 21702 USA. EM peranton@ncifcrf.gov FU Intramural NIH HHS NR 70 TC 50 Z9 51 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD DEC 7 PY 2006 VL 25 IS 58 BP 7555 EP 7564 DI 10.1038/sj.onc.1209742 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 114GU UT WOS:000242655500001 PM 16799645 ER PT J AU Chotai, J Murphy, DL Constantino, JN AF Chotai, Jayanti Murphy, Dennis L. Constantino, John N. TI Cerebrospinal fluid monoamine metabolite levels in human newborn infants born in winter differ from those born in summer SO PSYCHIATRY RESEARCH LA English DT Article DE season of birth; dopamine; serotonin ID MORNINGNESS-EVENINGNESS PREFERENCE; BIRTH VARIATIONS; PRENATAL STRESS; GENERAL-POPULATION; RHESUS-MONKEYS; HUMAN ADULTS; SEASON; SCHIZOPHRENIA; DOPAMINE; SEROTONIN AB An earlier study has shown significant differences in the CSF monoamine metabolite levels in adults born during different seasons of the year. We study here the relationship between season of birth and CSF monoamine metabolite levels in 283 newborn febrile infants without neurological abnormalities, with an age distribution ranging from birth to about 3 months, adjusting for the confounding variables age and time at lumbar puncture, weight at birth, estimated gestational age at birth, gender, race, and medicaid status. Each of the three metabolite levels as well as their ratios HVA/5-HIAA and 5-HIAA/MHPG showed significant month-of-birth variations, but not the ratio HVA/MHPG. For HVA and MHPG levels, the maximum was obtained around the winter birth months November December, whereas for 5-HIAA level, the maximum was obtained around the summer birth months June-July. The correlations between HVA and 5-HIAA were, in general, significantly positive within the different birth seasons and races. Among summer-born Caucasian infants, MHPG was significantly positively correlated with HVA and with 5-HIAA, whereas among winter-born Black infants, MHPG was significantly positively correlated with HVA. Season of birth is an unspecific environmental factor that may be proxy for several possible seasonally varying environmental circumstances such as the length of photoperiod, temperature, infections, nutrition, stress and lifestyle. Studies relating season of birth to monoaminergic turnover at different stages of life may yield important clues about the gestational and perinatal origins of neurodevelopment. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Umea Univ, Dept Clin Sci, Div Psychiat, SE-90185 Umea, Sweden. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Chotai, J (reprint author), Umea Univ, Dept Clin Sci, Div Psychiat, SE-90185 Umea, Sweden. EM jayanti.chotai@vll.se NR 47 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 7 PY 2006 VL 145 IS 2-3 BP 189 EP 197 DI 10.1016/j.psychres.2005.11.008 PG 9 WC Psychiatry SC Psychiatry GA 118AX UT WOS:000242915500011 PM 17074397 ER PT J AU Burlison, JA Neckers, L Smith, AB Maxwell, A Blagg, BSJ AF Burlison, Joseph A. Neckers, Len Smith, Andrew B. Maxwell, Anthony Blagg, Brian S. J. TI Novobiocin: Redesigning a DNA gyrase inhibitor for selective inhibition of Hsp90 SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID POTENT COUMARIN INHIBITORS; MOLECULAR CHAPERONE; ATPASE ACTIVITY; IN-VIVO; NUCLEOTIDE-BINDING; TUMOR SELECTIVITY; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; PROTEIN; GELDANAMYCIN AB Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase. Recent studies have shown that novobiocin binds to a previously unrecognized ATP-binding site at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at similar to 700 mu M. In an effort to develop more efficacious inhibitors of the C-terminal binding site, a library of novobiocin analogues was prepared and initial structure-activity relationships revealed. These data suggested that the 4-hydroxy moiety of the coumarin ring and the 3'-carbamate of the noviose appendage were detrimental to Hsp90 inhibitory activity. In an effort to confirm these findings, 4-deshydroxy novobiocin (DHN1) and 3'-descarbamoyl-4-deshydroxynovobiocin (DHN2) were prepared and evaluated against Hsp90. Both compounds were significantly more potent than the natural product, and DHN2 proved to be more active than DHN1. In an effort to determine whether these moieties are important for DNA gyrase inhibition, these compounds were tested for their ability to inhibit DNA gyrase and found to exhibit significant reduction in gyrase activity. Thus, we have established the first set of compounds that clearly differentiate between the C-terminus of Hsp90 and DNA gyrase, converted a well-established gyrase inhibitor into a selective Hsp90 inhibitor, and confirmed essential structure-activity relationships for the coumermycin family of antibiotics. C1 Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. NCI, Urol Oncol Branch, NIH, Rockville, MD 20850 USA. John Innes Ctr Plant Sci Res, Dept Biol Chem, Norwich NR4 7UH, Norfolk, England. RP Blagg, BSJ (reprint author), Univ Kansas, Dept Med Chem, 1251 Wescoe Hall Dr,Malott Hall 4070, Lawrence, KS 66045 USA. EM bblagg@ku.edu OI Maxwell, Anthony/0000-0002-5756-6430 FU NCI NIH HHS [1 R01 CA120458] NR 67 TC 131 Z9 134 U1 4 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 6 PY 2006 VL 128 IS 48 BP 15529 EP 15536 DI 10.1021/ja065793p PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 110GS UT WOS:000242367000037 PM 17132020 ER PT J AU Decarli, A Calza, S Masala, G Specchia, C Palli, D Gail, MH AF Decarli, Adriano Calza, Stefano Masala, Giovanna Specchia, Claudia Palli, Domenico Gail, Mitchell H. TI Gail model for prediction of absolute risk of invasive breast cancer: Independent evaluation in the Florence-European Prospective Investigation Into Cancer and Nutrition Cohort SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POPULATION ATTRIBUTABLE RISK; FAMILY-HISTORY; WOMEN; VALIDATION; DIET; CHEMOPREVENTION; EPIDEMIOLOGY; PREVENTION; TAMOXIFEN; PROJECT AB Background. The Gail model 2 (GM) for predicting the absolute risk of invasive breast cancer has been used for counseling and to design intervention studies. Although the GM has been validated in US populations, its performance in other populations is unclear because of the wide variation in international breast cancer rates. Methods: We used data from a multicenter case-control study in Italy and from Italian cancer registries to develop a model (IT-GM) that uses the same risk factors as the GM. We evaluated the accuracy of the IT-GM and the GM using independent data from the Florence-European Prospective Investigation Into Cancer and Nutrition (EPIC) cohort. To assess model calibration (i.e., how well the model predicts the observed numbers of events in subsets of the population), we compared the number of expected incident breast cancers (E) predicted by these models with the number of observed incident breast cancers (0), and we computed the concordance statistic to measure discriminatory accuracy. Results: The overall E/O ratios were 0.96 (95% confidence interval [CI] = 0.84 to 1.11) and 0.93 (95% CI = 0.81 to 1.08) for the IT-GM and the GM, respectively. The IT-GM was somewhat better calibrated than GM in women younger than 50 years, but the GM was better calibrated when age at first live birth categories were considered (e.g., 20- to 24-year age-at-first-birth category E/O = 0.68, 95% CI = 0.53 to 0.94 for the IT-GM and E/O = 0.75, 95% CI = 0.58 to 1.03 for the GM). The concordance statistic was approximately 59% for both models, with 95% confidence intervals indicating that the models perform statistically significantly better than pure chance (concordance statistic of 50%). Conclusions: There was no statistically significant evidence of miscalibration overall for either the IT-GM or the GM, and the models had equivalent discriminatory accuracy. The good performance of the IT-GM when applied on the independent data from the Florence-EPIC cohort indicates that GM can be improved for use in populations other than US populations. Our findings suggest that the Italian data may be useful for revising the GM to include additional risk factors for breast cancer. C1 Univ Milan, Med Stat & Biometry Inst, I-20133 Milan, Italy. Natl Canc Inst, Unit Med Stat & Biometry, Milan, Italy. Univ Brescia, Med Stat & Biometry Sect, Dept Biomed Sci & Biotechnol, Brescia, Italy. Sci Inst Tuscany, Canc Res & Prevent Ctr, Mol & Nutr Epidemiol Unit, Florence, Italy. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Decarli, A (reprint author), Univ Milan, Med Stat & Biometry Inst, Via Venezian 1, I-20133 Milan, Italy. EM adriano.decarli@unimi.it RI Calza, Stefano/B-1915-2010; Decarli, Adriano/C-3129-2017; OI Masala, Giovanna/0000-0002-5758-9069; Calza, Stefano/0000-0003-4996-7995; Decarli, Adriano/0000-0003-1451-8292; PALLI, Domenico/0000-0002-5558-2437 NR 41 TC 53 Z9 56 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 6 PY 2006 VL 98 IS 23 BP 1686 EP 1693 DI 10.1093/jnci/djj463 PG 8 WC Oncology SC Oncology GA 116MY UT WOS:000242808200007 PM 17148770 ER PT J AU Cusatis, G Gregorc, V Li, J Spreafico, A Ingersoll, RG Verweij, J Ludovini, V Villa, E Hidalgo, M Sparreboom, A Baker, SD AF Cusatis, George Gregorc, Vanesa Li, Jing Spreafico, Anna Ingersoll, Roxann G. Verweij, Jaap Ludovini, Vienna Villa, Eugenio Hidalgo, Manuel Sparreboom, Alex Baker, Sharyn D. TI Pharmacogenetics of ABCG2 and adverse reactions to gefitinib SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE; MULTIDRUG TRANSPORTER; DRUG-RESISTANCE; INTRON 1; INHIBITOR; IRESSA; POLYMORPHISM; EXPRESSION AB Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase with activity in non-small-cell lung cancer. Diarrhea and skin toxicity are prominent gefitinib-related adverse events that potentially limit its use. Gefitinib is a substrate for ABCG2 (ABCP, BCRP, MXR), a polymorphic efflux transporter protein that is highly expressed in the intestines and liver. Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients. One variant, a common functional single-nucleotide polymorphism (SNP) in the ABCG2 gene, was associated with diarrhea in 124 patients treated with oral getitinib 250 mg once daily; seven (44%) of 16 patients heterozygous for ABCG2 421C > A (Q141K) developed diarrhea, versus only 13 (12%) of 108 patients homozygous for the wild-type sequence (P = .0046). However, this SNP was not associated with skin toxicity (P = .99). The finding suggests that patients with reduced ABCG2 activity due to a common genetic variant are at increased risk for substrate drug-induced diarrhea, with implications for optimizing treatment with such agents. C1 St Jude Childrens Hosp, Pharmaceut Sci Dept, Memphis, TN 38105 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Hosp San Raffaele, Sci Inst, Div Med Oncol, Milan, Italy. Policlin Monteluce Hosp, Div Med Oncol, Perugia, Italy. Johns Hopkins Univ, Sch Med, Inst Genet Med, Baltimore, MD USA. Eramus MD Daniel Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. NCI, Bethesda, MD USA. RP Baker, SD (reprint author), St Jude Childrens Hosp, Pharmaceut Sci Dept, 332 N Lauderdale St,Mail Stop 314, Memphis, TN 38105 USA. EM sharyn.baker@stjude.org RI Sparreboom, Alex/B-3247-2008; Cusatis, Gianluca/G-2539-2011; HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 NR 26 TC 140 Z9 146 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 6 PY 2006 VL 98 IS 23 BP 1739 EP 1742 DI 10.1093/jnci/djj469 PG 4 WC Oncology SC Oncology GA 116MY UT WOS:000242808200013 PM 17148776 ER PT J AU Johnson, C Drgon, T Liu, QR Walther, D Edenberg, H Rice, J Foroud, T Uhl, GR AF Johnson, Catherine Drgon, Tomas Liu, Qing-Rong Walther, Donna Edenberg, Howard Rice, John Foroud, Tatiana Uhl, George R. TI Pooled association genome scanning for alcohol dependence using 104,268 SNPs: Validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE microarray; complex genetics; substance dependence; addiction ID SUBSTANCE-ABUSE VULNERABILITY; DRUG-ABUSE; ADDICTION VULNERABILITY; TWIN PAIRS; LINKAGE; SAMPLES; DNA; CONSUMPTION; POPULATION; FAMILIES AB Association genome scanning can identify markers for the allelic variants that contribute to vulnerability to complex disorders, including alcohol dependence. To improve the power and feasibility of this approach, we report validation of "100k" microarray-based allelic frequency assessments in pooled DNA samples. We then use this approach with unrelated alcohol-dependent versus control individuals sampled from pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA). Allele frequency differences between alcohol-dependent and control individuals are assessed in quadruplicate at 104,268 autosomal SNPs in pooled samples. One hundred eighty-eight SNPs provide (1) the largest allele frequency differences between dependent versus control individuals; (2) t values >= 3 for these differences; and (3) clustering, so that 51 relatively small chromosomal regions contain at least three SNPs that satisfy criteria 1 and 2 above (Monte Carlo P = 0.00034). These positive SNP clusters nominate interesting genes whose products are implicated in cellular signaling, gene regulation, development, "cell adhesion," and Mendelian disorders. The results converge with linkage and association results for alcohol and other addictive phenotypes. The data support polygenic contributions to vulnerability to alcohol dependence. These SNPs provide new tools to aid the understanding, prevention, and treatment of alcohol abuse and dependence. (c) 2006 Wiley-Liss, Inc. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD USA. Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Indiana Univ, Dept Med, Indianapolis, IN USA. RP Uhl, GR (reprint author), Suite 3510,333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012; OI Liu, Qing-Rong/0000-0001-8477-6452; Edenberg, Howard/0000-0003-0344-9690 FU Intramural NIH HHS [Z01 DA000401-10]; NIAAA NIH HHS [U10 AA008401, U10 AA008401-19, U10AA008401] NR 44 TC 102 Z9 104 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2006 VL 141B IS 8 BP 844 EP 853 DI 10.1002/ajmg.b.30346 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 112SD UT WOS:000242546400003 PM 16894614 ER PT J AU Drgon, T D'Addario, C Uhl, GR AF Drgon, Tomas D'Addario, Claudio Uhl, George R. TI Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA receptor gene cluster: Candidate gene variants for addictions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE GABA receptors; addiction; linkage disequilibrium ID SUBSTANCE-ABUSE VULNERABILITY; SINGLE-NUCLEOTIDE POLYMORPHISMS/; POPULATION-BASED SAMPLE; VENTRAL TEGMENTAL AREA; AMINOBUTYRIC ACID GABA; ALCOHOL DEPENDENCE; ETHANOL INTAKE; ENVIRONMENTAL-INFLUENCES; CRAYFISH MUSCLE; LOCI AB Strong genetic contributions to individual differences in vulnerability to addictions are well supported by classical genetic studies. Linkage and association genome scans for addiction vulnerability have provided converging evidence for several chromosomal regions which are likely to harbor allelic variants that contribute to such vulnerability. We and others have delineated a candidate addiction-associated chromosome 4p12 "rSA3" region based on convergent data from association genome scanning studies in polysubstance abusers [Uhl et al. (2001); Am J Hum Genet 69(6):1290-1300], linkage-based studies in alcoholism [Long et al. (1998); Am J Med Genet 81(3):216-221; Reich et al. (1998); Am J Med Genet 81(3):207-215] and association-based studies for alcoholism and association-based studies for individual differences in electroencephalographic (EEG) spectral power phenotypes [Porjesz et al. (2002); Proc Natl Acad Sci USA 99(6):3729-3733; Edenberg et al. (2004); Am J Hum Genet 74(4): 705-714]. The rSA3 region contains interesting candidate genes that encode the alpha 2, alpha 4, beta 1, and gamma 1 receptor subunits for the principal brain inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) [Covault et al. (2004); Am J Med Genet Part B 129B:104-109; Edenberg et al. (2004); Am J Hum Genet 74(4):705-714; Lappalainen et al. (2005); Alcohol Clin Exp Res 29(4):493-498]. We now report assessment of single nucleotide polymorphism (SNP) genotypes in this region in three samples of substance abusers and controls. These results delineate the haplotypes and patterns of linkage disequilibrium in this region, focus attention of the GABRA2 gene and identify modest associations between GABRA2 genotypes and addiction phenotypes. These results are consistent with modest roles for GABRA2 variants in addiction vulnerabilities. (c) 2006 Wiley-Liss, Inc. C1 NIDA, Mol Neurobiol Branch, NIH, Intramural Res Program,DHHS, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, NIH, Intramural Res Program,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI d'addario, claudio/A-5970-2010; OI d'addario, claudio/0000-0002-1275-098X FU Intramural NIH HHS [Z01 DA000401-10] NR 35 TC 53 Z9 53 U1 3 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2006 VL 141B IS 8 BP 854 EP 860 DI 10.1002/ajmg.b.30349 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 112SD UT WOS:000242546400004 PM 16894595 ER PT J AU Liu, QR Drgon, T Johnson, C Walther, D Hess, J Uhl, GR AF Liu, Qing-Rong Drgon, Tomas Johnson, Catherine Walther, Donna Hess, Judith Uhl, George R. TI Addiction molecular genetics: 639,401 SNP whole genome association identifies many "cell adhesion" genes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE association genome scanning; substance dependence; microarray; pooled; neuronal connections ID MILD MENTAL IMPAIRMENT; POOLED DNA; ABUSE-VULNERABILITY; SYNAPTIC PLASTICITY; MEMORY; LOCI; DISEASE; ALCOHOL; SAMPLES; DRUGS AB Addictions are substantially heritable complex disorders. We now report whole genome association studies that identify 89 genes likely to contain variants that contribute to addiction vulnerability, using previously- and newly-validated microarray based pooling assays. Each gene contains clustered single nucleotide polymorphisms (SNPs) that display significant allele frequency differences between abusers and controls in each of the two samples studied with 639,401 SNP arrays and confirmatory SNPs from each of two other abuser/control samples. These genes are implicated in interesting functions, including "cell adhesion" processes that help to establish and maintain neuronal connections of special relevance to addiction's memory-like features. (c) 2006 Wiley-Liss, Inc. C1 NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD USA. RP Uhl, GR (reprint author), POB 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS NR 35 TC 94 Z9 94 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2006 VL 141B IS 8 BP 918 EP 925 DI 10.1002/ajmg.b.30436 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 112SD UT WOS:000242546400015 PM 17099884 ER PT J AU Bondy, C Bakalov, VK Lange, ED Ceniceros, I AF Bondy, Carolyn Bakalov, Vladimir K. Lange, Eileen Dunn Ceniceros, Irene TI Deficient medical care for adults with the Turner syndrome SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bondy, C (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 5 TC 20 Z9 20 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 5 PY 2006 VL 145 IS 11 BP 866 EP 867 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 114PE UT WOS:000242677300016 PM 17146077 ER PT J AU Dzavik, V Buller, CE Lamas, GA Rankin, JM Mancini, J Cantor, WJ Carere, RJ Ross, JR Atchison, D Forman, S Thomas, B Buszman, P Vozzi, C Glanz, A Cohen, EA Meciar, P Devlin, G Mascette, A Sopko, G Knatterud, GL Hochman, JS AF Dzavik, Vladimik Buller, Christopher E. Lamas, Gervasio A. Rankin, James M. Mancini, John Cantor, Warren J. Carere, Ronald J. Ross, John R. Atchison, Deborah Forman, Sandra Thomas, Boban Buszman, Pawel Vozzi, Carlos Glanz, Anthony Cohen, Eric A. Meciar, Peter Devlin, Gerald Mascette, Alice Sopko, George Knatterud, Genell L. Hochman, Judith S. CA TOSCA-2 Invest TI Randomized trial of percutaneous coronary intervention for subacute infarct-related coronary artery occlusion to achieve long-term patency and improve ventricular function - The total occlusion study of Canada (TOSCA)-2 trial SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE myocardial infarction; occlusion; angioplasty; remodeling; cardiac volume; stents ID ACUTE MYOCARDIAL-INFARCTION; LATE REPERFUSION; ANGIOPLASTY; DYSFUNCTION; ADVANTAGES; CAPTOPRIL; SURVIVAL; THERAPY; BALLOON; TOSCA AB Background-In the present study, we sought to determine whether opening a persistently occluded infarct-related artery (IRA) by percutaneous coronary intervention (PCI) in patients beyond the acute phase of myocardial infarction (MI) improves patency and indices of left ventricular (LV) size and function. Methods and Results-Between May 2000 and July 2005, 381 patients with an occluded native IRA 3 to 28 days after MI (median 10 days) were randomized to PCI with stenting (PCI) or optimal medical therapy alone. Repeat coronary and LV angiography was performed 1 year after randomization (n=332, 87%). Coprimary end points were IRA patency and change in LV ejection fraction. Secondary end points included change in LV end-systolic and end-diastolic volume indices and wall motion. PCI was successful in 92%. At 1 year, 83% of PCI versus 25% of medical therapy-only patients had a patent IRA (P < 0.001). LV ejection fraction increased significantly (P < 0.001) in both groups, with no between-group difference: PCI 4.2 +/- 8.9 (n=150) versus medical therapy 3.5 +/- 8.2 (n=136; P=0.47). Median change (interquartile range) in LV end-systolic volume index was -0.5 (-9.3 to 5.0) versus 1.0 (-5.7 to 7.3) mL/m(2) (P=0.10), whereas median change (interquartile range) in LV end-diastolic volume index was 3.2 (-8.2 to 13.3) versus 5.3 (-4.6 to 23.2) mL/m(2) (P=0.07) in the PCI (n=86) and medical therapy-only (n=76) groups, respectively. Conclusions-PCI with stenting of a persistently occluded IRA in the subacute phase after MI effectively maintains long-term patency but has no effect on LV ejection fraction. On the basis of these findings and the lack of clinical benefit in the main Occluded Artery Trial, routine PCI is not recommended for stable patients with a persistently occluded IRA after MI. C1 Univ Toronto, Hlth Network, Toronto, ON M5G 2C4, Canada. Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, St Pauls Hosp, Vancouver, BC, Canada. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Royal Perth Hosp, Perth, WA, Australia. Maryland Med Res Inst, Baltimore, MD USA. Hosp Fernando Fonseca, Amadora, Portugal. Upper Silesian Med Ctr, Katowice, Poland. Hemodynamia Rosario, Rosario, Argentina. Hop Hotel Dieu, Windsor, ON, Canada. Cent Slovak Inst Cardiovasc Dis, Banska Bystrica, Slovakia. Waikato Hosp, Hamilton, New Zealand. NIH, Bethesda, MD 20892 USA. NYU, New York, NY USA. RP Dzavik, V (reprint author), Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Cardiol, 6-246 EN,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM vlad.dzavik@uhn.on.ca OI Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [R01 HL067683-03, HL67683-01A1, R01 HL067683, R01 HL067683-01A1, R01 HL067683-02, R01 HL067683-04] NR 22 TC 89 Z9 100 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 5 PY 2006 VL 114 IS 23 BP 2449 EP 2457 DI 10.1161/CIRCULATIONAHA.106.669432 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XT UT WOS:000243477500008 PM 17105848 ER PT J AU Dyke, CK Steinhubl, SR Kleiman, NS Cannon, RO Aberle, LG Lin, M Myles, SK Melloni, C Harrington, RA Alexander, JH Becker, RC Rusconi, CP AF Dyke, Christopher K. Steinhubl, Steven R. Kleiman, Neal S. Cannon, Richard O. Aberle, Laura G. Lin, Min Myles, Shelley K. Melloni, Chiara Harrington, Robert A. Alexander, John H. Becker, Richard C. Rusconi, Christopher P. TI First-in-human experience of an antidote-controlled anticoagulant using RNA aptamer technology - A phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity SO CIRCULATION LA English DT Article; Proceedings Paper CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc DE anticoagulants; coagulation; pharmacology; aptamers, nucleotide; thrombosis; trials ID ACUTE CORONARY SYNDROMES; THROMBIN GENERATION; BYPASS-SURGERY AB Background-Selectivity, titratability, rapidity of onset, and active reversibility are desirable pharmacological properties of anticoagulant therapy administered for acute indications and collectively represent an attractive platform to maximize patient safety. A novel anticoagulation system (REG1, Regado Biosciences), developed using a protein-binding oligonucleotide to factor IXa (drug, RB006) and its complementary oligonucleotide antidote (RB007), was evaluated in healthy volunteers. The primary objective was to determine the safety profile and to characterize the pharmacodynamic responses in this first-in-human study. Methods and Results-Regado 1a was a subject-blinded, dose-escalation, placebo-controlled study that randomized 85 healthy volunteers to receive a bolus of drug or placebo followed 3 hours later by a bolus of antidote or placebo. Pharmacodynamic samples were collected serially. Subject characteristics were the following: median age, 32 years (interquartile range, 23 to 39 years); female gender, 35%; and median weight, 79 kg (interquartile range, 70 to 87 kg). No significant differences were found in median hemoglobin, platelet, creatinine, or liver function studies. There were no significant bleeding signals associated with RB006, and overall, both drug and antidote were well tolerated. One serious adverse event, an episode of transient encephalopathy, occurred in a subject receiving the low intermediate dose of RB006. The subject's symptoms resolved rapidly, and no further sequelae occurred. A predictable dose- pharmacodynamic response, reflected in activated partial thromboplastin time measurements, was seen after administration of the bolus of drug, with a clear correlation between the peak posttreatment activated partial thromboplastin time and post hoc weight-adjusted dose of drug (correlation coefficient, 0.725; P < 0.001). In subjects treated with drug, antidote administration reversed the pharmacological activity of the drug, with a rapid (mean time, 1 to 5 minutes across all dose levels) and sustained return of activated partial thromboplastin time to within the normal range. The activated clotting time followed a similar anticoagulant response and reversal pattern. As anticipated, prothrombin time remained unchanged compared with baseline. Conclusions-These observations represent a first-in-human experience of an RNA aptamer and its complementary oligonucleotide antidote used as an anticoagulant system. The findings contribute to an emerging platform of selective, actively reversible anticoagulant drugs for use among patients with thrombotic disorders of the venous and arterial circulations. C1 Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA. Univ Kentucky, Lexington, KY USA. Methodist Debakey Heart Ctr, Houston, TX USA. NHLBI, Bethesda, MD 20892 USA. Regado Biosci Inc, Durham, NC USA. RP Dyke, CK (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27715 USA. EM cdyke@alaskaheart.com; becke021@mc.duke.edu NR 17 TC 117 Z9 124 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 5 PY 2006 VL 114 IS 23 BP 2490 EP 2497 DI 10.1161/CIRUCLATIONAHA.106.668434 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 125XT UT WOS:000243477500013 PM 17101847 ER PT J AU Buckley-Beason, VA Johnson, WE Nash, WG Stanyon, R Menninger, JC Driscoll, CA Howard, J Bush, M Page, JE Roelke, ME Stone, G Martelli, PP Wen, C Ling, L Duraisingam, RK Lam, PV O'Brien, SJ AF Buckley-Beason, Valerie A. Johnson, Warren E. Nash, Willliam G. Stanyon, Roscoe Menninger, Joan C. Driscoll, Carlos A. Howard, JoGayle Bush, Mitch Page, John E. Roelke, Melody E. Stone, Gary Martelli, Paolo P. Wen, Ci Ling, Lin Duraisingam, Ratna K. Lam, Phan V. O'Brien, Stephen J. TI Molecular evidence for species-level distinctions in clouded leopards SO CURRENT BIOLOGY LA English DT Article ID NEOFELIS-NEBULOSA; MICROSATELLITES; EVOLUTION; FELIDAE; CATS; PHYLOGEOGRAPHY; INFERENCE; ANCESTRY; PATTERNS; MAMMALIA AB Among the 37 living species of Felidae, the clouded leopard (Neofelis nebulosa) is generally classified as a monotypic genus basal to the Panthera lineage of great cats [1-5]. This secretive, mid-sized (16-23 kg) carnivore, now severely endangered, is traditionally subdivided into four southeast Asian subspecies (Figure 1A) [4-8]. We used molecular genetic methods to re-evaluate subspecies partitions and to quantify patterns of population genetic variation among 109 clouded leopards of known geographic origin (Figure 1A, Tables S1 and S2 in the Supplemental Data available online). We found strong phylogeographic monophyly and large genetic distances between N. n. nebulosa (mainland) and N. n. diardi (Borneo; n = 3 individuals) with mtDNA (771 bp), nuclear DNA (3100 bp), and 51 microsatellite loci. Thirty-six fixed mitochondrial and nuclear nucleotide differences and 20 microsatellite loci with nonoverlapping allele-size ranges distinguished N. n. nebulosa from N. n. diardi. Along with fixed subspecies-specific chromosomal differences, this degree of differentiation is equivalent to, or greater than, comparable measures among five recognized Panthera species (lion, tiger, leopard, jaguar, and snow leopard). These distinctions increase the urgency of clouded leopard conservation efforts, and if affirmed by morphological analysis and wider sampling of N. n. diardi in Borneo and Sumatra, would support reclassification of N. n. diardi as a new species (Neofelis diardt). C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Hood Coll, Biomed Sci Grad Program, Frederick, MD 21702 USA. H&W Cytogenet Serv, Lovettsville, VA 20180 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Sci Appl Int Corp Frederic, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Abingdon, Oxon, England. Singapore Zool Gardens, Singapore 729826, Singapore. Asian Wildlife Consultancy Co Ltd, Taipei 552, Taiwan. Saigon Zoo & Bot Gardens, Ho Chi Minh City, Vietnam. Natl Zool Pk, Washington, DC 20008 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@mail.ncifcrf.gov RI Johnson, Warren/D-4149-2016; OI Johnson, Warren/0000-0002-5954-186X; Stanyon, Roscoe/0000-0002-7229-1092; Driscoll, Carlos/0000-0003-2392-505X NR 34 TC 51 Z9 57 U1 3 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD DEC 5 PY 2006 VL 16 IS 23 BP 2371 EP 2376 DI 10.1016/j.cub.2006.08.066 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114BS UT WOS:000242642300031 PM 17141620 ER PT J AU Shibusawa, Y Takeuchi, N Sugawara, K Yanagida, A Shindo, H Ito, Y AF Shibusawa, Yoichi Takeuchi, Naoko Sugawara, Kazusa Yanagida, Akio Shindo, Heisaburo Ito, Yoichiro TI Aqueous-aqueous two-phase systems composed of low molecular weight of polyethylene glycols and dextrans for counter-current chromatographic purification of proteins SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE aqueous-aqueous two-phase systems; counter-current chromatography; proteins; glucosyltransferase ID COIL PLANET CENTRIFUGE; POLYMER PHASE SYSTEM; STREPTOCOCCUS-MUTANS; CRUDE EXTRACT; HUMAN SERUM; GLUCOSYLTRANSFERASE; SEPARATION; DEHYDROGENASE; LIPOPROTEINS; PARTITION AB New aqueous-aqueous two-phase systems composed of relatively low molecular weight polymers such as polyethylene glycol (PEG) (Mr: 1000-1000) and dextran (Mr: 10,000 and 40,000) were evaluated for purification of proteins by counter-current chromatography (CCC). The compositions of aqueous two-phase systems were optimized by measuring parameters such as viscosity and volume ratio between the two phases. CCC purification of a glucosyltransferase (GTF) from Streptococcus mutans (SM) cell-lysate was successfully demonstrated with a 7.5% PEG 3350-10% dextran T40 system containing 10 mM potassium phosphate buffer at pH 9.0. After CCC purification, both PEG and dextran contained in the CCC fractions were easily removed by ultrafiltration in a short period of time. The fractionated column contents containing GTF were analyzed by enzymatic activity as well as sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The recovery of the enzyme from CCC fraction was over 95% as estimated by enzymatic activities. (c) 2006 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 Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Struct Biol & Analyt Sci, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. EM sibusawa@ps.toyaku.ac.jp NR 28 TC 18 Z9 20 U1 0 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD DEC 5 PY 2006 VL 844 IS 2 BP 217 EP 222 DI 10.1016/j.jchromb.2006.07.028 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 117AC UT WOS:000242843900004 PM 16891164 ER PT J AU Horvath, KA AF Horvath, Keith A. TI Percutaneous laser revascularization does not equal transmyocardial laser revascularization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter C1 NHLBI, NIH, Cardiothorac Surg Res Program, Bethesda, MD 20892 USA. RP Horvath, KA (reprint author), NHLBI, NIH, Cardiothorac Surg Res Program, 10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM khorvath@nih.gov NR 1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 5 PY 2006 VL 48 IS 11 BP 2354 EP 2354 DI 10.1016/j.jacc.2006.09.009 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 112JD UT WOS:000242520900034 PM 17161272 ER PT J AU Turk, DC Dworkin, RH Burke, LB Gershon, R Rothman, M Scott, J Allen, RR Atkinson, JH Chandler, J Cleeland, C Cowan, P Dimitrova, R Dionne, R Farrar, JT Haythornthwaite, JA Hertz, S Jadad, AR Jensen, MP Kellstein, D Kerns, RD Manning, DC Martin, S Max, MB McDermott, MP McGrath, P Moulin, DE Nurmikko, T Quessy, S Raja, S Rappaport, BA Rauschkolb, C Robinson, JP Royal, MA Simon, L Stauffer, JW Stucki, G Tollett, J von Stein, T Wallace, MS Wernicke, J White, RE Williams, AC Witter, J Wyrwich, KW AF Turk, Dennis C. Dworkin, Robert H. Burke, Laurie B. Gershon, Richard Rothman, Margaret Scott, Jane Allen, Robert R. Atkinson, J. Hampton Chandler, Julie Cleeland, Charles Cowan, Penny Dimitrova, Rozalina Dionne, Raymond Farrar, John T. Haythornthwaite, Jennifer A. Hertz, Sharon Jadad, Alejandro R. Jensen, Mark P. Kellstein, David Kerns, Robert D. Manning, Donald C. Martin, Susan Max, Mitchell B. McDermott, Michael P. McGrath, Patrick Moulin, Dwight E. Nurmikko, Turo Quessy, Steve Raja, Srinivasa Rappaport, Bob A. Rauschkolb, Christine Robinson, James P. Royal, Mike A. Simon, Lee Stauffer, Joseph W. Stucki, Gerold Tollett, Jane von Stein, Thorsten Wallace, Mark S. Wernicke, Joachim White, Richard E. Williams, Amanda C. Witter, James Wyrwich, Kathleen W. TI Developing patient-reported outcome measures for pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID PATIENTS PERSPECTIVE; END-POINTS; PERCEPTIONS; ASSESSMENTS C1 Univ Washington, Seattle, WA 98195 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. US FDA, Rockville, MD 20857 USA. Northwestern Univ, Chicago, IL 60611 USA. Johnson & Johnson, Raritan, NY USA. AstraZeneca, Wilmington, DE USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Merck & Co Inc, Blue Bell, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Amer Chron Pain Assoc, Rocklin, CA USA. Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Hlth Network, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Novartis Pharmaceut, E Hanover, NJ USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, New Haven, CT 06520 USA. Celgene Corp, Warren, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. Dalhousie Univ, Halifax, NS, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Johnson & Johnson, Raritan, NJ USA. Alpharma, Elizabeth, NJ USA. Harvard Univ, Sch Med, Boston, MA USA. Alpharma, Piscataway, NJ USA. Univ Munich, Munich, Germany. US Dept Vet Affairs, Washington, DC USA. NeurogesX Inc, San Carlos, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. St Thomas Hosp, London, England. St Louis Univ, St Louis, MO 63103 USA. RP Turk, DC (reprint author), Univ Washington, Seattle, WA 98195 USA. EM Turkdc@u.washington.edu RI Williams, Amanda/C-7816-2009; Farrar, John/A-1037-2007; OI Farrar, John/0000-0001-8656-5157; Yang, Shuman/0000-0002-9638-0890; Williams, Amanda/0000-0003-3761-8704; McGrath, Patrick/0000-0002-9568-2571 NR 23 TC 129 Z9 132 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2006 VL 125 IS 3 BP 208 EP 215 DI 10.1016/j.pain.2006.09.028 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 114NO UT WOS:000242673100005 PM 17069973 ER PT J AU Diatchenko, L Nackley, AG Slade, GD Bhalang, K Belfer, I Max, MB Goldman, D Maixner, W AF Diatchenko, Luda Nackley, Andrea G. Slade, Gary D. Bhalang, Kanokporn Belfer, Inna Max, Mitchell B. Goldman, David Maixner, William TI Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli SO PAIN LA English DT Article DE catechol-O-methyltransferase (COMT); pain perception; single nucleotide polymorphism (SNP); haplotype; COMT val158met polymorphism; sensitivity to heat pain; sensitivity to ischemic pain; sensitivity to pressure pain; temporal summation of heat pain; pain sensitivity; windup ID HAPLOTYPE RECONSTRUCTION; COMT; SCHIZOPHRENIA; METAANALYSIS AB Variations in the gene encoding catechol-O-methyltransferase (COMT) are linked to individual differences in pain sensitivity. A single nucleotide polymorphisin (SNP) in codon 158 (val(158)met), which affects CONIT protein stability, has been associated with the human experience of pain. We recently demonstrated that three common COMT haplotypes, which affect the efficiency of COMT translation, are strongly associated with a global measure of pain sensitivity derived from individuals' responses to noxious thermal, ischemic, and pressure stimuli. Specific haplotypes were associated with low (LPS), average (APS), or high (UPS) pain sensitivity. Although these haplotypes included the val(158)met SNP, a significant association with val(158)met variants was not observed. In the present study, we examined the association between CONIT genotype and specific pain-evoking stimuli. Threshold and tolerance to thermal, ischemic, and mechanical stimuli, as well as temporal summation to heat pain, were determined. LPS/LPS homozygotes had the least, APS/APS homozygotes had average, and APS/HPS heterozygotes had the greatest pain responsiveness. Associations were strongest for measures of thermal pain. However, the rate of temporal summation of heat pain did not differ between haplotype combinations. In contrast, the val(158)met genotype was associated with the rate of temporal summation of heat pain, but not with the other pain measures. This suggests that the val(158)met SNP plays a primary role in variation in temporal summation of pain, but that other SNPs of the COMT haplotype exert a greater influence on resting nociceptive sensitivity. Here, we propose a mechanism whereby these two genetic polymorphisms differentially affect pain perception. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27514 USA. Univ Adelaide, Sch Dent, Australian Researcher Ctr Populat Oral Hlth, Adelaide, SA, Australia. Chulalongkorn Univ, Dept Oral Med, Bangkok, Thailand. NIDCR, US Dept HHS, NIH, Bethesda, MD USA. NIAAA, US Dept HHS, NIH, Rockville, MD 20852 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. RP Maixner, W (reprint author), Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27514 USA. EM Bill_Maixner@dentistry.unc.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA000301]; NIAID NIH HHS [AR/AI-44030, AR/AI-44564]; NIAMS NIH HHS [5-P60 AR-30701-14]; NIDCR NIH HHS [DE00366, DE007333, DE07509, DE16558] NR 24 TC 208 Z9 215 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC 5 PY 2006 VL 125 IS 3 BP 216 EP 224 DI 10.1016/j.pain.2006.05.024 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 114NO UT WOS:000242673100006 PM 16837133 ER PT J AU Patel, S Xi, ZF Seo, EY McGaughey, D Segre, JA AF Patel, Satyakarn Xi, Zong Fang Seo, Eun Young McGaughey, David Segre, Julia A. TI Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; transcription factor; skin; glucocorticoid receptor ID KRUPPEL-LIKE FACTOR; GLUCOCORTICOID RECEPTOR; PERMEABILITY BARRIER; FETAL MATURATION; SKIN DEVELOPMENT; THYROID-HORMONE; DIFFERENTIATION; PROTEIN; CELLS; MOUSE AB Premature infants are at an increased risk for infections and dehydration because of incomplete development of the epidermis, which attains its essential function as a barrier only during the last stages of in utero development. When a premature birth is anticipated, antenatal corticosteroids are administered to accelerate lung epithelium differentiation. One pleiotropic, but beneficial, effect of antenatal corticosteroids is acceleration of skin barrier establishment by an unknown mechanism. In mice, the transcription factor Klf4 is both necessary and sufficient, within a developmental field of competence, to establish this skin barrier, as demonstrated by targeted ablation and transgenic expression of Klf4, respectively. Here, we report that Klf4 and corticosteroid treatment coordinately accelerate barrier acquisition in vivo. Transcriptional profiling reveals that the genes regulated by corticosteroids and Klf4 during the critical window of epidermal development significantly overlap. KLF4 activates the proximal promoters of a significant subset of these genes. Dissecting the intersection of the genetic and pharmacological pathways, regulated by KLF4 and corticosteroids, respectively, leads to a mechanistic understanding of the normal process of epidermal development in utero. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), NHGRI, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov FU Intramural NIH HHS NR 41 TC 35 Z9 38 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 2006 VL 103 IS 49 BP 18668 EP 18673 DI 10.1073/pnas.0608658103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 114TZ UT WOS:000242689800052 PM 17130451 ER PT J AU Venturi, V Kedzierska, K Price, DA Doherty, PC Douek, DC Turner, SJ Davenport, MP AF Venturi, Vanessa Kedzierska, Katherine Price, David A. Doherty, Peter C. Douek, Daniel C. Turner, Stephen J. Davenport, Miles P. TI Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diversity; repertoire; selection; public response ID STRUCTURAL BASIS; TCR REPERTOIRE; VIRAL PEPTIDE; INFLUENZA-A; RECOGNITION; VIRUS; SELECTION; INFECTION; ALPHA; DETERMINANT AB Public responses where identical T cell receptors (TCRs) are clonally dominant and shared between different individuals are a common characteristic of CD8(+) T cell-mediated immunity. Focusing on TCR sharing, we analyzed approximate to 3,400 TCR beta chains (TCR beta s) from mouse CD8(+) T cells responding to the influenza A virus (DNP366)-N-b and D(b)PA(224) epitopes. Both the "public" (DNP366)-N-b-Specific and "private" D(b)PA(224)-specific TCR repertoires contain a high proportion (approximate to 36%) of shared TCR beta s, although the numbers of mice sharing TCR beta s in each repertoire varies greatly. Sharing of both the TCR beta amino acid and TCR beta nucleoticle sequence was negatively correlated with the prevalence of random nucleoticle additions in the sequence. However, the extent of TCR beta amino acid sequence sharing among mice was strongly correlated with the level of diversity in the encoding nucleotide sequences, suggesting that a key feature of public TCRs is that they can be made in a variety of ways. Using a computer simulation of random V(D)J recombination, we estimated the relative production frequencies and variety of production mechanisms for TCR beta sequences and found strong correlations with the sharing of both TCR beta amino acid sequences and TCR beta nucleoticle sequences. The overall conclusion is that "convergent recombination," rather than a bias in recombination or subsequent selection, provides the mechanistic basis for TCR sharing between individuals responding to identical peptide plus MHC class I glycoprotein complexes. C1 Univ New S Wales, Ctr Vasc Res, Kensington, NSW, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. Natl Inst Allergy & Infect Dis, Vaccine Res Ctr, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Doherty, PC (reprint author), Prince Wales Hosp, Dept Haematol, Kensington, NSW 2052, Australia. EM peter.doherty@stjude.org; m.davenport@unsw.edu.au RI Price, David/C-7876-2013; Doherty, Peter Charles/C-4185-2013 OI Price, David/0000-0001-9416-2737; Kedzierska, Katherine/0000-0001-6141-335X; Doherty, Peter Charles/0000-0002-5028-3489 FU Medical Research Council [G108/441] NR 28 TC 60 Z9 62 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 2006 VL 103 IS 49 BP 18691 EP 18696 DI 10.1073/pnas.0608907103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 114TZ UT WOS:000242689800056 PM 17130450 ER PT J AU Nakayama, K Nakayama, N Davidson, B Sheu, JJC Jinawath, N Santillan, A Salani, R Bristow, RE Morin, PJ Kurman, RJ Wang, TL Shih, IM AF Nakayama, Kentaro Nakayama, Naomi Davidson, Ben Sheu, Jim J. -C. Jinawath, Natini Santillan, Antonio Salani, Ritu Bristow, Robert E. Morin, Patrice J. Kurman, Robert J. Wang, Tian-Li Shih, Ie-Ming TI A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE oncogene; ovarian cancer; serial analysis of gene expression ID OVARIAN-CANCER; GENE-EXPRESSION; SURGICAL CYTOREDUCTION; INTERACTION MOTIF; CARCINOMA; COCAINE; DOMAIN; COMPLEXES; LEUKEMIA; POKEMON AB Recent studies have suggested an oncogenic role of the BTB/POZ-domain genes in hematopoietic malignancy. The aim of this study is to identify and characterize BTB/POZ-domain genes in the development of human epithelial cancers, i.e., carcinomas. In this study, we focused on ovarian carcinoma and analyzed gene expression levels using the serial analysis of gene expression (SAGE) data in all 130 deduced BTB/POZ genes. Our analysis reveals that NAC-1 is significantly overexpressed in ovarian serous carcinomas and several other types of carcinomas. Immunohistochemistry studies in ovarian serous carcinomas demonstrate that NAC-1 is localized in discrete nuclear bodies (tentatively named NAC-1 bodies), and the levels of NAC-1 expression correlate with tumor recurrence. Furthermore, intense NAC-1 immunoreactivity in primary tumors predicts early recurrence in ovarian cancer. Both coimmunoprecipitation and double immunofluorescence staining demonstrate that NAC-1 molecules homooligomerize through the BTB/POZ domain. Induced expression of the NAC-1 mutant containing only the BTB/POZ domain disrupts NAC-1 bodies, prevents tumor formation, and promotes tumor cell apoptosis in established tumors in a mouse xenograft model. Overexpression of full-length NAC-1 enhanced tumorigenicity of ovarian surface epithelial cells and NIH 3T3 cells in athymic nu/nu mice. In summary, NAC-1 is a tumor recurrence-associated gene with oncogenic potential, and the interaction between BTB/POZ domains of NAC-1 proteins is critical to form the discrete NAC-1 nuclear bodies and essential for tumor cell proliferation and survival. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21231 USA. Johns Hopkins Med Inst, Dept Gynecol & Obstet, Baltimore, MD 21231 USA. Norwegian Radium Hosp, Oslo 0310, Norway. NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. RP Shih, IM (reprint author), Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA. EM ishih@jhmi.edu RI Salani, Ritu/E-4008-2011 FU NCI NIH HHS [CA 103937, R01 CA103937, R01 CA103937-03] NR 32 TC 75 Z9 83 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 5 PY 2006 VL 103 IS 49 BP 18739 EP 18744 DI 10.1073/pnas.0604083103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 114TZ UT WOS:000242689800064 PM 17130457 ER PT J AU Troisi, R Masters, MN Joshipura, K Douglass, C Cole, BF Hoover, RN AF Troisi, R. Masters, M. N. Joshipura, K. Douglass, C. Cole, B. F. Hoover, R. N. CA Natl Osteosarcoma Etiology Grp TI Perinatal factors, growth and development, and osteosarcoma risk SO BRITISH JOURNAL OF CANCER LA English DT Article DE osteosarcoma; birth weight; height; growth; puberty ID CHILDHOOD; STATURE; TUMORS; BONE AB Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients (n = 158) and controls with benign orthopaedic conditions (n = 141) under age 40 were recruited from US orthopaedic surgery departments. Exposures were ascertained by interview, birth, and growth records. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age- and sex-specific height percentiles were not associated with osteosarcoma risk. Male cases, however, appeared to have an earlier adolescent growth period, and earlier attainment of final height (OR = 7.1; 95% CI = 1.6-50 for < 19 vs 19 + years), whereas earlier puberty appeared protective with ORs of 0.41 (95% CI 0.18-0.89) and 0.68 (95% CI 0.31-1.5) for developing facial and pubic hair, respectively. High birth weight was associated with an elevated osteosarcoma risk (OR = 3.9; CI = 1.7-10 for 4000 g vs 3000-3500 g), although there was no trend in risk with increasing weight. These data provide some evidence that osteosarcoma is related to size at birth and in early adolescence, while earlier puberty in male subjects may be protective. C1 NCI, Div Canc epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Westat Corp, Rockville, MD USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Univ Puerto Rico, San Juan, PR 00936 USA. RP Troisi, R (reprint author), NCI, Div Canc epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM troisir@mail.nih.gov OI Joshipura, Kaumudi/0000-0003-1964-7579 NR 14 TC 19 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 4 PY 2006 VL 95 IS 11 BP 1603 EP 1607 DI 10.1038/sj.bjc.6603474 PG 5 WC Oncology SC Oncology GA 115PI UT WOS:000242745800023 PM 17106438 ER PT J AU Motegi, A Sood, R Moinova, H Markowitz, SD Liu, PP Myung, K AF Motegi, Akira Sood, Raman Moinova, Helen Markowitz, Sanford D. Liu, Pu Paul Myung, Kyungjae TI Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GROSS CHROMOSOMAL REARRANGEMENTS; DEFECTIVE POSTREPLICATION REPAIR; DNA-POLYMERASE-ETA; SACCHAROMYCES-CEREVISIAE; MONOUBIQUITINATED PCNA; XERODERMA-PIGMENTOSUM; DAMAGE BYPASS; UBIQUITIN; RAD6; SUMO AB Differential modi. cations of proliferating cell nuclear antigen ( PCNA) determine DNA repair pathways at stalled replication forks. In yeast, PCNA monoubiquitination by the ubiquitin ligase (E3) yRad18 promotes translesion synthesis (TLS), whereas the lysine63 - linked polyubiquitination of PCNA by yRad5 (E3) promotes the error-free mode of bypass. The yRad5-dependent pathway is important to prevent genomic instability during replication, although its exact molecular mechanism is poorly understood. This mechanism has remained totally elusive in mammals because of the lack of apparent RAD5 homologues. We report that a putative tumor suppressor gene, SHPRH, is a human orthologue of yeast RAD5. SHPRH associates with PCNA, RAD18, and the ubiquitin-conjugating enzyme UBC13 (E2) and promotes methyl methanesulfonate (MMS)-induced PCNA polyubiquitination. The reduction of SHPRH by stable short hairpin RNA increases sensitivity to MMS and enhances genomic instability. Therefore, the yRad5/SHPRH-dependent pathway is a conserved and fundamental DNA repair mechanism that protects the genome from genotoxic stress. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, Genome Instabil Sect, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Howard Hughes Med Inst, Cleveland, OH 44106 USA. RP Myung, K (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, Genome Instabil Sect, NIH, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU Intramural NIH HHS NR 24 TC 103 Z9 111 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 4 PY 2006 VL 175 IS 5 BP 703 EP 708 DI 10.1083/jcb.200606145 PG 6 WC Cell Biology SC Cell Biology GA 115YP UT WOS:000242770000004 PM 17130289 ER PT J AU Stambolian, D Ibay, G Reider, L Dana, D Moy, C Schlifka, M Holmes, TN Ciner, E Bailey-Wilson, JE AF Stambolian, Dwight Ibay, Grace Reider, Lauren Dana, Debra Moy, Chris Schlifka, Melissa Holmes, Taura N. Ciner, Elise Bailey-Wilson, Joan E. TI Genome-wide scan of additional Jewish families confirms linkage of a myopia susceptibility locus to chromosome 22q12 SO MOLECULAR VISION LA English DT Article ID OCULAR REFRACTION; PARENTAL HISTORY; SIB-PAIR; HETEROGENEITY; PREVALENCE; ONSET; MAPS; SCHOOLCHILDREN; POPULATION; PREDICTORS AB PURPOSE: A genome-wide scan was previously reported for myopia in Ashkenazi Jews. In order to confirm the previous linkage peaks, a collection of DNA samples from 19 new Ashkenazi Jewish families were tested for linkage in a genome wide scan. METHODS: Families were ascertained from an Orthodox Ashkenazi Jewish community through mailings. Myopia was defined as equal to or greater than -1 diopter in both meridians in both eyes. The genome wide scan used markers from a modified Cooperative Human Linkage Center version 9 (402 markers). Parametric two-point linkage was calculated with FASTLINK while multipoint linkage was calculated with GENEHUNTER. RESULTS: The results for the 19 families demonstrated several regions of suggestive linkage on chromosomes 7, 1, 17, and 22. A combined analysis of the 19 families and 44 previously reported families demonstrated an increase in the LOD score to 4.73 for the chromosome 22 locus. CONCLUSIONS: Multiple chromosomal regions have exhibited some evidence of linkage to a myopia susceptibility gene in this Ashkenazi Jewish population. The strongest evidence of linkage to such a susceptibility gene in these data is on chromosome 22. C1 Univ Penn, Dept Ophthalmol, Stellar Chance Labs, Philadelphia, PA 19104 USA. NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. RP Stambolian, D (reprint author), Univ Penn, Dept Ophthalmol, Stellar Chance Labs, Room 313,422 Curie Blvd, Philadelphia, PA 19104 USA. EM stamboli@mail.med.upenn.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS; NEI NIH HHS [R01 EY012226] NR 49 TC 15 Z9 16 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 4 PY 2006 VL 12 IS 168-71 BP 1499 EP 1505 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 121AR UT WOS:000243129300004 PM 17167407 ER PT J AU Gallo, SA Reeves, JD Garg, H Foley, B Doms, RW Blumenthal, R AF Gallo, Stephen A. Reeves, Jacqueline D. Garg, Himanshu Foley, Brian Doms, Robert W. Blumenthal, Robert TI Kinetic studies of HIV-1 and HIV-2 envelope glycoprotein-mediated fusion SO RETROVIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP41 CYTOPLASMIC TAIL; CORECEPTOR-BINDING-SITE; LEUCINE-ZIPPER DOMAIN; MEMBRANE-FUSION; 6-HELIX BUNDLE; TRANSMEMBRANE PROTEIN; SYNTHETIC PEPTIDE; ENTRY INHIBITORS; ENV AB Background: HIV envelope glycoprotein (Env)-mediated fusion is driven by the concerted coalescence of the HIV gp41 N-helical and C-helical regions, which results in the formation of 6 helix bundles. Kinetics of HIV Env-mediated fusion is an important determinant of sensitivity to entry inhibitors and antibodies. However, the parameters that govern the HIV Env fusion cascade have yet to be fully elucidated. We address this issue by comparing the kinetics HIV-1(IIIB) Env with those mediated by HIV-2 from two strains with different affinities for CD4 and CXCR4. Results: HIV-1 and HIV-2 Env-mediated cell fusion occurred with half times of about 60 and 30 min, respectively. Binding experiments of soluble HIV gp120 proteins to CD4 and co-receptor did not correlate with the differences in kinetics of fusion mediated by the three different HIV Envs. However, escape from inhibition by reagents that block gp120-CD4 binding, CD4-induced CXCR4 binding and 6-helix bundle formation, respectively, indicated large difference between HIV-1 and HIV-2 envelope glycoproteins in their CD4-induced rates of engagement with CXCR4. Conclusion: The HIV-2 Env proteins studied here exhibited a significantly reduced window of time between the engagement of gp120 with CD4 and exposure of the CXCR4 binding site on gp120 as compared with HIV-1(IIIB) Env. The efficiency with which HIV-2 Env undergoes this CD4-induced conformational change is the major cause of the relatively rapid rate of HIV-2 Env mediated-fusion. C1 NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21701 USA. Los Alamos Natl Lab, Los Alamos, NM USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. RP Blumenthal, R (reprint author), NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21701 USA. EM sgallo@aibs.org; jreeves@MonogramBio.com; gargh@ncifcrf.gov; btf@lanl.gov; doms@mail.med.upenn.edu; blumen@helix.nih.gov RI Reeves, Jacqueline/I-5379-2012; OI Gallo, Stephen/0000-0001-6043-2153; Foley, Brian/0000-0002-1086-0296 FU Intramural NIH HHS; NIMHD NIH HHS [L60 MD003100] NR 43 TC 12 Z9 12 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 4 PY 2006 VL 3 AR 90 DI 10.1186/1742-4690-3-90 PG 8 WC Virology SC Virology GA 114DG UT WOS:000242646300001 PM 17144914 ER PT J AU Zerhouni, EA AF Zerhouni, Elias A. TI International medical graduates in the United States: A view from an ECFMG certificant SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Conference on Impact of International Medical Graduates on United and Statees and Global Health Care CY JUL 21-22, 2006 CL Philadelphia, PA SP ECFMG AB The author was instilled with a passion for mathematics and physics by his father, who taught those subjects in a small Algerian town. Another indelible influence came during a high school mathematics class when his teacher gave the class a problem to solve. Little did the students know that it was Fermat's Last Theorem, which stumped them, and before that, every mathematician since 1630. This experience taught the author that failing to get the final answer was part of learning. He became enchanted with imaging techniques and after earning his medical degree in Algeria, came to study at Johns Hopkins. There he received the training he desired in diagnostic radiology. The author believes science has no borders and would like to see the opportunities that were extended to him in 1975 given to immigrants today. Although the United States produces many graduates in the sciences and mathematics, the nation still has a shortfall and must, he argues, work harder to educate and inspire this country's youth in addition to welcoming the brightest and most able scientists from around the world. He also discusses the crucial role of the National Institutes of Health in furthering global health by funding international biomedical research and by transforming medicine in the 21st century. C1 NIH, Off Commun & Publ Liais, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Off Commun & Publ Liais, 9000 Rockville Pike,Room 344, Bethesda, MD 20892 USA. EM burklowj@od.nih.gov NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 2006 VL 81 IS 12 SU S BP S40 EP S42 DI 10.1097/01.ACM.0000243348.55441.3b PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 113WR UT WOS:000242629200008 PM 17086045 ER PT J AU Summers, RM Huang, A Yao, J Campbell, SR Dempsey, JE Dwyer, AJ Franaszek, M Brickman, DS Bitter, I Petrick, N Hara, AK AF Summers, Ronald M. Huang, Adam Yao, Jianhua Campbell, Shannon R. Dempsey, Jennifer E. Dwyer, Andrew J. Franaszek, Marek Brickman, Danny S. Bitter, Ingmar Petrick, Nicholas Hara, Amy K. TI Assessment of polyp and mass histopathology by intravenous contrast-enhanced CT colonography SO ACADEMIC RADIOLOGY LA English DT Article DE CT; colon; CT; 3D reconstruction; colon cancer; image processing; intravenous contrast enhancement ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL NEOPLASIA; VIRTUAL COLONOSCOPY; LESIONS; CANCER; SCREEN AB Rationale and Objectives. We sought to demonstrate that intravenous contrast-enhanced CT colonography (CTC) can distinguish colonic adenomas from carcinomas. Methods. Supine intravenous contrast-enhanced CTC with colonoscopic and/or surgical correlation was performed on 25 patients with colonic adenomas or carcinomas. Standard deviation of mean polyp CT attenuation was computed and assessed using ANOVA and receiver-operating characteristic analyses. Results. Colonoscopy confirmed 32 polyps or masses 1 to 8 cm in size. The standard deviations of CT attenuation were carcinomas (n = 13; 36 +/- 6 HU; range 28-48 HU) and adenomas (n = 19; 49 +/- 14 HU; range 31-100 HU) (P = 0.005). At a standard deviation threshold of 42 HU, the sensitivity and specificity for classifying a polyp or mass as a carcinoma were 92% and 79%, respectively. The area under the receiver-operating characteristic curve was 0.89 +/- 0.06 (95% confidence interval 0.73-0.96). Conclusions. Measurement of the standard deviation of CT attenuation on intravenous contrast-enhanced CTC permits histopathologic classification of polyps 1 cm or larger as carcinomas versus adenomas. The presence of ulceration or absence of muscular invasion in carcinomas creates overlap with adenomas, reducing the specificity of carcinoma classification. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Mayo Clin, Dept Radiol, Scottsdale, AZ 85259 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 15 TC 5 Z9 6 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2006 VL 13 IS 12 BP 1490 EP 1495 DI 10.1016/j.acra.2006.09.051 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 115LY UT WOS:000242737000007 PM 17138117 ER PT J AU Frentz, SM Summers, RM AF Frentz, Suzanne M. Summers, Ronald M. TI Current status of CT colonography SO ACADEMIC RADIOLOGY LA English DT Review ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; CONTRAST BARIUM ENEMA; MULTIDETECTOR ROW CT; AIDED POLYP DETECTION; VIRTUAL COLONOSCOPY; COLORECTAL-CANCER; CONVENTIONAL COLONOSCOPY; PREOPERATIVE EVALUATION; CATHARTIC PREPARATION; EXTRACOLONIC FINDINGS C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C351,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU CLC NIH HHS [Z01 CL040003-03]; Intramural NIH HHS NR 117 TC 12 Z9 12 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2006 VL 13 IS 12 BP 1517 EP 1531 DI 10.1016/j.acra.2006.09.056 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 115LY UT WOS:000242737000011 PM 17138120 ER PT J AU Wang, JW Dauter, M Dauter, Z AF Wang, Jiawei Dauter, Miroslawa Dauter, Zbigniew TI What can be done with a good crystal and an accurate beamline? SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID X-RAY-DIFFRACTION; CHROMIUM RADIATION; IN-HOUSE; ANOMALOUS SIGNAL; MACROMOLECULAR CRYSTALLOGRAPHY; PROTEIN CRYSTALLOGRAPHY; STRUCTURE REFINEMENT; MOUNTING METHOD; MODEL; SAD AB X-ray single-wavelength anomalous diffraction (SAD) data from a crystal of proteinase K were collected using synchrotron radiation of 0.98 angstrom wavelength at SER-CAT 22-ID beamline, Advanced Photon Source, Argonne National Laboratory. At this wavelength, the expected Bijvoet ratio resulting from the presence of one calcium, one chloride and ten S atoms in the 279-residue protein is extremely small at similar to 0.46%. The direct-methods program SHELXD located 11 anomalous sites using data truncated to 2 A resolution. SHELXE was used to produce an easily interpretable electron-density map. This study shows that an accurate beamline and a good-quality crystal provide the possibility of successfully using a very weak anomalous signal of sulfur measured at a short wavelength for phasing a protein structure, even if a small degree of radiation damage is present. C1 NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA. SAIC Frederick Inc, Basic Res Program, Argonne Natl Lab, Argonne, IL 60439 USA. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA. EM dauter@anl.gov FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 38 TC 18 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2006 VL 62 BP 1475 EP 1483 DI 10.1107/S0907444906038534 PN 12 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 108JW UT WOS:000242237100006 PM 17139083 ER PT J AU Snow, JB AF Snow, James B., Jr. TI Strategies of the tinnitus research consortium SO ACTA OTO-LARYNGOLOGICA LA English DT Article; Proceedings Paper CT Actualities on Thiazolidinediones Conference 2004 CY OCT 15, 2004 CL Paris, FRANCE DE animal models; confounding variables; electrical suppression of tinnitus; gabapentin; outcome measures; plasticity; questionnaires; selective serotonin reuptake inhibitor antidepressants; somatic tinnitus; tinnitus retraining therapy ID INTENSE SOUND AB Conclusions: Research supported by private philanthropy complements governmental support of research, and its organization can undertake analysis of the whole field, identify the initial steps required to advance the field, draw attention to the intellectual challenge of a field such as tinnitus, recruit scientists to a neglected area, direct support to the most promising research approaches and opportunities, and dedicate support to those endeavors. Objectives: The efforts of the Tinnitus Research Consortium (TRC) are to accelerate progress in basic and clinical research on tinnitus. Methods: The TRC analyzes the field of tinnitus research, brainstorms for new research approaches to tinnitus and provides guidance to the scientific community through requests for applications (RFAs) on promising research approaches and opportunities. The analysis of the research field has focused on the validity of animal models of tinnitus, the need for a standardized outcome measure in clinical trials, and the control of confounding variables in basic and clinical studies of the mechanisms of and site(s) associated with tinnitus. Results: The TRC judged that the existing animal models were worthy of further study and refinement and that additional animal models should be developed. In response to an RFA, a project for the development and validation of the new Tinnitus Functional Index was initiated. A confounding aspect of experimental induction of tinnitus is the occurrence of hearing loss. The experimental manipulation causing the hearing loss may or may not cause tinnitus. Segregation of the correlates of tinnitus from the consequences of hearing loss requires the inclusion of a second control group: animals that have been subjected to the manipulation for the induction of tinnitus and have a hearing loss but fail to exhibit signs of tinnitus. Comparison of normal animals, animals with hearing loss without tinnitus and animals with hearing loss and tinnitus greatly enhances the value of the research. Clinical research on the mechanisms and sites of tinnitus is also confounded by this problem, and the solution is to include controls matched for hearing loss without tinnitus. C1 Tinnitus Res Consortium, W Grove, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Snow, JB (reprint author), 327 Greenbriar Lane, W Grove, PA 19390 USA. EM jandssnow@comcast.net NR 12 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD DEC PY 2006 VL 126 SU 556 BP 89 EP 92 DI 10.1080/03655230600895325 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 123XG UT WOS:000243329700017 ER PT J AU Lee, GD Wilson, MA Zhu, M Wolkow, CA de Cabo, R Ingram, DK Zou, SG AF Lee, Garrick D. Wilson, Mark A. Zhu, Min Wolkow, Catherine A. de Cabo, Rafael Ingram, Donald K. Zou, Sige TI Dietary deprivation extends lifespan in Caenorhabditis elegans SO AGING CELL LA English DT Article DE ad libitum; aging; Caenorhabditis elegans; calorie restriction; dietary restriction; reproduction ID DAUER LARVA FORMATION; CALORIC RESTRICTION; C-ELEGANS; DROSOPHILA-MELANOGASTER; SIGNALING PATHWAY; OXIDATIVE STRESS; LONGEVITY; DAF-16; GENES; LONG AB Dietary restriction (DR) is well known as a nongenetic intervention that robustly extends lifespan in a variety of species; however, its underlying mechanisms remain unclear. We have found in Caenorhabditis elegans that dietary deprivation (DD) during adulthood, defined as removal of their food source Escherichia coli after the completion of larval development, increased lifespan and enhanced thermotolerance and resistance to oxidative stress. DD-induced longevity was independent of one C. elegans SIRTUIN, sir-2.1, which is required for the effects of DR, and was independent of the daf-2/insulin-like signaling pathway that independently regulates longevity and larval diapause in C. elegans. DD did not significantly alter lifespan of fem-1(hc17); eat-2(ad465) worms, a genetic model of DR. These findings suggest that DD and DR share some downstream effectors. In addition, DD was detrimental for longevity when imposed on reproductively active young adults, suggesting that DD may only be beneficial in the absence of competing metabolic demands, such as fertility. Adult-onset DD offers a new paradigm for investigating dietary regulation of longevity in C. elegans. This study presents the first evidence that long-term DD, instead of being detrimental, can extend lifespan of a multicellular adult organism. C1 NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutrit Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. RP Zou, SG (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS [NIH0011061953, Z01 AG000320-06] NR 55 TC 137 Z9 145 U1 5 U2 29 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2006 VL 5 IS 6 BP 515 EP 524 DI 10.1111/j.1474-9726.2006.00241.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 107VI UT WOS:000242198700008 PM 17096674 ER PT J AU Maraldi, C Ble, A Zuliani, G Guralnik, JM Mussi, C Fellin, R Volpato, S AF Maraldi, Cinzia Ble, Alessandro Zuliani, Giovanni Guralnik, Jack M. Mussi, Chiara Fellin, Renato Volpato, Stefano TI Association between anemia and physical disability in older patients: role of comorbidity SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; anemia; comorbidity; disability; epidemiology ID QUALITY-OF-LIFE; EXPENDITURES; PERFORMANCE; PREVALENCE; PARAMETERS; PREDICTORS; INCHIANTI; PEOPLE; INDEX; HOME AB Background and aims: In older persons, anemia is a common medical disorder and is often associated with comorbidity and poor health outcomes. We evaluated the relationship between anemia and physical disability in a sample of older hospitalized patients, taking into account the role of comorbidity. Methods: Cross-sectional analysis of the baseline data of the Italian Group of Pharmacoepidemiology in the Elderly Study. Patients aged 65 years or older (n=10,903), admitted to participating centers in the 1993-1998 survey period, were included. Anemia was defined according to the World Health Organization (WHO) criteria; physical disability was defined as need for assistance in performing at least one Activity of Daily Living (ADL) in the week before admission. Comorbidity was ascertained using the Charlson Index. Results: Prevalence of anemia was 41.1%. In the unadjusted analysis, anemia was associated with increased likelihood of disability, in both women (Odds Ratio [OR]: 1.54; 95% Confidence Interval [Cl]: 1.38-1.71) and men (OR 1.70; CI 1.52-1.90). After inclusion of demographics and life-style factors in multiuariate analysis, the strength of association was only modestly attenuated, whereas nutritional factors and disease-related variables resulted in a greater reduction of the strength of association. In analyses stratified by comorbidity severity, the association between anemia and disability was statistically significant only in patients with the lowest comorbidity levels (p for anemia*Charlson Index interaction term < 0.05, in both women and men). Conclusions: Among hospitalized subjects, anemia is associated with ADL disability. The disablement process associated with anemia may be partially explained by nutritional and disease-related factors. However, anemia appears to have an independent effect, particularly in subjects with low comorbidity. C1 Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. NIH, NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, JMG, Bethesda, MD 20892 USA. Univ Modena, Geriatr Sect, I-41100 Modena, Italy. RP Volpato, S (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy. EM vlt@unife.it RI Mussi, Chiara/G-3955-2016; VOLPATO, STEFANO/H-2977-2014 OI Mussi, Chiara/0000-0001-5598-9969; VOLPATO, STEFANO/0000-0003-4335-6034 NR 30 TC 13 Z9 13 U1 3 U2 3 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 DEC PY 2006 VL 18 IS 6 BP 485 EP 492 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 137UD UT WOS:000244316900004 PM 17255637 ER PT J AU Boyce-Rustay, JM Wiedholz, LM Millstein, RA Carroll, J Murphy, DL Daws, LC Holmes, A AF Boyce-Rustay, Janel M. Wiedholz, Lisa M. Millstein, Rachel A. Carroll, Jenna Murphy, Dennis L. Daws, Lynette C. Holmes, Andrew TI Ethanol-related behaviors in serotonin transporter knockout mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE EtOH; serotonin transporter; knockout; antidepressant; reward ID GENE REGULATORY REGION; EARLY-ONSET ALCOHOLISM; BRAIN-SEROTONIN; REUPTAKE INHIBITORS; PLACE PREFERENCE; COCAINE REWARD; DEFICIENT MICE; ANIMAL-MODELS; SWIM TEST; CONSUMPTION AB Background: Increasing evidence supports a role for 5-hydroxytryptamine (5-HT) and the 5-HT transporter (5-HTT) in modulating the neural and behavioral actions of ethanol (EtOH) and other drugs of abuse. Methods: We used a 5-HTT knockout (KO) mouse model to further study this relationship. 5-Hydroxytryptamine transporter KO mice were tested for the sedative/hypnotic, hypothermia-inducing, motor-incoordinating (via accelerating rotarod), and depression-related (via tail suspension test) effects of acute EtOH administration. Reward-related effects of EtOH were assessed in 5-HTT KO mice using the conditioned place preference (CPP) paradigm. 5-Hydroxytryptamine transporter KO mice were tested for voluntary consumption of EtOH in a modified 2-bottle choice test that measured the temporal organization of drinking over the circadian cycle via "lickometers." Results: Replicating previous findings, 5-HTT KO mice exhibited significantly increased sensitivity to EtOH-induced sedation/hypnosis relative to wild-type controls. Additionally, 5-HTT KO mice showed motor-coordination deficits at baseline and in response to EtOH. Hypothermic, pro-depressive-like, and reward-related effects of EtOH were no different across genotypes. Gross EtOH consumption was modestly reduced in 5-HTT KO mice, due to significantly lesser consumption during the peak period of drinking in the early dark phase. Conclusions: Data extend the finding that loss of 5-HTT gene function alters certain neural and behavioral effects of EtOH, with implications for better understanding the pathophysiology and treatment of alcoholism. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78285 USA. RP Boyce-Rustay, JM (reprint author), Abbott Labs, R4CY AP13A-2,100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM janel.boyce-rustay@abbott.com FU Intramural NIH HHS NR 65 TC 59 Z9 59 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2006 VL 30 IS 12 BP 1957 EP 1965 DI 10.1111/j.1530-0277.2006.00241.x PG 9 WC Substance Abuse SC Substance Abuse GA 105OQ UT WOS:000242041800001 PM 17117959 ER PT J AU Ding, JZ Nicklas, BJ Fallin, MD de Rekeneire, N Kritchevsky, SB Pahor, M Rodondi, N Li, RL Zmuda, JM Harris, TB AF Ding, Jingzhong Nicklas, Barbara J. Fallin, Margaret D. de Rekeneire, Nathalie Kritchevsky, Stephen B. Pahor, Marco Rodondi, Nicolas Li, Rongling Zmuda, Joseph M. Harris, Tamara B. TI Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; 4G/5G POLYMORPHISM; PAI-1 GENE; INSERTION/DELETION POLYMORPHISM; 4G/4G GENOTYPE; PROMOTER; RISK; MORTALITY; HISTORY; COHORT AB Background The 4G allele in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene is associated with higher plasma PAI-1 levels and activity, but its association with cardiovascular diseases is unclear. We investigated the association of polymorphisms and common haplotypes of the PAI-1 gene with plasma PAI-1 levels, as well as the risk of myocardial infarction and stroke. Methods and Results This study is a prospective analysis of 2995 community-based participants (41% blacks and 51% women) aged 70 to 79 years old in the Health, Aging, and Body Composition Study. From 1997/1998 to 200 1, 177 myocardial infarction events and 101 stroke events were identified. In addition to the 4G/5G polymorphism, 2 potential functional variants and other 4 haplotype-tagging variants were genotyped. In general linear models, the 4G allele was associated with higher PAI-1 levels after adjusting for age, sex, race, and site (26, 29, and 32 ng/mL for 5G/5G, 4G/5G, and 4G/4G, respectively; P for trend < .0001), but none of the other 6 polymorphisms was associated with PAI-1 levels. Haplotype analysis produced similar results. However, in Cox proportional hazard models, neither the polymorphisms nor the common haplotypes of the PAI-1 gene was associated with the risk of either myocardial infarction or stroke. Conclusions The 4G allele is associated with higher PAI-1 levels, but this study does not support an association of the PAI gene polymorphisms with the risk of either myocardial infarction or stroke. C1 Wake Forest Univ, Baptist Med Ctr, Dept Internal Med Geriatr, Winston Salem, NC 27157 USA. Wake Forest Univ, Ctr Human Genom, Baptist Med Ctr, Winston Salem, NC 27157 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Ding, JZ (reprint author), Wake Forest Univ, Baptist Med Ctr, Dept Internal Med Geriatr, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jding@wfubmc.edu OI Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2102, N01-AG-6-2106, P30-AG21332] NR 26 TC 44 Z9 45 U1 0 U2 0 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 DEC PY 2006 VL 152 IS 6 BP 1109 EP 1115 DI 10.1016/j.ahj.2006.06.021 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120TZ UT WOS:000243110400022 PM 17161063 ER PT J AU Cabral, ES Auerbaeh, A Killian, JK Barrett, TL Cassarino, DS AF Cabral, Erik S. Auerbaeh, Aaron Killian, J. Keith Barrett, Terry L. Cassarino, David S. TI Distinction of benign sebaceous proliferations from sebaceous carcinomas by immunohistochemistry SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE sebaceous adenoma; sebaceoma; sebaceous carcinoma; sebaceous hyperplasia ID ANDROGEN RECEPTORS; GLAND CARCINOMA; OCULAR ADNEXA; EXPRESSION; P53; DIFFERENTIATION; C-ERBB-2; ANTIGEN; PROTEIN; EYELIDS AB Sebaceous lesions, including sebaceous hyperplasia, sebaceomas. and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD 117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant. C1 Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. Armed Forces Inst Pathol, Dept Hematopathol, Washington, DC 20306 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75230 USA. RP Cassarino, DS (reprint author), Stanford Univ, Med Ctr, Dept Pathol, 300 Pasteur Lane,Room H2122, Stanford, CA 94305 USA. EM dcassari@stanford.edu NR 21 TC 34 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD DEC PY 2006 VL 28 IS 6 BP 465 EP 471 DI 10.1097/01.dad.0000245200.65600.a4 PG 7 WC Dermatology SC Dermatology GA 172GR UT WOS:000246792600001 PM 17122489 ER PT J AU Raimondi, S Paracchini, V Autrup, H Barros-Dios, JM Benhamou, S Boffetta, P Cote, ML Dialyna, IA Dolzan, V Filiberti, R Garte, S Hirvonen, A Husgafvel-Pursiainen, K Imyanitov, EN Kalina, I Kang, D Kiyohara, C Kohno, T Kremers, P Lan, Q London, S Povey, AC Rannug, A Reszka, E Risch, A Romkes, M Schneider, J Seow, A Shields, PG Sobti, RC Sorensen, M Spinola, M Spitz, MR Strange, RC Stucker, I Sugimura, H To-Figueras, J Tokudome, S Yang, P Yuan, JM Warholm, M Taioli, E AF Raimondi, S. Paracchini, V. Autrup, H. Barros-Dios, J. M. Benhamou, S. Boffetta, P. Cote, M. L. Dialyna, I. A. Dolzan, V. Filiberti, R. Garte, S. Hirvonen, A. Husgafvel-Pursiainen, K. Imyanitov, E. N. Kalina, I. Kang, D. Kiyohara, C. Kohno, T. Kremers, P. Lan, Q. London, S. Povey, A. C. Rannug, A. Reszka, E. Risch, A. Romkes, M. Schneider, J. Seow, A. Shields, P. G. Sobti, R. C. Sorensen, M. Spinola, M. Spitz, M. R. Strange, R. C. Stucker, I. Sugimura, H. To-Figueras, J. Tokudome, S. Yang, P. Yuan, J-M. Warholm, M. Taioli, E. TI Meta- and pooled analysis of GSTT1 and lung cancer: A HuGE-GSEC review SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE disease susceptibility; epidemiology; genes; genetic predisposition to disease; GSTT1; lung neoplasms; meta-analysis ID GLUTATHIONE-S-TRANSFERASE; ENVIRONMENTAL TOBACCO-SMOKE; GENETIC-POLYMORPHISM; CHROMOSOMAL LOCALIZATION; ADENOCARCINOMA SUSCEPTIBILITY; INDIVIDUAL SENSITIVITY; GSTP1 POLYMORPHISMS; TISSUE DISTRIBUTION; EPOXIDE HYDROLASE; ETHYLENE-OXIDE AB Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15232 USA. Policlin Milano, Milan, Italy. Univ Aarhus, Inst Publ Hlth, DK-8000 Aarhus C, Denmark. Univ Santiago de Compostela, Dept Prevent Med & Publ Hlth, Santiago De Compostela, Spain. INSERM, Evry, France. Evry Univ, Evry, France. Int Agcy Res Canc, Genet & Epidemiol Cluster, F-69372 Lyon, France. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Univ Crete, Dept Virol, Iraklion, Greece. Univ Ljubljana, Inst Biochem, Ljubljana 61000, Slovenia. Natl Inst Canc Res, Dept Epidemiol & Biostat, Genoa, Italy. Res Genet Inc, Milan, Italy. Finnish Inst Occupat Hlth, Helsinki, Finland. NN Petrov Oncol Res Inst, St Petersburg 188646, Russia. Safarik Univ, Sch Med, Dept Med Biol, Kosice 04154, Slovakia. Seoul Natl Univ, Inst Environm Med, Seoul 151, South Korea. Kyushu Univ, Grad Sch Med Sci, Dept Prevent Med, Fukuoka 812, Japan. Natl Inst Canc Res, Div Biol, Tokyo, Japan. Inst Pathol, Serv Med Chem, Liege, Belgium. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Manchester, Ctr Occupat & Environm Hlth, Manchester M13 9PL, Lancs, England. Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. Inst Occupat Med, Dept Toxicol & Carcinogenesis, Lodz, Poland. DKFZ German Canc Res Ctr, Dept Toxicol & Canc Risk Factors, Heidelberg, Germany. Univ Giessen, Inst Occupat & Social Med, D-35390 Giessen, Germany. Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. Georgetown Univ, Med Ctr, Canc Genet & Epidemiol, Washington, DC 20007 USA. Panjab Univ, Dept Biotechnol, Chandigarh 160014, India. Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark. Ist Nazl Tumori, Dept Expt Oncol, I-20133 Milan, Italy. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Keele, N Staffordshire Hosp, Ctr Cell & Mol Med, Keele ST5 5BG, Staffs, England. INSERM, Unit Epidemiol Stat Res Environm & Hlth, F-94800 Villejuif, France. Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 43131, Japan. Hosp Clin Prov Toxicol Unit, Barcelona, Spain. Nagoya City Univ, Grad Sch Med Sci, Dept Hlth Promot & Prevent Med, Mizuho Ku, Nagoya, Aichi 467, Japan. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. RP Taioli, E (reprint author), Univ Pittsburgh, Dept Epidemiol, 5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM taiolien@upmc.edu RI Shields, Peter/I-1644-2012; Kang, Dae Hee/E-8631-2012; Benhamou, Simone/K-6554-2015; Raimondi, Sara/J-5236-2016; Risch, Angela/H-2669-2013; OI Raimondi, Sara/0000-0003-4673-9049; Risch, Angela/0000-0002-8026-5505; Sorensen, Mette/0000-0002-7302-4789; Yuan, Jian-Min/0000-0002-4620-3108; London, Stephanie/0000-0003-4911-5290 NR 105 TC 95 Z9 98 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2006 VL 164 IS 11 BP 1027 EP 1042 DI 10.1093/aje/kwj321 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000001 PM 17000715 ER PT J AU Howards, PP Hertz-Picciotto, I AF Howards, Penelope P. Hertz-Picciotto, Irva TI Invited commentary: Disinfection by-products and pregnancy loss - Lessons SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID SPONTANEOUS-ABORTION; DRINKING-WATER; RECURRENT MISCARRIAGE; EXPOSURE ASSESSMENT; GENE POLYMORPHISMS; BROMODICHLOROMETHANE; ASSOCIATION; WEIGHT; RISK; RECEPTOR C1 Univ Calif Davis, Dept Publ Hlth Sci, Div Environm & Occupat Hlth, Davis, CA 95616 USA. Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Hertz-Picciotto, I (reprint author), Univ Calif Davis, Dept Publ Hlth Sci, Div Environm & Occupat Hlth, TB 168, Davis, CA 95616 USA. EM ihp@ucdavis.edu FU Intramural NIH HHS; NCI NIH HHS [1 R01-CA96525]; NIEHS NIH HHS [1 P01-ES11269] NR 25 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2006 VL 164 IS 11 BP 1052 EP 1055 DI 10.1093/aje/kwj301 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000003 PM 16957028 ER PT J AU Hernandez-Diaz, S Schisterman, EF Hernan, MA AF Hernandez-Diaz, Sonia Schisterman, Enrique F. Hernan, Miguel A. TI The birth weight "paradox" uncovered? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth weight; confounding factors (epidemiology); infant; low birth weight; infant mortality; smoking ID LOWER MORTALITY-RATE; PERINATAL-MORTALITY; CAUSAL DIAGRAMS; SMOKING; EPIDEMIOLOGY; KNOWLEDGE; INFERENCE; TIME AB Low birth weight (LBW) infants have lower infant mortality in groups in which LBW is most frequent. For example, in 1991, US infants born to smokers had higher risks of both LBW and infant mortality than infants born to nonsmokers. However, among LBW infants, infant mortality was lower for infants born to smokers (relative rate = 0.79). There are competing theories regarding this so-called "paradox." One is that maternal smoking is beneficial for LBW infants. The authors use causal diagrams to show that, even in the absence of any beneficial effect of smoking, an inverse association due to stratification on birth weight can be found. This variable is affected by the exposure of interest and shares common causes with the outcome. That is, LBW infants born to smokers may have a lower risk of mortality than other LBW infants whose LBW is due to causes associated with high mortality (e.g., birth defects). Under realistic causal diagrams, adjustment for birth weight is unwarranted when the analytical goal is to estimate overall effects of prenatal variables on infant mortality. Even for estimating direct effects of prenatal variables, adjustment for birth weight may be invalid when there is an unmeasured common cause of LBW and mortality. An appropriate justification for conditioning on birth weight requires specifying 1) the causal question motivating this analytical approach and 2) the assumptions regarding the proposed underlying biologic mechanisms. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. RP Hernandez-Diaz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM shernan@hsph.harvard.edu OI Schisterman, Enrique/0000-0003-3757-641X FU NIAID NIH HHS [K08-AI 49392] NR 24 TC 109 Z9 109 U1 5 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2006 VL 164 IS 11 BP 1115 EP 1120 DI 10.1093/aje/kwj275 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000010 PM 16931543 ER PT J AU Wilcox, AJ AF Wilcox, Allen J. TI Invited commentary: The perils of birth weight - A lesson from directed acyclic graphs SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE birth weight; confounding factors (epidemiology); infant; low birth weight; infant mortality; smoking ID MORTALITY AB The strong association of birth weight with infant mortality is complicated by a paradoxical finding: Small babies in high-risk populations usually have lower risk than small babies in low-risk populations. In this issue of the Journal, Hernandez-Diaz et al. (Am J Epidemiol 2006;164:1115-20) address this "birth weight paradox" using directed acyclic graphs (DAGs). They conclude that the paradox is the result of bias created by adjustment for a factor (birth weight) that is affected by the exposure of interest and at the same time shares causes with the outcome (mortality). While this bias has been discussed before, the DAGs presented by Hernandez-Diaz et al. provide more firmly grounded criticism. The DAGs demonstrate (as do many other examples) that seemingly reasonable adjustments can distort epidemiologic results. In this commentary, the birth weight paradox is shown to be an illustration of Simpson's Paradox. It is possible for a factor to be protective within every stratum of a variable and yet be damaging overall. Questions remain as to the causal role of birth weight. C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM wilcox@niehs.nih.gov OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 9 TC 13 Z9 13 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2006 VL 164 IS 11 BP 1121 EP 1123 DI 10.1093/aje.kwj276 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000011 PM 16931545 ER PT J AU Hernandez-Diaz, S Schisterman, EF Hernan, MA AF Hernandez-Diaz, Sonia Schisterman, Enrique F. Hernan, Miguel A. TI Hernandez-Diaz et al. Respond to "The perils of birth weight" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID DEFECTS EPIDEMIOLOGY C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. RP Hernandez-Diaz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM shernan@hsph.harvard.edu OI Schisterman, Enrique/0000-0003-3757-641X NR 8 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 DEC 1 PY 2006 VL 164 IS 11 BP 1124 EP 1125 DI 10.1093/aje/kwj277 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000012 ER PT J AU Howards, PP Hertz-Picciotto, I Weinberg, CR Poole, C AF Howards, Penelope P. Hertz-Picciotto, Irva Weinberg, Clarice R. Poole, Charles TI Misclassification of gestational age in the study of spontaneous abortion SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abortion; spontaneous; bias (epidemiology); gestational age; pregnancy; proportional hazards models ID LAST MENSTRUAL PERIOD; RUMP LENGTH MEASUREMENT; EXPECTANT MANAGEMENT; ULTRASOUND ASSESSMENT; RANDOMIZED-TRIAL; PREGNANCY; WOMEN; DATE; EPIDEMIOLOGY; DELIVERY AB Most studies of spontaneous abortion are subject to left truncation, because conception is not observed and thus pregnant women are enrolled postconception. Cox regression can account for left truncation but uses gestational age data, which may be inaccurate. Dating is affected by reporting errors and variability in the day of ovulation. These errors may be differential by outcome, because gestational ages are more likely to be clinically corrected in continuing pregnancies than in pregnancies ending in spontaneous abortion. Errors may be differential by exposure status as well, if exposures affect the time of ovulation. The authors designed a simulation to examine bias caused by errors in gestational age. Pregnancies were assigned true and alternative gestational ages using different assumptions about random reporting error and error due to variation in the time between the last menstrual period and ovulation. In separate scenarios, the errors were differential by outcome, differential by exposure, differential by both exposure and outcome, or nondifferential. Hazard ratios were compared using accurate versus erroneous gestational ages. For proportional hazards, bias was only introduced when the error in gestational age was differential by exposure status. Bias was greatest when the magnitude of error for pregnancies at higher risk was much larger than that for pregnancies at lower risk. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. Univ Calif Davis, Dept Publ Hlth Sci, Div Environm & Occupat Hlth, Davis, CA 95616 USA. Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. RP Howards, PP (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03C,MSC 7510, Rockville, MD 20852 USA. EM howardsp@mail.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [P30ES10126] NR 42 TC 9 Z9 9 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2006 VL 164 IS 11 BP 1126 EP 1136 DI 10.1093/aje/kwj327 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 108MX UT WOS:000242245000013 PM 16985078 ER PT J AU Weedon, MN Clark, VJ Qian, YD Ben-Shlomo, Y Timpson, N Ebrahim, S Lawlor, DA Pembrey, ME Ring, S Wilkin, TJ Voss, LD Jeffery, AN Metcalf, B Ferrucci, L Corsi, AM Murray, A Melzer, D Knight, B Shields, B Smith, GD Hattersley, AT Di Rienzo, A Frayling, TM AF Weedon, Michael N. Clark, Vanessa J. Qian, Yudong Ben-Shlomo, Yoav Timpson, Nicholas Ebrahim, Shah Lawlor, Debbie A. Pembrey, Marcus E. Ring, Susan Wilkin, Terry J. Voss, Linda D. Jeffery, Alison N. Metcalf, Brad Ferrucci, Luigi Corsi, Anna Maria Murray, Anna Melzer, David Knight, Bridget Shields, Bev Smith, George Davey Hattersley, Andrew T. Di Rienzo, Anna Frayling, Tim M. TI A common haplotype of the glucokinase gene alters fasting glucose and birth weight: Association in six studies and population-genetics analyses SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEPENDENT DIABETES-MELLITUS; LINKAGE DISEQUILIBRIUM; STATISTICAL-METHOD; MITOCHONDRIAL-DNA; BLOOD-GLUCOSE; FETAL GROWTH; RISK-FACTORS; FOLLOW-UP; POLYMORPHISM; EVOLUTION AB Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P = 10(-9)). rs3757840 was also highly significantly associated with fasting glucose (P = 8 x 10(-7)), but haplotype analysis revealed that this is explained by linkage disequilibrium (r(2) = 0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P = .002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth. C1 Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Bristol, Dept Social Med, Bristol BS8 1TH, Avon, England. Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 1TH, Avon, England. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. Peninsula Med Sch, Dept Endocrinol & Metab, Plymouth, Devon, England. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. Natl Inst Res & Care Aging, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. RP Frayling, TM (reprint author), Peninsula Med Sch, Inst Biomed & Clin Sci, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM Tim.Frayling@pms.ac.uk RI Fox, Laura /C-6249-2016; Davey Smith, George/A-7407-2013; OI Davey Smith, George/0000-0002-1407-8314; Monsalve, Beatriz Elena/0000-0002-5994-866X; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS [Z99 AG999999]; Medical Research Council [G0500070, G9815508]; NIDDK NIH HHS [R01 DK056670, DK66974, F32 DK066974] NR 47 TC 84 Z9 85 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2006 VL 79 IS 6 BP 991 EP 1001 DI 10.1086/509517 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 106WB UT WOS:000242131600001 PM 17186458 ER PT J AU Chatterjee, N Kalaylioglu, Z Moslehi, R Peters, U Wacholder, S AF Chatterjee, Nilanjan Kalaylioglu, Zeynep Moslehi, Roxana Peters, Ulrike Wacholder, Sholom TI Powerful multilocus tests of genetic association in the presence of gene-gene and gene-environment interactions SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE ANALYSIS; N-ACETYLTRANSFERASE; COMPLEX DISEASES; NAT2 ALLOZYMES; GENOTYPE DATA; HUMAN GENOME; TRAITS; STRATEGIES; MAP AB In modern genetic epidemiology studies, the association between the disease and a genomic region, such as a candidate gene, is often investigated using multiple SNPs. We propose a multilocus test of genetic association that can account for genetic effects that might be modified by variants in other genes or by environmental factors. We consider use of the venerable and parsimonious Tukey's 1-degree-of-freedom model of interaction, which is natural when individual SNPs within a gene are associated with disease through a common biological mechanism; in contrast, many standard regression models are designed as if each SNP has unique functional significance. On the basis of Tukey's model, we propose a novel but computationally simple generalized test of association that can simultaneously capture both the main effects of the variants within a genomic region and their interactions with the variants in another region or with an environmental exposure. We compared performance of our method with that of two standard tests of association, one ignoring gene-gene/gene-environment interactions and the other based on a saturated model of interactions. We demonstrate major power advantages of our method both in analysis of data from a case-control study of the association between colorectal adenoma and DNA variants in the NAT2 genomic region, which are well known to be related to a common biological phenotype, and under different models of gene-gene interactions with use of simulated data. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Informat Management Syst, Rockville, MD USA. RP Chatterjee, N (reprint author), 6120 Execut Blvd,EPS 8038, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU Intramural NIH HHS NR 39 TC 103 Z9 103 U1 0 U2 3 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 DEC PY 2006 VL 79 IS 6 BP 1002 EP 1016 DI 10.1086/509704 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 106WB UT WOS:000242131600002 PM 17186459 ER PT J AU Riazuddin, S Ahmed, ZM Fanning, AS Lagziel, A Kitajiri, S Ramzan, K Khan, SN Chattaraj, P Friedman, PL Anderson, JM Belyantseva, IA Forge, A Riazuddin, S Friedman, TB AF Riazuddin, Saima Ahmed, Zubair M. Fanning, Alan S. Lagziel, Ayala Kitajiri, Shin-ichiro Ramzan, Khushnooda Khan, Shaheen N. Chattaraj, Parna Friedman, Penelope L. Anderson, James M. Belyantseva, Inna A. Forge, Andrew Riazuddin, Sheikh Friedman, Thomas B. TI Tricellulin is a tight-junction protein necessary for hearing SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECESSIVE DEAFNESS DFNB29; INTERCELLULAR-JUNCTIONS; INNER-EAR; MOLECULAR PHYSIOLOGY; STRIA VASCULARIS; EPITHELIAL-CELLS; FREEZE-FRACTURE; MUTATIONS; OCCLUDIN; GENE AB The inner ear has fluid-filled compartments of different ionic compositions, including the endolymphatic and perilymphatic spaces of the organ of Corti; the separation from one another by epithelial barriers is required for normal hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ) protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues. We show that, in humans, four different recessive mutations of TRIC cause nonsyndromic deafness (DFNB49), a surprisingly limited phenotype, given the widespread tissue distribution of tricellulin in epithelial cells. In the inner ear, tricellulin is concentrated at the tricellular TJs in cochlear and vestibular epithelia, including the structurally complex and extensive junctions between supporting and hair cells. We also demonstrate that there are multiple alternatively spliced isoforms of TRIC in various tissues and that mutations of TRIC associated with hearing loss remove all or most of a conserved region in the cytosolic domain that binds to the cytosolic scaffolding protein ZO-1. A wild-type isoform of tricellulin, which lacks this conserved region, is unaffected by the mutant alleles and is hypothesized to be sufficient for structural and functional integrity of epithelial barriers outside the inner ear. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27515 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. NIH, Internal Med Consult Serv, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. UCL, Ear Inst, Ctr Auditory Res, London WC1E 6BT, England. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov RI Nasim Khan, Shaheen/F-2135-2015 FU Intramural NIH HHS; NIDCD NIH HHS [T32 DC000035, Z01 DC000035-08, Z01 DC000039, Z01 DC000039-08]; NIDDK NIH HHS [R56 DK061397, DK61397, R01 DK061397]; Wellcome Trust NR 43 TC 128 Z9 132 U1 0 U2 7 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 DEC PY 2006 VL 79 IS 6 BP 1040 EP 1051 DI 10.1086/510022 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 106WB UT WOS:000242131600005 PM 17186462 ER PT J AU Levey, AS Greene, T Samak, MJ Wang, X Beck, GJ Kusek, JW Collins, AJ Kopple, JD AF Levey, Andrew S. Greene, Tom Samak, Mark J. Wang, Xuelei Beck, Gerald J. Kusek, John W. Collins, Allan J. Kopple, Joel D. TI Effect of dietary protein restriction on the progression of kidney disease: Long-term follow-up of the Modification of Diet in Renal Disease (MDRD) study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol DE chronic kidney disease (CKD); low-protein diet; clinical trial ID BLOOD-PRESSURE; ANTIHYPERTENSIVE THERAPY; FAILURE; TRIAL; INSUFFICIENCY; METAANALYSIS; REQUIREMENTS; DECLINE; ADULTS AB Background The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown. We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study. Methods Study A was a randomized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate (25 to 55 mL/min/1.73 m(2) [0.42 to 0.92 mL/s/1.73 m(2)]) assigned to a low- versus usual-protein diet (0.58 versus 1.3 g/kg/d). We used registries to ascertain the development of kidney failure (initiation of dialysis therapy or transplantation) or a composite of kidney failure and all-cause mortality through December 31, 2000. We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet, adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate. We estimated hazard ratios for the entire follow-up period and then, in time-dependent analyses, separately for 2 consecutive 6-year periods of follow-up. Results Kidney failure and the composite outcome occurred in 327 (56%) and 380 patients (65%), respectively. After adjustment for baseline factors, hazard ratios were 0.89 (95% confidence interval [Cl], 0.71 to 1.12) and 0.88 (95% Cl, 0.71 to 1.08), respectively. Adjusted hazard ratios for both outcomes were lower during the first 6 years (0.68; 95% Cl, 0.51 to 0.93 and 0.66; 95% Cl, 0.50 to 0.87, respectively) than afterward (1.27; 95% Cl, 0.90 to 1.80 and 1.29; 95% Cl, 0.94 to 1.78; interaction P = 0.008 and 0.002, respectively). Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial. Conclusion: The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive. Future studies should include a longer duration of intervention and follow-up. C1 Tufts Univ, New England Med Ctr, Div Nephrol, Sch Med, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH USA. NIDDK, Bethesda, MD USA. Univ Minnesota, US Renal Data Syst, Sch Med, Minneapolis, MN 55455 USA. Univ Calif Los Angeles, Sch Publ Hlth, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Los Angels Biomed Res Inst Harbor, Div Nephrol, Los Angeles, CA 90024 USA. RP Levey, AS (reprint author), Tufts Univ, New England Med Ctr, Div Nephrol, Sch Med, Box 391,750 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [K23 DK 02904, UO1 DK 35073] NR 33 TC 50 Z9 57 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2006 VL 48 IS 6 BP 879 EP 888 DI 10.1053/j.ajkd.2006.08.023 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 197FW UT WOS:000248541000001 PM 17162142 ER PT J AU Tomona, N Smith, ACM Guadagnini, JP Hart, TC AF Tomona, Natalia Smith, Ann C. M. Guadagnini, Jean Pierre Hart, Thomas C. TI Craniofacial and dental phenotype of Smith-Magenis syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE del(17p11.2); hypodontia; taurodontism ID RAI1; PREVALENCE; MUTATIONS; DYSPLASIA; DELETION AB The aim of this study was to assess and characterize dental and craniofacial findings in individuals with a confirmed diagnosis of Smith-Magenis syndrome (SMS). Extraoral and intraoral examination including dental and craniofacial radiographs and three-dimensional facial photoimaging were performed for 15 cases between ages 4 and 19 years old. Tooth agenesis (13/15 cases) affecting primarily the mandibular second premolars and taurodontism (13/ 15 cases) were common findings. Dilaceration of the tooth roots was present in one-third of the cases. At least one dental anomaly was present in each case. These findings occur with greater frequency than in the general population (P < 0.001). An age-related increase in decayed and restored teeth was found. Poorer oral hygiene, increased dental plaque, and increased gingival inflammation progressed from childhood to teenage years. Radiographic findings suggest the prognathic appearance is not caused by excessive mandibular growth. Other findings including protrusion of the mandibular anterior teeth, increased bony chin size, and macroglossia were noted, which may contribute to the prognathic appearance. The high prevalence of dental anomalies (> 90%) further expands the phenotype and indicates that dental evaluation may aid in the diagnosis of SMS. Published 2006 Wiley-Liss, Inc. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Georgetown Univ, Sch Med, Washington, DC USA. RP Hart, TC (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 10 Ctr Dr,Bldg 10,Room 5-2531, Bethesda, MD 20892 USA. EM thart@mail.nih.gov FU Intramural NIH HHS NR 28 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2006 VL 140A IS 23 BP 2556 EP 2561 DI 10.1002/ajmg.a.31371 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 111PQ UT WOS:000242466100009 PM 17001665 ER PT J AU Ribeiro, LA El-Jaick, KB Muenke, M Richieri-Costa, A AF Ribeiro, Lucilene Arilho El-Jaick, Kenia B. Muenke, Maximilian Richieri-Costa, Antonio TI SIX3 mutations with holoprosencephaly SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE missense mutations; frameshift mutations; double mutation; severe phenotype ID GENE; SPECTRUM; SHH AB Here, we report six Brazilian patients with holoprosencephaly caused by SIX3 mutations. Missense mutations were more common than frameshift mutations. Comparison of patients with missense versus frameshift mutations was essentially Unremarkable. Our cases suggest that SIX3 mutations result in a more severe phenotype than other gene imitations for holoprosencephaly. One patient had a double SIX3 mutation, which has not been reported previously. In our SIX3 mutations, three were transmitted by the paternal side, two were transmitted by the m maternal side, and one was a de novo event. Mutations in normal parents with severe involvement of their offspring does not allow prediction of phenotypic severity, which makes genetic counseling difficult. (c) 2006 Wiley-Liss, Inc. C1 HRAC USP, Genet Mol Lab, BR-17012900 Bauru, SP, Brazil. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Richieri-Costa, A (reprint author), HRAC USP, Genet Mol Lab, POB 620,Rua Silvio Marchione 320, BR-17012900 Bauru, SP, Brazil. EM richieri@usp.br RI Richieri-Costa, Antonio/B-2514-2013; Ribeiro-Bicudo, Lucilene/G-9528-2013; OI Ribeiro-Bicudo, Lucilene/0000-0002-3716-336X NR 9 TC 21 Z9 22 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2006 VL 140A IS 23 BP 2577 EP 2583 DI 10.1002/ajmg.a.31377 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 111PQ UT WOS:000242466100012 PM 17001667 ER PT J AU Khoury, MJ Romero, R AF Khoury, Muin J. Romero, Roberto TI The integration of genomics into obstetrics and gynecology: A HuGE challenge SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID EPIDEMIOLOGY; ASSOCIATION; NETWORK C1 Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Coordinat Ctr Hlth Promot, Atlanta, GA 30341 USA. NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Coordinat Ctr Hlth Promot, 4770 Buford Hwy,Mail Stop K89, Atlanta, GA 30341 USA. EM awarfiel@med.wayne.edu NR 24 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 BP 1503 EP 1505 DI 10.1016/j.ajog.2006.10.883 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116RG UT WOS:000242819400001 PM 17132472 ER PT J AU Newman, RB Iams, JD Das, A Goldenberg, RL Meis, P Moawad, A Sibai, BM Caritis, SN Miodovnik, M Paul, RH Dombrowski, MP Fischer, M AF Newman, Roger B. Iams, Jay D. Das, Anita Goldenberg, Robert L. Meis, Paul Moawad, Atef Sibai, Baha M. Caritis, Steve N. Miodovnik, Menachem Paul, Richard H. Dombrowski, Mitchell P. Fischer, Molly CA Natl Inst Child Hlth Human Dev TI A prospective masked observational study of uterine contraction frequency in twins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE contraction frequency; twin gestations; preterm birth ID LOW-BIRTH-WEIGHT; PRETERM DELIVERY; UNITED-STATES; GESTATIONS; PREGNANCY; RISK AB Objective: This study was undertaken to compare uterine contraction frequency in twins versus singletons and to determine if contraction frequency can be an efficient predictor of spontaneous preterm birth in twin gestations. Study design: Fifty-nine twin and 306,singleton gestations were enrolled between 22 and 24 weeks at 11 centers. Contraction frequency was recorded with a home uterine activity monitor (HUAM) 2 or more times per day on 2 or more days per week until delivery or 36-6/7 weeks. Masked HUAM data were interpreted according to standard protocol. Repeated measures analyses were used to determine whether mean or maximum uterine contraction frequency per hour differed between singleton and twin gestations across gestational age, by time of day, and by delivery before 35 weeks or beyond. Uterine contraction frequency was also evaluated by logistic regression and receiver operator characteristic (ROC) curves as tests to predict spontaneous preterm birth. Results: There were 34,908 hours of HUAM data recorded by the 306 singleton gestations and 5,427 hours by the 59 women with twins. Uterine contraction frequency was significantly greater in twins (P = .002) compared with singletons, regardless of gestational age. Contraction frequency in twins increased significantly with gestational age and time of day (1600-0359 hours); but was not associated with spontaneous preterm birth. Maximum uterine contraction frequency was associated with preterm birth less than 35 weeks but only in the morning (Am) recording (0400-1559) and at the 29- to 30-week gestational age interval. This relationship was modest (odds ratio 1-2) and not consistent across gestational age or between the Am and afternoon/evening (pm) monitoring sessions. ROC analysis revealed no contraction frequency that efficiently identified twins who delivered prematurely at any 2-week gestational age interval. Conclusion: Mean uterine contraction frequency was significantly higher for twin gestations than singletons throughout the latter half of pregnancy and between 1600 and 0359 hours but was not higher among twins who delivered less than 35 weeks' gestation. Neither maximum AM Or PM contraction frequency predicted spontaneous preterm birth less than 35 weeks' gestation in twin pregnancies. (c) 2006 Mosby, Inc. All rights reserved. C1 Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Tennessee, Memphis, TN USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Cincinnati, Cincinnati, OH USA. Univ So Calif, Los Angeles, CA USA. Wayne State Univ, Detroit, MI USA. George Washington Univ, Ctr Biostat, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. RP Newman, RB (reprint author), Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD 27869, HD 19897, HD 21410, HD 21414, HD 21434, HD 27860, HD 27861, HD 27883, HD 27889, HD 27905, HD 27915, HD 27917] NR 16 TC 17 Z9 17 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 BP 1564 EP 1570 DI 10.1016/j.ajog.2006.03.063 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116RG UT WOS:000242819400011 PM 16769014 ER PT J AU Saldana, TM Siega-Riz, AM Adair, LS Suchindran, C AF Saldana, Tina M. Siega-Riz, Anna Maria Adair, Linda S. Suchindran, Chirayath TI The relationship between pregnancy weight gain and glucose tolerance status among black and white women in central North Carolina SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE gestational diabetes; impaired glucose tolerance; weight gain; pregnancy ID GESTATIONAL DIABETES-MELLITUS; TOTAL-BODY WATER; INCREASING PREVALENCE; INSULIN RESISTANCE; RISK; COMPLICATIONS; DETERMINANTS; OBESITY; DENSITY AB Objective: The objective of the study was to examine weight and its relationship to glucose intolerance during pregnancy. Study design: Women were classified into mutually exclusive glucose tolerance groups, impaired glucose tolerance of pregnancy defined as 1 high value on the oral glucose tolerance test, gestational diabetes mellitus as 2 high values, and normal glucose tolerance as a normal value on the universal screen test. Logistic regression was used to examine the relationship between prepregnancy body mass index and weight gain, and glucose tolerance status and predicted probabilities were calculated. Results: Weight gain ratio (observed/expected) was significantly higher for women with gestational diabetes mellitus, compared with women with normal glucose tolerance. The likelihood of developing gestational diabetes mellitus was significantly increased by both prepregnancy overweight (odds ratio 2.2, 95% confidence interval 1.1-4.3) and obese status (odds ratio 3.7, 95% confidence interval 2.2-6.3) but only marginally by weight gain ratio. In contrast, the likelihood of developing impaired glucose tolerance was increased by weight gain ratio for women who started pregnancy overweight. Conclusion: Prepregnancy weight was strongly associated with gestational diabetes mellitus, whereas weight gain during pregnancy was associated with impaired glucose tolerance only among overweight women. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA. RP Saldana, TM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. FU NIDDK NIH HHS [DK56350]; NIGMS NIH HHS [R25GM55336]; PHS HHS [NICHD 28684] NR 46 TC 52 Z9 55 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 BP 1629 EP 1635 DI 10.1016/j.ajog.2006.05.017 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116RG UT WOS:000242819400021 PM 16824460 ER PT J AU Bradley, CS Brown, MB Cundiff, GW Goode, PS Kenton, KS Nygaard, IE Whitehead, WE Wren, PA Weber, AM AF Bradley, Catherine S. Brown, Morton B. Cundiff, Geoffrey W. Goode, Patricia S. Kenton, Kimberly S. Nygaard, Ingrid E. Whitehead, William E. Wren, Patricia A. Weber, Anne M. CA Pelvic Floor Disorders Network TI Bowel symptoms in women planning surgery for pelvic organ prolapse SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the Society-of-Gynecologic-Surgeons CY APR 03-05, 2006 CL Tucson, AZ DE bowel symptoms; pelvic organ prolapse; constipation; questionnaires ID FLOOR DISORDERS; CONSTIPATION AB Objective: The objective of the study was to measure associations between bowel symptoms and prolapse. Study design: Baseline data were analyzed from 322 women in the Colpopexy And Urinary Reduction Efforts trial of sacrocolpopexy with or without Burch colposuspension. Women completed the Colorectal-Anal Distress Inventory and Colorectal-Anal Impact Questionnaire and underwent Pelvic Organ Prolapse Quantification. Associations between symptoms and questionnaire scores and Pelvic Organ Prolapse Quantification measures were assessed. Results: Mean age was 61 +/- 10 years. Pelvic Organ Prolapse Quantification stages were II (14%), III (67%), and IV (19%). Colorectal-Anal Distress Inventory symptoms did not increase with prolapse stage. Colo rectal-Anal Distress Inventory obstructive subscale scores were higher in stage II women (median 29 [interquartile range 8,92] versus 17 [0,33] and 25 [0,38] for stages III and IV, respectively; adjusted P =.01). The few statistically significant correlations between symptoms and vaginal descent were negative and weak (less than 0.2). Conclusion: Bowel symptoms and questionnaire scores do not increase with prolapse stage in women presenting for sacrocolpopexy. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD USA. Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Bradley, CS (reprint author), Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. FU NICHD NIH HHS [H10 HD41268, U01 HD41249, U10 HD041261, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41269, U10 HD41248] NR 15 TC 20 Z9 20 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 BP 1814 EP 1819 DI 10.1016/j.ajog.2006.07.008 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116RG UT WOS:000242819400050 PM 16996465 ER PT J AU Aagaard-Tillery, K AF Aagaard-Tillery, Kjersti TI Pharmacogenomics of maternal tobacco use: Metabolic gene polymorphisms modify risk of adverse pregnancy outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 70 BP S31 EP S31 DI 10.1016/j.ajog.2006.10.081 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500071 ER PT J AU Alexander, J AF Alexander, James TI The MFMU cesarean registry: Failed operative vaginal delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 726 BP S217 EP S217 DI 10.1016/j.ajog.2006.10.787 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500723 ER PT J AU Baschat, A Reddy, U Towbin, J Harman, C Weiner, C AF Baschat, Ahmet Reddy, Uma Towbin, Jeffrey Harman, Christopher Weiner, Carl TI When are amniotic fluid viral PCR studies indicated in prenatal diagnosis? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ Maryland, Baltimore, MD 21201 USA. NICHHD, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Maryland, Kansas City, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 539 BP S166 EP S166 DI 10.1016/j.ajog.2006.10.544 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500539 ER PT J AU Blackwell, S AF Blackwell, Sean TI Relationship between consistency of meconium-stained amniotic fluid and intrapartum fetal oxygen saturation in the first stage of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 676 BP S204 EP S204 DI 10.1016/j.ajog.2006.10.733 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500674 ER PT J AU Cameroni, I Toso, L Schmidt, C Abebe, D Bissell, S Spong, C AF Cameroni, Irene Toso, Laura Schmidt, Cecilia Abebe, Daniel Bissell, Stephanie Spong, Catherine TI Glial deficit in down syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ Milano Bicocca, Milan, Italy. NIH, Unit Perinatal & Devt Neurobiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 484 BP S150 EP S150 DI 10.1016/j.ajog.2006.10.527 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500484 ER PT J AU Caritis, S Rouse, D AF Caritis, Steve Rouse, Dwight TI A randomized controlled trial of 17-hydroxyprogesterone caproate (17-DHPC) for the prevention of preterm birth in twins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 1 BP S2 EP S2 DI 10.1016/j.ajog.2006.10.003 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500002 ER PT J AU Driggers, R Gabreab, T Macedonia, C Miller, J AF Driggers, Rita Gabreab, Tadesse Macedonia, Christian Miller, Jeri TI Use of ultrasonographic evaluation of respiratory fluid dynamics in predicting newborn respiratory status: Correlations with biochemical scores SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Natl Naval Med Ctr, Pulm Dis Sect, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 124 BP S49 EP S49 DI 10.1016/j.ajog.2006.10.140 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500125 ER PT J AU Ehrenberg, H AF Ehrenberg, Hugh TI The impact of maternal obesity on uterine activity and the risk of spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 127 BP S50 EP S50 DI 10.1016/j.ajog.2006.10.143 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500128 ER PT J AU Erez, O Kim, SS Kim, JS Kim, YM Wildman, DE Than, NG Gotsch, F Espinoza, J Hassan, S Kim, CJ Romero, R AF Erez, Offer Kim, Sung-Su Kim, Jung-Sun Kim, Yeon Mee Wildman, Derek E. Than, Nandor Gabor Gotsch, Francesca Espinoza, Jimmy Hassan, Sonia Kim, Chong Jai Romero, Roberto TI Over-expression of the thrombin receptor in the placenta of patients with preeclampsia: The intersection between coagulation and inflammation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Gent, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 433 BP S136 EP S136 DI 10.1016/j.ajog.2006.10.472 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500433 ER PT J AU Erez, O Espinoza, J Chatworapongsa, T Gotsch, F Kusanovic, JP Than, NG Mazaki-Tovi, S Papp, Z Yoon, BH Hoppensteadt, D Fareed, J Hassan, S Romero, R AF Erez, Offer Espinoza, Jimmy Chatworapongsa, Tinnakorn Gotsch, Francesca Kusanovic, Juan Pedro Than, Nandor Gabor Mazaki-Tovi, Shali Papp, Zoltan Yoon, Bo Hyun Hoppensteadt, Debra Fareed, Jawed Hassan, Sonia Romero, Roberto TI Tissue factor and tissue pathway inhibitor: A link between a hemostatic disorder and preterm PROM? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, DHHS, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Semmelweis Univ, Dept Obstet Gynecol, Budapest, Hungary. Seoul Natl Univ, Coll Med, Dept Obstet Gynecol, Seoul, South Korea. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 130 BP S51 EP S51 DI 10.1016/j.ajog.2006.10.147 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500131 ER PT J AU Espinoza, J Hassan, S Edwin, SS Gotsch, F Kusanovic, JP Kim, CJ Than, NG Pineles, BL Erez, O Friel, L Nien, JK Gomez, R Romero, R AF Espinoza, Jimmy Hassan, Sonia Edwin, Samuel S. Gotsch, Francesca Kusanovic, Juan Pedro Kim, Chong Jai Than, Nandor Gabor Pineles, Beth L. Erez, Offer Friel, Lara Nien, Jyh Kae Gomez, Ricardo Romero, Roberto TI Differences and similarities in the plasma cytokine profile (pro- and anti-inflammatory) in SGA and preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI USA. Pontificia Univ Catolica Chile, Sotero Rio Hosp, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 603 BP S183 EP S183 DI 10.1016/j.ajog.2006.10.655 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500603 ER PT J AU Espinoza, J Kindzelski, A Kusanovic, JP Chaiworapongsa, T Hassan, S Yoon, BH Petty, H Romero, R AF Espinoza, Jimmy Kindzelski, Andrei Kusanovic, Juan Pedro Chaiworapongsa, Tinnakorn Hassan, Sonia Yoon, Bo Hyun Petty, Howard Romero, Roberto TI Preeclampsia is characterized by a large number of neutrophils displaying a high amplitude of NAD(P)H metabolic oscillations: A link between intravascular inflammation, endothelial cell dysfunction and preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 473 BP S147 EP S147 DI 10.1016/j.ajog.2006.10.516 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500473 ER PT J AU Espinoza, J Edwin, S Chefetz, I Sammar, M Meiri, H Tal, Y Kuhnreich, I Cuckle, H AF Espinoza, Jimmy Edwin, Sam Chefetz, Ilana Sammar, Marei Meiri, Hamutal Tal, Yossi Kuhnreich, Ido Cuckle, Howard TI Assessment of first trimester maternal serum PP13 in early vs. term sever preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Perinatol Res Branch,Intramural Div, Detroit, MI USA. NICHHD, Perinatol Res Branch, Detroit, MI USA. Diagnost Technol Ltd, Yokneam, Israel. Technostat, Kefar Sava, Israel. Univ Leeds, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 422 BP S133 EP S133 DI 10.1016/j.ajog.2006.10.461 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500422 ER PT J AU Espinoza, J Kusanovic, JP Hassan, S Edwin, SS Gotsch, F Kim, CJ Than, NG Erez, O Nien, JK Gomez, R Yoon, BH Romer, R AF Espinoza, Jimmy Kusanovic, Juan Pedro Hassan, Sonia Edwin, Samuel S. Gotsch, Francesca Kim, Chong Jai Than, Nandor Gabor Erez, Offer Nien, Jyh Kae Gomez, Ricardo Yoon, Bo Hyun Romer, Roberto TI Evidence for a polarized Th1 response in the maternal circulation in women with preterm labor and intra-amniotic inflammation/infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NIH, NICHD, DHHS, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstet Gynecol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 131 BP S51 EP S51 DI 10.1016/j.ajog.2006.10.148 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500132 ER PT J AU Fejzo, MS Ingles, SA Wilson, ML Wang, W Macgibbon, KW Romero, R Murphy Goodwin, T AF Fejzo, Marlena S. Ingles, Sue Ann Wilson, Melissa L. Wang, Wei Macgibbon, Kimber W. Romero, Roberto Murphy Goodwin, T. TI Familial aggregation of hyperemesis gravidarum SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ So Calif, Los Angeles, CA USA. Hyperemesis Educ & Res Fdn, Leesburg, VA USA. NIH, NICHD, DHHS, Perinatology Res Branch, Detroit, MI USA. OI MacGibbon, Kimber/0000-0002-6534-3114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 631 BP S191 EP S191 DI 10.1016/j.ajog.2006.10.686 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500631 ER PT J AU Friel, L Espinoza, J Edwin, S Nien, JK Gomez, R Hassan, S Chaiworapongsa, T Romero, R AF Friel, Lara Espinoza, Jimmy Edwin, Samuel Nien, Jyh Kae Gomez, Ricardo Hassan, Sonia Chaiworapongsa, Tinnakorn Romero, Roberto TI The calcium binding protein S100, a marker for neurologic injury in the perinatal period, is increased in the amniotic fluid of women with preterm labor and intact membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. Catholic Univ Chile, Sotero Rio Hosp, CEDIP, Puente Alto, Chile. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 22 BP S10 EP S10 DI 10.1016/j.ajog.2006.10.027 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500023 ER PT J AU Gotsch, F Friel, L Kusanovic, JP Espinoza, J Erez, O Than, NG Mittal, P Edwin, S Yoon, BH Mazaki-Tovi, S Hassan, S Romero, R AF Gotsch, Francesca Friel, Lara Kusanovic, Juan Pedro Espinoza, Jimmy Erez, Offer Than, Nandor Gabor Mittal, Pooja Edwin, Samuel Yoon, Bo Hyun Mazaki-Tovi, Shali Hassan, Sonia Romero, Roberto TI Is CXCL10/IP10 the missing link between inflammation and anti-angiogenesis in preeclampsia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHHD, Natl Inst Hlth, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 495 BP S153 EP S153 DI 10.1016/j.ajog.2006.10.538 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500495 ER PT J AU Grobman, W AF Grobman, William TI The MFMU cesarean registry: Does information available on admission for delivery improve the accuracy of a prediction model for VBAC success? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 665 BP S201 EP S201 DI 10.1016/j.ajog.2006.10.722 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500663 ER PT J AU Grobman, W AF Grobman, William TI The MFMU cesarean registry: Can uterine rupture during a trial of labor in women with one prior LTCS be predicted? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 663 BP S201 EP S201 DI 10.1016/j.ajog.2006.10.720 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500661 ER PT J AU Grobman, W AF Grobman, William TI The MFMU cesarean registry: Can a predictive model for VBAC success identify women who are no more likely to have morbidity with a trial of labor (TOL) than with an elective repeat cesarean (ERCS)? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 664 BP S201 EP S201 DI 10.1016/j.ajog.2006.10.721 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500662 ER PT J AU Habli, M Levine, R Qian, C Ghulmiyyah, L Sibai, BM AF Habli, Mounira Levine, Richard Qian, Cong Ghulmiyyah, Labib Sibai, Baha M. TI Neonatal outcomes in pregnancies with preeclampsia or gestational hypertension and in normotensive pregnancies delivered at 35, 36, or 37 weeks SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ Cincinnati, Cincinnati, OH USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 636 BP S192 EP S192 DI 10.1016/j.ajog.2006.10.691 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500635 ER PT J AU Hassan, S Romero, R Tarca, AL Draghici, S Khalek, N Camacho, N Mittal, P Yoon, BH Espinoza, J Sorokin, Y Malone, J AF Hassan, Sonia Romero, Roberto Tarca, Adi L. Draghici, Sorin Khalek, Nahla Camacho, Natalia Mittal, Pooja Yoon, Bo Hyun Espinoza, Jimmy Sorokin, Yoram Malone, John, Jr. TI Gene expression signature pathways in the human uterine cervix before and after spontaneous term parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, NIH, US Dept HHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 69 BP S30 EP S30 DI 10.1016/j.ajog.2006.10.080 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500070 ER PT J AU Hediger, ML Luke, B Grainger, DA Witter, F Newman, R Gonzalez-Quintero, VH AF Hediger, Mary L. Luke, Barbara Grainger, David A. Witter, Frank Newman, Roger Gonzalez-Quintero, Victor Hugo TI Twin intrapair crown-rump length discordancy and risk of very preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHHD, NIH, DESPR, Washington, DC USA. Univ Miami, Sch Nursing & Hlth Studies, Coral Gables, FL 33124 USA. Univ Kansas, Wichita, KS USA. Johns Hopkins Univ, Baltimore, MD USA. Med Univ S Carolina, Mt Pleasant, MI USA. Univ Miami, Miami, FL 33152 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 155 BP S57 EP S57 DI 10.1016/j.ajog.2006.10.174 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500156 ER PT J AU Jehan, I Goldenberg, R Solat, S Rizvi, S McClure, E Moss, N Pasha, O Harris, H Wright, L AF Jehan, Imtiaz Goldenberg, Robert Solat, Sohail Rizvi, Sameera McClure, Elizabeth Moss, Nancy Pasha, Omrana Harris, Hillary Wright, Linda TI Stillbirths in a prospectively evaluated birth cohort in Pakistan SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Aga Khan Univ, Karachi, Pakistan. Univ Alabama, Birmingham, AL USA. Res Triangle Inst, Chapel Hill, NC USA. Natl Inst Child & Human Dev, Rockville, MD USA. RTI Int, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 588 BP S179 EP S179 DI 10.1016/j.ajog.2006.10.639 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500588 ER PT J AU Kim, CJ Kim, JS Kim, YM Mazaki-Tovi, S Friel, L Kusanovic, JP Espinoza, J Hassan, S Romero, R AF Kim, Chong Jai Kim, Jung-Sun Kim, Yeon Mee Mazaki-Tovi, Shali Friel, Lara Kusanovic, Juan Pedro Espinoza, Jimmy Hassan, Sonia Romero, Roberto TI Villitis of unknown etiology: The pathophysiologic equivalent of graft-versus-host disease in human pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NICHD NIH DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dep Obstetrics & Gynecol, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 267 BP S90 EP S90 DI 10.1016/j.ajog.2006.10.292 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500267 ER PT J AU Klebanoff, M AF Klebanoff, Mark TI Impact of 17alpha hydroxyprogesterone caproate administration on salivary progesterone and estriol SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 450 BP S140 EP S140 DI 10.1016/j.ajog.2006.10.490 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500450 ER PT J AU Korst, LM Poursharif, B Macgibbon, KW Fejzo, MS Romero, R Murphy Goodwin, T AF Korst, Lisa M. Poursharif, Borzouyeh Macgibbon, Kimber W. Fejzo, Marlena S. Romero, Roberto Murphy Goodwin, T. TI Symptomatology and outcomes of women with hyperemesis gravidarum as reported in a large registry SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ So Calif, Los Angeles, CA USA. Hyperemesis Educ & Gynecol Fdn, Leesburg, VA USA. NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. OI MacGibbon, Kimber/0000-0002-6534-3114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 702 BP S211 EP S211 DI 10.1016/j.ajog.2006.10.761 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500699 ER PT J AU Kusanovic, JP Espinoza, J Hassan, S Gotsch, F Erez, O Than, NG Edwin, S Mazaki-Tovi, S Friel, L Mittal, P Yoon, BH Romero, R AF Kusanovic, Juan Pedro Espinoza, Jimmy Hassan, Sonia Gotsch, Francesca Erez, Offer Than, Nandor Gabor Edwin, Samuel Mazaki-Tovi, Shah Friel, Lara Mittal, Pooja Yoon, Bo Hyun Romero, Roberto TI Preeclampsia and SCD30 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Ginecol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 469 BP S146 EP S146 DI 10.1016/j.ajog.2006.10.512 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500469 ER PT J AU Levine, R Oian, C Yu, K Sibai, B Karumanchi, A AF Levine, Richard Oian, Cong Yu, Kai Sibai, Baha Karumanchi, Ananth TI Circulating angiogenic factors in smokers and non-smokers during normotensive pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. Allied Technol Grp, Rockville, MD USA. Univ Cincinnati, Cincinnati, OH USA. Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Dept Med, Div Nephrol, Boston, MA 02215 USA. NR 0 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 86 BP S37 EP S37 DI 10.1016/j.ajog.2006.10.100 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500087 ER PT J AU Louis, J AF Louis, Judette TI Impact of environmental exposures on asthma control in pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 714 BP S214 EP S214 DI 10.1016/j.ajog.2006.10.774 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500711 ER PT J AU Luke, B Hediger, ML Min, L Nugent, C Newman, R Hankins, G Grainger, DA AF Luke, Barbara Hediger, Mary L. Min, Linda Nugent, Clark Newman, Roger Hankins, Gary Grainger, David A. TI The effect of weight gain by 20 weeks gestation on twin birthweight and postpartum weight SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ Miami, Sch Nursing & Hlth Studies, Coral Gables, FL 77550 USA. NICHHD, NIH, Dist Columbia, Washington, DC USA. NICHHD, NIH, Dist Columbia, Washington, DC USA. Med Univ S Carolina, Mt Pleasant, MI USA. Univ Texas, Med Branch, Galveston, TX USA. Univ Kansas, Wichita, KS USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 248 BP S85 EP S85 DI 10.1016/j.ajog.2006.10.271 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500248 ER PT J AU McClure, E Wright, L Goldenberg, R Goudar, S Mohapatra, A Jehan, I Tshefu, A Chomba, E Garces, A Althabe, F Harris, H Carlo, W AF McClure, Elizabeth Wright, Linda Goldenberg, Robert Goudar, Shiva Mohapatra, Arjit Jehan, Imtiaz Tshefu, Antoinette Chomba, Elwyn Garces, Ana Althabe, Fernando Harris, Hillary Carlo, Waldemar TI A prospective study of stillbirths in developing countries SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Res Triangle Inst, Chapel Hill, NC USA. NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. JN Med Coll, Belgaum, India. SCB Med Coll, Orissa, India. Aga Khan Univ, Karachi, Pakistan. Univ Kinshasa, Sch Publ Hlth, Kinshasa, Zaire. Univ Zambia, Lusaka, Zambia. FANCAP, Guatemala City, Guatemala. CLAP PAHO WHO, Latim Amer Ctr Perinatol & Human Dev, Montevideo, Uruguay. Res Triangle Inst, Durham, NC USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 739 BP S220 EP S220 DI 10.1016/j.ajog.2006.10.801 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500736 ER PT J AU Mittal, P Tarca, AL Draghici, S Espinoza, J Nien, JK Gomez, R Yoon, BH Kusanovic, JP Hassan, S Romero, R Tromp, G AF Mittal, Pooja Tarca, Adi L. Draghici, Sorin Espinoza, Jimmy Nien, Jyh Kae Gomez, Ricardo Yoon, Bo Hyun Kusanovic, Juan Pedro Hassan, Sonia Romero, Roberto Tromp, Gerard TI The myometrial transcriptome in spontaneous labor at term and in failure to progress in labor (arrest of dilatation and arrest of descent) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Catholic Univ Chile, Sotero Rio Hosp, CEDIP, Puente Alto, Chile. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 429 BP S135 EP S135 DI 10.1016/j.ajog.2006.10.468 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500429 ER PT J AU Mittal, P Hassan, S Espinoza, J Kusanovic, JP Edwin, S Gotsch, F Erez, O Than, G Mazaki-Tovi, S Romero, R AF Mittal, Pooja Hassan, Sonia Espinoza, Jimmy Kusanovic, Juan Pedro Edwin, Sam Gotsch, Francesca Erez, Offer Than, Gabor Mazaki-Tovi, Shali Romero, Roberto TI The effect of gestational age and labor on placental growth hormone in amniotic fluid SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal-Fetal Med C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 428 BP S134 EP S134 DI 10.1016/j.ajog.2006.10.467 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500428 ER PT J AU Mittal, P Espinoza, J Hassan, S Kusanovic, JP Edwin, SS Nien, JK Gotsch, F Than, N Erez, O Mazaki-Tovi, S Romero, R AF Mittal, Pooja Espinoza, Jimmy Hassan, Sonia Kusanovic, Juan Pedro Edwin, Samuel S. Nien, Jyh Kae Gotsch, Francesca Than, Nandor Erez, Offer Mazaki-Tovi, Shali Romero, Roberto TI Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, NIH, NHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 427 BP S134 EP S134 DI 10.1016/j.ajog.2006.10.466 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500427 ER PT J AU Montenegro, D Romero, R Pineles, BL Tarca, AL Kim, YM Draghici, S Kusanovic, JP Erez, O Mazakitovi, S Hassan, S Espinoza, J Kim, CJ AF Montenegro, Daniel Romero, Roberto Pineles, Beth L. Tarca, Adi L. Kim, Yeon Mee Draghici, Sorin Kusanovic, Juan Pedro Erez, Offer Mazakitovi, Shali Hassan, Sonia Espinoza, Jimmy Kim, Chong Jai TI A role for microRNAs - Key regulators of gene expression - In chorioamnionitis and parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 26 BP S11 EP S11 DI 10.1016/j.ajog.2006.10.031 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500027 ER PT J AU Northen, A AF Northen, Allison TI 4-year follow-up of children exposed to 17alpha hydroxyprogesterone caproate (17P) in utero SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 14 BP S6 EP S6 DI 10.1016/j.ajog.2006.10.017 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500015 ER PT J AU Pineles, BL Romero, R Montenegro, D Kim, JS Tarca, AL Kusanovic, JP Mittal, P Hassan, S Espinoza, J Kim, CJ AF Pineles, Beth L. Romero, Roberto Montenegro, Daniel Kim, Jung-Sun Tarca, Adi L. Kusanovic, Juan Pedro Mittal, Pooja Hassan, Sonia Espinoza, Jimmy Kim, Chong Jai TI Spontaneous labor at term is characterized by specific differential expression of microRNAs: A novel mechanism for post-transcriptional gene expression regulation in human parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH NICHD DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dep Obstet & Gynecol, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 250 BP S85 EP S85 DI 10.1016/j.ajog.2006.10.273 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500250 ER PT J AU Pineles, BL Romero, R Montenegro, D Tarca, AL Han, YM Kim, YM Kusanovic, JP Mittal, P Hassan, S Espinoza, J Kim, CJ AF Pineles, Beth L. Romero, Roberto Montenegro, Daniel Tarca, Adi L. Han, Yu Mi Kim, Yeon Mee Kusanovic, Juan Pedro Mittal, Pooja Hassan, Sonia Espinoza, Jimmy Kim, Chong Jai TI Evidence for a stereotypic difference in post-transcriptional regulation of placental gene expression in preeclampsia and SGA: An explanation for the two different phenotypes? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 35 BP S15 EP S15 DI 10.1016/j.ajog.2006.10.041 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500036 ER PT J AU Poursharif, B Fejzo, MS MacGibbon, KW Korst, LM Romero, R Goodwin, TM AF Poursharif, Borzouyeh Fejzo, Marlena S. MacGibbon, Kimber W. Korst, Lisa M. Romero, Roberto Goodwin, T. Murphy TI Psychosocial burden of hyperemesis gravidarum SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Univ So Calif, Los Angeles, CA 90089 USA. Hyperemesis Educ & Res Fdn, Leesburg, VA USA. NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. OI MacGibbon, Kimber/0000-0002-6534-3114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 252 BP S86 EP S86 DI 10.1016/j.ajog.2006.10.276 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500252 ER PT J AU Rana, S Karumanchi, A Levine, R Thadhani, R AF Rana, Sarosh Karumanchi, Ananth Levine, Richard Thadhani, Ravi TI Sequential changes in angiogenic factors in early pregnancy and risk of developing preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Brown Univ, Women & Infants Hosp, Providence, RI USA. Beth Israel Deaconess Med Ctr, Dept Med, Ctr Vascular Biol, Div Nephrol, Boston, MA 02215 USA. Natl Inst Hlth, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 413 BP S131 EP S131 DI 10.1016/j.ajog.2006.10.451 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500413 ER PT J AU Reddy, L Ko, CW Willinger, M AF Reddy, Uma Ko, Chia-Wen Willinger, Marian TI Late preterm deliveries and mortality rates in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 667 BP S202 EP S202 DI 10.1016/j.ajog.2006.10.724 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500665 ER PT J AU Reddy, U Ko, CW Willinger, M AF Reddy, Uma Ko, Chia-Wen Willinger, Marian TI "Early" term births (37-38 weeks) are associated with increased mortality SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHHD, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 8 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 668 BP S202 EP S202 DI 10.1016/j.ajog.2006.10.725 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500666 ER PT J AU Reddy, U Towbin, J Harman, C Weiner, C Baschat, A AF Reddy, Uma Towbin, Jeffrey Harman, Christopher Weiner, Carl Baschat, Ahmet TI Prevalence of viral genome in amniotic fluid is not increased with fetal aneuploidy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Natl Inst Hlth, NICHHD, Bethesda, MD USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. Univ Maryland Baltimore Cty, Kansas City, KS USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 202 BP S70 EP S70 DI 10.1016/j.ajog.2006.10.221 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500202 ER PT J AU Richani, K Soto, E Romero, R Han, YM Pineles, B Kim, YM Cushenberry, E Yoon, BH Kusanovic, JP Espinoza, J Kim, CJ AF Richani, Karina Soto, Eleazar Romero, Roberto Han, Yu Mi Pineles, Beth Kim, Yeon Mee Cushenberry, Enola Yoon, Bo Hyun Kusanovic, Juan P. Espinoza, Jimmy Kim, Chong Jai TI Decreased mRNA expression of complement regulatory proteins in chorioamnionitis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynaecol, Detroit, MI USA. Univ Sch Med, Dept Obstet & Ginecol, Detroit, MI USA. NIH, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Ginecol, Seoul, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 203 BP S71 EP S71 DI 10.1016/j.ajog.2006.10.222 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500203 ER PT J AU Roberson, R Cameroni, I Toso, L Abebe, D Bissell, S Spong, C AF Roberson, Robin Cameroni, Irene Toso, Laura Abebe, Daniel Bissell, Stephanie Spong, Catherine TI Alterations in P-CREB activity: A pathway for FAS related neurotoxiticity SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIAAA, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. Univ Milano Bicocca, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 421 BP S133 EP S133 DI 10.1016/j.ajog.2006.10.459 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500421 ER PT J AU Santolaya-Forgas, J Edwin, S Pitt, A Wolf, R Romero, R AF Santolaya-Forgas, Joaquin Edwin, Sam Pitt, Adam Wolf, Roman Romero, Roberto TI A study in mature fetuses to determine their base-line operational capacity for responding to inflammatory insults SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ Oklahoma, Hlth Sci Ctr, Div Anim Res, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 472 BP S147 EP S147 DI 10.1016/j.ajog.2006.10.515 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500472 ER PT J AU Sawady, J Mercer, B AF Sawady, Joram Mercer, Brian TI Impact of repeated doses of antenatal corticosteroids on placental growth and histology SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 210 BP S73 EP S73 DI 10.1016/j.ajog.2006.10.231 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500210 ER PT J AU Sokol, R Pawlosky, R Hannigan, J Stark, K Salem, N AF Sokol, Robert Pawlosky, Robert Hannigan, John Stark, Ken Salem, Norman TI Maternal smoking and decreased 5-methyltetrahydrofolate in umbilical cord plasma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Detroit, MI USA. NIAAA, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 55 BP S25 EP S25 DI 10.1016/j.ajog.2006.10.065 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500056 ER PT J AU Soto, E Romero, R Richani, K Chaiworapongsa, T Yoon, BH Nien, JK Edwin, S Kusanovic, JP Espinoza, J AF Soto, Eleazar Romero, Roberto Richani, Karina Chaiworapongsa, Tinnakorn Yoon, Bo Hyun Nien, Jyh Kae Edwin, Sam Kusanovic, Juan Pedro Espinoza, Jimmy TI Evidence for complement activation in premature labor associated with intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NIH, NICHD, DHHS, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstetrics & Gynecol, Seoul, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 216 BP S74 EP S74 DI 10.1016/j.ajog.2006.10.237 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500216 ER PT J AU Spong, C AF Spong, Catherine TI The MFMU cesarean registry: Risk factors for neonatal sepsis among women with chorioamnionitis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 217 BP S74 EP S74 DI 10.1016/j.ajog.2006.10.238 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500217 ER PT J AU Spong, CY AF Spong, Catherine Y. TI The MFMU cesarean registry: Risk of uterine rupture and adverse perinatal outcome at term after cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 751 BP S223 EP S223 DI 10.1016/j.ajog.2006.10.813 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500748 ER PT J AU Than, NG Wildman, DE Erez, O Edwin, SS Espinoza, J Kim, CJ Han, YM Mazaki-Tovi, S Kusanovic, JP Hassan, S Papp, Z Romero, R AF Than, Nandor Gabor Wildman, Derek E. Erez, Offer Edwin, Samuel S. Espinoza, Jimmy Kim, Chong Jai Han, Yu Mi Mazaki-Tovi, Shali Kusanovic, Juan Pedro Hassan, Sonia Papp, Zoltan Romero, Roberto TI Trophoblast, galectin-1 and pre-eclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Ctr Mol Molecular Med & Gent, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 442 BP S138 EP S138 DI 10.1016/j.ajog.2006.10.481 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500442 ER PT J AU Toso, L Abebe, D Roberson, R Spong, CY AF Toso, Laura Abebe, Daniel Roberson, Robin Spong, Catherine Y. TI Alcohol-induced learning deficits are not prevented through GABA-A3 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neubiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 617 BP S187 EP S187 DI 10.1016/j.ajog.2006.10.670 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500617 ER PT J AU Toso, L Cameroni, I Abebe, D Spong, C AF Toso, Laura Cameroni, Irene Abebe, Daniel Spong, Catherine TI Developmental enhancement in the neonatal period in healthy mice SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. Univ Milan, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 75 BP S34 EP S34 DI 10.1016/j.ajog.2006.10.087 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500076 ER PT J AU Toso, L Cameroni, I Schmidt, C Abebe, D Spong, CY AF Toso, Laura Cameroni, Irene Schmidt, Cecilia Abebe, Daniel Spong, Catherine Y. TI Down syndrome: Phenotypic assessment of the segmental trisomic TS65DN mouse SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. Univ Milan, Monza, Italy. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 620 BP S188 EP S188 DI 10.1016/j.ajog.2006.10.673 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500620 ER PT J AU Toso, L Roberson, R Abebe, D Spong, C AF Toso, Laura Roberson, Robin Abebe, Daniel Spong, Catherine TI Adult administration of peptides resulting in learning enhancement is not mediated through NMDA and GABA receptor expression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal-Fetal Med C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. Univ Milan, Monza, Italy. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 618 BP S188 EP S188 DI 10.1016/j.ajog.2006.10.671 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500618 ER PT J AU Toso, L Cameroni, I Schmidt, C Abebe, D Bissell, S Spong, C AF Toso, Laura Cameroni, Irene Schmidt, Cecilia Abebe, Daniel Bissell, Stephanie Spong, Catherine TI Prevention of developmental delays in a Down Syndrome model SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal-Fetal Med C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. Univ Milan, Milan, Italy. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 28 BP S13 EP S13 DI 10.1016/j.ajog.2006.10.033 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500029 ER PT J AU Toso, L Bissell, S Abebe, D Cameroni, I Schmidt, C Spong, C AF Toso, Laura Bissell, Stephanie Abebe, Daniel Cameroni, Irene Schmidt, Cecilia Spong, Catherine TI Alterations in NMDA and GABA receptors: Mechanism for learning deficit in Down syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. Univ Milan, Monza, Italy. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 619 BP S188 EP S188 DI 10.1016/j.ajog.2006.10.672 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500619 ER PT J AU Toso, L Abebe, D Roberson, R Spong, CY AF Toso, Laura Abebe, Daniel Roberson, Robin Spong, Catherine Y. TI Neuroprotective peptides prevent the alcohol-induced alteration in GABA-A3 which plays a role in cleft lip and palate in fetal alcohol syndrome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, NICHD, NIAAA, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 29 BP S13 EP S13 DI 10.1016/j.ajog.2006.10.035 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500030 ER PT J AU Tsai, J Yu, K Qian, C Lam, C Karumanchi, A Levine, R AF Tsai, Jillian Yu, Kai Qian, Cong Lam, Chun Karumanchi, Ananth Levine, Richard TI Association of maternal serum levels of soluble endoglin with small-for-gestational-age and preterm births SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 Vanderbilt Univ, Sch Med, Nashville, TN USA. NICHD, Dept Hlth & Human Dev, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. Allied Technol Grp, Rockville, MD USA. Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Dept Med, Div Nephrol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 602 BP S183 EP S183 DI 10.1016/j.ajog.2006.10.654 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500602 ER PT J AU Wapner, R AF Wapner, Ronald TI Long term follow-up of infants receiving single vs repeat courses of antenatal corticosteroids (ACS) from the MFMU RCT SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 2 BP S2 EP S2 DI 10.1016/j.ajog.2006.10.004 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500003 ER PT J AU Zhang, J Villar, J Sun, W Yu, K AF Zhang, Jun Villar, Jose Sun, Wenyu Yu, Kai TI Blood pressure dynamics during pregnancy and spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2007 CL San Francisco, CA SP Soc Maternal Fetal Med C1 NIH, Epidemiol Branch, Bethesda, MD USA. WHO, CH-1211 Geneva, Switzerland. Natl Inst Child Hlth & Human Devt, Div Epidemiol, Stat & Prevent Res, Stat & Prevent Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2006 VL 195 IS 6 SU S MA 232 BP S79 EP S79 DI 10.1016/j.ajog.2006.10.254 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 116WM UT WOS:000242834500232 ER PT J AU Patronas, M Smith, JA Levy-Clarke, GA Reed, GF Buggage, RR AF Patronas, Marena Smith, Janine A. Levy-Clarke, Grace A. Reed, George F. Buggage, Ronald R. TI Hypergammaglobulinemia and corneal opacities in patients with human T-cell lymphotrophic virus type-1 SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LEUKEMIA-LYMPHOMA AB PURPOSE: To investigate the relationship between serum immunoglobulin levels and corneal opacities in a cohort of patients with human T-cell lymphotrophic virus type-1 (HTLV-1). DESIGN: Retrospective case series. METHODS: Complete ophthalmologic examination was performed on 44 patients with HTLV,1 infection (25 patients with adult T-cell leukemia/lymphoma [ATL], 18 patients with HTLV-1 that was associated myelopathy/ tropical spastic paraparesis [HAM/TSP], and one patient who was asymptomatic). Corneal opacities were described by shape, size, color, and location. Serum immunoglobulin (Ig) levels (IgG, IgM, and IgA) were measured by nephelometry. RESULTS: Corneal opacities were identified in 15 of 25 patients (60%) with ATL and five of 18 patients (28%) with HAM/TSP. The prevalence of corneal opacities was associated statistically with elevated IgG level (P = .023) in patients with ATL, but not in patients with HAM/ TSP (P > .99). CONCLUSION: Although the mechanism remains unclear, hypergammaglobulinemia is associated with the development of the corneal opacities in patients of African descent with ATL. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Levy-Clarke, GA (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,MSC 1863,Bldg 10 RM10S218C, Bethesda, MD 20892 USA. EM clarkeg@nei.nih.gov FU Intramural NIH HHS NR 7 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2006 VL 142 IS 6 BP 1088 EP 1089 DI 10.1016/j.ajo.2006.07.028 PG 2 WC Ophthalmology SC Ophthalmology GA 114MU UT WOS:000242671100038 PM 17157606 ER PT J AU Bandinelli, S Pozzi, M Lauretani, F Phillips, C Shumway-Cook, A Guralnik, JM Ferrucci, L AF Bandinelli, Stefania Pozzi, Martina Lauretani, Fulvio Phillips, Caroline Shumway-Cook, Anne Guralnik, Jack M. Ferrucci, Luigi TI Adding challenge to performance-based tests of walking - The walking InCHIANTI toolkit (WIT) SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE InCHIANTI study; mobility; performance tests; reproducibility; aging ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; OLDER PERSONS; WOMENS HEALTH; DISABILITY; MOBILITY; AGE; ASSOCIATION; PREDICTOR; MORTALITY AB Objective: In this report, we provide a detailed description of and reproducibility data on the 14 performance-based tests of lower limb function included in the Walking InCHIANTI Toolkit, which were designed to mimic challenging situations that are encountered while walking in daily life. Design: Five women and five men were randomly selected from each of the age strata, 65-74, 75-84, and >= 85 yrs, among those who received a functional evaluation in the Greve site at the second InCHIANTI study follow-up (total n = 30). Walking tests were administered twice at 2-wk intervals. Analyses were aimed at assessing reproducibility of the Walking InCHIANTI Toolkit components and the existence of a learning effect. Results: Performance remained stable for eight walking tests and slightly but significantly improved for the 25-cm narrow-path walk, 7-m usual-pace, 7-m obstacle normal light, 7-m holding a package, and 7-m talking while walking tests. Test-retest reliability was in general very high, with 11 of 14 (79%) of the intraclass; correlation coefficient values > 0.80 and all except one (7-m holding a package) > 0.75. Conclusion: The walking tests included in the Walking InCHIANTI Toolkit show very good medium-term reproducibility and modest learning effect. Administering components of the Walking InCHIANTI Toolkit may help in the understanding of the effect of challenges encountered in daily life on walking performance. C1 Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, Longitudinal Studies Sect, Baltimore Longitudinal Study Aging, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-916413, N01-AG-821336]; NIMHD NIH HHS [R01 MD009164] NR 21 TC 17 Z9 17 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2006 VL 85 IS 12 BP 986 EP 991 DI 10.1097/01.phm.0000233210.69400.d4 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 111PO UT WOS:000242465900008 PM 17033595 ER PT J AU Balaban, RS AF Balaban, Robert S. TI Modeling mitochondrial function SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article ID RAT-LIVER MITOCHONDRIA; NICOTINAMIDE-ADENINE DINUCLEOTIDE; PYRUVATE-DEHYDROGENASE COMPLEX; ELECTRON-TRANSPORT CHAIN; TRICARBOXYLIC-ACID CYCLE; STEADY-STATE KINETICS; CYTOCHROME-C-OXIDASE; OXIDATIVE-PHOSPHORYLATION; HEART-MITOCHONDRIA; PYRIDINE-NUCLEOTIDE C1 NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. EM rsb@nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 93 TC 21 Z9 22 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 2006 VL 291 IS 6 BP C1107 EP C1113 DI 10.1152/ajpcell.00223.2006 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 104WT UT WOS:000241992000003 PM 16971500 ER PT J AU Yang, YB Zhu, WZ Joiner, ML Zhang, R Oddis, CV Hou, Y Yang, JY Price, EE Gleaves, L Eren, M Ni, GM Vaughan, DE Xiao, RP Anderson, ME AF Yang, Yingbo Zhu, Wei-Zhong Joiner, Mei-Ling Zhang, Rong Oddis, Carmine V. Hou, Yue Yang, Jinying Price, Edward E. Gleaves, Linda Eren, Mesut Ni, Gemin Vaughan, Douglas E. Xiao, Rui-Ping Anderson, Mark E. TI Calmodulin kinase II inhibition protects against myocardial cell apoptosis in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial infarction; isoproterenol; programmed cell death; phospholamban ID BETA-ADRENERGIC STIMULATION; NONFAILING HUMAN MYOCARDIUM; HEART-FAILURE; SARCOPLASMIC-RETICULUM; DILATED CARDIOMYOPATHY; VENTRICULAR MYOCYTES; BETA(1)-ADRENERGIC STIMULATION; DEPENDENT FACILITATION; PHOSPHOLAMBAN ABLATION; CARDIAC-HYPERTROPHY AB Inhibition of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) or depletion of sarcoplasmic reticulum (SR) Ca2+ stores protects against apoptosis from excessive isoproterenol (Iso) stimulation in cultured ventricular myocytes, suggesting that CaMKII inhibition could be a novel approach to reducing cell death in conditions of increased adrenergic tone, such as myocardial infarction (MI), in vivo. We used mice with genetic myocardial CaMKII inhibition due to transgenic expression of a highly specific CaMKII inhibitory peptide (AC3-I) to test whether CaMKII was important for apoptosis in vivo. A second line of mice expressed a scrambled, inactive form of AC3-I (AC3-C). AC3-C and wild-type (WT) littermates were used as controls. AC3-I mice have reduced SR Ca2+ content and are resistant to Iso- and MI-induced apoptosis compared with AC3-C and WT mice. Phospholamban (PLN) is a target for modulation of SR Ca2+ content by CaMKII. PLN-/- mice have increased susceptibility to Iso- induced apoptosis. Verapamil pretreatment prevented Iso- induced apoptosis in PLN-/- mice, indicating the involvement of a Ca2+-dependent pathway. AC3-I and AC3-C mice were bred into a PLN-/- background. Loss of PLN increased and equalized SR Ca2+ content in AC3-I, AC3-C, and WT mice and abolished the resistance to apoptosis in AC3-I mice after MI. There was a trend (P = 0.07) for increased Iso- induced apoptosis in AC3-I mice lacking PLN compared with AC3-I mice with PLN. These findings indicate CaMKII is proapoptotic in vivo and suggest that regulation of SR Ca2+ content by PLN contributes to the antiapoptotic mechanism of CaMKII inhibition. C1 Univ Iowa, Dept Med, Carver Coll Med, Iowa City, IA 52242 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Univ Iowa, Dept Physiol, Carver Coll Med, Iowa City, IA 52242 USA. RP Anderson, ME (reprint author), Univ Iowa, Dept Med, Carver Coll Med, Iowa City, IA 52242 USA. EM mark-e-anderson@uiowa.edu RI Eren, Mesut/J-3818-2016 FU NHLBI NIH HHS [HL-046681, HL-070250, HL-62494] NR 43 TC 80 Z9 80 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2006 VL 291 IS 6 BP H3065 EP H3075 DI 10.1152/ajpheart.00353.2006 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 103AO UT WOS:000241855900063 PM 16861697 ER PT J AU Aslamkhan, AG Thompson, DM Perry, JL Bleasby, K Wolff, NA Barros, S Miller, DS Pritchard, JB AF Aslamkhan, Amy G. Thompson, Deborah M. Perry, Jennifer L. Bleasby, Kelly Wolff, Natascha A. Barros, Scott Miller, David S. Pritchard, John B. TI The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3 SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE OAT1; OAT3; renal; isolated tubules ID PROTEIN-KINASE-C; MOLECULAR-CLONING; CATION TRANSPORTERS; CHOROID-PLEXUS; RAT-KIDNEY; EXPRESSION CLONING; PROXIMAL TUBULE; WINTER FLOUNDER; DRUG TRANSPORT; FAMILY AB The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3. Am J Physiol Regul Integr Comp Physiol 291: R1773-R1780, 2006. First published July 20, 2006; doi:10.1152/ajpregu.00326.2006.- The flounder renal organic anion transporter (fOat) has substantial sequence homology to mammalian basolateral organic anion transporter orthologs (OAT1/Oat1 and OAT3/Oat3), suggesting that fOat may have functional properties of both mammalian forms. We therefore compared uptake of various substrates by rat Oat1 and Oat3 and human OAT1 and OAT3 with the fOat clone expressed in Xenopus oocytes. These data confirm that estrone sulfate is an excellent substrate for mammalian OAT3/Oat3 transporters but not for OAT1/Oat1 transporters. In contrast, 2,4-dichlorophenoxyacetic acid and adefovir are better transported by mammalian OAT1/Oat1 than by the OAT3/Oat3 clones. All three substrates were well transported by fOat-expressing Xenopus oocytes. fOat Km values were comparable to those obtained for mammalian OAT/Oat1/3 clones. We also characterized the ability of these substrates to inhibit uptake of the fluorescent substrate fluorescein in intact teleost proximal tubules isolated from the winter flounder (Pseudopleuronectes americanus) and killifish (Fundulus heteroclitus). The rank order of the IC50 values for inhibition of cellular fluorescein accumulation was similar to that for the Km values obtained in fOat-expressing oocytes, suggesting that fOat may be the primary teleost renal basolateral Oat. Assessment of the zebrafish (Danio rerio) genome indicated the presence of a single Oat (zfOat) with similarity to both mammalian OAT1/Oat1 and OAT3/Oat3. The puffer fish (Takifugu rubripes) also has an Oat (pfOat) similar to mammalian OAT1/Oat1 and OAT3/Oat3 members. Furthermore, phylogenetic analyses argue that the teleost Oat1/3-like genes diverged from a common ancestral gene in advance of the divergence of the mammalian OAT1/Oat1, OAT3/Oat3, and, possibly, Oat6 genes. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. Zentrum Physiol, Abt Vegetat Physiol & Pathophysiol, Gottingen, Germany. RP Aslamkhan, AG (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES048014-06, Z01 ES080031-29] NR 47 TC 19 Z9 19 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 2006 VL 291 IS 6 BP R1773 EP R1780 DI 10.1152/ajpregu.00326.2006 PG 8 WC Physiology SC Physiology GA 101VG UT WOS:000241768400025 PM 16857889 ER PT J AU Ewing, R Brownson, RC Berrigan, D AF Ewing, Reid Brownson, Ross C. Berrigan, David TI Relationship between urban sprawl and weight of United States youth SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RESIDENTIAL NEIGHBORHOOD TYPE; FACTOR SURVEILLANCE SYSTEM; INCOME PRESCHOOL-CHILDREN; BODY-MASS INDEX; PHYSICAL-ACTIVITY; TRAVEL BEHAVIOR; RISK-FACTOR; US ADULTS; LAND-USE; INCREASING PREVALENCE AB Among United States youth there is an obesity epidemic with potential life-long health implications. To date, relationships between the built environment and body mass index (BMI) have not been evaluated for youth, and have not been evaluated longitudinally. Objectives: To determine if urban sprawl is associated with BMI for U.S. youth. Methods: Using data from the 1997 National Longitudinal Survey of Youth (NLSY97), both cross-sectional and longitudinal analyses were conducted. Hierarchical modeling was used to relate characteristics of individuals, households, and places to BMI. Individual and household data were extracted from the NLSY97. The independent variable of interest was the county sprawl index, which was derived with principal components analyses from census and other data. Results: In a cross-sectional analysis, the likelihood of U.S. adolescents (aged 12-17 years) being overweight or at risk of over-weight (>= 85th percentile relative to the Centers for Disease Control growth charts) was associated with county sprawl (p=0.022). In another cross-sectional analysis, after controlling for sociodemographic and behavioral covariates, the likelihood of young adults (aged 18-23 years) being obese was also associated with county sprawl (p=0.048). By contrast, in longitudinal analyses, BMI growth curves for individual youth over the 7 years of NLSY97, and BMI changes for individual youth who moved between counties, were not related to county sprawl (although coefficient signs were as expected). Conclusions: Cross-sectional analyses suggest that urban form is associated with being overweight among U.S. youth. The strength of these relationships proved comparable to those previously reported for adults. Longitudinal analyses show no such relationship. It is unclear why these approaches give different results, but sample sizes, latent effects, and confounders may contribute. (Am J Prev Med 2006;31(6):464-474) (c) 2006 American journal of Preventive Medicine C1 Univ Maryland, Ctr Smart Growth Res & Educ, ARCH, College Pk, MD 20742 USA. St Louis Univ, Sch Publ Hlth, Dept Community Hlth, St Louis, MO 63103 USA. St Louis Univ, Sch Publ Hlth, Prevent Res Ctr, St Louis, MO 63103 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ewing, R (reprint author), Univ Maryland, Ctr Smart Growth Res & Educ, ARCH, 1112 Preinkert Field House, College Pk, MD 20742 USA. EM rewing1@umd.edu FU Intramural NIH HHS [Z99 CA999999] NR 69 TC 137 Z9 141 U1 5 U2 26 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 DEC PY 2006 VL 31 IS 6 BP 464 EP 474 DI 10.1016/j.amepre.2006.08.020 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 119UK UT WOS:000243039200002 PM 17169708 ER PT J AU Avenevoli, S Merikangas, KR AF Avenevoli, Shelli Ries Merikangas, Kathleen TI Implications of high-risk family studies for prevention of depression SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT NIMH Workshop on the Prevention of Depression in Children and Adolescents CY JUN 21-22, 2004 CL Rockville, MD SP NIMH, NIDA ID GENERALIZED ANXIETY DISORDER; PARTLY DIFFERENT ENVIRONMENTS; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; MATERNAL DEPRESSION; COMMUNITY SAMPLE; PANIC DISORDER; PARENTAL DEPRESSION; MENTAL-DISORDERS; EARLY-ADULTHOOD AB The high-risk family study is a powerful design that facilitates identification of early forms of expression of depression and premorbid vulnerability, risk, and protective factors that are important for defining prevention targets and program foci. This paper (1) highlights the strengths of high-risk studies for informing early intervention efforts; (2) summarizes findings of familial aggregation from controlled high-risk studies of depression; and (3) briefly reviews evidence for potential mediators (i.e., early forms of expression, vulnerability factors) that explain familial risk and for moderators (i.e., interactive risk and protective factors) that enhance or minimize familial risk. New data from the Yale High-Risk Study of Comorbidity of Substance Use and Affective Disorders are presented to exemplify strategies for identifying specific familial pathways to depression among offspring of parents with substance and anxiety disorders. Likewise, parental depression is associated with a range of emotional and behavioral problems, including anxiety and conduct disorder, in their offspring. These nonspecific effects, together with emerging findings on mechanisms of risk, support early intervention efforts that target a range of youth at risk for depression through multipronged approaches that attend to the individual characteristics of the child and parent, clinical comorbidity, and the broader family and social context. C1 NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIMH, Div Pediat Translat Res & Treatment Dev, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Avenevoli, S (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, US Dept HHS, Bldg 35,Room 1A-201,35 Convent Dr, Bethesda, MD 20892 USA. EM shelli.avenevoli@nih.gov NR 93 TC 25 Z9 25 U1 3 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 DEC PY 2006 VL 31 IS 6 SU 1 BP S126 EP S135 DI 10.1016/j.amepre.2006.07.003 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 121ZY UT WOS:000243196700003 PM 17175407 ER PT J AU Sims, BE Nottelmann, E Koretz, D Pearson, J AF Sims, Belinda E. Nottelmann, Editha Koretz, Doreen Pearson, Jane TI Prevention of depression in children and adolescents SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID DISORDERS; INTERVENTION; PREVALENCE; CHILDHOOD C1 NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. NIH, Div Pediat Res & Treatment Dev, Bethesda, MD 20892 USA. NIH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Sims, BE (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, NIH, 6001 Execut Blvd,Room 5185,MSC 9589, Bethesda, MD 20892 USA. EM bsims@nida.nih.gov NR 37 TC 3 Z9 3 U1 0 U2 3 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 DEC PY 2006 VL 31 IS 6 SU 1 BP S99 EP S103 DI 10.1016/j.amepre.2006.07.014 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 121ZY UT WOS:000243196700001 PM 17175405 ER PT J AU Towbin, KE AF Towbin, Kenneth E. TI Gaining: Pediatric patients and use of atypical antipsychotics SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; WEIGHT-GAIN; METFORMIN; CHILDREN; ADOLESCENTS; DRUGS; TRENDS C1 NIMH, DIRP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Towbin, KE (reprint author), NIMH, DIRP, Mood & Anxiety Disorders Program, CRC Rm 1-3633,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kenneth.towbin@nih.gov FU Intramural NIH HHS NR 13 TC 3 Z9 3 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2034 EP 2036 DI 10.1176/appi.ajp.163.12.2034 PG 3 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000003 PM 17151148 ER PT J AU Insel, T Volkow, N Li, TK AF Insel, Thomas Volkow, Nora Li, Ting-Kai TI Research funding: The view from NIH SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Insel, T (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2043 EP 2045 DI 10.1176/appi.ajp.163.12.2043 PG 3 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000005 PM 17151151 ER PT J AU Compton, WM Conway, KP Stinson, FS Grant, BF AF Compton, Wilson M. Conway, Kevin P. Stinson, Frederick S. Grant, Bridget F. TI Changes in the prevalence of major depression and comorbid substance use disorders in the United States between 1991-1992 and 2001-2002 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; DSM-IV ALCOHOL; MENTAL-DISORDERS; DRUG MODULES; PSYCHIATRIC-DISORDERS; 12-MONTH PREVALENCE; ANXIETY DISORDERS AB Objective: The authors examined changes inthe prevalence of major depression in the United States between 1991-1992 and 2001-2002 and sought to determine whether changes in depression rates were associated with changes in rates of comorbid substance use disorder. Method: Data were drawn from two large (Ns exceeding 42,000) cross-sectional surveys of representative samples of the U. S. population conducted 10 years apart. Both surveys used face-to-face interviews, the same diagnostic criteria, and consistent assessment instruments. Rates of past-year major depressive episode in the total samples and among subjects with and without co-occurring substance use disorders in major demographic groups were compared. Results: From 1991-1992 to 2001-2002, the prevalence of major depression among U. S. adults increased from 3.33% to 7.06%. Increases were statistically significant for whites, blacks, and Hispanics and for all age groups. For Hispanic men overall and Hispanic women 18-29 years of age, rates increased but not significantly. The hypothesis that increases in the rates of depression could be explained by concomitant increases in cooccurring substance use disorders was supported only for black men 18-29 years of age. Conclusions: Rates of major depression rose markedly over the past decade in the United States, and increases were noted for most sociodemographic subgroups of the population. If the prevalence continues to increase at the rate it did during the past decade, the demand for services will increase dramatically in the coming years. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rm 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Conway, Kevin/0000-0002-7638-339X FU Intramural NIH HHS NR 35 TC 175 Z9 178 U1 1 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2006 VL 163 IS 12 BP 2141 EP 2147 DI 10.1176/appi.ajp.163.12.2141 PG 7 WC Psychiatry SC Psychiatry GA 113VL UT WOS:000242626000021 PM 17151166 ER PT J AU Garantziotis, S Brass, DM Savov, J Hollingsworth, JW McElvania-TeKippe, E Berman, K Walker, JKL Schwartz, DA AF Garantziotis, Stavros Brass, David M. Savov, Jordan Hollingsworth, John W. McElvania-TeKippe, Erin Berman, Katie Walker, Julia K. L. Schwartz, David A. TI Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE airway hyperreactivity; airway remodeling; endotoxin; IL-10 ID INTERLEUKIN-10 GENE-TRANSFER; TOLL-LIKE RECEPTOR-4; AIRWAY INFLAMMATION; GRAIN DUST; LUNG INFLAMMATION; EPITHELIAL-CELLS; NITRIC-OXIDE; ASTHMA; MICE; RESPONSES AB Endotoxin (LPS), a Gram-negative cell wall component, has potent proinflammatory properties. Acute LPS exposure causes airway inflammation; chronic exposure causes airway hyperreactivity and remodeling. IL-10 is an important antiinflammatory cytokine, which is decreased in patients with airway disease, such as asthma and cystic fibrosis. To examine the physiologic and therapeutic role of IL-10 in acute and chronic LPS-incluced airway disease. Mice were exposed to aerosolized LPS once or daily for 4 wk. Endpoints were airway inflammation, airway reactivity to methacholine, extracellular matrix protein expression, and histologic analysis. IL-10-deficient mice developed significantly enhanced airway cellularity and remodeling when compared with C5713L/6 mice after chronic LPS inhalation. However they demonstrated less airway hyperreactivity associated with higher inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and lung lavage fluid nitrite levels. In a bone marrow transplantation model, the IL-10 antiinflammatory effect was dependent on the hematopoletic but not on the parenchymal IL-10 expression. Induced epithelial human IL-10expression protected from the LPS effects and led to decreased Collagen production. IL-10 attenuates chronic LPS-incluced airway inflammation and remodeling. Physiologically, the antiinflammatory effect of IL-10 is mediated by hematopoietic cells. Therapeutically, adenovirus-driven expression of human IL-10 in airway epithelia is sufficient for its protective effect on inflammation and remodeling. The role of IL-10 on airway hyperreactivity is complex: IL-10 deficiency protects against LPS-induced hyperreactivity, and is associated with higher eNOS, iNOS, and airway nitrate levels. C1 Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Garantziotis, S (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Box 3683, Durham, NC 27710 USA. EM garan001@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU NIEHS NIH HHS [ES11375, ES011961, ES012496, ES07498, ES12717] NR 35 TC 16 Z9 16 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2006 VL 35 IS 6 BP 662 EP 667 DI 10.1165/rcmb.2006-0055OC PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 115OL UT WOS:000242743500005 PM 16809636 ER PT J AU Bredella, MA Steinbach, LS Morgan, S Ward, M Davis, JC AF Bredella, Miriam A. Steinbach, Lynne S. Morgan, Stephanie Ward, Michael Davis, John C. TI MRI of the sacroiliac joints in patients with moderate to severe ankylosing spondylitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE ankylosing spondylitis; bone; joint; MRI; musculoskeletal imaging; sacroiliac joints; sacroiliitis ID RESONANCE-IMAGING EXAMINATIONS; DISEASE-ACTIVITY; INFLIXIMAB; PATHOLOGY; THERAPY; PROTEIN; SPINE AB OBJECTIVE. The objectives of our study were to evaluate whether MRI findings of the sacroiliac joints are able to distinguish between active and inactive disease in patients with established ankylosing spondylitis and to determine whether these findings correlate with markers of clinical activity, disease duration, severity, and degree of radiographic damage. MATERIALS AND METHODS. Eighteen patients with symptomatic moderate to severe ankylosing spondylitis were evaluated. MRI of the sacroiliac joint (1.5 T) was performed using fat-saturated T2-weighted, T1-weighted, STIR, and fat-saturated contrast-enhanced T1-weighted sequences. The sacroiliac joints were evaluated by two radiologists for enhancement, subchondral bone marrow edema, erosions, and subchondral fatty marrow infiltration. Findings on MRI were analyzed for correlation with multiple clinical characteristics and measures of disease activity, including radiographic scoring. RESULTS. In 17 patients, MRI showed abnormal findings of the sacroiliac joint. Ten patients showed active disease on MRI as measured by abnormal enhancement and subchondral bone marrow edema. Disease activity detected using MRI correlated in a positive fashion with only C-reactive protein (CRP) level. There was no correlation with the other measures of disease activity or with disease duration. In 14 patients, fatty subchondral bone marrow was detected on MRI. These changes were seen in patients with active and chronic disease and correlated with higher radiographic scores but not with disease duration or markers of disease activity. CONCLUSION. Contrast-enhanced MRI of the sacroiliac joint is sensitive in depicting sacroiliitis in patients with established ankylosing spondylitis. Subchondral edema and enhancement correlate with high CRP levels. Subchondral fatty bone marrow changes were seen in both active and chronic sacroiliitis and are correlated with higher radiographic scores; these changes may be a marker of more advanced disease. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Internal Med, Div Rheumatol, San Francisco, CA 94143 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Yawkey Bldg,6400 6E, Boston, MA 02114 USA. EM mbredella@partners.org NR 18 TC 54 Z9 59 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2006 VL 187 IS 6 BP 1420 EP 1426 DI 10.2214/AJR.05.1423 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109DX UT WOS:000242289200006 PM 17114530 ER PT J AU Taplin, SH Rutter, CM Lehman, CD AF Taplin, Stephen H. Rutter, Carolyn M. Lehman, Constance D. TI Testing the effect of computer-assisted detection on interpretive performance in screening mammography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE BI-RADS; breast cancer; computer-assisted detection; diagnosis; screening mammography ID QUALITY STANDARDS ACT; AIDED DETECTION CAD; BREAST-CANCER; DIGITAL MAMMOGRAPHY; AMERICAN-COLLEGE; DATA SYSTEM; RADIOLOGISTS; VARIABILITY; ACCURACY; ASSOCIATION AB OBJECTIVE. The objective of our study was to test whether the use of computer-assisted detection (CAD) improves sensitivity at no cost to specificity for the detection of breast cancer and enables more accurate assessment of fatty breast tissue compared with dense breast tissue. MATERIALS AND METHODS. We created a stratified random sample of screening mammograms weighted with difficult cases split evenly among women with fatty breast tissue and those with dense breast tissue: 114 patients were cancer-free, 114 had cancer 1 year after screening, and 113 had cancer 13-24 months after screening. In test settings 6 months apart, 19 community radiologists interpreted 341 bilateral screening mammograms with and without CAD. We compared the sensitivity and specificity using regression models adjusting for repeated measures. RESULTS. CAD assistance did not affect overall sensitivity (cancer by 1 year: 63.2% without CAD and 62.0% with CAD; cancer in 13-24 months: 33.5% without CAD and 32.3% with CAD), but its effect differed for visible masses that were marked by CAD compared with those that were not marked by CAD (hereafter referred to as "unmarked"). CAD was associated with improved sensitivity for marked visible cancers and decreased sensitivity for unmarked visible masses; the sensitivities without and with CAD, respectively, were as follows: marked cancer by 1 year, 82.7% versus 83.1%; marked cancer in 13-24 months, 44.2% versus 57.9%; unmarked cancer by 1 year, 37.4% versus 30.1%; unmarked cancer in 13-24 months, 29.7% versus 23.0% (p < 0.03 for both interactions between assistance and CAD marking for cancer by 1 year and cancer in 13-24 months). CAD marked 77% (70/91) of the visible cancers by 1 year and 67.3% (37/55) of the visible cancers in 13-24 months. CAD marked more visible calcified lesions (86%) than masses and asymmetric densities (67%) (p < 0.05). Overall specificity was 72% without and 75% with CAD (p < 0.02). CAD had a greater effect on both specificity (p < 0.02) and sensitivity (p < 0.03) among radiologists who interpret more than 50 mammograms per week. The results were the same for fatty breast tissue and dense breast tissue. CONCLUSION. In this experiment, CAD increased interpretive specificity but did not affect sensitivity because visible noncalcified lesions that went unmarked by CAD were less likely to be assessed as abnormal by radiologists. Breast density did not affect CAD's performance. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Washington, Seattle Canc Care Alliance, Dept Radiol, Seattle, WA 98109 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. RP Taplin, SH (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7004,EPN 4500, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA63731] NR 36 TC 29 Z9 30 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2006 VL 187 IS 6 BP 1475 EP 1482 DI 10.2214/AJR.05.0940 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109DX UT WOS:000242289200016 PM 17114540 ER PT J AU Goeleven, A Robberecht, W Sonies, B Carbonez, A Dejaeger, E AF Goeleven, Ann Robberecht, Wim Sonies, Barbara Carbonez, An Dejaeger, Eddy TI Manofluorographic evaluation of swallowing in amyotrophic lateral sclerosis and its relationship with clinical evaluation of swallowing SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE amyotrophic lateral sclerosis; swallowing; videofluoroscopy; manometry ID MOTOR-NEURON DISEASE; DYSPHAGIA; MANAGEMENT; DISORDERS; MECHANISMS; PATTERNS AB The aim of this cross-sectional study was, first, to identify swallowing dysfunctions in an ALS population of 40 consecutive patients through combined videofluoroscopy and manometry. Secondly, these objective swallowing data were correlated with the functional feeding status as reported by the patient or family member. Videofluoroscopic evaluation showed dysfunctions in the oral phase of swallowing, pharyngeal initiation and pharyngeal transport. In addition, manometric data revealed low tongue driving forces and pharyngeal contraction amplitudes but normal relaxation of the upper oesophageal sphincter (UES). Aspiration was noted in a not negligible number of 9/40 patients. These objective data were then correlated with the clinical swallowing and feeding status, assessed by means of the ALS Swallowing Severity Scale. Patients receiving scores of 6 or lower on the ALSSSS, report dietary consistency changes but are considered 'safe oral feeders'. Nevertheless, our data revealed that these patients showed significant aspiration during videofluoroscopy. Although not every patient with ALS should be referred routinely for radiographic evaluation of swallowing, our findings suggest referral for a radiological examination as soon as the ALSSSS drops to a score of 6 or lower, to evaluate the presence of (silent) aspiration. C1 Katholieke Univ Leuven Hosp, Dept ENT Head & Neck Surg, Swallowing Clin, B-3000 Louvain, Belgium. Katholieke Univ Leuven Hosp, Dept Neurol, B-3000 Louvain, Belgium. NIH, Bethesda, MD 20892 USA. Catholic Univ Louvain VIB, Univ Ctr Stat, B-3000 Louvain, Belgium. Katholieke Univ Leuven Hosp, Dept Geriatr Med, Swallowing Clin, B-3000 Louvain, Belgium. RP Goeleven, A (reprint author), Katholieke Univ Leuven Hosp, Dept ENT Head & Neck Surg, Swallowing Clin, Kapucijnenvoer 33, B-3000 Louvain, Belgium. EM Ann.Goeleven@uz.kuleuven.ac.be NR 23 TC 6 Z9 6 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD DEC PY 2006 VL 7 IS 4 BP 235 EP 240 DI 10.1080/17482960600664870 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 118AK UT WOS:000242914200006 PM 17127562 ER PT J AU Papalia, GA Leavitt, S Bynum, MA Katsamba, PS Wilton, R Qiu, HW Steukers, M Wang, SM Bindu, L Phogat, S Giannetti, AM Ryan, TE Pudlak, VA Matusiewicz, K Michelson, KM Nowakowski, A Pham-Baginski, A Brooks, J Tieman, BC Bruce, BD Vaughn, M Baksh, M Cho, YH De Wit, M Smets, A Vandersmissen, J Michiels, L Myszka, DG AF Papalia, Giuseppe A. Leavitt, Stephanie Bynum, Maggie A. Katsamba, Phinikoula S. Wilton, Rosemarie Qiu, Huawei Steukers, Mieke Wang, Siming Bindu, Lakshman Phogat, Sanjay Giannetti, Anthony M. Ryan, Thomas E. Pudlak, Victoria A. Matusiewicz, Katarzyna Michelson, Klaus M. Nowakowski, Agnes Pham-Baginski, Anh Brooks, Jonathan Tieman, Bryan C. Bruce, Barry D. Vaughn, Michael Baksh, Michael Cho, Yun Hee De Wit, Mieke Smets, Alexandra Vandersmissen, Johan Michiels, Lieve Myszka, David G. TI Comparative analysis of 10 small molecules binding to carbonic anhydrase II by different investigators using Biacore technology SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Biacore; surface plasmon resonance; protein-protein interaction; kinetics; SPR ID OPTICAL BIOSENSOR LITERATURE; KINETIC-ANALYSIS; USERS AB In this benchmark study, 26 investigators were asked to characterize the kinetics and affinities of 10 sulfonamide inhibitors binding to the enzyme carbonic anhydrase II using Biacore optical biosensors. A majority of the participants collected data that could be fit to a 1:1 interaction model, but a subset of the data sets obtained from some instruments were of poor quality. The experimental errors in the k(a), k(d), and K-D parameters determined for each of the compounds averaged 34, 24, and 37%, respectively. As expected, the greatest variation in the reported constants was observed for compounds with exceptionally weak affinity and/or fast association rates. The binding constants determined using the biosensor correlated well with solution-based titration calorimetry measurements. The results of this study provide insight into the challenges, as well as the level of experimental variation, that one would expect to observe when using Biacore technology for small molecule analyses. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Utah, Ctr Biomol Interact Anal, Sch Med, Salt Lake City, UT 84132 USA. Gilead Sci, Foster City, CA 94404 USA. Agilent Technol, Palo Alto, CA 94304 USA. Argonne Natl Lab, Argonne, IL 60439 USA. Genzyme Corp, Framingham, MA 01701 USA. Dyaxsa, B-4000 Liege 1, Belgium. Georgia State Univ, Atlanta, GA 30302 USA. NCI, Frederick, MD 21702 USA. NIAID, Bethesda, MD 20892 USA. Reichert Analyt Instruments, Depew, NY 14043 USA. Adamed, PL-05152 Czosnow, Poland. Amgen Inc, Thousand Oaks, CA 91320 USA. diaDexus, San Francisco, CA 94080 USA. Wyeth, Andover, MA 01810 USA. Wyeth, Cambridge, MA 02140 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Human Genome Sci, Rockville, MD 20850 USA. Tibotec, B-2800 Mechelen, Belgium. RP Myszka, DG (reprint author), Univ Utah, Ctr Biomol Interact Anal, Sch Med, Salt Lake City, UT 84132 USA. EM dmyszka@cores.utah.edu OI Katsamba, Phinikoula/0000-0003-3981-1604 NR 14 TC 71 Z9 72 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 2006 VL 359 IS 1 BP 94 EP 105 DI 10.1016/j.ab.2006.08.021 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 106NY UT WOS:000242108900012 PM 17007806 ER PT J AU Uzzaman, A Metcalfe, DD Komarow, HD AF Uzzaman, Ashraf Metcalfe, Dean D. Komarow, Hirsh D. TI Acoustic rhinometry in the practice of allergy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID NASAL PROVOCATION TEST; CROSS-SECTIONAL AREAS; COMPUTED-TOMOGRAPHY; CONTROLLED-TRIAL; CAVITY GEOMETRY; DOUBLE-BLIND; RHINOMANOMETRY; RHINITIS; AIRWAY; PATENCY AB Objective: To provide a comprehensive practical overview of the use of acoustic rhinometry in the practice of allergy. Data Sources: An all-inclusive PubMed search was conducted for articles on acoustic rhinometry that were published in peer-reviewed journals, between 1989 and 2006, using the keywords acoustic rhinometry, allergic rhinitis, and nasal provocation testing. Study Selection: The expert opinion of the authors was used to select studies for inclusion in this review. Results: Acoustic rhinometry is a sound-based technique used to measure nasal cavity area and volume. It has been validated by comparison to measurements with computed tomography and magnetic resonance imaging. Acoustic rhinometry requires minimal patient cooperation and may be used in adults, children, and infants. It is used by medical practitioners to diagnose and evaluate therapeutic responses in conditions such as rhinitis and to measure nasal dimensions during allergen provocation testing. Acoustic rhinometry also provides a visual reflection of the nasal response to therapy, which may be useful in increasing compliance to prescribed medications. Conclusions: Acoustic rhinometry is a safe, noninvasive, objective, and validated measure of nasal obstruction that appears to be of practical use in the diagnosis and management of inflammatory diseases of the upper airways. C1 NIAID, NIH, LAD, Bethesda, MD 20892 USA. RP Komarow, HD (reprint author), NIAID, NIH, LAD, Bldg 10,Room 11S 231,10 Ctr Dr, Bethesda, MD 20892 USA. EM komarowh@niaid.nih.gov FU Intramural NIH HHS NR 70 TC 18 Z9 18 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2006 VL 97 IS 6 BP 745 EP 752 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 119OJ UT WOS:000243021300004 PM 17201232 ER PT J AU Lacey, JV Leitzmann, M Brinton, LA Lubin, JH Sherman, ME Schatzkin, A Schairer, C AF Lacey, James V., Jr. Leitzmann, Michael Brinton, Louise A. Lubin, Jay H. Sherman, Mark E. Schatzkin, Arthur Schairer, Catherine TI Weight, height, and body mass index and risk for ovarian cancer in a cohort study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE ovarian carcinoma; anthropometry; obesity; body mass index ID PROGESTIN REPLACEMENT THERAPY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; UNITED-STATES; MENOPAUSAL ESTROGEN; CIRCULATING LEVELS; PHYSICAL-ACTIVITY; STEROID-HORMONES; SEX-HORMONES; HEALTH-RISK AB PURPOSE: Reported associations between ovarian cancer and body size are inconsistent. We assessed ovarian cancer and anthropometry in the Breast Cancer Detection Demonstration Project Follow-Up Study. METHODS: The 46,026 participants completed a baseline interview and mailed questionnaires between 1979 and 1998. By using multiple sources, we identified 346 incident ovarian cancers during follow-up. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) to estimate relative risks for developing ovarian cancer associated with height and weight (measured 1973 to 1980) and self-reported current and usual adult weight (collected during follow-up). RESULTS: Neither taller height (>= 66 versus < 62 inches; RR, 0.90; 95% Cl, 0.64-1.26) nor greater weight (>= 161 versus <= 120 lbs; RR, 1.09; 95% CI, 0.77-1.55) was associated with ovarian cancer. Compared with normal weight (body mass index [BMI], 18.5 to 24.9 kg/m(2)), overweight (BMI, 25 to 29.9 kg/m(2); RR, 1.00; 95% Cl, 0.78-1.29) and obesity (BMI, 30 to 34.9 kg/m(2); RR, 0.94; 95% CI, 0.59-1-48) were not associated with ovarian cancer. Severe obesity (BMI >= 35 kg/m(2)) produced a nonsignificantly elevated RR (1.55; 95% Cl, 0.84-2.84). Associations with histologic types and statistical interactions with menopausal status and hormone therapy use were null. CONCLUSIONS: Based on height and weight measured before baseline, overweight and obesity were not significantly associated with ovarian cancer in this cohort. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Div Epidemiol & Genet, Rockville, MD 20852 USA. RP Lacey, JV (reprint author), NCI, Div Epidemiol & Genet, 6120 Execut Bldg,MSC 7234, Rockville, MD 20852 USA. EM jimlacey@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS NR 37 TC 13 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2006 VL 16 IS 12 BP 869 EP 876 DI 10.1016/j.annepidem.20065.07.011 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120LK UT WOS:000243086000002 PM 17027285 ER PT J AU Driscoll, I Resnick, SM Troncoso, JC An, Y O'Brien, R Zonderman, AB AF Driscoll, Ira Resnick, Susan M. Troncoso, Juan C. An, Yang O'Brien, Richard Zonderman, Alan B. TI Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly SO ANNALS OF NEUROLOGY LA English DT Article ID NEUROFIBRILLARY TANGLES; NEURITIC PLAQUES; BETA-A4 DEPOSITS; AMYLOID PLAQUES; UNITED-STATES; DISEASE; DEMENTIA; NEUROPATHOLOGY; IMPAIRMENT; BRAIN AB Objective: Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. Methods: Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. Results: Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. Interpretation: Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly. C1 NIA, LPC, GRC, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. RP Driscoll, I (reprint author), NIA, LPC, GRC, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM driscolli@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS; NIA NIH HHS [AG05146] NR 51 TC 86 Z9 86 U1 0 U2 5 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 DEC PY 2006 VL 60 IS 6 BP 688 EP 695 DI 10.1002/ana.21031 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 122BO UT WOS:000243200900008 PM 17192929 ER EF