FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Woody, GE Poole, SA Subramaniam, G Dugosh, K Bogenschutz, M Abbott, P Patkar, A Publicker, M McCain, K Potter, JS Forman, R Vetter, V McNicholas, L Blaine, J Lynch, KG Fudala, P AF Woody, George E. Poole, Sabrina A. Subramaniam, Geetha Dugosh, Karen Bogenschutz, Michael Abbott, Patrick Patkar, Ashwin Publicker, Mark McCain, Karen Potter, Jennifer Sharpe Forman, Robert Vetter, Victoria McNicholas, Laura Blaine, Jack Lynch, Kevin G. Fudala, Paul TI Extended vs Short-term Buprenorphine-Naloxone for Treatment of Opioid-Addicted Youth A Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID METHADONE-MAINTENANCE TREATMENT; DRUG-USERS; DEPENDENCE; ABUSE; PHARMACOLOGY; NALTREXONE; INJECTION; RELAPSE AB Context The usual treatment for opioid- addicted youth is detoxification and counseling. Extended medication- assisted therapy may be more helpful. Objective To evaluate the efficacy of continuing buprenorphine- naloxone for 12 weeks vs detoxification for opioid- addicted youth. Design, Setting, and Patients Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine- naloxone or a 14- day taper (detox). Interventions Patients in the 12- week buprenorphine- naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. Main Outcome Measure Opioid- positive urine test result at weeks 4, 8, and 12. Results The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioidpositive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P =. 09). At week 4, 59 detox patients had positive results ( 61%; 95% confidence interval [CI]= 47%-75%) vs 58 12- week buprenorphine- naloxone patients (26%; 95% CI= 14%- 38%). At week 8, 53 detox patients had positive results ( 54%; 95% CI= 38%- 70%) vs 52 12- week buprenorphine- naloxone patients ( 23%; 95% CI= 11%- 35%). At week 12, 53 detox patients had positive results (51%; 95% CI= 35%- 67%) vs 49 12- week buprenorphine-naloxone patients (43%; 95% CI= 29%-57%). By week 12, 16 of 78 detox patients ( 20.5%) remained in treatment vs 52 of 74 12- week buprenorphine-naloxone patients ( 70%; chi(2)(1) = 32.90, P <. 001). During weeks 1 through 12, patients in the 12- week buprenorphine- naloxone group reported less opioid use (chi(2)(1) = 18.45, P <. 001), less injecting (chi(2)(1) = 6.00, P =. 01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P <. 001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. Conclusions Continuing treatment with buprenorphine- naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer- term treatment with buprenorphine for young individuals with opioid dependence. Trial Registration clinicaltrials. gov Identifier: NCT00078130. C1 [Woody, George E.; Poole, Sabrina A.; Dugosh, Karen; Forman, Robert; McNicholas, Laura; Lynch, Kevin G.; Fudala, Paul] Univ Penn, Dept Psychiat, Treatment Res Inst, Philadelphia, PA 19106 USA. [Subramaniam, Geetha] Johns Hopkins Univ, Div Child & Adolescent Psychiat, Baltimore, MD USA. [Bogenschutz, Michael; Abbott, Patrick] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Bogenschutz, Michael] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. [Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Addict Program, Albuquerque, NM 87131 USA. [Abbott, Patrick] Univ New Mexico, Hlth Sci Ctr, Substance Abuse Program, Albuquerque, NM 87131 USA. [Patkar, Ashwin] Duke Univ, Med Ctr, Durham, NC USA. [Publicker, Mark] Mercy Recovery Ctr, Westbrook, ME USA. [McCain, Karen] Duke Univ, Duke Addict Program, Durham, NC USA. [Potter, Jennifer Sharpe] Harvard Univ, Sch Med, Boston, MA USA. [Potter, Jennifer Sharpe] McLean Hosp, Belmont, MA 02178 USA. [Vetter, Victoria] Childrens Hosp Philadelphia, Div Pediat Cardiol, Philadelphia, PA 19104 USA. [Woody, George E.; McNicholas, Laura; Fudala, Paul] Vet Affairs Med Ctr, Philadelphia, PA USA. [Blaine, Jack] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. RP Woody, GE (reprint author), Univ Penn, Dept Psychiat, Treatment Res Inst, 150 S Independence Mall W,Ste 600, Philadelphia, PA 19106 USA. EM woody@tresearch.org RI Potter, Jennifer/C-6720-2008 OI Potter, Jennifer/0000-0002-7250-4422 FU National Institute on Drug Abuse [U10-DA013711, U10-DA015831, U10-DA13034, K12-DA000357, U10-DA1533, U10DA13043, KO5-DA17009] FX This study was supported by the following grants from the National Institute on Drug Abuse: U10-DA013711 to Duke University (Dr Patkar); U10-DA015831 to Harvard University (Dr Weiss); U10-DA13034 to Johns Hopkins University (Dr Stitzer); K12-DA000357 (Dr Subramaniam); U10-DA1533 to the University of New Mexico (Dr Miller); and U10DA13043 and KO5-DA17009 (Dr Woody). Reckitt Benckiser provided medication for the study. NR 35 TC 138 Z9 139 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 2008 VL 300 IS 17 BP 2003 EP 2011 DI 10.1001/jama.2008.574 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 368EX UT WOS:000260605400020 PM 18984887 ER PT J AU Denny, CC Emanuel, EJ AF Denny, Colleen C. Emanuel, Ezekiel J. TI US Health Aid Beyond PEPFAR The Mother & Child Campaign SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MILLENNIUM DEVELOPMENT GOALS; COST-EFFECTIVENESS ANALYSIS; DEVELOPING-COUNTRIES; INTERVENTIONS; STRATEGIES; HIV/AIDS C1 [Denny, Colleen C.; Emanuel, Ezekiel J.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 15 TC 30 Z9 31 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 2008 VL 300 IS 17 BP 2048 EP 2051 DI 10.1001/jama.2008.556 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 368EX UT WOS:000260605400027 PM 18984893 ER PT J AU Dizhoor, AM Woodruff, ML Olshevskaya, EV Cilluffo, MC Cornwall, MC Sieving, PA Fain, GL AF Dizhoor, Alexander M. Woodruff, Michael L. Olshevskaya, Elena V. Cilluffo, Marianne C. Cornwall, M. Carter Sieving, Paul A. Fain, Gordon L. TI Night Blindness and the Mechanism of Constitutive Signaling of Mutant G90D Rhodopsin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE photoreceptor; rod; transduction; adaptation; rhodopsin; vision ID LEBER CONGENITAL AMAUROSIS; KNOCK-OUT MICE; ROD PHOTORECEPTORS; VISUAL PIGMENT; RETINAL RODS; OPSIN ACTIVATION; MOUSE MODEL; DARK NOISE; LIGHT; DEGENERATION AB The G90D rhodopsin mutation is known to produce congenital night blindness in humans. This mutation produces a similar condition in mice, because rods of animals heterozygous (D+) or homozygous (D+/+) for this mutation have decreased dark current and sensitivity, reduced Ca2+, and accelerated values of tau(REC) and tau(D), similar to light-adapted wild-type (WT) rods. Our experiments indicate that G90D pigment activates the cascade, producing an equivalent background light of similar to 130 Rh-star rod(-1) for D+ and 890 Rh-star rod(-1) for D+/+. The active species of the G90D pigment could be unregenerated G90D opsin or G90D rhodopsin, either spontaneously activated (as Rh-star) or in some other form. Addition of 11-cis-retinal in lipid vesicles, which produces regeneration of both WT and G90D opsin in intact rods and ROS membranes, had no effect on the waveform or sensitivity of dark-adapted G90D responses, indicating that the active species is not G90D opsin. The noise spectra of dark-adapted G90D and WT rods are similar, and the G90D noise variance is much less than of a WT rod exposed to background light of about the same intensity as the G90D equivalent light, indicating that Rh-star is not the active species. We hypothesize that G90D rhodopsin undergoes spontaneous changes in molecular conformation which activate the transduction cascade with low gain. Our experiments provide the first indication that a mutant form of the rhodopsin molecule bound to its 11-cis-chromophore can stimulate the visual cascade spontaneously at a rate large enough to produce visual dysfunction. C1 [Woodruff, Michael L.; Fain, Gordon L.] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA. [Dizhoor, Alexander M.; Olshevskaya, Elena V.] Salus Univ, Pennsylvania Coll Optometry, Hafter Res Labs, Elkins Pk, PA 19027 USA. [Cilluffo, Marianne C.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Cornwall, M. Carter] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. [Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Fain, Gordon L.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Fain, GL (reprint author), Univ Calif Los Angeles, Dept Physiol Sci, 3836 Life Sci, Los Angeles, CA 90095 USA. EM gfain@ucla.edu OI Cornwall, M./0000-0002-0847-939X FU National Institutes of Health [EY11522, EY01157, EY01844, EY 00331]; National Eye Institute; National Institute on Deafness and Other Communication Disorders Intramural; Pennsylvania Lions Sight Preservation Foundation; UCLA FX This work was supported by National Institutes of Health Grants EY11522 (A. M. D.), EY01157 (M. C. C.), EY01844 (G. L. F.), and EY 00331 [Jules Stein Eye Institute, University of California, Los Angeles (UCLA) Core, M. L. W., G. L. F.], National Eye Institute, National Institute on Deafness and Other Communication Disorders Intramural funding (P. A. S.), the Pennsylvania Lions Sight Preservation Foundation (A. M. D.), and the Microscopic Techniques Core Service Fund of UCLA (M. C. C.). A. M. D. is the Martin and Florence Hafter Chair Professor of Pharmacology. We thank Rosalie Crouch of the Medical University of South Carolina for providing 11-cis retinal, Roxana Radu of the Jules Stein Eye Institute, UCLA for assaying the purity of the retinal, Dean Bok and the members of the Bok laboratory of the Jules Stein Eye Institute, UCLA for providing tissue blocks of Rpe65 knock-out mice for measurement of outer segment dimensions, and Dan Tranchina of New York University for help with statistical testing. NR 40 TC 19 Z9 19 U1 1 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 NOV 5 PY 2008 VL 28 IS 45 BP 11662 EP 11672 DI 10.1523/JNEUROSCI.4006-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 369AV UT WOS:000260665900024 PM 18987202 ER PT J AU Lau, P Verrier, JD Nielsen, JA Johnson, KR Notterpek, L Hudson, LD AF Lau, Pierre Verrier, Jonathan D. Nielsen, Joseph A. Johnson, Kory R. Notterpek, Lucia Hudson, Lynn D. TI Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE microRNA; posttranscriptional regulation; oligodendrocyte; PMP22; myelin; glia ID PERIPHERAL MYELIN PROTEIN-22; MAMMALIAN MICRORNAS; ANIMAL MICRORNAS; GENOMIC ANALYSIS; GENE-EXPRESSION; BRAIN; DISEASE; DIFFERENTIATION; SPECIFICATION; DROSOPHILA AB MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile (" microRNAome") contains 43 miRNAs whose expression dynamically changes during the transition from A2B5(+) oligodendrocyte progenitor cells to premyelinating GalC(+) cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3' untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome. C1 [Lau, Pierre; Nielsen, Joseph A.; Hudson, Lynn D.] NINDS, Sect Dev Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Johnson, Kory R.] NINDS, Bioinformat Neurosci Grp, Informat Technol Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Verrier, Jonathan D.; Notterpek, Lucia] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. RP Hudson, LD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM hudsonl1@od.nih.gov FU National Institute of Neurological Disorders and Stroke; Muscular Dystrophy Association; McKnight Brain Institute; Joshua Benjamin Weitzel Fund for Developmental Neurobiology FX This work was supported by intramural funds from National Institute of Neurological Disorders and Stroke (NINDS) (L. D. H.), the Muscular Dystrophy Association (L. N.), the McKnight Brain Institute (L. N.), and the Joshua Benjamin Weitzel Fund for Developmental Neurobiology (L. N.). We thank Naser Muja (Johns Hopkins University, Baltimore, MD) for preliminary experiments and Jo Ann Berndt (NINDS) and Elena Romm (NINDS) for expert technical assistance. We are indebted to Dragan Maric (NINDS) for purification of oligodendrocytes and Abdel Elkahloun (National Human Genome Research Institute) for Affymetrix microarray processing. We are grateful to Jim Nagle (NINDS) and Deborah Kauffman (NINDS) for their support in DNA sequencing. We thank Christopher Brown (Applied Biosystems) and David Armistead (Applied Biosystems) for their expertise in real-time PCR. We thank Monique Dubois- Dalcq (NINDS) for critical reading of this manuscript. The miRNA microarray data reported in this study is deposited in the European Molecular Biology Laboratory/European Bioinformatics Institute ArrayExpress database (accession E-MEXP-1589) and the DNA microarray data in the Gene Expression Omnibus database (accession GSE11218). NR 43 TC 132 Z9 142 U1 1 U2 11 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 NOV 5 PY 2008 VL 28 IS 45 BP 11720 EP 11730 DI 10.1523/JNEUROSCI.1932-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 369AV UT WOS:000260665900030 PM 18987208 ER PT J AU Hollingshead, MG AF Hollingshead, Melinda G. TI Antitumor Efficacy Testing in Rodents SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID DRUG DEVELOPMENT; PRECLINICAL MODELS; MDA-MB-435 CELLS; BREAST-CANCER; ANIMAL-MODELS; TUMOR-MODELS; IN-VITRO; MICE; PHARMACOKINETICS; THERAPEUTICS C1 NCI, Biol Testing Branch, Dev Therapeut Program, Fairview Ctr, Frederick, MD 21701 USA. RP Hollingshead, MG (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, Fairview Ctr, Ste 205,1003 W 7th St, Frederick, MD 21701 USA. EM hollingm@mail.nih.gov NR 49 TC 6 Z9 6 U1 2 U2 3 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 NOV 5 PY 2008 VL 100 IS 21 DI 10.1093/jnci/djn351 PG 11 WC Oncology SC Oncology GA 373OQ UT WOS:000260981900006 ER PT J AU Wacholder, S Chatterjee, N Caporaso, N AF Wacholder, Sholom Chatterjee, Nilanjan Caporaso, Neil TI Intermediacy and Gene-Environment Interaction: The Example of CHRNA5-A3 Region, Smoking, Nicotine Dependence, and Lung Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; ACETYLCHOLINE-RECEPTORS; CANDIDATE GENES; SUSCEPTIBILITY; EPIDEMIOLOGY; DISEASE; RISK; LOCI; SNPS C1 [Wacholder, Sholom; Chatterjee, Nilanjan; Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM WacholdS@mail.NIH.gov NR 43 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 5 PY 2008 VL 100 IS 21 DI 10.1093/jnci/djn380 PG 4 WC Oncology SC Oncology GA 373OQ UT WOS:000260981900002 ER PT J AU Yu, L Putnak, JR Pletnev, AG Markoff, L AF Yu, Li Putnak, J. Robert Pletnev, Alexander G. Markoff, Lewis TI Attenuated West Nile viruses bearing 3 ' SL and envelope gene substitution mutations SO VACCINE LA English DT Article DE Live West Nile vaccine; Flavivirus 3 ' SL mutation; Attenuation of neurovirulence ID JAPANESE ENCEPHALITIS-VIRUS; CD8(+) T-CELLS; LETHAL CHALLENGE; MOLECULAR-BASIS; UNITED-STATES; NY99 STRAIN; GENOMIC RNA; VACCINE; FLAVIVIRUS; NEUROVIRULENCE AB Four viable West Nile (WN) 3'SL-mutant Viruses were evaluated for neuroinvasiveness and neurovirulence in mice. All mutants were highly attenuated for neuroinvasiveness. However, only one of these four (WNmutE virus) was significantly attenuated for neurovirulence. To attenuate WNmutE virus further, we introduced five substitution mutations into the envelope (env) gene segment in wild-type (wt) WN and WNmutE genomes, based on differences in the env gene Sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its virulent parent. The env gene mutations had an attenuating effect in the context of the wt WNV genome but only a Marginal enhancing effect on the attenuation of WNmutE virus. Published by Elsevier Ltd. C1 [Yu, Li; Markoff, Lewis] US FDA, Div Viral Prod, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. [Putnak, J. Robert] Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA. [Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yu, L (reprint author), Bg 29A,Room 1B18,NIH Campus,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Li.Yu@fda.hhs.gov FU National Vaccine Program FX The authors thank Dr. V. Yamshchikov for the gift of the West Nile Virus strain B956 infectious DNA. This work was partially supported by a grant from the National Vaccine Program. NR 36 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 5 PY 2008 VL 26 IS 47 BP 5981 EP 5988 DI 10.1016/j.vaccine.2008.08.064 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 384MZ UT WOS:000261750200014 PM 18805457 ER PT J AU Vasan, RS Demissie, S Cupples, LA Benjamin, EJ White, C Kimura, M Gardner, JP Cao, X Aviv, A Rifai, N Wang, TJ Levy, D AF Vasan, Ramachandran S. Demissie, Serkalem Cupples, L. Adrienne Benjamin, Emelia J. White, Charles Kimura, Masayuki Gardner, Jeffrey P. Cao, Xiaogian Aviv, Abraham Rifai, Nader Wang, Thomas J. Levy, Daniel TI Association of Leukocyte Telomere Length With Circulating Biomarkers of the Renin-Angiotensin-Aldosterone System: The Framingham Heart Study Response SO CIRCULATION LA English DT Letter C1 [Vasan, Ramachandran S.; Demissie, Serkalem; Cupples, L. Adrienne; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [White, Charles] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Kimura, Masayuki; Gardner, Jeffrey P.; Cao, Xiaogian; Aviv, Abraham] Univ Med & Dent New Jersey, Ctr Human Dev & Aging, Newark, NJ 07103 USA. [Rifai, Nader] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiol, Boston, MA 02115 USA. [Levy, Daniel] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 4 PY 2008 VL 118 IS 19 BP E689 EP E689 DI 10.1161/CIRCULATIONAHA.108.791111 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368DW UT WOS:000260602500017 ER PT J AU Siluk, D Kim, HS Cole, T Wainer, IW AF Siluk, Danuta Kim, Hee Seung Cole, Tyler Wainer, Irving W. TI HPLC-electrospray mass spectrometric assay for the determination of (R,R)-fenoterol in rat plasma SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Fenoterol; HPLC-MS; SPE; Rat plasma ID BETA-AGONISTS; FENOTEROL; DERIVATIZATION; BLOOD AB A fast and specific liquid chromatography-mass spectrometry method for the determination of (R,R)fenoterol ((R,R)-Fen) in rat plasma has been developed and validated. (R,R)-Fen was extracted from 125 p,1 of plasma using solid phase extraction and analyzed on Atlantis HILIC Silica 3 mu m column. The mobile phase was composed of acetonitrile: ammonium acetate (pH 4.1; 20 mM) (85:15, v/v), at a flow rate of 0.2 ml/min. The lower limit of detection (LLOD) was 2 ng/ml. The procedure was validated and applied to the analysis of plasma samples from rats previously administered (R,R)-Fen in an intravenous bolus. Published by Elsevier B.V. C1 [Siluk, Danuta] NIA, Clin Invest Lab, Gerontol Res Ctr, NIH,Bioanalyt & Drug Discovery Sect, Baltimore, MD 21224 USA. RP Siluk, D (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, NIH,Bioanalyt & Drug Discovery Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM silukd@mail.nih.gov FU Intramural Research Program of the National Institute on Aging/NIH FX This work was supported by funds from the Intramural Research Program of the National Institute on Aging/NIH. NR 14 TC 12 Z9 12 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV 4 PY 2008 VL 48 IS 3 BP 960 EP 964 DI 10.1016/j.jpba.2008.05.034 PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 362KL UT WOS:000260196500064 PM 18617349 ER PT J AU Mouw, T Koster, A Wright, ME Blank, MM Moore, SC Hollenbeck, A Schatzkin, A AF Mouw, Traci Koster, Annemarie Wright, Margaret E. Blank, Madeleine M. Moore, Steven C. Hollenbeck, Albert Schatzkin, Arthur TI Education and Risk of Cancer in a Large Cohort of Men and Women in the United States SO PLOS ONE LA English DT Article ID SOCIOECONOMIC-STATUS; ASSOCIATION; ALCOHOL; HEALTH; LEVEL; DIET AB Background: Education inequalities in cancer incidence have long been noted. It is not clear, however, whether such inequalities persist in the United States, especially for less common malignancies and after adjustment for individual risk factors. Methodology/Principal Findings: Within the NIH-AARP Diet and Health Study, we examined the association between education and the risk of developing cancers in a prospective cohort of 498 455 participants who were 50-71 year old and without cancer at enrollment in 1995/96. During a maximum 8.2 years of follow-up we identified 40 443 cancers in men and 18 367 in women. In age-adjusted models, the least educated men (, high school), compared to those with the most education (post-graduate), had increased risks of developing cancers of the esophagus (RR: 2.64, 95% CI: 1.86-3.75), head and neck ( 1.98, 1.54-2.54), stomach (2.32, 1.68-3.18), colon (1.31, 1.12-1.53), rectum (1.68, 1.32-2.13), liver (1.90, 1.22-2.95), lung (3.67, 3.25-4.15), pleura (4.01, 1.91-8.42), bladder (1.56, 1.33-1.83) and combined smoking-related cancers (2.41, 2.22-2.62). In contrast, lower education level was associated with a decreased risk of melanoma of the skin (0.43, 0.35-0.54) and local prostate cancers (0.79, 0.74-0.85). Women with the least education had increased risks of colon (1.60, 1.24-2.05), lung (2.14, 1.79-2.56), kidney (1.68, 1.12-2.54) and combined smoking-related cancers (1.66, 1.43-1.92) but a lower risk of melanoma of the skin (0.33, 0.22-0.51), endometrial (0.67, 0.51-0.89) and invasive breast cancers (0.72, 0.61-0.84). Adjustment for smoking and other risk factors did not eliminate these associations, except those for cancers of the head and neck, colon, and liver in men and kidney in women. Conclusions/Significance: We found a higher risk of malignant disease, particularly smoking-related cancers, among those in the lowest educational attainment category. Only some of the educational gradient is attributable to smoking. The persistence of substantial education inequalities in cancer incidence poses a challenge for etiologic research and public health policy. C1 [Mouw, Traci] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, Fac Med, London, England. [Koster, Annemarie] NIA, Lab Epidemiol, Demography, & Biomet, NIH, Bethesda, MD USA. [Koster, Annemarie] Univ Maastricht, Fac Hlth, Med & Life Sci, Maastricht, Netherlands. [Wright, Margaret E.] Univ Illinois, Dept Pathol, Chicago, IL 60680 USA. [Blank, Madeleine M.; Moore, Steven C.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Mouw, T (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, Fac Med, London, England. EM schatzka@mail.nih.gov RI Koster, Annemarie/E-7438-2010; Moore, Steven/D-8760-2016 OI Moore, Steven/0000-0002-8169-1661 FU Intramural Research Programs at the National Cancer Institute; National Institute on Aging, NIH FX This research was supported (in part) by the Intramural Research Programs at the National Cancer Institute and the National Institute on Aging, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 28 Z9 28 U1 0 U2 2 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 NOV 4 PY 2008 VL 3 IS 11 AR e3639 DI 10.1371/journal.pone.0003639 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432LJ UT WOS:000265134300009 PM 18982064 ER PT J AU Seo, EJ Liu, FR Kawagishi-Kobayashi, M Ung, TL Cao, C Dar, AC Sicheri, F Dever, TE AF Seo, Eun Joo Liu, Furong Kawagishi-Kobayashi, Makiko Ung, Tekly L. Cao, Chune Dar, Arvin C. Sicheri, Frank Dever, Thomas E. TI Protein kinase PKR mutants resistant to the poxvirus pseudosubstrate K3L protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE eIF2; translational control ID VACCINIA VIRUS K3L; STRANDED-RNA BINDING; SUBSTRATE RECOGNITION; CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; GENE-PRODUCT; INITIATION FACTOR-2-ALPHA; SACCHAROMYCES-CEREVISIAE; FUNCTIONALLY SUBSTITUTE; EIF2 ALPHA AB As part of the mammalian cell innate immune response, the double-stranded RNA activated protein kinase PKR phosphorylates the translation initiation factor eIF2 alpha to inhibit protein synthesis and thus block viral replication. Poxviruses including vaccinia and smallpox viruses express PKR inhibitors such as the vaccinia virus K3L protein that resembles the N-terminal substrate-targeting domain of eIF2 alpha. Whereas high-level expression of human PKR was toxic in yeast, this growth inhibition was suppressed by coexpression of the K3L protein. We used this yeast assay to screen for PKR mutants that are resistant to K3L inhibition, and we identified 12 mutations mapping to the C-terminal lobe of the PKR kinase domain. The PKR mutations specifically conferred resistance to the K3L protein both in yeast and in vitro. Consistently, the PKR-D486V mutation led to nearly a 15-fold decrease in K3L binding affinity yet did not impair eIF2 alpha phosphorylation. Our results support the identification of the eIF2 alpha-binding site on an extensive face of the C-terminal lobe of the kinase domain, and they indicate that subtle changes to the PIKR kinase domain can drastically impact pseudosubstrate inhibition while leaving substrate phosphorylation intact. We propose that these paradoxical effects of the PKR mutations on pseudosubstrate vs. substrate interactions reflect differences between the rigid K3L protein and the plastic nature of eIF2 alpha around the Ser-51 phosphorylation site. C1 [Seo, Eun Joo; Liu, Furong; Kawagishi-Kobayashi, Makiko; Ung, Tekly L.; Cao, Chune; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA. [Dar, Arvin C.; Sicheri, Frank] Mt Sinai Hosp, Program Syst Biol, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Dar, Arvin C.; Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. RP Dever, TE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA. EM tdever@nih.gov RI Sicheri, Frank/F-8856-2013; OI Dever, Thomas/0000-0001-7120-9678 FU National Institute for Child Health and Human Development; National Institutes of Health; National Cancer Institute of Canada; Canadian Institutes for Health Research FX We thank members of the laboratories of T.E.D., F.S., and Alan Hinnebusch for advice and discussions and Alan Hinnebusch for comments on the manuscript. We thank Eileen Chou for assistance with the genetic characterization of the PKR mutants and Craig Cameron (Pennsylvania State University) for the pGEX-3X-K3L plasmid. This work was supported in part by the Intramural Research Program of the National Institute for Child Health and Human Development, National Institutes of Health (T.E.D.) and by grants from the National Cancer Institute of Canada (to F.S.). A.C.D. was a recipient of a Canadian Graduate Scholarship from the Canadian Institutes for Health Research. F.S. is a recipient of a National Cancer Institute of Canada Scientist award. NR 21 TC 15 Z9 17 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 16894 EP 16899 DI 10.1073/pnas.0805524105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800020 PM 18971339 ER PT J AU Wu, JY Purton, LE Rodda, SJ Chen, M Weinstein, LS McMahon, AP Scadden, DT Kronenberg, HM AF Wu, Joy Y. Purton, Louise E. Rodda, Stephen J. Chen, Min Weinstein, Lee S. McMahon, Andrew P. Scadden, David T. Kronenberg, Henry M. TI Osteoblastic regulation of B lymphopoiesis is mediated by G(s)alpha-dependent signaling pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B lymphocyte; G protein; osteoblast ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW; PARATHYROID-HORMONE; DIFFERENTIATION; RECEPTOR; MICE; NICHES; MOUSE; MAINTENANCE; DEFICIENCY AB Osteoblasts play an increasingly recognized role in supporting hematopoietic development and recently have been implicated in the regulation of B lymphopoiesis. Here we demonstrate that heterotrimeric G protein a subunit G(s)alpha is required in cells of the osteoblast lineage for normal postnatal B lymphocyte production. Deletion of G(s)alpha early in the osteoblast lineage results in a 59% decrease in the percentage of B cell precursors in the bone marrow. Analysis of peripheral blood from mutant mice revealed a 67% decrease in the number of circulating B lymphocytes by 10 days age. Strikingly, other mature hematopoietic lineages are not decreased significantly. Mice lacking Gsa in cells of the lineage exhibit a reduction in pro-B and pre-B cells. Furthermore, interleukin (IL)-7 expression is attenuated in G(s)alpha-deficient blasts, and exogenous IL-7 is able to restore B cell populations in the bone marrow of mutant mice. Finally, the in B lymphopoiesis can be rescued by transplantation into a microenvironment. These findings confirm that osteoblasts are an important component of the B lymphocyte niche and demonstrate in vivo that G(s)alpha-dependent signaling pathways in cells of the osteoblast lineage extrinsically regulate bone marrow B lymphopoiesis, at least partially in an IL-7-dependent manner. C1 [Wu, Joy Y.; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Purton, Louise E.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Purton, Louise E.; McMahon, Andrew P.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rodda, Stephen J.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org FU National Institutes of Health [AR053781, DK071773, HL081030, DK117940, DK056246]; National Institute of Diabetes and Digestive and Kidney Diseases' Intramural Research Program; National Health and Medical Research Council of Australia [301299]; Arthritis Foundation [401683] FX We thank Drs. Sean Wu, Carl Walkley, and Heather Fleming for discussion and helpful suggestions; Dr. Natalie Sims for quantitation of osteoblast surfaces; David Dombkowski and Laura Prickett for assistance with FACS sorting; James Oh for technical assistance; and the MGH Center for Comparative Medicine staff for caring for the mice in this study. This work was supported in part by National Institutes of Health Grants AR053781 (to J.Y.W.), DK071773 (to L.E.P.), HL081030 (to H.M.K. and D.T.S.), DK117940 (to H.M.K.), and DK056246 (to A.P.M.), and by the National Institute of Diabetes and Digestive and Kidney Diseases' Intramural Research Program (M.C. and L.S.W.). S.R. was supported by postdoctoral fellowships from the National Health and Medical Research Council of Australia (301299) and the Arthritis Foundation (401683). NR 42 TC 93 Z9 95 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 16976 EP 16981 DI 10.1073/pnas.0802898105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800034 PM 18957542 ER PT J AU Chen, WZ Zhu, ZY Feng, Y Dimitrov, DS AF Chen, Weizao Zhu, Zhongyu Feng, Yang Dimitrov, Dimiter S. TI Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neutralization; therapeutic; epitope; steric restriction ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR-BINDING-SITE; GLYCOPROTEIN; EXPRESSION; LIBRARY; CORE; GP41 AB The antibody access to some conserved structures on the HIV-1 envelope glycoprotein (Env) is sterically restricted. We have hypothesized that the smallest independently folded antibody fragments (domains) could exhibit exceptionally potent and broadly cross-reactive neutralizing activity by targeting hidden conserved epitopes that are not accessible by larger antibodies. To test this hypothesis, we constructed a large (size 2.5 x 1010), highly diversified library of human antibody variable domains (domain antibodies) and used it for selection of binders to conserved Env structures by panning sequentially against Envs from different isolates. The highest affinity binder, m36, neutralized all tested HIV-1 isolates from clades A- D with an activity on average higher than that of C34, a peptide similar to the fusion inhibitor T20, which is in clinical use, and that of m9, which exhibits a neutralizing activity superior to known potent cross-reactive antibodies. Large-size fusion proteins of m36 exhibited diminished neutralizing activity but preincubation of virions with soluble CD4 restored it, suggesting that m36 epitope is sterically restricted and induced by CD4 (CD4i). M36 bound to gp120-CD4 complexes better than to gp120 alone and competed with CD4i antibodies. M36 is the only reported representative of a promising class of potent, broadly cross-reactive HIV-1 inhibitors based on human domain antibodies. It has potential for prevention and therapy and as an agent for exploration of the closely guarded conserved Env structures with implications for design of small molecule inhibitors and elucidation of mechanisms of virus entry and evasion of immune responses. C1 [Chen, Weizao; Zhu, Zhongyu; Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Zhu, Zhongyu] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov FU National Institutes of Health (NIH); National Cancer Institute; Center for Cancer Research; National Cancer Institute, NIH [N01-CO-12400]; Gates Foundation FX We thank Christopher Broder, Gerald Quinnan, Dennis Burton, and Tim Fouts for providing reagents and the members of our group John Owens, Meiyun Zhang, and Xiadong Xiao for help. This project was supported by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health (NIH), by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400, and by the Gates Foundation (D.S.D.). NR 20 TC 46 Z9 48 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 4 PY 2008 VL 105 IS 44 BP 17121 EP 17126 DI 10.1073/pnas.0805297105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372PP UT WOS:000260913800059 PM 18957538 ER PT J AU Castillo, CG Mendoza-Trejo, S Aguilar, MB Freed, WJ Giordano, M AF Castillo, Claudia G. Mendoza-Trejo, Soledad Aguilar, Manuel B. Freed, William J. Giordano, Magda TI Intranigral transplants of a GABAergic cell line produce long-term alleviation of established motor seizures SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE neural transplantation; human glutamate decarboxylase-67; (GAD67); gamma-aminobutyric acid (GABA); temporal lobe epilepsy; animal models; substantia nigra pars reticulata; GABAergic cell line; kainic acid; high performance liquid chromatography; status epilepticus ID TEMPORAL-LOBE EPILEPSY; KAINATE-INDUCED EPILEPSY; RAT SUBSTANTIA-NIGRA; LESIONED CA3 REGION; LARGE T-ANTIGEN; KINDLING EPILEPSY; ADULT HIPPOCAMPUS; KAINIC ACID; NORADRENALINE RELEASE; BEHAVIORAL SEIZURES AB We have previously shown that intranigral transplants of immortalized GABAergic cells decrease the number of kainic acid-induced seizures [Castillo CG, Mendoza S, Freed WJ, Giordano M. Intranigral transplants Of immortalized GABAergic cells decrease the expression of kainic acid-induced seizures in the rat. Behav Brain Res 2006; 171:409-15] in an animal model. In the present Study, recurrent spontaneous behavioral seizures were established by repeated systemic injections of this excitotoxin into male Sprague-Dawley rats. After the seizures had been established, cells were transplanted into the substantia nigra. Animals with transplants of control cells (without hGAD67 expression) OF with sham transplants showed a death rate of more than 40% over the 12 weeks of observation, whereas in animals with M213-20 CL-4 transplants, the death rate was reduced to less than 20%. The M213-20 CL-4 transplants significantly reduced the percentage of animals showing behavioral seizures; animals with these transplants also showed a lower occurrence of stage V seizures than animals in the other groups. In vivo and in vitro analyses provided evidence that the GABAergic cells show sustained expression of both GAD67 and hGAD67 cDNA, as well as increased gamma-aminobutyric acid (GABA) levels in the ventral mesencephalon of transplanted animals. Therefore, transplantation of GABA-producing cells can produce long-term alleviation of behavioral seizures in an animal model. (C) 2008 Elsevier B.V. All rights reserved. C1 [Castillo, Claudia G.; Mendoza-Trejo, Soledad; Giordano, Magda] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Queretaro 76230, Qto, Mexico. [Aguilar, Manuel B.] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Queretaro 76230, Qto, Mexico. [Freed, William J.] Natl Inst Drug Abuse, NIH, DHHS, Baltimore, MD 21224 USA. RP Giordano, M (reprint author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Blvd Juriquilla 3001, Queretaro 76230, Qto, Mexico. EM cgcastillo@cbm.uam.es; solecito75@yahoo.com; maguilar@servidor.unam.mx; WFREED@intra.nida.nih.gov; giordano@servidor.unam.mx OI Giordano, Magda/0000-0002-4335-7953 FU CONACyT [IN225305, 46161-M, 41477-Q, 153810]; NIDA; NIH; DHHS; DGEP-UNAM FX The authors acknowledge the technical assistance of J. Mejia, A. Marquez, A. Falcon, L. Gonzalez, L. Lara, and E. N. Hernandez; Leonor Casanova executive coordinator of graduate Studies: M. Garcia head of the Animal Care Facility; Dr. Michael C. Jeziorski, Dr. Aurea Orozco, and M.C. Patricia Villalobos for advice on detection of the transgene; and Dr. D. Pless for editing of the manuscript. This work was supported by grants IN225305 from PAPIIT-DGAPA, 46161-M and 41477-Q from CONACyT, and in part by the NIDA Intramural program, NIH, DHHS. C.G. Castillo was supported by a fellowship from CONACyT (153810) and DGEP-UNAM. NR 47 TC 22 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 3 PY 2008 VL 193 IS 1 BP 17 EP 27 DI 10.1016/j.bbr.2008.04.023 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 341TQ UT WOS:000258738400002 PM 18571743 ER PT J AU Iyer, LM Burroughs, AM Aravind, L AF Iyer, Lakshminarayan M. Burroughs, A. M. Aravind, L. TI Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination SO BIOLOGY DIRECT LA English DT Article ID STRUCTURE PREDICTION; ALIGNMENT ALGORITHM; CRYSTAL-STRUCTURE; GAMMA-GLUTAMYL; IDENTIFICATION; PROTEASOME; DATABASE; COMPLEX; KINASE; SERVER AB Recently Mycobacterium tuberculosis was shown to possess a novel protein modification, in which a small protein Pup is conjugated to the epsilon-amino groups of lysines in target proteins. Analogous to ubiquitin modification in eukaryotes, this remarkable modification recruits proteins for degradation via archaeal-type proteasomes found in mycobacteria and allied actinobacteria. While a mycobacterial protein named PafA was found to be required for this conjugation reaction, its biochemical mechanism has not been elucidated. Using sensitive sequence profile comparison methods we establish that the PafA family proteins are related to the gamma-glutamyl-cysteine synthetase and glutamine synthetase. Hence, we predict that PafA is the Pup ligase, which catalyzes the ATP-dependent ligation of the terminal gamma-carboxylate of glutamate to lysines, similar to the above enzymes. We further discovered that an ortholog of the eukaryotic PAC2 (e.g. cg2106) is often present in the vicinity of the actinobacterial Pup-proteasome gene neighborhoods and is likely to represent the ancestral proteasomal chaperone. Pup-conjugation is sporadically present outside the actinobacteria in certain lineages, such as verrucomicrobia, nitrospirae, deltaproteobacteria and planctomycetes, and in the latter two lineages it might modify membrane proteins. Reviewers: This article was reviewed by M. Madan Babu and Andrei Osterman C1 [Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Burroughs, A. M.] RIKEN, Yokohama Inst, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM lakshmin@mail.nih.gov; burrough@gsc.riken.jp; aravind@mail.nih.gov FU National Library of Medicine at the National Institutes of Health, USA FX Work by LMI and LA is supported by the intramural funds of the National Library of Medicine at the National Institutes of Health, USA. NR 21 TC 53 Z9 55 U1 0 U2 2 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 NOV 3 PY 2008 VL 3 AR 45 DI 10.1186/1745-6150-3-45 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 381AX UT WOS:000261508300001 PM 18980670 ER PT J AU Kaur, S Samant, GV Pramanik, K Loscombe, PW Pendrak, ML Roberts, DD Ramchandran, R AF Kaur, Sukhbir Samant, Ganesh V. Pramanik, Kallal Loscombe, Philip W. Pendrak, Michael L. Roberts, David D. Ramchandran, Ramani TI Silencing of directional migration in roundabout4 knockdown endothelial cells SO BMC CELL BIOLOGY LA English DT Article ID REPULSIVE AXON GUIDANCE; TUMOR ANGIOGENESIS; SLIT-ROBO; MAGIC ROUNDABOUT; RECEPTORS; EXPRESSION; ZEBRAFISH; COMPLEX; CHEMOTAXIS; REPELLENT AB Background: Roundabouts are axon guidance molecules that have recently been identified to play a role in vascular guidance as well. In this study, we have investigated gene knockdown analysis of endothelial Robos, in particular roundabout 4 (robo4), the predominant Robo in endothelial cells using small interfering RNA technology in vitro. Results: Robo1 and Robo4 knockdown cells display distinct activity in endothelial cell migration assay. The knockdown of robo4 abrogated the chemotactic response of endothelial cells to serum but enhanced a chemokinetic response to Slit2, while robo1 knockdown cells do not display chemotactic response to serum or VEGF. Robo4 knockdown endothelial cells unexpectedly show up regulation of Rho GTPases. Zebrafish Robo4 rescues both Rho GTPase homeostasis and serum reduced chemotaxis in robo4 knockdown cells. Robo1 and Robo4 interact and share molecules such as Slit2, Mena and Vilse, a Cdc42-GAP. In addition, this study mechanistically implicates IRSp53 in the signaling nexus between activated Cdc42 and Mena, both of which have previously been shown to be involved with Robo4 signaling in endothelial cells. Conclusion: This study identifies specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells. C1 [Samant, Ganesh V.; Pramanik, Kallal; Ramchandran, Ramani] Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, Milwaukee, WI 53226 USA. [Kaur, Sukhbir] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Loscombe, Philip W.] Univ Scranton, Dept Biol, Scranton, PA 18510 USA. [Pendrak, Michael L.; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Ramchandran, R (reprint author), Med Coll Wisconsin, Dept Pediat, Childrens Res Inst, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM kaurs@mail.nih.gov; samant@mcw.edu; kpramani@mcw.edu; ploscombe@gmail.com; mpendrak@helix.nih.gov; droberts@helix.nih.gov; rramchan@mcw.edu RI Roberts, David/A-9699-2008; Xiao, Yang/B-5668-2012 OI Roberts, David/0000-0002-2481-2981; FU NCI CRTA; State of Wisconsin Breast Cancer Research Post-doctoral Fellowship; NIH; NCI; Center of Cancer Research FX We thank Jessica Baer and James Cherry of Gene Expression Laboratory, NCI, Frederick, MD for assistance with real time PCR analysis. S. K. is a recipient of NCI CRTA fellowship award; R. R. is a recipient of NCI Scholar grant. G. V. S. is a recipient of a State of Wisconsin Breast Cancer Research Post-doctoral Fellowship award. D. D. R. was supported by the Intramural Research Program of the NIH, NCI, Center of Cancer Research. The authors have no conflicting financial interests. NR 36 TC 26 Z9 30 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD NOV 3 PY 2008 VL 9 AR 61 DI 10.1186/1471-2121-9-61 PG 12 WC Cell Biology SC Cell Biology GA 390QQ UT WOS:000262179200001 PM 18980679 ER PT J AU Parthasarathy, N Saksena, R Kovac, P DeShazer, D Peacock, SJ Wuthiekanun, V Heine, HS Friedlander, AM Cote, CK Welkos, SL Adamovicz, JJ Bavari, S Waag, DM AF Parthasarathy, N. Saksena, R. Kovac, P. DeShazer, D. Peacock, S. J. Wuthiekanun, V. Heine, H. S. Friedlander, A. M. Cote, C. K. Welkos, S. L. Adamovicz, J. J. Bavari, S. Waag, D. M. TI Application of carbohydrate microarray technology for the detection of Burkholderia pseudomallei, Bacillus anthracis and Francisella tularensis antibodies SO CARBOHYDRATE RESEARCH LA English DT Article DE Carbohydrate microarray; Burkholderia pseudomallei (melioidosis); Bacillus anthracis (anthrax); Francisella tularensis (tularemia); Serum antibodies ID GLYCAN ARRAYS; O-ANTIGEN; EXOSPORIUM; LIPOPOLYSACCHARIDE; MELIOIDOSIS; BCLA; OLIGOSACCHARIDE; GLYCOMICS; IDENTIFICATION; GLYCOPROTEIN AB We developed a microarray platform by immobilizing bacterial 'signature' carbohydrates onto epoxide modified glass slides. The carbohydrate microarray platform was probed with sera from non-melioidosis and melioidosis (Burkholderia pseudomallei) individuals. The platform was also probed with sera from rabbits vaccinated with Bacillus anthracis spores and Francisella tularensis bacteria. By employing this microarray platform, we were able to detect and differentiate B. pseudomallei, B. anthracis and F. tularensis antibodies in infected patients, and infected or vaccinated animals. These antibodies were absent in the sera of naive test subjects. The advantages of the carbohydrate microarray technology over the traditional indirect hemagglutination and microagglutination tests for the serodiagnosis of melioidosis and tularemia are discussed. Furthermore, this array is a multiplex carbohydrate microarray for the detection of all three biothreat bacterial infections including melioidosis, anthrax and tularemia with one, multivalent device. The implication is that this technology could be expanded to include a wide array of infectious and biothreat agents. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Parthasarathy, N.; DeShazer, D.; Heine, H. S.; Cote, C. K.; Welkos, S. L.; Adamovicz, J. J.; Bavari, S.; Waag, D. M.] USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA. [Saksena, R.; Kovac, P.] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Peacock, S. J.; Wuthiekanun, V.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand. RP Parthasarathy, N (reprint author), USA, Med Res Inst Infect Dis, Bacteriol Div, Frederick, MD 21702 USA. EM Narayanan.Parthasarathy@us.army.mil FU US Army Medical Research and Materiel Command [2.10018_06 _RD-B, 2.10019_07_RD-B, 5.10023_08_RD-B]; Welcome Trust Career Development fellowship in Clinical Tropical Medicine; Human Use Committee [FY 06-36, HP-06-36] FX The research described herein was sponsored by the US Army Medical Research and Materiel Command under projects 2.10018_06 _RD-B, 2.10019_07_RD-B and 5.10023_08_RD-B. The authors thank Sarah L. Norris for statistical analysis. The authors also thank Dr. Sharan VedBrat (KamTek Inc., Gaithersburg, MD) for carbohydrate printing. The support of staff at Sappasithiprasong Hospital, Ubon Ratchathani, and the Mahidol Oxford Tropical Medicine Research Unit, particularly Dr. Direk Limmathurotsakul and Dr. Allen Chang, is gratefully acknowledged. S.P. is funded by a Welcome Trust Career Development fellowship in Clinical Tropical Medicine. The use of human serum samples was approved by the Human Use Committee (FY 06-36, HP-06-36). Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility where this research was conducted is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. Opinions, interpretations, conclusions and recommendations are those of the authors and not endorsed by the US Army. NR 38 TC 19 Z9 19 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 3 PY 2008 VL 343 IS 16 BP 2783 EP 2788 DI 10.1016/j.carres.2008.05.021 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 370AU UT WOS:000260735900010 PM 18558401 ER PT J AU Rojas, R van Vlijmen, T Mardones, GA Prabhu, Y Rojas, AL Mohammed, S Heck, AJR Raposo, G van der Sluijs, P Bonifacino, JS AF Rojas, Raul van Vlijmen, Thijs Mardones, Gonzalo A. Prabhu, Yogikala Rojas, Adriana L. Mohammed, Shabaz Heck, Albert J. R. Raposo, Graca van der Sluijs, Peter Bonifacino, Juan S. TI Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; GROWTH-FACTOR RECEPTOR; TRANS-GOLGI NETWORK; TO-TGN TRANSPORT; SORTING NEXIN-1; RETROGRADE TRANSPORT; ADAPTER PROTEIN; ENDOCYTIC COMPARTMENTS; MEMBRANE-PROTEINS; CARGO PROTEINS AB The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate-enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes. In this study, we demonstrate that the guanosine triphosphatase Rab7 contributes to this recruitment. The Vps26/29/35 trimer specifically binds to Rab7-guanosine triphosphate (GTP) and localizes to Rab7-containing endosomal domains. Interference with Rab7 function causes dissociation of the Vps26/29/35 trimer but not the SNX dimer from membranes. This blocks retrieval of mannose 6-phosphate receptors to the TGN and impairs cathepsin D sorting. Rab5-GTP does not bind to the Vps26/29/35 trimer, but perturbation of Rab5 function causes dissociation of both the SNX and Vps26/29/35 components from membranes through inhibition of a pathway involving phosphatidylinositol 3-kinase. These findings demonstrate that Rab5 and Rab7 act in concert to regulate retromer recruitment to endosomes. C1 [van Vlijmen, Thijs; van der Sluijs, Peter] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. [Rojas, Raul; Mardones, Gonzalo A.; Prabhu, Yogikala; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Rojas, Adriana L.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Mohammed, Shabaz; Heck, Albert J. R.] Univ Med Ctr Utrecht, Dept Biomol Mass Spectrometry, NL-3584 CX Utrecht, Netherlands. [Raposo, Graca] CNRS, Inst Curie, UMR 144, F-75248 Paris, France. RP van der Sluijs, P (reprint author), Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. EM p.vandersluijs@umcutrecht.nl; juan@helix.nih.gov RI van Vlijmen, Thijs/B-4069-2009; Heck, Albert/D-7098-2011; Mohammed, Shabaz/D-1042-2010; Rojas, Adriana/G-2403-2011; OI van Vlijmen, Thijs/0000-0002-5882-6660; Heck, Albert/0000-0002-2405-4404; Mohammed, Shabaz/0000-0003-2640-9560; Rojas, Adriana/0000-0002-7358-3505; Bonifacino, Juan S./0000-0002-5673-6370 FU National Institute of Child Health and Human Development; Netherlands Proteomics Center FX This work was supported by the Intramural Program of the National Institute of Child Health and Human Development, the National Institutes of Health (J.S. Bonifacino), and the Netherlands Proteomics Center (P. van der Sluijs and A. J. R. Heck). NR 63 TC 177 Z9 179 U1 4 U2 12 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 NOV 3 PY 2008 VL 183 IS 3 BP 513 EP 526 DI 10.1083/jcb.200804048 PG 14 WC Cell Biology SC Cell Biology GA 374RA UT WOS:000261060200017 PM 18981234 ER PT J AU Luo, WM Yu, QS Tweedie, D Deschamps, J Parrish, D Holloway, HW Li, YZ Brossi, A Greig, NH AF Luo, Weiming Yu, Qian-Sheng Tweedie, David Deschamps, Jeffery Parrish, Damon Holloway, Harold W. Li, Yazhou Brossi, Arnold Greig, Nigel H. TI Syntheses of Aromatic Substituted 6 '-Thiothalidomides SO SYNTHESIS-STUTTGART LA English DT Article DE 6 '-thiothalidomides; TNF-alpha; thionation; regioselectivity; HMBC ID ERYTHEMA-NODOSUM LEPROSUM; ORGANOPHOSPHORUS COMPOUNDS; ALPHA PRODUCTION; THALIDOMIDE; DERIVATIVES; ANALOGS; INHIBITION; ACIDS AB A resurgence of interest in thalidomide has occurred as a consequence of its diverse immunomodulatory and anticancer actions. which has fuelled interest in synthetic analogues with higher potencies or less undesirable side effect profiles. Several novel aromatic substituted 6'-thiothalidomides were synthesized whose synthetic route and strategy were developed on the basis of an analysis of reaction mechanisms. The regioselectivity of mono-thionation of aromatic substituted thalidomides with Lawesson's reagent is described, and the chemoselectivity of hydrogenation between the nitro group and 6'-thiocarbonyl group is discussed. Full characterization of eight substituted 6'-thiothalidomides is reported. C1 [Luo, Weiming; Yu, Qian-Sheng; Tweedie, David; Holloway, Harold W.; Li, Yazhou; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Deschamps, Jeffery; Parrish, Damon] USN, Res Lab, Dept Navy, Struct Matter Lab, Washington, DC 20375 USA. [Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Greign@grc.nia.nih.gov OI Deschamps, Jeffrey/0000-0001-5845-0010 FU National Institute on Aging; National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The authors are indebted to the Intramural Research Program of the National Institute on Drug Abuse, NIH, for use of NMR equipment. NR 19 TC 10 Z9 10 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV 3 PY 2008 IS 21 BP 3415 EP 3422 DI 10.1055/s-0028-1083179 PG 8 WC Chemistry, Organic SC Chemistry GA 375MO UT WOS:000261118200009 ER PT J AU Schuckit, MA Smith, TL Trim, R Heron, J Horwood, J Davis, JM Hibbeln, JR AF Schuckit, Marc A. Smith, Tom L. Trim, Ryan Heron, Jon Horwood, Jeremy Davis, John M. Hibbeln, Joseph R. CA ALSPAC Study Team TI The performance of elements of a 'level of response to alcohol'-based model of drinking behaviors in 13-year-olds SO ADDICTION LA English DT Article DE Alcohol; environment; genetics; structural equation models; response to alcohol; young adolescents ID USE DISORDERS; RISK; QUESTIONNAIRE; ADOLESCENTS; CONSUMPTION; POPULATION; PREDICTORS; DEPENDENCE; MODERATOR; CHILDREN AB Aim The goals of this paper are to evaluate whether drinking practices among peers mediates the relationship between a low level of response (LR) to alcohol and a person's heavier drinking and alcohol-related problems in 12-14-year-olds. Design Correlations and structural equation models (SEM) were used to test a hypothesized model of the relationships among key variables in adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal birth cohort study in Bristol, England. Participants These included 688 boys (40.4%) and girls who were offspring of the pregnant women who had been selected as ALSPAC participants in 1991 and 1992. The offspring were interviewed at about age 13 years, and those who had ever consumed a full drink completed the Self-Report of the Effects of Alcohol (SRE) questionnaire indicating the number of drinks required for up to four effects early in their drinking histories. A higher number of drinks required for effects indicated a low LR per drink consumed. Findings The SEM explained 58% of the variance of the alcohol pattern, and had good fit characteristics. A low LR was related to heavier drinking and more alcohol problems both directly and as mediated partially by drinking in peers. The model performed well across the narrow age range, and applied equally well in boys and girls. Conclusions The perceived drinking practices of peers is a potentially important mediator of how a low LR to alcohol relates to drinking practices during early adolescence. The findings may be useful in developing approaches to prevent heavier drinking in this young group. C1 [Schuckit, Marc A.; Smith, Tom L.; Trim, Ryan] VA San Diego Healthcare Syst, San Diego, CA USA. [Heron, Jon] ALSPAC, Dept Social Med, Bristol, Avon, England. [Horwood, Jeremy] Univ Bristol, Dept Social Med, MRC Hlth Serv Res Collaborat, Bristol, Avon, England. [Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Hibbeln, Joseph R.] NIAAA, LMBB, Bethesda, MD USA. [ALSPAC Study Team] Univ Bristol, ALSPAC, Bristol, Avon, England. [Schuckit, Marc A.; Smith, Tom L.; Trim, Ryan] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA. RP Schuckit, MA (reprint author), Univ Calif San Diego, Dept Psychiat 116A, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM mschuckit@ucsd.edu RI Heron, Jon/D-5884-2011 OI Heron, Jon/0000-0001-6199-5644 FU UK Medical Research Council; Wellcome Trust; University of Bristol; University of California, San Francisco; NIAAA [2R01 AA05526] FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, who also serve as guarantors for the contents of this paper. This work was supported by the Veterans Affairs Research Service with funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco; and by NIAAA Grant 2R01 AA05526. NR 49 TC 13 Z9 13 U1 5 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2008 VL 103 IS 11 BP 1786 EP 1792 DI 10.1111/j.1360-0443.2008.02325.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 361MD UT WOS:000260130900005 PM 18778389 ER PT J AU Grossman, C Hadley, W Brown, LK Houck, CD Peters, A Tolou-Shams, M AF Grossman, Cynthia Hadley, Wendy Brown, Larry K. Houck, Christopher D. Peters, April Tolou-Shams, Marina CA Project SHIELD Study Grp TI Adolescent Sexual Risk: Factors Predicting Condom Use Across the Stages of Change SO AIDS AND BEHAVIOR LA English DT Article DE Adolescent; Sexual risk behavior; Stages of change; Condom use ID TRANSTHEORETICAL MODEL; PSYCHOSOCIAL FACTORS; SELF-EFFICACY; DECISIONAL BALANCE; BEHAVIORAL-CHANGE; HIV PREVENTION; TRANSITIONS; INTERCOURSE; INTERVENTION; ADOPTION AB This study examined factors associated with high-risk adolescents' movement toward or away from adopting consistent condom use behavior using the Transtheoretical Model Stages of Change. Participants drawn from the inactive comparison condition of a randomized HIV prevention trial (Project SHIELD) responded to items assessing pros and cons of condom use, peer norms, condom communication, and perceived invulnerability to HIV. Participants were categorized based on their condom use behavior using the Transtheoretical Model. Multiple logistic regressions found that progression to consistent condom use was predicted by continuing to perceive more advantages to condom use, reporting greater condom use communication with partners, and less perceived invulnerability to HIV. Movement away from adopting consistent condom use was predicted by a decrease in perceived advantages to condom use, increased perceived condom disadvantages, and fewer condom discussions. Future interventions may be tailored to enhance these factors that were found to change over time. C1 [Grossman, Cynthia] NIMH, Bethesda, MD 20892 USA. [Hadley, Wendy; Brown, Larry K.; Houck, Christopher D.; Peters, April; Tolou-Shams, Marina] Rhode Isl Hosp, Brown Med Sch, Providence, RI USA. Project SHIELD Study Grp, Providence, RI USA. RP Grossman, C (reprint author), NIMH, 6001 Execut Blvd,Rm 6201, Bethesda, MD 20892 USA. EM grossmanc@mail.nih.gov FU PHS HHS [U10 SMS2073] NR 33 TC 19 Z9 19 U1 4 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD NOV PY 2008 VL 12 IS 6 BP 913 EP 922 DI 10.1007/s10461-008-9396-y PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 359CC UT WOS:000259962800010 PM 18427971 ER PT J AU Johnson, MO Dilworth, SE Neilands, TB Chesney, MA Rotheram-Borus, MJ Remien, RH Weinhardt, L Ehrhardt, AA Morin, SF AF Johnson, Mallory O. Dilworth, Samantha E. Neilands, Torsten B. Chesney, Margaret A. Rotheram-Borus, Mary Jane Remien, Robert H. Weinhardt, Lance Ehrhardt, Anke A. Morin, Stephen F. CA NIMH HLP Team TI Predictors of Attrition Among High Risk HIV-Infected Participants Enrolled in a Multi-Site Prevention Trial SO AIDS AND BEHAVIOR LA English DT Article DE Clinical trials; Prevention; Retention; Depression ID PROGRAM; DEPRESSION; MORTALITY AB Retaining high-risk individuals is critical for HIV prevention trials. The current analyses examined predictors of trial dropout among HIV-infected men and women in a multi-site HIV prevention trial. Results indicated that dropouts (n = 74) were more likely to be younger, depressed, and not taking antiretroviral therapy (ART) than those who continued (n = 815). No other background, substance use, or transmission risk differences were found, suggesting no direct evidence of dropout bias on key outcomes. Efforts may be warranted for early detection and treatment of depression and for improving retention of younger participants and those not on ART. C1 [Johnson, Mallory O.; Dilworth, Samantha E.; Neilands, Torsten B.; Chesney, Margaret A.; Rotheram-Borus, Mary Jane; Morin, Stephen F.] Univ Calif San Francisco, San Francisco, CA 94105 USA. [Chesney, Margaret A.] NIH, Natl Ctr Complementary & Alternat Med, Los Angeles, CA USA. [Weinhardt, Lance] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIMH HLP Team, Rockville, MD USA. RP Johnson, MO (reprint author), Univ Calif San Francisco, 50 Beale St,Suite 1300, San Francisco, CA 94105 USA. EM Mallory.Johnson@ucsf.edu FU NIMH NIH HHS [P30 MH043520, U10 MH057616, U10 MH057616-07] NR 12 TC 8 Z9 8 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD NOV PY 2008 VL 12 IS 6 BP 974 EP 977 DI 10.1007/s10461-007-9356-y PG 4 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 359CC UT WOS:000259962800017 PM 18202908 ER PT J AU Marsden, MD Xu, J Hamer, D Zack, JA AF Marsden, Matthew D. Xu, Jie Hamer, Dean Zack, Jerome A. TI Short Communication Activating Stimuli Enhance Immunotoxin-Mediated Killing of HIV-Infected Macrophages SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; GREEN-FLUORESCENT PROTEIN; CD4(+) T-CELLS; IN-VIVO; MONONUCLEAR PHAGOCYTES; REPLICATION-COMPETENT; COMBINATION THERAPY; LATENT RESERVOIR; BRAIN-TISSUE AB Strategies for purging persistent reservoirs in human immunodeficiency virus (HIV)-infected individuals may be enhanced by including agents that specifically kill virus-expressing cells. Anti-HIV envelope immunotoxins (ITs) represent one class of candidate molecules that could fulfill this function. We have previously utilized an anti-gp120 IT in conjunction with various stimulants to kill latently infected T cells ex vivo. Here we show that primary macrophages expressing HIV Env are relatively refractory to killing by IT when used alone. However, including stimulants such as prostratin or granulocyte-macrophage colony-stimulating factor to increase HIV gene expression in infected macrophages enhanced IT-mediated killing. Therefore, "activation-elimination" strategies similar to those proposed for purging the latent HIV reservoir may prove useful in clearing chronically infected macrophages in vivo. C1 [Marsden, Matthew D.; Xu, Jie; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Marsden, Matthew D.; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA. [Xu, Jie; Zack, Jerome A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA. [Hamer, Dean] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. RP Zack, JA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, 615 Charles E Young Dr,S BSRB 173, Los Angeles, CA 90095 USA. EM jzack@ucla.edu FU NIH [AI70010, AI036059] FX This work was supported by NIH Grants AI70010, AI036059, and the UCLA CFAR. NR 53 TC 9 Z9 10 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2008 VL 24 IS 11 BP 1399 EP 1404 DI 10.1089/aid.2008.0082 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 380UT UT WOS:000261491600008 PM 19000022 ER PT J AU Schuckit, MA Smith, TL Trim, RS Heron, J Horwood, J Davis, J Hibbeln, J AF Schuckit, Marc A. Smith, Tom L. Trim, Ryan S. Heron, Jon Horwood, Jeremy Davis, John Hibbeln, Joseph CA ALSPAC Study Team TI The Self-Rating of the Effects of Alcohol Questionnaire as a Predictor of Alcohol-Related Outcomes in 12-Year-Old Subjects SO ALCOHOL AND ALCOHOLISM LA English DT Article ID LOW-LEVEL; USE DISORDERS; ADOLESCENTS; SENSITIVITY; DEPENDENCE; RISK; CHALLENGE; RESPONSES; CHILDREN; DRINKING AB Aims: A low level of response (LR), or low sensitivity, to alcohol as established by alcohol challenges has been shown to predict future heavier drinking, alcohol-related problems and alcohol use disorders. To date, only one study has evaluated the predictive validity of a second measure of LR as determined by the Self-Report of the Effects of Alcohol (SRE) Questionnaire. The current analyses evaluate the ability of SRE scores as determined at age 12 to predict heavier drinking and alcohol-related problems 2 years later in a sample from the United Kingdom. Methods: The subjects were 156 boys (54.5%) and girls from the Avon Longitudinal Study of Parents and Children (ALSPAC) who had reported consuming one or more standard drinks by age 12 and who were followed up 2 years later. Results: The age 12 SRE scores correlated with the number of drinks per week, maximum drinks and the number of alcohol problems both at baseline and at age 14 follow-ups. In these evaluations, a larger number of drinks required for effects on the SRE (i.e. a lower LR per drink consumed) related to heavier intake and alcohol-related difficulties. Simultaneous entry multiple regression analyses revealed that the age 12 SRE score maintained a significant relationship with age 14 higher number of drinks per week and the number of alcohol problems even when the age 12 values for alcohol intake and problems were used as covariates. Conclusion: The SRE scores appear to have value in predicting future heavier drinking and alcohol problems in 12-year olds that go beyond the information offered by the earlier drinking pattern alone. C1 [Schuckit, Marc A.] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. [Heron, Jon] Univ Bristol, Avon Longitudinal Study Parents & Children ALSPAC, Bristol BS8 1TH, Avon, England. [Davis, John] Univ Illinois, Chicago, IL USA. [Hibbeln, Joseph] NIAAA, NIH, Bethesda, MD USA. RP Schuckit, MA (reprint author), Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. EM mschuckit@ucsd.edu RI Heron, Jon/D-5884-2011 OI Heron, Jon/0000-0001-6199-5644 FU Veterans Affairs Research Service; NIAAA [2R01 AA05526]; State of California for medical research on alcohol and substance abuse through the University of California, San Francisco FX We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. TheUKMedical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors who also serve as guarantors for the contents of this paper. This work was supported by the Veterans Affairs Research Service, NIAAA Grant 2R01 AA05526 and funds were provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco. NR 40 TC 20 Z9 20 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2008 VL 43 IS 6 BP 641 EP 646 DI 10.1093/alcalc/agn077 PG 6 WC Substance Abuse SC Substance Abuse GA 365BN UT WOS:000260381000007 PM 18845530 ER PT J AU Signore, C Aros, S Morrow, JD Troendle, J Conley, MR Flanigan, EY Cassorla, F Mills, JL AF Signore, Caroline Aros, Sofia Morrow, Jason D. Troendle, James Conley, Mary R. Flanigan, Elizabeth Y. Cassorla, Fernando Mills, James L. TI Markers of Oxidative Stress and Systemic Vasoconstriction in Pregnant Women Drinking >= 48 g of Alcohol per Day SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Pregnancy; Isoprostanes; Prostacyclin; Thromboxane; Fetal Alcohol Spectrum Disorders ID CHROMATOGRAPHY MASS-SPECTROMETRY; LIPID-PEROXIDATION; OXIDANT STRESS; IN-VIVO; 8-ISO-PROSTAGLANDIN F2-ALPHA; MATERNAL THROMBOXANE; BIOACTIVE PRODUCTS; BIOLOGICAL-FLUIDS; HUMAN PLACENTA; BLOOD-FLOW AB Background: The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods: Pregnant women consuming >= 48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8-isoprostane F2 alpha, and of the vasoactive prostaglandin metabolites, 2,3-dinor-6-keto-prostaglandin F1 alpha (a vasodilator) and 11-dehydro-thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. Results: In crude analyses, there was no significant difference in 8-isoprostane F2 alpha between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3-dinor-6-keto-prostaglandin F1 alpha (1.03 vs. 1.17 ng/mg creatinine, repectively, p = 0.50), 11-dehydro-thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Conclusion: Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus. C1 [Mills, James L.] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res,NIH,US Dept Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Aros, Sofia] Univ Chile, San Borja Arriaran Clin Hosp, Sch Med, Dept Pediat, Santiago, Chile. [Morrow, Jason D.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Med, Nashville, TN 37212 USA. [Morrow, Jason D.] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Pharmacol, Nashville, TN 37212 USA. [Troendle, James] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD USA. [Flanigan, Elizabeth Y.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Washington, DC USA. [Flanigan, Elizabeth Y.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Cassorla, Fernando] Univ Chile, Inst Maternal & Child Res, Dept Pediat, Div Pediat Endocrinol, Santiago, Chile. RP Mills, JL (reprint author), NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res,NIH,US Dept Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM MillsJ@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health [GM15431, DK48831, ES13125] FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by National Institutes of Health grants GM15431, DK48831 and ES13125. NR 47 TC 8 Z9 9 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2008 VL 32 IS 11 BP 1893 EP 1898 DI 10.1111/j.1530-0277.2008.00773.x PG 6 WC Substance Abuse SC Substance Abuse GA 362FK UT WOS:000260183400005 PM 18715278 ER PT J AU Bain, LJ Jedrziewski, K Morrison-Bogorad, M Albert, M Cotman, C Hendrie, H Trojanowski, JQ AF Bain, Lisa J. Jedrziewski, Kathy Morrison-Bogorad, Marcelle Albert, Marilyn Cotman, Carl Hendrie, Hugh Trojanowski, John Q. TI Healthy brain aging: A meeting report from the Sylvan M. Cohen Annual Retreat of the University of Pennsylvania Institute on Aging SO ALZHEIMERS & DEMENTIA LA English DT Article ID ALZHEIMER-DISEASE; UNITED-STATES; DEMENTIA; EXERCISE; MEMORY; OLDER; RISK C1 [Bain, Lisa J.; Jedrziewski, Kathy; Trojanowski, John Q.] Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Bain, Lisa J.; Jedrziewski, Kathy; Trojanowski, John Q.] Univ Penn, Sch Med, Dept Pathol & Lab, Philadelphia, PA 19104 USA. [Morrison-Bogorad, Marcelle] NIA, NIH, Bethesda, MD 20892 USA. [Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Cotman, Carl] Univ Calif Irvine, Irvine, CA USA. [Hendrie, Hugh] Indiana Univ, Sch Med, Indianapolis, IN USA. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. EM trojanow@mail.med.upenn.edu FU NIA NIH HHS [P30 AG010124, P30 AG010124-18] NR 20 TC 10 Z9 10 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2008 VL 4 IS 6 BP 443 EP 446 DI 10.1016/j.jalz.2008.08.006 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 374PS UT WOS:000261056800011 PM 18945646 ER PT J AU Keaney, JF Lipinska, I Larson, MG Dupuis, J Freedman, JE Hamburg, NM Massaro, JM Rong, J Sutherland, P Vita, JA Vasan, RS Benjamin, EJ AF Keaney, John F., Jr. Lipinska, Izabella Larson, Martin G. Dupuis, Josee Freedman, Jane E. Hamburg, Naomi M. Massaro, Joseph M. Rong, Jian Sutherland, Patrice Vita, Joseph A. Vasan, Ramachandran S. Benjamin, Emelia J. TI Clinical correlates, heritability, and genetic linkage of circulating CD40 ligand in the Framingham Offspring Study SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; SOLUBLE CD40L; ENDOTHELIAL-CELLS; CARDIOVASCULAR RISK; ADHESION MOLECULE; HYPER-IGM; ATHEROSCLEROSIS; EXPRESSION; PLASMA; INFLAMMATION AB Background The CD40 receptor and its ligand (CD40L) are known to modulate both inflammation and thrombosis-2 processes important for the development and clinical expression of atherosclerosis. Circulating soluble CD40L (sCD40L) concentration predicts cardiovascular risk in selected patient samples. The purpose of this study was to determine the predictors of sCD40L in a large, community-based sample. Methods We determined both serum and plasma sCD40L concentration in 3,259 participants (54% women) from the Framingham Offspring Study. Results In multivariable models, advancing age was the only consistent (inverse) correlate of both serum and plasma sCD40L concentration. Overall, the variability explained by clinical covariates was very low for both measurements of sCD40L; with values of only 1.4% and 2.7% for serum and plasma, respectively. We observed that genetic factors accounted for a modest (12% serum; 14% plasma) amount of the adjusted variability in sCD40L. Conclusions Circulating sCD40L concentration was poorly associated with known cardiovascular disease (CVD) risk factors and was modestly heritable. Determining if either serum or plasma sCD40L are predictive of CVD risk in the community will require longitudinal follow-up. (Am Heart J 2008;156:1003-9.) C1 [Keaney, John F., Jr.; Freedman, Jane E.; Hamburg, Naomi M.; Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA. [Keaney, John F., Jr.; Lipinska, Izabella; Freedman, Jane E.; Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Larson, Martin G.; Rong, Jian; Sutherland, Patrice; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. [Dupuis, Josee; Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Massaro, Joseph M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. RP Keaney, JF (reprint author), UMASS Med Sch, Div Cardiovasc Med, 55 Lake Ave N,S3-855, Worcester, MA 01655 USA. EM john.keaney@umassmed.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336; Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institutes of Health's Framingham Heart Study [N01-HC-25195, HL076784, HL64753, NS17950, HL04334, AG027081, HL68758] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195). This work was supported by the National Institutes of Health's Framingham Heart Study N01-HC-25195, HL076784, and HL64753 (E.J.B.), NS17950 and HL04334 (R.S.V.), and AG027081 and HL68758 (J.F.K.). NR 39 TC 9 Z9 9 U1 1 U2 6 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 NOV PY 2008 VL 156 IS 5 BP 1003 EP 1009 DI 10.1016/j.ahj.2008.06.041 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 369NB UT WOS:000260700100033 PM 19061720 ER PT J AU Aronow, HD Lincoff, AM Quinn, MJ Mcrae, AT Gurm, HS Houghtaling, PL Granger, CB Harrington, RA de Werf, FV Topol, EJ Lauer, MS AF Aronow, Herbert D. Lincoff, A. Michael Quinn, Martin J. McRae, A. Thomas Gurm, Hitinder S. Houghtaling, Penny L. Granger, Christopher B. Harrington, Robert A. de Werf, Franz Van Topol, Eric J. Lauer, Michael S. CA Gusto Ilb TI Relation Between Previous Lipid-Lowering Therapy and Infaret Size (Creatine Kinase-MB Level) in Patients Presenting With Acute Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; STATIN THERAPY; HEART-DISEASE; NITRIC-OXIDE; SECONDARY PREVENTION; PROPENSITY SCORES; CHOLESTEROL; INJURY; WITHDRAWAL; ROSUVASTATIN AB Animal experimental data have shown that lipid-lowering agents reduce myocardial infarct size. This association has not been well studied in humans. We compared infarct size in 10,548 patients in the GUSTO IIb and PURSUIT trials who were (n = 1,028) or were not (n = 9,520) on lipid-lowering therapy before an enrolling myocardial infarction (MI). Patients using lipid-lowering agents before their index MI had smaller infarcts than those who were not using these agents (median peak creatine kinase [CK]-MB 4.2 vs 5.2 times the upper limit of normal [ULN]; p <0.0001). Similarly, in an unadjusted model, patients on previous lipid-lowering therapy were less likely to have a peak CK-MB >3 times the ULN (620 of 1,028 [60.3%] vs 6,486 of 9,520 patients [68.1%]; p <0.001; relative risk 0.88, 95% confidence interval 0.84 to 0.93, p <0.0001). In a covariate- and propensity-adjusted multivariable model, the association between pretreatment with lipid-lowering agents and smaller infarct size persisted (relative risk for CK-MB >3 times the ULN 0.94, 95% confidence interval 0.88 to 0.99, p = 0.04). In conclusion, patients on lipid-lowering agents before an MI had significantly smaller infarcts. These findings suggest that lipid-lowering therapy may exert additional salutary effects in the setting of acute coronary syndromes. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1119-1124) C1 [Aronow, Herbert D.] St Joseph Mercy Hosp, Michigan Heart & Vasc Inst, Clin Scholars Program, Ann Arbor, MI 48104 USA. [Lincoff, A. Michael; Houghtaling, Penny L.] Cleveland Clin, Cleveland, OH 44106 USA. [Quinn, Martin J.] St Vincents Univ Hosp, Dublin 4, Ireland. [McRae, A. Thomas] Centennial Heart Cardiovasc Consultants, Nashville, TN USA. [Gurm, Hitinder S.] Univ Michigan, Sch Med, Div Cardiovasc Med, Ann Arbor, MI USA. [Granger, Christopher B.; Harrington, Robert A.] Duke Clin Res Inst, Durham, NC USA. [de Werf, Franz Van] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. [Topol, Eric J.] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. [Lauer, Michael S.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Aronow, HD (reprint author), St Joseph Mercy Hosp, Michigan Heart & Vasc Inst, Clin Scholars Program, Ann Arbor, MI 48104 USA. EM haronow@michiganheart.com RI Lauer, Michael/L-9656-2013; Granger, Christopher/D-3458-2014 OI Lauer, Michael/0000-0002-9217-8177; Granger, Christopher/0000-0002-0045-3291 FU COR Therapeutics, Inc., San Francisco, California, and Schering-Plough Research Institute, Kenilworth, New Jersey; Ciba-Geigy, Inc.. Summit, New Jersey Boehringer-Mannheim. Indianapolis, Indiana; Guidant Corp., Redwood City, California FX Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) was supported by COR Therapeutics, Inc., San Francisco, California, and Schering-Plough Research Institute, Kenilworth, New Jersey; and Global Use of Streptokinase or t-PA for Occluded Coronary Arteries IIb (GUSTO IIb) was supported by Ciba-Geigy, Inc.. Summit, New Jersey Boehringer-Mannheim. Indianapolis, Indiana: and Guidant Corp., Redwood City. California. NR 29 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2008 VL 102 IS 9 BP 1119 EP 1124 DI 10.1016/j.amjcard.2008.06.032 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373XT UT WOS:000261007500001 PM 18940276 ER PT J AU Hoffmann, U Massaro, JM Fox, CS Manders, E O'Donnell, CJ AF Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Manders, Emily O'Donnell, Christopher J. TI Defining Normal Distributions of Coronary Artery Calcium in Women and Men (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; RISK-ASSESSMENT; CT; REPRODUCIBILITY; QUANTIFICATION; GENDER; COHORT; MESA; AGE AB Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CRD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177). Absolute AS and relative cutoffs for CAC increased with age and FRS, were higher in men compared with women in each of the 3 cohorts, and increased from the healthy subset to the overall cohort to subjects at intermediate risk. However, in subjects with CAC, there was substantial disagreement between absolute and relative cut-off values for labeling subjects as having increased CAC. In general, more subjects were considered to have increased CAC using relative cut-off values, especially in women and younger subjects. Fewer subjects at intermediate FRS had increased CAC using comparable absolute versus relative cutoffs (men 32% at AS > 100 vs 36% at > 75th percentile; women 24% at AS > 100 vs 34% at >75th percentile). In conclusion, we provided distributions of CAC in a healthy subset, the overall cohort, and subjects at intermediate risk from the Framingham Heart Study for both absolute and relative cut-off values for CAC. Absolute cutoffs underestimated the proportion of subjects with increased CAC, specifically in women, younger persons, and persons at intermediate CHD risk. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fox, Caroline S.; Manders, Emily; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiol Div, Boston, MA USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Cardiac MR PET CT Program, Boston, MA 02115 USA. EM uhoffmann@partners.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart. Lung, and Blood Institute (NHLBI) Framingham Heart Study [N01-HC-25195] FX This work was supported by the National Heart. Lung, and Blood Institute (NHLBI) Framingham Heart Study (National Institutes Of Health/NHLBI Contract N01-HC-25195. Bethesda. maryland), Framingham, Massachusetts. NR 13 TC 58 Z9 63 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2008 VL 102 IS 9 BP 1136 EP 1141 DI 10.1016/j.amjcard.2008.06.038 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373XT UT WOS:000261007500004 PM 18940279 ER PT J AU Parikh, NI Hwang, SJ Yang, Q Larson, MG Guo, CY Robins, SJ Sutherland, P Benjamin, EJ Levy, D Fox, CS AF Parikh, Nisha I. Hwang, Shih-Jen Yang, Qiong Larson, Martin G. Guo, Chao-Yu Robins, Sander J. Sutherland, Patrice Benjamin, Emelia J. Levy, Daniel Fox, Caroline S. TI Clinical Correlates and Heritability of Cystatin C (from the Framingham Offspring Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; SERUM CREATININE; ARTERIAL STIFFNESS; ELDERLY PERSONS; HEALTH; RISK; DYSFUNCTION; COMMUNITY; OUTCOMES AB Cystatin C (CysC) is associated with cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined the clinical correlates and heritability of CysC and determined if associations between CVD risk factors and CysC differed by CKD status. Among Framingham Heart Study offspring (examined from 1998-2001, n = 3,241, mean age 61 years, 54% women), the 95(th) percentile cut-point was developed for CysC in a healthy subset (n = 779) after excluding participants with diabetes, hypertension, low high-density lipoproteins, obesity, smoking, high triglycerides, prevalent CVD, and CKD (as defined by glomerular filtration rate <60 mL/min per 1.73 m(2)). Multivariable logistic regression was used to evaluate the association between CVD risk factors and high CysC (CysC >= 95(th) percentile cut-point). In a family-based subset (n = 1,188), we estimated CysC heritability using the variance-components method. The cut-point for high CysC was 1.07 mg/L. Age, hypertension treatment, low diastolic blood pressure, body mass index, low high-density lipoprotein cholesterol, and smoking were associated with high CysC in multivariable models. These factors and estimated glomerular filtration rate (egFR) explained 39.2% of CysC variability (R(2)). Excluding CKD did not materially change associations. Multivariable-adjusted heritability for CysC was 0.35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1194-1198) C1 [Parikh, Nisha I.; Hwang, Shih-Jen; Larson, Martin G.; Robins, Sander J.; Sutherland, Patrice; Benjamin, Emelia J.; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Yang, Qiong; Guo, Chao-Yu] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. RI Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart. Lung and Blood Institute [N01-HC-25195] FX The Framingham Heart Study was supported by Grant N01-HC-25195 from the National Heart. Lung and Blood Institute. NR 27 TC 26 Z9 29 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2008 VL 102 IS 9 BP 1194 EP 1198 DI 10.1016/j.amjcard.2008.06.039 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373XT UT WOS:000261007500015 PM 18940290 ER PT J AU Craft, LL Guralnik, JM Ferrucci, L Liu, K Tian, L Criqui, MH Tan, J McDermott, MM AF Craft, Lynette L. Guralnik, Jack M. Ferrucci, Luigi Liu, Kiang Tian, Lu Criqui, Michael H. Tan, Jin McDermott, Mary M. TI Physical Activity During Daily Life and Circulating Biomarker Levels in Patients With Peripheral Arterial Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; ANKLE BRACHIAL INDEX; C-REACTIVE PROTEIN; RISK-FACTORS; MUSCLE CHARACTERISTICS; D-DIMER; INFLAMMATION; RESTENOSIS; MORTALITY; CLAUDICATION AB Higher levels of inflammation are associated with adverse outcomes in patients with lower extremity peripheral arterial disease (PAD). This study evaluated associations of physical activity during daily life with levels of inflammatory biomarkers, D-dimer, and homocysteine in patients with PAD. Participants were 244 men and women (mean age 74.4 +/- 8.2 years) with PAD (ankle brachial index < 0.90). C-reactive protein, interleukin-6, soluble intracellular adhesion molecule-1, soluble vascular cellular adhesion molecule-1, D-dimer, and homocysteine were assessed at study entry. Physical activity was objectively assessed with a vertical accelerometer, which participants wore continuously for 7 days. After adjusting for age, gender, race, body mass index, smoking, co-morbidities, ankle brachial index, and other potential confounders, higher physical activity levels were associated linearly and significantly with lower levels of all measured circulating biomarkers: soluble vascular cellular adhesion molecule-1 (p trend = 0.001), D-dimer (p trend = 0.005), homocysteine (p trend = 0.006), interleukin-6 (p trend = 0.010), C-reactive protein (p trend = 0.028), and soluble intracellular adhesion molecule-1 (p trend = 0.033). In conclusion, higher levels of physical activity were associated independently with lower levels of inflammatory markers, homocysteine, and D-dimer in patients with PAD. 0 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1263-268) C1 [Craft, Lynette L.; Liu, Kiang; Tian, Lu; Tan, Jin; McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Guralnik, Jack M.; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Craft, LL (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM lynette-craft@northwestern.edu FU National Heart Lung and Blood Institute, Bethesda, Maryland [R01-HL58099, R01-HL64739, R01-HL71223, R01-HL076298]; National Center for Research Resources, [RR-00048]; National Institutes of Health, Bethesda, Maryland; Intramural Research Program; National Institute on Aging; National Institutes of Health FX This study was supported by Grants R01-HL58099, R01-HL64739, R01-HL71223, and R01-HL076298 from the National Heart Lung and Blood Institute, Bethesda, Maryland; by Grant RR-00048 from the National Center for Research Resources, National Institutes of Health, Bethesda, Maryland: and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 24 TC 14 Z9 18 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2008 VL 102 IS 9 BP 1263 EP 1268 DI 10.1016/j.amjcard.2008.06.051 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373XT UT WOS:000261007500029 PM 18940304 ER PT J AU Koster, A Leitzmann, MF Schatzkin, A Adams, KF van Eijk, JTM Hollenbeck, AR Harris, TB AF Koster, Annemarie Leitzmann, Michael F. Schatzkin, Arthur Adams, Kenneth F. van Eijk, Jacques T. M. Hollenbeck, Albert R. Harris, Tamara B. TI The combined relations of adiposity and smoking on mortality SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; CIGARETTE-SMOKING; PROSPECTIVE COHORT; UNITED-STATES; RISK-FACTORS; HEALTH-RISK; US ADULTS; OBESITY; WEIGHT AB Background: Smoking and high adiposity are strong independent health risk factors but are also interrelated. Smoking is related to a lower body mass index (BMI) but not necessarily with a smaller waist circumference. Smoking cessation is associated with increased body weight and a substantial increase in waist circumference. How this affects mortality risk is unknown. Objective: This study examined the combined relations of smoking status with BMI and waist circumference and smoking status to all-cause mortality. Design: Data were from 149 502 men and 88 184 women aged 51-72 y participating in the National Institutes of Health-AARP Diet and Health Study. All-cause mortality was assessed over 10 y of follow-up from 1996 to 2006. Results: Current smokers with a BMI (in kg/m(2)) < 18.5 or >= 35 had a mortality risk 6-8 times that of persons within the normal BMI range who never smoked. Current smokers with a large waist circumference had a mortality risk about 5 times that of never smokers with a waist circumference in the second quintile. Conclusion: Both smoking and adiposity are independent predictors of mortality, but the combination of current or recent smoking with a BMI >= 35 or a large waist circumference is related to an especially high mortality risk. Am J Clin Nutr 2008; 88: 1206-12. C1 [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Koster, Annemarie; van Eijk, Jacques T. M.] Univ Maastricht, Fac Hlth Med & Life Sci, Maastricht, Netherlands. [Leitzmann, Michael F.; Schatzkin, Arthur; Adams, Kenneth F.] Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM kostera@mail.nih.gov RI Koster, Annemarie/E-7438-2010 FU NIH, National Cancer Institute; NIH, National Institute on Aging FX Supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and the Intramural Research Program of the NIH, National Institute on Aging. NR 37 TC 39 Z9 39 U1 0 U2 4 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV 1 PY 2008 VL 88 IS 5 BP 1206 EP 1212 DI 10.3945/ajcn.2008.26298 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 370OD UT WOS:000260770600006 PM 18996854 ER PT J AU Sieri, S Krogh, V Ferrari, P Berrino, F Pala, V Thiebaut, ACM Tjonneland, A Olsen, A Overvad, K Jakobsen, MU Clavel-Chapelon, F Chajes, V Boutron-Ruault, MC Kaaks, R Linseisen, J Boeing, H Nothlings, U Trichopoulou, A Naska, A Lagiou, P Panico, S Palli, D Vineis, P Tumino, R Lund, E Kumle, M Skeie, G Gonzalez, CA Ardanaz, E Amiano, P Tormo, MJ Martinez-Garcia, C Quiros, JR Berglund, G Gullberg, B Hallmans, G Lenner, P Bueno-de-Mesquita, HB van Duijnhoven, FJB Peeters, PHM van Gils, CH Key, TJ Crowe, FL Bingham, S Khaw, KT Rinaldi, S Slimani, N Jenab, M Norat, T Riboli, E AF Sieri, Sabina Krogh, Vittorio Ferrari, Pietro Berrino, Franco Pala, Valeria Thiebaut, Anne C. M. Tjonneland, Anne Olsen, Anja Overvad, Kim Jakobsen, Marianne Uhre Clavel-Chapelon, Francoise Chajes, Veronique Boutron-Ruault, Marie-Christine Kaaks, Rudolf Linseisen, Jakob Boeing, Heiner Noethlings, Ute Trichopoulou, Antonia Naska, Androniki Lagiou, Pagona Panico, Salvatore Palli, Domenico Vineis, Paolo Tumino, Rosario Lund, Eiliv Kumle, Merethe Skeie, Guri Gonzalez, Carlos A. Ardanaz, Eva Amiano, Pilar Tormo, Maria Jose Martinez-Garcia, Carmen Quiros, Jose R. Berglund, Goeran Gullberg, Bo Hallmans, Goeran Lenner, Per Bueno-de-Mesquita, H. Bas van Duijnhoven, Fraenzel J. B. Peeters, Petra H. M. van Gils, Carla H. Key, Timothy J. Crowe, Francesca L. Bingham, Sheila Khaw, Kay Tee Rinaldi, Sabina Slimani, Nadia Jenab, Mazda Norat, Teresa Riboli, Elio TI Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; HORMONE-REPLACEMENT THERAPY; RELATIVE VALIDITY; FOLLOW-UP; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT; MEASUREMENT ERROR; EPIC PROJECT; HEALTH; REPRODUCIBILITY AB Background: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer. Objective: We aimed to investigate the association between fat consumption and breast cancer. Design: We prospectively investigated fat consumption in a large (n = 319 826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer. Results: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable]. Conclusions: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy. Am J Clin Nutr 2008; 88: 1304-12. C1 [Sieri, Sabina; Krogh, Vittorio; Pala, Valeria] Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, I-20133 Milan, Italy. [Ferrari, Pietro; Rinaldi, Sabina; Slimani, Nadia; Jenab, Mazda] WHO, IARC, Lyon, France. [Berrino, Franco] Ist Nazl Tumori, Fdn IRCCS, Etiol & Prevent Epidemiol Unit, I-20133 Milan, Italy. [Thiebaut, Anne C. M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Tjonneland, Anne; Olsen, Anja] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Overvad, Kim; Jakobsen, Marianne Uhre] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, INSERM, ERI 20, Villejuif, France. [Chajes, Veronique] Inst Gustave Roussy, CNRS, FRE 2939, Villejuif, France. [Kaaks, Rudolf; Linseisen, Jakob] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. [Boeing, Heiner; Noethlings, Ute] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. [Trichopoulou, Antonia; Naska, Androniki; Lagiou, Pagona] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. [Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy. [Palli, Domenico] Sci Inst Tuscany, CSPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Vineis, Paolo] Univ Turin, Turin, Italy. [Tumino, Rosario] MP Arezzo Civ Hosp, Canc Registry, Ragusa, Italy. [Lund, Eiliv; Kumle, Merethe; Skeie, Guri] Univ Tromso, Inst Community Med, Tromso, Norway. [Gonzalez, Carlos A.] Catalan Inst Oncol, Dept Epidemiol, Barcelona, Spain. [Ardanaz, Eva] Publ Hlth Inst Navarra, Pamplona, Spain. [Ardanaz, Eva] CIBERESP, Pamplona, Spain. [Amiano, Pilar] Publ Hlth Div Gipuzkoa, Donostia San Sebastian, Spain. [Tormo, Maria Jose] Murcia Hlth Council, Dept Epidemiol, Murcia, Spain. [Tormo, Maria Jose] CIBERESP, Murcia, Spain. [Martinez-Garcia, Carmen] Andalusian Sch Publ Hlth, Granada, Spain. [Martinez-Garcia, Carmen] CIBERESP, Granada, Spain. [Quiros, Jose R.] Publ Hlth & Hlth Planning Directorate, Hlth Informat Unit, Asturias, Spain. [Berglund, Goeran; Gullberg, Bo] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Hallmans, Goeran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Lenner, Per] Umea Univ, Dept Radiat Sci, Oncol Unit, Umea, Sweden. [Bueno-de-Mesquita, H. Bas; van Duijnhoven, Fraenzel J. B.] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands. [Peeters, Petra H. M.; van Gils, Carla H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Crowe, Francesca L.] Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England. [Bingham, Sheila; Khaw, Kay Tee] MRC, Dunn Human Nutr Unit, Cambridge, England. [Norat, Teresa; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. RP Krogh, V (reprint author), Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, Via Venezian 1, I-20133 Milan, Italy. EM vittorio.krogh@istitutotumori.mi.it RI Nothlings, Ute/B-2713-2010; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Gonzalez, Carlos A/O-4651-2014; Boutron-Ruault, Marie-Christine/H-3936-2014; Krogh, Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016; Panico, Salvatore/K-6506-2016 OI PALLI, Domenico/0000-0002-5558-2437; Skeie, Guri/0000-0003-2476-4251; Linseisen, Jakob/0000-0002-9386-382X; Gonzalez, Carlos A/0000-0003-2822-9715; Krogh, Vittorio/0000-0003-0122-8624; Sieri, Sabina/0000-0001-5201-172X; Panico, Salvatore/0000-0002-5498-8312 FU European Commission; Deutsche Krebshilfe; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Spanish Ministry of Health [CIBERESP, RETIC-RD06/0020]; Spanish Institute of Health Carlos III; Catalan Institute of Oncology; Cancer Research UK; Medical Research Council, United Kingdom; Stroke Association, United Kingdom; British Heart Foundation; Department of Health, United Kingdom; Food Standards Agency, United Kingdom; Wellcome Trust, United Kingdom; Greek Ministry of Health and Social Solidarity; Hellenic Health Foundation; Italian Association for Research on Cancer; Dutch Ministry of Public Health, Welfare and Sports; National Cancer Registry; World Cancer Research Fund; Swedish Cancer Society; Swedish Scientific Council; Norwegian Research Council; University of Tromso FX Supported by the Public Health and Consumer Protection Directorate 1993-2004 and the Research Directorate-General 2005 of the European Commission; Deutsche Krebshilfe; the German Cancer Research Center; the German Federal Ministry of Education and Research; the Danish Cancer Society; the Health Research Fund of the Spanish Ministry of Health (CIBERESP and RETIC-RD06/0020); the Spanish Institute of Health Carlos III; the regional governments of Andalusia, Asturias, Basque Country, Murcia, and Navarra in Spain; the Catalan Institute of Oncology; Cancer Research UK; the Medical Research Council, United Kingdom; the Stroke Association, United Kingdom; the British Heart Foundation; the Department of Health, United Kingdom; the Food Standards Agency, United Kingdom; the Wellcome Trust, United Kingdom; the Greek Ministry of Health and Social Solidarity and the Hellenic Health Foundation; the Italian Association for Research on Cancer; the Dutch Ministry of Public Health, Welfare and Sports; the National Cancer Registry and the regional cancer registries of Amsterdam, East, and Maastricht in the Netherlands; the World Cancer Research Fund; the Swedish Cancer Society; the Swedish Scientific Council; the regional government of Skane, Sweden; and the Norwegian Research Council and the University of Tromso. NR 63 TC 69 Z9 70 U1 3 U2 16 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV 1 PY 2008 VL 88 IS 5 BP 1304 EP 1312 DI 10.3945/ajcn.2008.26090 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 370OD UT WOS:000260770600019 PM 18996867 ER PT J AU Sattler, FR Rajicic, N Mulligan, K Yarasheski, KE Koletar, SL Zolopa, A Alston, B Zackin, SR Bistrian, B AF Sattler, Fred R. Rajicic, Natasa Mulligan, Kathleen Yarasheski, Kevin E. Koletar, Susan L. Zolopa, Andrew Alston, Beverly Zackin, Smith Robert Bistrian, Bruce CA ACTG 392 Study Team TI Evaluation of high-protein supplementation in weight-stable HIV-positive subjects with a history of weight loss: a randomized, double-blind, multicenter trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BODY CELL MASS; ACTIVE ANTIRETROVIRAL THERAPY; INCREASING NITROGEN INTAKE; TOTAL PARENTERAL-NUTRITION; INFECTED PATIENTS; AIDS PATIENTS; WASTING SYNDROME; WHEY PROTEINS; DISEASE RISK AB Background: HIV patients with wasting are at increased risk of opportunistic complications and fatality. Objective: We hypothesized that augmenting dietary intake with high-biologic-value protein would enhance weight and lean tissue in weight-stable subjects with a prior unintentional weight loss of >3%. Design: Fifty-nine subjects with HIV RNA concentrations <5000 copies/mL were randomly assigned to receive a 280-kcal supplement containing 40 g whey protein or a matched isocaloric control supplement without added protein twice daily for 12 wk. Results: Before the study, intake of total energy and protein exceeded estimated requirements (44.3 +/- 12.6 kcal . kg(-1) . d(-1) and 1.69 +/- 0.55 g . kg(-1) . d(-1), respectively). Both supplements failed to increase total energy intake because of decreases in self-selected food intake. Changes in weight (0.8 +/- 2.4 and 0.7 +/- 2.4 kg) and lean body mass (0.3 +/- 1.4 and 0.3 +/- 1.5 kg) did not differ significantly between the whey protein and control groups, respectively. Waist-to-hip ratio improved more with whey protein (-0.02 +/- 0.05) than with the control (0.01 +/- 0.03; P = 0.025) at week 6 but not at week 12. Fasting triacylglycerol increased by 39 +/- 98 mg/dL with the control supplement and decreased by 16 +/- 62 mg/dL with whey protein at week 12 (P = 0.03). CD4 lymphocytes increased by 31 +/- 84 cells/mm3 with whey protein and decreased by 5 +/- 124 cells/mm(3) with the control supplement at 12 wk (P = 0.03). Gastrointestinal symptoms occurred more often with whey protein. Conclusions: A whey protein supplement did not increase weight or lean body mass in HIV-positive subjects who were eating adequately, but it did increase CD4 cell counts. The control supplement with rapidly assimilable carbohydrate substituted for protein increased cardiovascular disease risk factors. Careful dietary and weight history should be obtained before starting nutritional supplements in subjects with stable weight loss and good viral control. Am J Clin Nutr 2008; 88: 1313-21. C1 [Sattler, Fred R.] Univ So Calif, Keck Sch Med, LAC USC Med Ctr, Los Angeles, CA 90033 USA. [Rajicic, Natasa; Zackin, Smith Robert] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mulligan, Kathleen] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Yarasheski, Kevin E.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Koletar, Susan L.] Ohio State Univ, Div Infect Dis, Columbus, OH 43210 USA. [Zolopa, Andrew] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Alston, Beverly] NIAID, Div Aids, Bethesda, MD 20892 USA. [Zackin, Smith Robert] Harvard Univ, Sch Publ Hlth, Dept Med, Boston, MA 02115 USA. [Bistrian, Bruce] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Sattler, FR (reprint author), Univ So Calif, Keck Sch Med, LAC USC Med Ctr, Room 6442,1200 N State St, Los Angeles, CA 90033 USA. EM fsattler@usc.edu RI Yarasheski, Kevin/A-3025-2008; OI Yarasheski, Kevin/0000-0001-5436-2451 FU National Institute of Allergy and Infectious Diseases through the Adult AIDS Clinical Trials Group U01 [AI20766, AI69474, AI27663, AI25903, AI27673, AI46386, AI34853, AI27668, AI27658, AI25897, AI34832, AI32770]; General Clinical Research Programs, NCRR, M01 [RR00070, RR00034, RR00043, RR00083, RR00052, RR00044, RR00051] FX Supported by the National Institute of Allergy and Infectious Diseases through the Adult AIDS Clinical Trials Group U01 grants (AI20766, AI69474, AI27663, AI25903, AI27673, AI46386, AI34853, AI27668, AI27658, AI25897, AI34832, and AI32770) and the General Clinical Research Programs, NCRR, M01 grants (RR00070, RR00034, RR00043, RR00083, RR00052, RR00044, and RR00051). Biomune Systems, Inc, provided the whey protein and control supplements. NR 53 TC 16 Z9 17 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV 1 PY 2008 VL 88 IS 5 BP 1313 EP 1321 DI 10.3945/ajcn.2006.23583 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 370OD UT WOS:000260770600020 PM 18996868 ER PT J AU Wright, ME Park, Y Subar, AF Freedman, ND Albanes, D Hollenbeck, A Leitzmann, MF Schatzkin, A AF Wright, Margaret E. Park, Yikyung Subar, Amy F. Freedman, Neal D. Albanes, Demetrius Hollenbeck, Albert Leitzmann, Michael F. Schatzkin, Arthur TI Intakes of Fruit, Vegetables, and Specific Botanical Groups in Relation to Lung Cancer Risk in the NIH-AARP Diet and Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; fruit; lung neoplasms; vegetables ID RETIRED-PERSONS DIET; BETA-CAROTENE; VITAMIN-C; AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES; CONSUMPTION; PREVENTION; COHORT; NUTRITION; SMOKERS AB Increased fruit and vegetable consumption may protect against lung cancer, although epidemiologic findings are inconclusive. The authors prospectively examined associations between lung cancer risk and intakes of fruit, vegetables, and botanical subgroups in 472,081 participants aged 50-71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline (1995-1996) with a 124-item dietary questionnaire. A total of 6,035 incident lung cancer cases were identified between 1995 and 2003. Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women. Higher consumption of several botanical subgroups, however, was significantly inversely associated with risk, but only in men. For example, the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae, convolvulaceae, and umbelliferae were 0.82 (95% confidence interval (CI): 0.73, 0.91), 0.86 (95% CI: 0.75, 0.96), and 0.86 (95% CI: 0.78, 0.96), respectively; corresponding relative risks in women were 0.97 (95% CI: 0.85, 1.12), 0.95 (95% CI: 0.83, 1.09), and 0.92 (95% CI: 0.80, 1.06). These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men, although the findings could also be due to residual confounding by smoking or chance. C1 [Wright, Margaret E.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA. [Wright, Margaret E.; Park, Yikyung; Freedman, Neal D.; Albanes, Demetrius; Leitzmann, Michael F.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Freedman, Neal D.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Wright, ME (reprint author), Univ Illinois, Coll Med, Dept Pathol MC 847, 840 S Wood St,Room 130, Chicago, IL 60612 USA. EM mewright@uic.edu RI Albanes, Demetrius/B-9749-2015; Freedman, Neal/B-9741-2015; OI Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS [Z99 CA999999] NR 43 TC 42 Z9 43 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2008 VL 168 IS 9 BP 1024 EP 1034 DI 10.1093/aje/kwn212 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 365BM UT WOS:000260380900008 PM 18791192 ER PT J AU Stolzenberg-Solomon, RZ Weinstein, S Pollak, M Tao, YZ Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, Rachael Z. Weinstein, Stephanie Pollak, Michael Tao, Yuzhen Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI Prediagnostic Adiponectin Concentrations and Pancreatic Cancer Risk in Male Smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adenocarcinoma; adiponectin; biological markers; case-control studies; diabetes mellitus; pancreatic neoplasms ID BODY-FAT DISTRIBUTION; PLASMA ADIPONECTIN; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; CIGARETTE-SMOKING; MASS INDEX; KOREAN MEN; OBESITY; COHORT; GLUCOSE AB Adiponectin, a hormone secreted by adipocytes, has insulin-sensitizing, antidiabetic, antiinflammatory, and antiangiogenic properties. The authors conducted a nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort, a cohort of male Finnish smokers aged 50-69 years at baseline, to test whether prediagnostic adiponectin concentrations are associated with pancreatic cancer. Between January 1985 and October 2004, 311 incident exocrine pancreatic cancer cases were diagnosed among cohort participants with serum samples. Controls (n = 510) were alive and free of cancer at the time the case was diagnosed and were matched to the cases by age and date of blood drawing. The authors used conditional logistic regression adjusted for smoking, blood pressure, and C-peptide level to calculate odds ratios and 95% confidence intervals for pancreatic cancer. Higher adiponectin concentrations were inversely associated with pancreatic cancer (for highest quintile (> 9.8 mu g/mL) vs. lowest (<= 4.6 mu g/mL), odds ratio = 0.65, 95% confidence interval: 0.39, 1.07; P-trend = 0.04). The inverse association was significant among cases diagnosed 5 or more years after blood collection (n = 238) (for highest quintile vs. lowest, odds ratio = 0.55, 95% confidence interval: 0.31, 0.98; P-trend = 0.03). These results support the hypothesis that higher adiponectin concentrations may be inversely associated with the development of pancreatic cancer. C1 [Stolzenberg-Solomon, Rachael Z.; Weinstein, Stephanie; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Pollak, Michael; Tao, Yuzhen] Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ, Canada. [Pollak, Michael; Tao, Yuzhen] McGill Univ, Montreal, PQ, Canada. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015 OI Pollak, Michael/0000-0003-3047-0604; FU Intramural Research Program of the National Institutes of Health; Division of Cancer Epidemiology and Genetics; National Cancer Institute; US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004] FX This research was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and by US Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute. NR 57 TC 34 Z9 38 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2008 VL 168 IS 9 BP 1047 EP 1055 DI 10.1093/aje/kwn221 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 365BM UT WOS:000260380900010 PM 18801887 ER PT J AU Sharma, P Wani, S Romero, Y Johnson, D Hamilton, F AF Sharma, Prateek Wani, Sachin Romero, Yvonne Johnson, David Hamilton, Frank TI Racial and Geographic Issues in Gastroesophageal Reflux Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; BODY-MASS INDEX; PROTON-PUMP INHIBITORS; BARRETTS-ESOPHAGUS; CLINICAL SPECTRUM; RISK-FACTORS; ENDOSCOPIC ESOPHAGITIS; GENERAL-POPULATION; ESOPHAGOGASTRIC JUNCTION; SWEDISH POPULATION AB Gastroesophageal reflux disease (GERD) is a common chronic disorder that is associated with a huge economic burden in the western countries and significantly decreased quality of life. This review focuses on the various multicultural issues in the epidemiology, pathophysiology, diagnosis, and treatment of GERD. The prevalence of GERD appears to be highest in North America and Europe, whereas epidemiologic data from the Indian subcontinent, Africa, South America, and the Middle East are sparse. A limited number of studies have elucidated ethnic differences in GERD in multiracial populations. African Americans and Asians appear to be at a lower risk for the development of complicated GERD including Barrett's esophagus (BE). Whether the pathophysiology of GERD differs among different populations remains to be answered satisfactorily. It appears that most of the factors involved in the pathogenesis of GERD, as described in western populations, are present in Asians but at a lower scale. The current recommendations for the management of GERD by the American College of Gastroenterology may not meet the need for different ethnic groups or for different geographic regions. Recognition of language barriers in understanding the common terms used to describe reflux symptoms should be borne in mind while treating GERD patients with different ethnic backgrounds. In addition, a universally accepted definition for treatment success in GERD patients is lacking. Given the negative impact on health-related quality of life, significant cost ramifications, and increased risk for BE and esophageal adenocarcinoma, the study of multicultural issues in GERD should be considered. C1 [Sharma, Prateek] Vet Affairs Med Ctr, Dept Gastroenterol 111, Kansas City, MO 64128 USA. [Sharma, Prateek; Wani, Sachin] Univ Kansas, Sch Med, Kansas City, MO USA. [Romero, Yvonne] Mayo Clin, Rochester, MN USA. [Johnson, David] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Hamilton, Frank] Natl Inst Hlth, Bethesda, MD USA. RP Sharma, P (reprint author), Vet Affairs Med Ctr, Dept Gastroenterol 111, 4801 E Linwood Blvd, Kansas City, MO 64128 USA. NR 110 TC 41 Z9 42 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2669 EP 2680 DI 10.1111/j.1572-0241.2008.02089.x PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900001 PM 19032462 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, Chung-Jyi Leitzmann, Michael F. Willett, Walter C. Giovannucci, Edward L. TI Macronutrients and Insulin Resistance in Cholesterol Gallstone Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID TRANS-FATTY-ACIDS; BILIARY LIPID SECRETION; DEPENDENT DIABETES-MELLITUS; MODERATE ALCOHOL INTAKE; DIETARY GLYCEMIC INDEX; HIGH-CARBOHYDRATE DIET; GALL STONE DISEASE; METABOLIC SYNDROME; GALLBLADDER-DISEASE; FISH-OIL AB Cholelithiasis is a major source of digestive morbidity worldwide. Cholesterol stones account for the majority of gallstones in the United States and other Western countries. The pathogenesis of cholesterol gallstone disease is multifactorial with key factors including cholesterol supersaturation of bile, altered biliary motility, and nucleation and growth of cholesterol crystals. Increasing evidence suggests that many, but not all, causative factors of cholesterol gallstones are related to insulin resistance which, in association with obesity, has reached an epidemic level worldwide. Experimental studies show that hyperinsulinemia, a key feature of insulin resistance, may cause increased hepatic cholesterol secretion and cholesterol supersaturation of bile and gallbladder dysmotility, and thereby may enhance gallstone formation. Insulin resistance syndrome can be modified by environmental factors, including dietary factors. The impact of diet on insulin sensitivity is mediated by both dietary composition and its energy content. The contribution of specific dietary elements to the prevalence and incidence of cholesterol gallstone disease has been explored in animal and human studies. There is considerable evidence to suggest that different types of fatty acids, independent of the total amount of fat consumption, affect insulin sensitivity and cholesterol gallstone disease differently. The effects of salt intake, consumption of protein and carbohydrates, and alcohol drinking on insulin resistance are controversial. Additional intervention trials and controlled experimental feeding studies are needed to further clarify these relationships and to provide useful prophylactic and therapeutic strategies. C1 [Tsai, Chung-Jyi] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. [Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. FU National Institute of Health [CA55075, DK46200] FX Research grants (CA55075 and DK46200) from the National Institute of Health. NR 122 TC 25 Z9 26 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2008 VL 103 IS 11 BP 2932 EP 2939 DI 10.1111/j.1572-0241.2008.02189.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367HU UT WOS:000260543900033 PM 18853969 ER PT J AU Anderson, RD Sizemore, BC Barrow, GM Johnson, BD Merz, CNB Sopko, G von Mering, GO Handberg, EM Nichols, WW Pepine, CJ AF Anderson, R. David Sizemore, B. Clay Barrow, Genevieve M. Johnson, B. Delia Merz, C. Noel Bairey Sopko, George von Mering, Gregory O. Handberg, Eileen M. Nichols, Wilmeer W. Pepine, Carl J. TI Pulse Pressure and Adverse Outcomes in Women: A Report From the Women's Ischemia Syndrome Evaluation (WISE) SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID CONVERTING-ENZYME-INHIBITION; LEFT-VENTRICULAR HYPERTROPHY; BLOOD-PRESSURE; HYPERTENSIVE PATIENTS; ARTERIAL STIFFNESS; CARDIOVASCULAR RISK; AORTIC STIFFNESS; SYSTOLIC HYPERTENSION; WAVE REFLECTIONS; CONTROLLED-TRIAL AB BACKGROUND Recent data suggest that brachia I pulse pressure (PP) maybe a better predictor of outcome than systolic or diastolic blood pressure (SBP/DBP). We sought to investigate the relative contributions of these indices to risk for adverse outcomes in women with suspected coronary artery disease (CAD) and myocardial ischemia. METHODS Among 857 women referred for angiography for suspected myocardial ischemia, baseline evaluations were performed, and the women were followed for clinical outcome. Relationships between baseline characteristics, blood pressure components, and outcomes were evaluated. Separate multivariate stepwise Cox regression models for PP and SBP (expressed in 10 mm Hg increments) were constructed and included covariates significantly associated with adverse outcomes. RESULTS After 5.2 years (mean), univariate testing identified higher PP associated with higher risk for cardiovascular (CV) mortality and adverse CV outcomes than SBP, DBP, or mean arterial pressure (MAP). Multivariate modeling identified both PP and SBP associated with adverse CV outcomes, but only PP was significantly associated with higher CV mortality. When both PP and SBP were included in the model, only PP remained an independent predictor of adverse outcomes for CV events. CONCLUSIONS In women with suspected CAD and myocardial ischemia, PP is a stronger predictor of adverse outcomes than SBP, DBP, or MAP with an 18% excess mortality risk for every 10 mm Hg increase in PP. Further investigations into pathophysiologic mechanisms and specific pharmacologic approaches to modifying this novel target are warranted. Am J Hypertens 2008; 21:1224-1230 (C) 2008 American Journal of Hypertension, Ltd. C1 [Anderson, R. David; Sizemore, B. Clay; von Mering, Gregory O.; Handberg, Eileen M.; Nichols, Wilmeer W.; Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA. [Barrow, Genevieve M.; Johnson, B. Delia] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med & Clin Psychol, Pittsburgh, PA USA. [Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Prevent & Rehabil Cardiac Ctr, Los Angeles, CA 90048 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. RP Pepine, CJ (reprint author), Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA. EM pepincj@medicine.ufl.edu FU NHLBI NIH HHS [N01 HV068163] NR 46 TC 5 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 2008 VL 21 IS 11 BP 1224 EP 1230 DI 10.1038/ajh.2008.268 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 364BV UT WOS:000260312100012 PM 18802432 ER PT J AU Foster, MC Keyes, MJ Larson, MG Vita, JA Mitchell, GF Meigs, JB Vasan, RS Benjamin, EJ Fox, CS AF Foster, Meredith C. Keyes, Michelle J. Larson, Martin G. Vita, Joseph A. Mitchell, Gary F. Meigs, James B. Vasan, Ramachandran S. Benjamin, Emelia J. Fox, Caroline S. TI Relations of Measures of Endothelial Function and Kidney Disease: The Framingham Heart Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; brachial reactivity; cystatin C; Framingham Heart Study ID FLOW-MEDIATED DILATION; CHRONIC-RENAL-FAILURE; CARDIOVASCULAR RISK-FACTORS; GLOMERULAR-FILTRATION-RATE; HEMODIALYSIS-PATIENTS; SERUM CREATININE; DEPENDENT DILATION; REACTIVE HYPEREMIA; BRACHIAL-ARTERY; FAMILY-HISTORY AB Background: Endothelial dysfunction is prevalent in individuals with end-stage renal disease. Whether endothelial dysfunction is present in patients with moderate chronic kidney disease (CKD) is uncertain. Study Design: Cross-sectional study. Settings & Participants: Brachial reactivity measurements were obtained during the seventh examination cycle in 2,818 (diameter measurements) and 2,256 (flow measurements) Framingham Heart Study Offspring cohort participants (53% women; mean age, 61 +/- 9 years). Predictor: Estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) derived from creatinine-and cystatin C-based estimating equations; microalbuminuria status. Outcome: Brachial reactivity measurements (baseline brachial diameter, flow-mediated dilation, baseline and hyperemic mean flow). Measurements: Linear regression models were used to model brachial measures as a function of CKD and microalbuminuria status. Results: Overall, 7.3% (n = 206) of participants had CKD, and of 2,301 with urinary measurements, 10.0% (n = 230) had microalbuminuria. Brachial reactivity measures did not differ significantly by CKD status in either creatinine- or cystatin C-based equations in either age- and sex- or multivariable-adjusted models. In age- and sex-adjusted models, microalbuminuria was associated with decreased hyperemic mean flow (47.2 +/- 1.4 versus 51.4 +/- 0.5 mg/g; P = 0.005), but the association was not significant after multivariable adjustment (P = 0.09). Limitations: Predominantly white ambulatory cohort; results may not be generalizable to other ethnic groups or individuals with severe CKD. Conclusions: Endothelial dysfunction was not a major correlate of CKD in our sample. Am J Kidney Dis 52:859-867. (C) 2008 by the National Kidney Foundation, Inc. C1 [Foster, Meredith C.; Keyes, Michelle J.; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Foster, Meredith C.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Cardiol Sect, Boston, MA 02215 USA. [Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Vasan, Ramachandran S.] Boston Univ, Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, RO1s HL70100, HL60040, HL076784, AG028321]; National Heart, Lung and Blood Institute, National Institutes of Health [2K24HL04334]; American Diabetes Association Career Development Award; National Center for Research Resources (NCRR) General Clinical Research Centers (GCRC) [M01-RR-01066] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195) and RO1s HL70100, HL60040, HL076784, AG028321 (E.J.B.). Dr Vasan is supported in part by grant 2K24HL04334 from the National Heart, Lung and Blood Institute, National Institutes of Health; American Diabetes Association Career Development Award; and the National Center for Research Resources (NCRR) General Clinical Research Centers (GCRC) grant M01-RR-01066 (J.B.M.). NR 52 TC 13 Z9 13 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2008 VL 52 IS 5 BP 859 EP 867 DI 10.1053/j.ajkd.2008.04.027 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 367ML UT WOS:000260556000008 PM 18617305 ER PT J AU Kottgen, A Hsu, CC Coresh, J Shuldiner, AR Berthier-Schaad, Y Gambhir, TR Smith, MW Boerwinkle, E Kao, WHL AF Koettgen, Anna Hsu, Charles C. Coresh, Josef Shuldiner, Alan R. Berthier-Schaad, Yvette Gambhir, Tejal Rami Smith, Michael W. Boerwinkle, Eric Kao, W. H. Linda TI The Association of Podocin R229Q Polymorphism With Increased Albuminuria or Reduced Estimated GFR in a Large Population-Based Sample of US Adults SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 47th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY FEB 28-MAR 03, 2007 CL Orlando, FL SP Amer Heart Assoc, Council Epidemiol & Prevent, Council Nutr, Phys Activ & Metab, Natl Heart, Lung & Blood Inst DE NPHS2; podocin; albuminuria; association study; functional variant; population-based sample ID FOCAL-SEGMENTAL GLOMERULOSCLEROSIS; RESISTANT NEPHROTIC SYNDROME; GLOMERULAR-FILTRATION-RATE; GENOME-WIDE ASSOCIATION; SERUM CREATININE; NPHS2 MUTATION; DISEASE; RISK; SPECTRUM; KIDNEY AB Background: Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis. The objective of this study is to assess the contribution of the commonly reported functional podocin polymorphism R229Q to kidney disease in the population at large and replicate a prior study of an association of R229Q and albuminuria in the general population. Study Design: Large sample of the Atherosclerosis Risk in Communities (ARIC) Study, a population-ased prospective study. Setting & Participants: 4,424 white and 3,746 black middle-aged adults. Predictor: Genotype at the R229Q polymorphism in podocin. Outcomes: Urinary albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) as measures of kidney damage/dysfunction. Measurements: Crude and multivariable adjusted linear and logistic regression models. Results: R229Q allele frequencies were 3.7% in 4,424 white and 0.6% in 3,746 black individuals. No significant association of R229Q with increased ACR or decreased eGFR was observed (adjusted odds ratio of ACR >= 3 mg/g in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.84; adjusted odds ratio of eGFR < 60 mL/min/1.73 m(2) in RQ/QQ versus RR carriers, 1.18; 95% confidence interval, 0.76 to 1.83). As expected, the established kidney disease risk factors hypertension and diabetes mellitus were associated strongly with measures of kidney damage/dysfunction, but the R229Q polymorphism was not associated with an additional increase in kidney disease measures. Limitations: Single measurement of ACR, subsample of all ARIC participants. Conclusion: No significant association of the relatively rare R229Q variant and ACR or eGFR was found in either white or black individuals. The phenotypic effect of a variant as R229Q would have to be of great magnitude to meaningfully contribute to the risk of kidney disease on a population level. The importance of such variants in the general population, as well as replication studies, can be evaluated best in large community-based studies that allow for accounting of established disease risk factors. Am J Kidney Dis 52:868-875. (C) 2008 by the National Kidney Foundation, Inc. C1 [Koettgen, Anna; Hsu, Charles C.; Coresh, Josef; Berthier-Schaad, Yvette; Gambhir, Tejal Rami; Kao, W. H. Linda] Johns Hopkins Univ, Baltimore, MD USA. [Shuldiner, Alan R.] Univ Maryland, Baltimore, MD 21201 USA. [Berthier-Schaad, Yvette; Smith, Michael W.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Smith, Michael W.] NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA. RP Kao, WHL (reprint author), 615 N Wolfe St,Rm W6513, Baltimore, MD 21205 USA. EM wkao@jhsph.edu RI Smith, Michael/B-5341-2012; Kottgen, Anna/D-2920-2012 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NHLBI NIH HHS [N01HC55019, N01 HC055016, N01 HC055018, N01 HC055019, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC55015, N01HC55016, N01HC55018, N01HC55020, N01HC55021, N01HC55022]; NIDDK NIH HHS [K01 DK067207, K01-DK-067207, R21 DK073482, R21 DK073482-02] NR 29 TC 15 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2008 VL 52 IS 5 BP 868 EP 875 DI 10.1053/j.ajkd.2008.02.306 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 367ML UT WOS:000260556000009 PM 18499321 ER PT J AU Denny, CC Wilfond, BS Peters, JA Giri, N Alter, BP AF Denny, Colleen C. Wilfond, Benjamin S. Peters, June A. Giri, Neelam Alter, Blanche P. TI All in the Family: Disclosure of "Unwanted" Information to an Adolescent to Benefit a Relative SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE ethics; genetic disclosure; minor children; dyskeratosis congenita; research results ID DYSKERATOSIS-CONGENITA; CHILDREN; MEDICINE; CANCER; ANEMIA; DONORS; HEALTH AB Ethical assessments of clinical decisions are typically based on the preferences and interests of the individual patient. However, some clinical interventions, Such as genetic testing or organ donation, may involve multiple family members. in these cases, one family member may have the potential to benefit, while another family member is exposed to potential physical or psychological risk. in the research setting, the balancing of benefits and risks between family members may be further complicated by uncertainty about their magnitude and likelihood. in addition, when the individual facing these apparently uncompensated risks is a child, the situation becomes particularly ethically complicated, as we appreciated in a recent case. Investigators at the National Cancer Institute were faced with a decision about whether it would be appropriate to disclose apparently "unwanted" research test results (length of telomeres in leukocyte subsets) to an adolescent about risk Of future disease (dyskeratosis congenita), possibly causing psychological harm and an ethical wrong. These issues were not expected at the outset of the fan-lily'S Study participation but rather emerged with new data about the research tests. Disclosure of the research finding was an important consideration in order to avoid using the adolescent as a stem-cell donor for his sister. Disclosure to the adolescent Could not be justified by merely considering the immediate interests and preferences of the adolescent. However, an expanded ethical analysis that considers the adolescent's familial context offers a more complete picture of the adolescent's interests and preferences which provides justification for disclosure. Published 2008 Wiley-Liss, Inc. C1 [Denny, Colleen C.; Wilfond, Benjamin S.] Natl Inst Hlth Clin Ctr, Dept Bioeth, Bethesda, MD USA. [Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Hosp, Treuman Katz Ctr Bioeth, Seattle, WA 98195 USA. [Wilfond, Benjamin S.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Peters, June A.; Giri, Neelam; Alter, Blanche P.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Bethesda, MD USA. RP Wilfond, BS (reprint author), Metropolitan Pk W,M-S,MPW 8-2,1100 Olive Way,Room, Seattle, WA 98101 USA. EM benjamin.wilfond@seattlechildrens.org FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX Grant sponsor: Intramural Research Program of the National Institutes of Health; Grant sponsor: National Cancer Institute. NR 18 TC 5 Z9 5 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 1 PY 2008 VL 146A IS 21 BP 2719 EP 2724 DI 10.1002/ajmg.a.32362 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 373PW UT WOS:000260985400002 PM 18831063 ER PT J AU Obafemi, AA Bulas, DI Troendle, J Marini, JC AF Obafemi, Abimbola A. Bulas, Dorothy I. Troendle, James Marini, Joan C. TI Popcorn Calcification in Osteogenesis Imperfecta: Incidence, Progression, and Molecular Correlation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE autosomal dominant osteogenesis imperfect; osteogenesis imperfect; popcorn calcification; calcification; collagen mutations ID PROLYL 3-HYDROXYLATION; GENETIC-HETEROGENEITY; DEFICIENCY; MUTATIONS; COLLAGEN; CHILDREN AB Osteogenesis imperfecta (OI) is a heritable disorder characterized by osteoporosis and increased susceptibility to fracture. All children with severe 01 have extreme short statute and some have "popcorn" calcifications, areas of disorganized hyperdense lines in the metaphysis and epiphysis around the growth plate on lower limb radiographs. Popcorn calcifications were noted on radiographs of two children with non-lethal type VIII 01, a recessive form caused by P3H1 deficiency. To determine the incidence, progression, and molecular correlations of popcorn calcifications, we retrospectively examined serial lower limb radiographs of 45 children with type III or IV OI and known dominant mutations in type I collagen. Popcorn calcifications were present in 13 of 25 type III (52%), but only 2 of 20 type IV (10%), OI children. The mean age of onset was 7.0 years, with a range of 4-14 years. All children with popcorn calcifications had this finding in their distal femora, and most also had calcifications in proximal tibiae. While unilateral popcorn calcification contributes to femoral growth deficiency and leg length discrepancy, severe linear growth deficiency, and metaphyseal flare do not differ significantly between type III OI patients with and without popcorn calcifications. The type I collagen Mutations associated with popcorn calcifications Occur equally in both COL1A1 and COL1A2, and have no preferential location along the chains. These data demonstrate that popcorn calcifications are a frequent feature of severe OI, but do not distinguish cases with defects in collagen structure (primarily dominant type III OI) or modification (recessive type VIII OI). Published 2008 Wiley-Liss, Inc. C1 [Obafemi, Abimbola A.; Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bone & Extracellular Mat Branch, Bethesda, MD 20892 USA. [Obafemi, Abimbola A.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Bulas, Dorothy I.] Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. [Troendle, James] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Biometry & Math Stat Branch DESPR, Bethesda, MD USA. RP Marini, JC (reprint author), NICHHD, NIH, Bone & Extracellular Mat Branch, Bldg 10,Rm 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov FU NICHD Intramural Funds; NIH; Pfizer, Inc FX Grant sponsor: NICHD Intramural Funds; Grant sponsor: NIH; Grant sponsor: Pfizer, Inc. NR 19 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 1 PY 2008 VL 146A IS 21 BP 2725 EP 2732 DI 10.1002/ajmg.a.32508 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 373PW UT WOS:000260985400003 PM 18798308 ER PT J AU Kazi, S Boroumand, S AF Kazi, Shazia Boroumand, Shahdokht TI Assessing Quality of Primary Care Provided to the HIV-Infected Ryan White Population in the Baltimore Eligible Metropolitan Area SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE Ryan White; HIV/AIDS; quality; primary care ID ANCILLARY SERVICES; ACT AB The Baltimore Eligible Metropolitan Area (EAU) receives Ryan White (RW) funds each year because of its high AIDS case rate. This study assessed the quality of primary care services provided to HIV-infected clients in the Baltimore EMA. Medical charts of 384 randomly selected clients served in 2004 were reviewed. A survey instrument was designed to assess the minimum requirements satisfied for CD4 and viral load count, highly active antiretroviral treatment, pneumocystitis carinii pneumonia and mycobacterium avium complex prophylaxis, tuberculosis, syphilis, hepatitis B and C screening and safe sex education. A numeric index of quality was developed for each client in the form of a total score. The clients were categorized into high, medium and low quality groups depending on their total scores. Only 32% of clients were in the high-quality category. Number of primary care visits per year (P <= .0001) was found to be significantly associated with quality of care. Proactive efforts are needed at the provider level to keep or reengage HIV clients in care. (Am J Med Qual 2008;23:484-491) C1 [Kazi, Shazia] City Baltimore Hlth Dept, Baltimore, MD USA. [Boroumand, Shahdokht] NIH, Bethesda, MD 20892 USA. RP Kazi, S (reprint author), 1001 E Fayette St, Baltimore, MD 21202 USA. EM shazia.kazi@baltimorecity.gov FU Baltimore City Health Department FX The authors are grateful to Baltimore City Health Department for supporting this study. NR 20 TC 4 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD NOV-DEC PY 2008 VL 23 IS 6 BP 484 EP 491 DI 10.1177/1062860608324174 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 374JB UT WOS:000261038500009 PM 19001104 ER PT J AU Alleyne, M Horne, MK Miller, JL AF Alleyne, Michael Horne, McDonald K. Miller, Jeffery L. TI Individualized Treatment for Iron-deficiency Anemia in Adults SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Anemia; Dosing cycles; Hepcidin; Iron ID DIFFERENTIAL-DIAGNOSIS; MANAGEMENT AB Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia. Published by Elsevier Inc. C1 [Miller, Jeffery L.] NIDDK, Sect Mol Genom & Therapeut, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Alleyne, Michael] NCI, Bethesda, MD 20892 USA. [Horne, McDonald K.] WG Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA. [Horne, McDonald K.] WG Magnuson Clin Ctr, Hematol Serv, Bethesda, MD USA. RP Miller, JL (reprint author), NIDDK, Sect Mol Genom & Therapeut, Mol Med Branch, NIH, Bldg 10,Room 9N311,10 Ctr Dr, Bethesda, MD 20892 USA. EM jm7f@nih.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX Funding: This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 23 TC 50 Z9 58 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2008 VL 121 IS 11 BP 943 EP 948 DI 10.1016/j.amjmed.2008.07.012 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 364XV UT WOS:000260369900004 PM 18954837 ER PT J AU Klebanoff, MA Meis, PJ Dombrowski, MP Zhao, Y Moawad, AH Northen, A Sibai, BM Iams, JD Varner, MW Caritis, SN O'Sullivan, MJ Leveno, KJ Miodovnik, M Conway, D Wapner, RJ Carpenter, M Mercer, BM Ramin, SM Thorp, JM Peaceman, AM AF Klebanoff, Mark A. Meis, Paul J. Dombrowski, Mitchell P. Zhao, Yuan Moawad, Atef H. Northen, Allison Sibai, Baha M. Iams, Jay D. Varner, Michael W. Caritis, Steve N. O'Sullivan, Mary J. Leveno, Kenneth J. Miodovnik, Menachem Conway, Deborah Wapner, Ronald J. Carpenter, Marshall Mercer, Brian M. Ramin, Susan M. Thorp, John M. Peaceman, Alan M. CA Natl Inst Child Hlth Human Dev TI Salivary progesterone and estriol among pregnant women treated with 17-alpha-hydroxyprogesterone caproate or placebo SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologic-Research CY JUN 18-19, 2007 CL Boston, MA SP Soc Pediat & Perinatal Epidemiol Res DE 17-alpha-hydroxyprogesterone caproate; longitudinal studies; preterm birth; salivary estriol; salivary progesterone ID RECURRENT PRETERM DELIVERY; FETAL MEMBRANES; INCREASED RISK; LABOR; TERM; ESTRADIOL; BIRTH; RATIO; PREMATURITY; PARTURITION AB OBJECTIVE: The objectives of the study was to determine whether salivary progesterone (P) or estriol (E3) concentration at 16-20 weeks' gestation predicts preterm birth or the response to 17 alpha-hydroxyprogesterone caproate (17OHPC) and whether 17OHPC treatment affected the trajectory of salivary P and E3 as pregnancy progressed. STUDY DESIGN: This was a secondary analysis of a clinical trial of 17OHPC to prevent preterm birth. Baseline saliva was assayed for P and E3. Weekly salivary samples were obtained from 40 women who received 17OHPC and 40 who received placebo in a multicenter randomized trial of 17OHPC to prevent recurrent preterm delivery. RESULTS: Both low and high baseline saliva P and E3 were associated with a slightly increased risk of preterm birth. However, 17OHPC prevented preterm birth comparably, regardless of baseline salivary hormone concentrations. 17OHPC did not alter the trajectory of salivary P over pregnancy, but it significantly blunted the rise in salivary E3 as well as the rise in the E3/P ratio. CONCLUSION: 17OHPC flattened the trajectory of E3 in the second half of pregnancy, suggesting that the drug influences the fetoplacental unit. C1 [Klebanoff, Mark A.] NICHHD, Bethesda, MD 20892 USA. [Zhao, Yuan] George Washington Univ, Ctr Biostat, Washington, DC USA. [Meis, Paul J.] Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. [Dombrowski, Mitchell P.] Wayne State Univ, Detroit, MI USA. [Moawad, Atef H.] Univ Chicago, Chicago, IL 60637 USA. [Northen, Allison] Univ Alabama, Birmingham, AL USA. [Sibai, Baha M.] Univ Cincinnati, Cincinnati, OH USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Miodovnik, Menachem; Wapner, Ronald J.] Columbia Univ, New York, NY USA. [Miodovnik, Menachem] Washington Hosp Ctr, Washington, DC 20010 USA. [Conway, Deborah] Univ Texas San Antonio, San Antonio, TX USA. [Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA. [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ramin, Susan M.] Univ Texas Houston, Houston, TX USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. RP Klebanoff, MA (reprint author), NICHHD, Bethesda, MD 20892 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Intramural NIH HHS [NIH0010045861]; NICHD NIH HHS [HD21410, HD21414, HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512, HD40544, HD40560, U01 HD036801, U10 HD021410, U10 HD027860, U10 HD027860-09, U10 HD027869, U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10 HD040500, U10 HD040512, U10 HD040544, U10 HD040560, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040560]; PHS HHS [NIH0010045861] NR 28 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 NOV PY 2008 VL 199 IS 5 AR 506.e1 DI 10.1016/j.ajog.2008.03.003 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367XL UT WOS:000260585800023 PM 18456237 ER PT J AU Lynch, CD Klebanoff, MA Louis, GMB AF Lynch, Courtney D. Klebanoff, Mark A. Louis, Germaine M. B. TI Is caffeine use during pregnancy really unsafe? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Lynch, Courtney D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Klebanoff, Mark A.; Louis, Germaine M. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD USA. RP Lynch, CD (reprint author), Ohio State Univ, Coll Publ Hlth, Div Epidemiol, B218 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM clynch@cph.osu.edu OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural NIH HHS [Z01 HD008770-04] NR 4 TC 2 Z9 2 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 NOV PY 2008 VL 199 IS 5 AR e16 DI 10.1016/j.ajog.2008.05.035 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367XL UT WOS:000260585800060 PM 18691688 ER PT J AU Christodoulou, MI Kapsogeorgou, EK Moutsopoulos, NM Moutsopoulos, HM AF Christodoulou, Maria I. Kapsogeorgou, Efstathia K. Moutsopoulos, Niki M. Moutsopoulos, Haralampos M. TI Foxp3(+) T-Regulatory Cells in Sjogren's Syndrome Correlation with the Grade of the Autoimmune Lesion and Certain Adverse Prognostic Factors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; GLAND EPITHELIAL-CELLS; RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; DENDRITIC CELLS; SYNOVIAL-FLUID; EXPRESSION; DISEASE; LYMPHOMA; CLASSIFICATION AB Sjogren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations, including lymphoma development. To investigate the potential implication of Foxp3(+) T-regulatory cells in the regulation of SS inflammatory responses, we studied their incidence in the minor salivary glands (MSGs) and their relationship with histopathological and clinical disease parameters. Similar percentages of infiltrating Foxp3(+) cells were observed in the MSG lesions of all SS patients (n = 30) and non-SS sialadenitis controls (n = 7). Foxp3(+) cells were not detected in sicca-complaining controls with negative biopsy (n = 6). In SS patients, Foxp3+ cell frequency varied according to lesion severity, with the highest and lowest frequencies obtained in intermediate and mild MSG lesions, respectively. In the peripheral blood of these patients, reverse distribution of Foxp3+ cells was observed. Furthermore, the frequency of Foxp3+ cells in the MSG lesions and peripheral blood was negatively associated (r = -0.6679, P = 0.0065). MSG-infiltrating Foxp3(+) cells were found to positively correlate with biopsy focus score (P = 0.05), infiltrating mononuclear cells, dendritic cells, and macrophages; (P <= 0.024 each), and serum C4 levels (P = 0.0328), whereas lower Foxp3(+) cell incidence correlated with adverse predictors for lymphoma development, such as the presence of C4 hypocomplementemia (P = 0.012) and SG enlargement (tendency, P = 0.067). our findings; suggest that the Foxp3(+) T-regulatory cell frequency in the MSG lesions of SS patients correlates with inflammation grade and certain risk factors for lymphoma development. (Am J Pathol 2008, 173:1389-1396; DOI: 10.2353/ajpath.2008.080246) C1 [Christodoulou, Maria I.; Kapsogeorgou, Efstathia K.; Moutsopoulos, Haralampos M.] Natl Univ Athens, Sch Med, Dept Pathophysiol, Immunol Lab, Athens 11527, Greece. [Moutsopoulos, Niki M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Moutsopoulos, HM (reprint author), Natl Univ Athens, Sch Med, Dept Pathophysiol, Immunol Lab, 75 Mikras Asias St, Athens 11527, Greece. EM hmoutsop@med.uoa.gr FU Hellenic Secretariat for Research and Technology; Lilian Voudouri Foundation FX Supported by the Hellenic Secretariat for Research and Technology and the Lilian Voudouri Foundation. NR 41 TC 60 Z9 62 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2008 VL 173 IS 5 BP 1389 EP 1396 DI 10.2353/ajpath.2008.080246 PG 8 WC Pathology SC Pathology GA 369XE UT WOS:000260726400014 PM 18818377 ER PT J AU Deshpande, N Ferrucci, L Metter, J Faulkner, KA Strotmeyer, E Satterfield, S Schwartz, A Simonsick, E AF Deshpande, Nandini Ferrucci, Luigi Metter, Jeffrey Faulkner, Kimberly A. Strotmeyer, Elsa Satterfield, Suzanne Schwartz, Ann Simonsick, Eleanor TI Association of Lower Limb Cutaneous Sensitivity with Gait Speed in the Elderly The Health ABC Study SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Gerontological-Society-of-America CY NOV, 2007 CL San Francisco, CA SP Gerontol Soc Amer DE Aging; Gait Speed; Cutaneous Vibration Sensitivity; Monofilament Sensitivity ID PERIPHERAL NEUROPATHY; OLDER-ADULTS; WALKING; FOOT; WOMEN; MUSCLES; PEOPLE; RISK; AGE; STIMULATION AB Objective: To examine the association of fast-adapting receptor-mediated vibrotactile sensitivity and slow-adapting receptor-mediated pressure sensitivity with self-selected usual gait speed and gait speed over a challenging narrow (20 cm wide) course. Design: Participants from the population-based older cohort of the Health ABC study were included (n = 1721; age: 76.4 +/- 2.8 yrs). Usual gait speed over 6 m and, gait speed over a 6-m narrow course were measured. Vibration perception threshold (100 Hz) was measured on the plantar surface, and monofilament testing (1.4 and 10 g) was performed on the dorsum of the great toe. Covariates including knee extensor torque, standing balance, visual acuity and contrast sensitivity, knee pain, depressive symptoms, high fasting glucose levels, and peripheral arterial disease were evaluated. Results: Vibrotactile and monofilament sensitivity were significantly worse in slower gait speed groups in both walking conditions (P < 0.001 to P = 0.015). Adjusting for covariates, vibrotactile (P < 0.001) but not monofilament sensitivity (P = 0.655) was independently associated with self-selected normal gait speed. Neither sensory function was associated with narrow-base gait speed. Conclusions: In the elderly, poor lower limb vibrotactile sensitivity measured on the plantar surface of the great toe, but not the pressure sensitivity as measured by monofilament testing on the dorsum of the great toe, is independently associated with slower self-selected normal gait speed. Narrow-based walking seems to depend on other neuromuscular mechanisms. C1 [Deshpande, Nandini] Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, Kansas City, KS 66160 USA. [Deshpande, Nandini; Ferrucci, Luigi; Metter, Jeffrey; Strotmeyer, Elsa] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. [Faulkner, Kimberly A.; Strotmeyer, Elsa] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Schwartz, Ann] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Deshpande, N (reprint author), Univ Kansas, Med Ctr, Dept Phys Therapy & Rehabil Sci, MS 2002,3901 Rainbow Blvd, Kansas City, KS 66160 USA. RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036 FU NIA NIH HHS [N01 AG062101, N01 AG062103, N01 AG062106, N01-AG-2103, N01-AG-2106, N01-AG-6-2101, R01 AG028050] NR 30 TC 14 Z9 15 U1 0 U2 1 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 NOV PY 2008 VL 87 IS 11 BP 921 EP 928 DI 10.1097/PHM.0b013e31818a5556 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 364MX UT WOS:000260340900007 PM 18936557 ER PT J AU Eisenhofer, G Huynh, TT Elkahloun, A Morris, JC Bratslavsky, G Linehan, WM Zhuang, Z Balgley, BM Lee, CS Mannelli, M Lenders, JWM Bornstein, SR Pacak, K AF Eisenhofer, Graeme Huynh, Thanh-Truc Elkahloun, Abdel Morris, John C. Bratslavsky, Gennady Linehan, W. Marston Zhuang, Zhengping Balgley, Brian M. Lee, Cheng S. Mannelli, Massimo Lenders, Jacques W. M. Bornstein, Stefan R. Pacak, Karel TI Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE secretion; exocytosis; von Hippel-Lindau; multiple endocrine neoplasia type 2 ID HIPPEL-LINDAU-SYNDROME; ENDOCRINE NEOPLASIA TYPE-2; TRANSCRIPTIONAL REPRESSOR REST; PC12 CELLS; CHROMAFFIN CELLS; ADRENAL-MEDULLA; GENE; NOREPINEPHRINE; EPINEPHRINE; EXOCYTOSIS AB Eisenhofer G, Huynh TT, Elkahloun A, Morris JC, Bratslavsky G, Linehan WM, Zhuang Z, Balgley BM, Lee CS, Mannelli M, Lenders JW, Bornstein SR, Pacak K. Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma. Am J Physiol Endocrinol Metab 295: E1223-E1233, 2008; doi:10.1152/ajpendo.90591.2008. - Pheochromocytomas in patients with von Hippel-Lindau (VHL) syndrome and multiple endocrine neoplasia type 2 (MEN 2) differ in the types and amounts of catecholamines produced and the resulting signs and symptoms. We hypothesized the presence of different processes of catecholamine release reflecting differential expression of components of the regulated secretory pathway among the two types of hereditary tumors. Differences in catecholamine secretion from tumors in patients with VHL syndrome (n = 47) and MEN 2 (n = 32) were examined using measurements of catecholamines in tumor tissue, urine, and plasma, the last of which was under baseline conditions in all subjects and in a subgroup of patients who received intravenous glucagon to provoke catecholamine release. Microarray and proteomics analyses, quantitative PCR, and Western blotting were used to assess expression of tumor tissue secretory pathway components. The rate constant for baseline catecholamine secretion was 20-fold higher in VHL than in MEN 2 tumors (0.359 +/- 0.094 vs. 0.018 +/- 0.009 day(-1)), but catecholamine release was responsive only to glucagon in MEN 2 tumors. Compared with tumors from MEN 2 patients, those from VHL patients were characterized by reduced expression of numerous components of the regulated secretory pathway (e. g., SNAP25, syntaxin, rabphilin 3A, annexin A7, calcium-dependent secretion activator). The mutation-dependent differences in expression of secretory pathway components indicate a more mature regulated secretory pathway in MEN 2 than VHL tumors. These data provide a unique mechanistic link to explain how variations in the molecular machinery governing exocytosis may contribute to clinical differences in the secretion of neurotransmitters or hormones and the subsequent presentation of a disease. C1 [Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Eisenhofer, Graeme; Bornstein, Stefan R.] Univ Dresden, Dept Med, D-01307 Dresden, Germany. [Huynh, Thanh-Truc; Pacak, Karel] NICHHD, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Bratslavsky, Gennady; Linehan, W. Marston] NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Balgley, Brian M.; Lee, Cheng S.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, Florence, Italy. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands. RP Eisenhofer, G (reprint author), Univ Dresden, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Graeme.Eisenhofer@uniklinikum-dresden.de RI Lenders, J.W.M./L-4487-2015; OI Balgley, Brian/0000-0002-3509-4567; Mannelli, Massimo/0000-0002-8001-9857 FU National Institute of Child Health and Human Development; Center for Cancer Research; National Cancer Institute; National Human Genome Research Institute; National Institute of Neurological Disorders and Stroke; National Institutes of Health, Bethesda, Maryland FX This work was supported by the intramural programs of the National Institute of Child Health and Human Development, the Center for Cancer Research, the National Cancer Institute, the National Human Genome Research Institute, and the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, Bethesda, Maryland. NR 41 TC 25 Z9 25 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2008 VL 295 IS 5 BP E1223 EP E1233 DI 10.1152/ajpendo.90591.2008 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 370OA UT WOS:000260770300027 PM 18854424 ER PT J AU Csiszar, A Labinskyy, N Perez, V Recchia, FA Podlutsky, A Mukhopadhyay, P Losonczy, G Pacher, P Austad, SN Bartke, A Ungvari, Z AF Csiszar, Anna Labinskyy, Nazar Perez, Viviana Recchia, Fabio A. Podlutsky, Andrej Mukhopadhyay, Partha Losonczy, Gyorgy Pacher, Pal Austad, Steven N. Bartke, Andrzej Ungvari, Zoltan TI Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE senescence; vascular disease; atherosclerosis; Prop1(df/df) mice ID GROWTH-FACTOR-I; MITOCHONDRIAL SUPEROXIDE-PRODUCTION; CARDIAC-SPECIFIC OVEREXPRESSION; HORMONE RECEPTOR KNOCKOUT; NAKED MOLE-RAT; CONTRACTILE DYSFUNCTION; NITRIC-OXIDE; LIFE-SPAN; VENTRICULAR MYOCYTES; CALORIC RESTRICTION AB Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol 295: H1882-H1894, 2008. First published August 29, 2008; doi:10.1152/ajpheart.412.2008. - Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O-2(center dot-) and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O-2(center dot-) and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu, Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O-2(center dot-) and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu, Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress. C1 [Csiszar, Anna; Labinskyy, Nazar; Recchia, Fabio A.; Ungvari, Zoltan] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. [Perez, Viviana; Podlutsky, Andrej; Austad, Steven N.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Recchia, Fabio A.] Scuola Super Sant Anna, Sector Med, Pisa, Italy. [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [Losonczy, Gyorgy; Ungvari, Zoltan] Semmelweis Univ, Dept Pulmonol, H-1085 Budapest, Hungary. [Bartke, Andrzej] So Illinois Univ, Sch Med, Dept Internal Med, Springfield, IL USA. [Bartke, Andrzej] So Illinois Univ, Sch Med, Dept Physiol, Springfield, IL USA. RP Ungvari, Z (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM zoltan_ungvari@nymc.edu RI Recchia, Fabio/F-2315-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Podlutsky, Andrej/F-5421-2015; Bartke, Andzej/D-6640-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Bartke, Andzej/0000-0002-2569-557X FU American Heart Association [0430108N, 0435140N]; American Diabetes Association; Philip Morris USA Inc; Philip Morris International; American Federation for Aging Research; Hungarian Scientific Research Fund [OTKA-K68758]; San Antonio Area Foundation; National Institutes of Health [HL-077256, HL-43023, AG-019899, U-19-AG-023122, PO1-HL-74237, AG-022873, K07-AG-025063]; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by grants from the American Heart Association (0430108N and 0435140N), the American Diabetes Association (to Z. Ungvari), Philip Morris USA Inc. and Philip Morris International (to Z. Ungvari), the American Federation for Aging Research (to A. Csiszar), the Hungarian Scientific Research Fund (OTKA-K68758), the San Antonio Area Foundation (to A. Podlutsky), and the National Institutes of Health (HL-077256 and HL-43023 to Z. Ungvari; AG-019899 and U-19-AG-023122 to A. Bartke; PO1-HL-74237 to F. A. Recchia; AG-022873 and K07-AG-025063 to S. Austad) and funded by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism (to P. Pacher). F. A. Recchia is an established investigator of the American Heart Association. NR 56 TC 78 Z9 78 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2008 VL 295 IS 5 BP H1882 EP H1894 DI 10.1152/ajpheart.412.2008 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 369VS UT WOS:000260722600007 PM 18757483 ER PT J AU Nayeem, MA Poloyac, SM Falck, JR Zeldin, DC Ledent, C Ponnoth, DS Ansari, HR Mustafa, SJ AF Nayeem, Mohammed A. Poloyac, Samuel M. Falck, John R. Zeldin, Darryl C. Ledent, Catherine Ponnoth, Dovenia S. Ansari, Habib R. Mustafa, S. Jamal TI Role of CYP epoxygenases in A(2A)AR-mediated relaxation using A(2A)AR-null and wild-type mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE epoxyeicosatrienoic acids; dihydroxyeicosatrienoic acids; vasodilation; vasoconstriction; adenosine; cytochrome P-450s ID SMOOTH-MUSCLE-CELLS; BOVINE CORONARY-ARTERIES; P450-DERIVED ARACHIDONATE METABOLITES; RAT PREGLOMERULAR MICROVESSELS; RECEPTOR-MEDIATED RELAXATION; PROTEIN-KINASE-C; K-ATP CHANNELS; EPOXYEICOSATRIENOIC ACIDS; ADENOSINE RECEPTOR; HYPERPOLARIZING FACTOR AB Nayeem MA, Poloyac SM, Falck JR, Zeldin DC, Ledent C, Ponnoth DS, Ansari HR, Mustafa SJ. Role of CYP epoxygenases in A(2A)AR-mediated relaxation using A(2A)AR-null and wild-type mice. Am J Physiol Heart Circ Physiol 295: H2068-H2078, 2008. First published September 19, 2008; doi: 10.1152/ajpheart.01333.2007.-We hypothesized that A(2A) adenosine receptor (A(2A)AR) activation causes vasorelaxation through cytochrome P-450 (CYP) epoxygenases and endothelium-derived hyperpolarizing factors, whereas lack of A(2A)AR activation promotes vasoconstriction through Cyp4a in the mouse aorta. Adenosine 5'-N-ethylcarboxamide (NECA; 10(-6) M), an adenosine analog, caused relaxation in wild-type A(2A)AR (A(2A)AR(+/+); + 33.99 +/- 4.70%, P < 0.05) versus contraction in A(2A)AR knockout (A(2A)AR(+/+); + 27.52 +/- 4.11%) mouse aortae. An A(2A)AR-specific antagonist (SCH-58261; 1 mu M) changed the NECA (10(-6) M) relaxation response to contraction (-35.82 +/- 4.69%, P < 0.05) in A(2A)AR(+/+) aortae, whereas no effect was noted in A(2A)AR(-/-) aortae. Significant contraction was seen in the absence of the endothelium in A(2A)AR(+/+) (-2.58 +/- 2.25%) aortae compared with endothelium intact aortae. An endothelial nitric oxide synthase inhibitor (N-nitroL-arginine methyl ester; 100 mu M) and a cyclooxygenase inhibitor (indomethacin; 10 mu M) failed to block NECA-induced relaxation in A(2A)AR(-/-) aortae. A selective inhibitor of CYP epoxygenases (methylsulfonyl-propargyloxyphenylhexanamide; 10(-6) M) changed NECA-mediated relaxation (-22.74 +/- 5.11% at 10(-6) M) and CGS-21680 mediated relaxation (-18.54 +/- 6.06% at 10 - 6 M) to contraction in A(2A)AR(+/+) aortae, whereas no response was noted in A(2A)AR(-/-) aortae. Furthermore, an epoxyeicosatrienoic acid (EET) antagonist [14,15-epoxyeicosa-5(Z)-enoic acid; 10 mu M] was able to block NECAinduced relaxation in A(2A)AR(+/+) aortae, whereas omega-hydroxylase inhibitors (10 mu M dibromo-dodecenyl-methylsulfimide and 10 mu M HET-0016) changed contraction into relaxation in A(2A)AR (-/-) aorta. Cyp2c29 protein was upregulated in A(2A)AR(+/+) aortae, whereas Cyp4a was upregulated in A(2A)AR(-/-) aortae. Higher levels of dihydroxyeicosatrienoic acids (DHETs; 14,15-DHET, 11,12-DHET, and 8,9-DHET, P < 0.05) were found in A(2A)AR(+/+) versus A(2A)AR(-/-) aortae. EET levels were not significantly different between A(2A)AR(+/+) and A(2A)AR(-/-) aortae. It is concluded that CYP epoxygenases play an important role in A(2A)AR-mediated relaxation, and the deletion of the A(2A)AR leads to contraction through Cyp4a. C1 [Mustafa, S. Jamal] W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Ctr Interdisciplinary Res Cardiovasc Sci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Ledent, Catherine] Univ Libre Bruxelles, Brussels, Belgium. [Poloyac, Samuel M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Mustafa, SJ (reprint author), W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Ctr Interdisciplinary Res Cardiovasc Sci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. EM smustafa@hsc.wvu.edu RI Nayeem, Mohammed/A-3949-2017; OI Nayeem, Mohammed/0000-0002-7827-4760; Falck, John/0000-0002-9219-7845 FU National Institutes of Health [HL027339, HL-094447, GM-31278, RO1-NS-052315, S10-RR-023461]; Intramural Research Program of the National Institute of Environmental Health Sciences FX This work was supported by National Institutes of Health Grants HL027339, HL-094447, GM-31278, RO1-NS-052315, S10-RR-023461, and RO1-NS-052315 and by the Intramural Research Program of the National Institute of Environmental Health Sciences. NR 69 TC 23 Z9 24 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2008 VL 295 IS 5 BP H2068 EP H2078 DI 10.1152/ajpheart.01333.2007 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 369VS UT WOS:000260722600028 PM 18805895 ER PT J AU Smirnov, MS Kiyatkin, EA AF Smirnov, Michael S. Kiyatkin, Eugene A. TI Fluctuations in central and peripheral temperatures associated with feeding behavior in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE eating; food seeking; deprivation; motivation; metabolic brain activation; peripheral vasoconstriction ID BRAIN TEMPERATURE; BLOOD-FLOW; SOMATOSENSORY STIMULATION; PATHOLOGICAL CONDITIONS; HYPERTHERMIA; SKIN; COCAINE; MONKEY AB We examined the pattern of temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and skin, along with locomotion in food-deprived and nondeprived rats following the presentation of an open or closed food container and during subsequent eating or food-seeking behavior without eating. Although rats in food-deprived, quiet resting conditions had more than twofold lower spontaneous locomotion and lower temperature values than in nondeprived conditions, after presentation of a container, they consistently displayed food-seeking behavior, showing much larger and longer temperature changes. When the container was open, rats rapidly retrieved food and consumed it. Food consumption was preceded and accompanied by gradual increases in brain and muscle temperatures (similar to 1.5 degrees C) and a weaker, delayed increase in skin temperature (similar to 0.8 degrees C). All temperatures began to rapidly fall immediately after eating was completed, but NAcc and muscle temperatures returned to baseline after similar to 35 min. When the container was closed and rats were unable to obtain food, they continued food-seeking activity during the entire period of presentation. Similar to eating, this activity was preceded and accompanied by gradual temperature increases in the brain and muscle, which were somewhat smaller than those during eating (similar to 1.2 degrees C), with no changes in skin temperature. In contrast to trials with eating, NAcc and muscle temperatures continued to increase for similar to 10 min after the container was removed from the cage and the rat continued food-seeking behavior, with a return to baselines after similar to 50 min. These temperature fluctuations are discussed with respect to alterations in metabolic brain activity associated with feeding behavior, depending upon deprivation state and food availability. C1 [Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov OI Smirnov, Michael/0000-0003-2248-8863 FU National Institutes of Health; National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse. NR 43 TC 6 Z9 7 U1 0 U2 0 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 NOV PY 2008 VL 295 IS 5 BP R1415 EP R1424 DI 10.1152/ajpregu.90636.2008 PG 10 WC Physiology SC Physiology GA 368DB UT WOS:000260600400007 PM 18799633 ER PT J AU Paukner, A Suomi, SJ AF Paukner, Annika Suomi, Stephen J. TI The Effects of Fur Rubbing on the Social Behavior of Tufted Capuchin Monkeys SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE Cebus apella; affiliation; aggression; group cohesion; proximity ID CEBUS-CAPUCINUS; APELLA; PLANTS AB Fur rubbing has often been attributed as a social as well as a medicinal function in capuchin monkeys, yet to date there have been no studies investigating the effects of fur rubbing on subsequent group dynamics. Here, we report for the first time how social group cohesion is affected by fur rubbing in tufted capuchin monkeys. Fifteen captive capuchins were each observed six times for 45 min, three times following the provision of materials typically used for fur rubbing (onion) and three times following control food items (apple). When compared with the apple condition, monkeys significantly increased proximity to one another in the first 15 min of the onion condition, which is when most fur rubbing took place. Moreover, monkeys were more likely to spend time in groups when fur rubbing but less likely to spend time in groups when manipulating the onion in other ways. In subsequent periods monkeys were less likely to be in proximity to one another in the onion condition compared with the apple condition. Aggression between group members was elevated whereas affiliation was decreased throughout the onion condition. In short, capuchins spent more time further apart and engaged in more aggressive acts and shorter affiliative acts following fur-rubbing bouts. It is possible that these differences in behavior could be owing to differences in how the monkeys competed for and interacted with the items presented in each condition rather than due to fur rubbing as such. Alternatively, fur rubbing with pungent materials might interfere with olfactory cues used to regulate social interactions within a group and thereby cause increased levels of aggression. Am. J. Primatol. 70:1007-1012, 2008. (c) 2008 Wiley-Liss, Inc. C1 [Paukner, Annika; Suomi, Stephen J.] NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Paukner, A (reprint author), NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. EM pauknera@mail.nih.gov FU Division of Intramural Research; NICHD FX Contract grant sponsor: Division of Intramural Research, NICHD. NR 10 TC 5 Z9 5 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD NOV PY 2008 VL 70 IS 11 BP 1007 EP 1012 DI 10.1002/ajp.20595 PG 6 WC Zoology SC Zoology GA 360NN UT WOS:000260064300001 PM 18626908 ER PT J AU Lutsey, PL Roux, AVD Jacobs, DR Burke, GL Harman, J Shea, S Folsom, AR AF Lutsey, Pamela L. Roux, Ana V. Diez Jacobs, David R., Jr. Burke, Gregory L. Harman, Jane Shea, Steven Folsom, Aaron R. TI Associations of Acculturation and Socioeconomic Status With Subclinical Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; ARTERY RISK DEVELOPMENT; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; ADOLESCENT HEALTH; NATIONAL SAMPLE; YOUNG-ADULTS; NHANES-III AB Objectives. We assessed whether markers of acculturation (birthplace and number of US generations) and socioeconomic status (SES) are associated with markers of subclinical cardiovascular disease-carotid artery plaque, internal carotid intima-media thickness, and albuminuria-in 4 racial/ethnic groups. Methods. With data from the Multi-Ethnic Study of Atherosclerosis (n =6716 participants aged 45-84years) and race-specific binomial regression models, we computed prevalence ratios adjusted for demographics and traditional cardiovascular risk factors. Results. The adjusted US-to foreign-born prevalence ratio for carotid plaque was 1.20 (99% confidence interval [CI]=0.97, 1.39) among Whites, 1.91 (99% CI=0.94, 2.94) among Chinese, 1.62 (99% CI=1.28, 2.06) among Blacks, and 1.23 (99% CI=1.15, 1.31) among Hispanics. Greater carotid plaque prevalence was found among Whites, Blacks, and Hispanics with a greater number of generations with US residence (P<.001) and among Whites with less education and among Blacks with lower incomes. Similar associations were observed with intima-media thickness. There was also evidence of an inverse association between albuminuria and SES among Whites and Hispanics. Conclusions. Greater US acculturation and lower SES were associated with a higher prevalence of carotid plaque and greater intima-media thickness but not with albuminuria. Maintenance of healthful habits among recent immigrants should be encouraged. (Am J Public Health. 2008;98:1963-1970. doi:10.2105/AJPH.2007.123844) C1 [Lutsey, Pamela L.; Jacobs, David R., Jr.; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Roux, Ana V. Diez] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Burke, Gregory L.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Harman, Jane] NHLBI, Bethesda, MD 20892 USA. [Shea, Steven] Columbia Univ, Dept Med & Epidemiol, New York, NY USA. RP Folsom, AR (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55455 USA. EM folsom@epi.umn.edu FU National Heart Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This research was supported by the National Heart Lung, and Blood Institute (contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169). P.L. Lutsey was supported by the National Heart Lung, and Blood Institute as a predoctoral fellow on a training grant (T32 HL07779).; The authors thank the other investigators, the staff, and the participants of the Multi-Ethnic Study of Atherosclorosis (MESA) study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesanhlbi.org. NR 49 TC 48 Z9 49 U1 1 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2008 VL 98 IS 11 BP 1963 EP 1970 DI 10.2105/AJPH.2007.123844 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 368LP UT WOS:000260622900016 PM 18511718 ER PT J AU Garantziotis, S Zudaire, E Trempus, CS Hollingsworth, JW Jiang, DH Lancaster, LH Richardson, E Zhu, LS Cuttitta, F Brown, KK Noble, PW Kimata, K Schwartz, DA AF Garantziotis, Stavros Zudaire, Enrique Trempus, Carol S. Hollingsworth, John W. Jiang, Dianhua Lancaster, Lisa H. Richardson, Elizabeth Zhu, Lisheng Cuttitta, Frank Brown, Kevin K. Noble, Paul W. Kimata, Koji Schwartz, David A. TI Serum Inter-alpha-Trypsin Inhibitor and Matrix Hyaluronan Promote Angiogenesis in Fibrotic Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE inter-alpha-trypsin inhibitor; hyaluronan; angiogenesis; pulmonary fibrosis ID IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL PNEUMONIA; LEUKOCYTE ADHESION; GENE-EXPRESSION; CD44; ACID; MICE; DEPOSITION; RETICULUM; CHEMOKINE AB Rationale. The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. Methods: An examination was undertaken of angiogenesis in IaI sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. IaI deficiency leads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. C1 [Garantziotis, Stavros] NIEHS, Clin Res Unit, Res Triangle Pk, NC 27709 USA. [Zudaire, Enrique; Cuttitta, Frank] NCI, Angiogenesis Core Facil, Gaithersburg, MD USA. [Hollingsworth, John W.; Jiang, Dianhua; Noble, Paul W.] Duke Univ, Med Ctr, Durham, NC USA. [Lancaster, Lisa H.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Zhu, Lisheng; Kimata, Koji] Aichi Med Univ, Inst Mol Sci Med, Aichi, Japan. [Brown, Kevin K.] Natl Jewish Med & Res Ctr, Denver, CO USA. [Schwartz, David A.] NHLBI, Bethesda, MD 20892 USA. RP Garantziotis, S (reprint author), NIEHS, Clin Res Unit, POB 12233, Res Triangle Pk, NC 27709 USA. EM garantziotis@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009; Jiang, Dianhua/B-1421-2009; Cuttitta, Frank/B-4758-2016 OI Garantziotis, Stavros/0000-0003-4007-375X; Jiang, Dianhua/0000-0002-4508-3829; FU National Institute of Environmental Health Services [ES11961]; National Heart, Lung, and Blood Institute [HL91335]; National Institutes of Health; National Institute of Environmental Health Sciences; National Cancer Institute; National Heart, Lung, and Blood Institute FX Supported in part by grants from National Institute of Environmental Health Services (ES11961) and National Heart, Lung, and Blood Institute (HL91335), and by the Intramural Research Program of the National Institutes of Health, the National Institute of Environmental Health Sciences, the National Cancer Institute, and the National Heart, Lung, and Blood Institute. NR 48 TC 20 Z9 22 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2008 VL 178 IS 9 BP 939 EP 947 DI 10.1164/rccm.200803-386OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 368HG UT WOS:000260611600011 PM 18703791 ER PT J AU Brass, DM Hollingsworth, JW Cinque, M Li, ZW Potts, E Toloza, E Foster, WM Schwartz, DA AF Brass, David M. Hollingsworth, John W. Cinque, Mark Li, Zhouwei Potts, Erin Toloza, Eric Foster, William M. Schwartz, David A. TI Chronic LPS Inhalation Causes Emphysema-Like Changes in Mouse Lung that Are Associated with Apoptosis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; COTTON DUST; INTRATRACHEAL INSTILLATION; EXPERIMENTAL CARDROOM; PROTEINASE-INHIBITOR; NEUTROPHIL ELASTASE; AIRWAY-OBSTRUCTION; INHALED ENDOTOXIN; TEXTILE WORKERS; UP-REGULATION AB Lipopolysaccharide (LPS) is ubiquitous in the environment. Recent epidemiologic data suggest that occupational exposure to inhaled LIPS can contribute to the progression of chronic obstructive pulmonary disease. To address the hypothesis that inhaled LIPS can cause emphysema-like changes in mouse pulmonary parenchyma, we exposed C57BL/6 mice to aerosolized LIPS daily for 4 weeks. By 3 days after the end of the 4-week exposure, LPS-exposed mice developed enlarged airspaces that persisted in the 4-week recovered mice. These architectural alterations in the lung are associated with enhanced type I, III, and IV procollagen mRNA as well as elevated levels of matrix metalloproteinase (MMP)-9 mRNA, all of which have been previously associated with human emphysema. Interestingly, MMP-9-deficient mice were not protected from the development of LPS-induced emphysema. However, we demonstrate that LPS-induced airspace enlargement was associated with apoptosis within the lung parenchyma, as shown by prominent TUNEL staining and elevated cleaved caspase 3 immunoreactivity. Antineutrophil antiserum-treated mice were partially protected from the lung destruction caused by chronic inhalation of LPS. Taken together, these findings demonstrate that inhaled LIPS can cause neutrophil-dependent emphysematous changes in lung architecture that are associated with apoptosis and that these changes may be occurring through mechanisms different than those induced by cigarette smoke. C1 [Brass, David M.; Cinque, Mark; Schwartz, David A.] NIEHS, NHLBI, Lab Resp Biol, Environm Lung Dis Res Grp, Res Triangle Pk, NC 27709 USA. [Hollingsworth, John W.; Li, Zhouwei; Potts, Erin; Foster, William M.] Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA. [Toloza, Eric] Duke Univ, Med Ctr, Div Thorac Surg, Durham, NC USA. RP Brass, DM (reprint author), Duke Univ, Med Ctr, Dept Pediat, Neonatal Perinatal Res Inst, 403 Alex R Sands Lab Bldg,DUMC Box 3373, Durham, NC 27710 USA. EM david.brass@duke.edu FU NIEHS; NHLBI; Department of Veterans Affairs (Merit Review) [ES11375, ES7498, ES9607, ES11961, A158161, HL91335] FX This work was funded by the intramural research programs at NIEHS and NHLBI and by the Department of Veterans Affairs (Merit Review), extramural grants (ES11375 [D.A.S.], ES7498 [D.A.S.], ES9607 [D.A.S.], ES11961 [J.W.H., W.M.F.], A158161 [J.W.H.], and HL91335 [J.W.H.]). NR 54 TC 45 Z9 50 U1 0 U2 4 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 NOV PY 2008 VL 39 IS 5 BP 584 EP 590 DI 10.1165/rcmb.2007-0448OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 366WM UT WOS:000260514300014 PM 18539952 ER PT J AU Van Uitert, RL Summers, RM White, JM Deshpande, KK Choi, JR Pickhardt, PJ AF Van Uitert, Robert L. Summers, Ronald M. White, Jacob M. Deshpande, Keshav K. Choi, J. Richard Pickhardt, Perry J. TI Temporal and Multiinstitutional Quality Assessment of CT Colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colon; colonography; CT; quality; virtual colonoscopy ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; OPTIMIZING COLONIC DISTENSION; COLORECTAL NEOPLASIA; VIRTUAL COLONOSCOPY; CARBON-DIOXIDE; RESIDUAL FLUID; INSUFFLATION; VALIDATION; EXPERIENCE AB OBJECTIVE. The purpose of this study was to investigate the variability of CT colonography (CTC) scan quality obtained within and between institutions by using previously validated automated quality assessment (QA) software that assesses colonic distention and surface area obscured by residual fluid. MATERIALS AND METHODS. The CTC scans of 120 patients were retrospectively selected, 30 from each of four institutions. The bowel preparation included oral contrast material for fecal and fluid tagging. Patients at one institution (institution 4) drank half the amount of oral contrast material compared with the patients at the other three institutions. Fifteen of the CTC scans were from the beginning of the protocol studied at each institution and 15 scans were from the same protocol acquired approximately 1 year later in the study. We used previously validated QA software to automatically measure the mean distention and residual fluid of each of five colonic segments (ascending, transverse, descending, sigmoid, and rectum). Adequate distention was defined as a colonic diameter of at least 2 cm. Residual fluid was determined by the percentage of colonic surface area covered by fluid. We compared how the quality varied across multiple institutions and over time within the same institution. RESULTS. No significant difference in the amount of colonic distention among the four institutions was found (p = 0.19). However, the distention in the prone position was significantly greater than the distention in the supine position (p < 0.001). Patients at institution 4 had about half the amount of residual colonic fluid compared with patients at the other three institutions (p < 0.01). The sigmoid and descending colons were the least distended segments, and the transverse and descending colons contained the most fluid on the prone and supine scans, respectively. More recently acquired studies had greater distention and less residual fluid, but the differences were not statistically significant (p = 0.30 and p = 0.96, respectively). CONCLUSION. Across institutions, a significant difference can exist in bowel preparation quality for CTC. This study reaffirms the need for standardized bowel preparation and quality monitoring of CTC examinations to reduce poor CTC performance. C1 [Van Uitert, Robert L.; Summers, Ronald M.; White, Jacob M.; Deshpande, Keshav K.] Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Choi, J. Richard] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. [Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. RP Summers, RM (reprint author), Natl Inst Hlth Clin Ctr, Bldg 10,Rm 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU National Institutes of Health Clinical Center FX This study was supported by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 25 TC 6 Z9 6 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2008 VL 191 IS 5 BP 1503 EP 1508 DI 10.2214/AJR.07.3591 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363DQ UT WOS:000260246700034 PM 18941092 ER PT J AU Yang, WJ Gu, DF Chen, J Jaquish, CE Rao, DC Wu, XG Hixson, JE Duan, XF Kelly, TN Hamm, LL Whelton, PK He, J AF Yang, Wenjie Gu, Dongfeng Chen, Jing Jaquish, Cashell E. Rao, D. C. Wu, Xigui Hixson, James E. Duan, Xiufang Kelly, Tanika N. Hamm, L. Lee Whelton, Paul K. He, Jiang CA GenSalt Collaborative Res Grp TI Agreement of Blood Pressure Measurements Between Random-Zero and Standard Mercury Sphygmomanometers SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Blood pressure measurements; Random-zero sphygmomanometer; Standard mercury sphygmomanometer; Agreement ID SOCIETY-OF-HYPERTENSION; EUROPEAN-SOCIETY; ANEROID SPHYGMOMANOMETERS; INTERNATIONAL PROTOCOL; MONITOR; CALIBRATION; VALIDATION; INACCURACY; BURDEN AB The random-zero sphygmomanometer has been widely used in observational studies and clinical trials for blood pressure measurement. We examined the agreement of blood pressure measurements between random-zero and standard mercury sphygmomanometers among 2007 Chinese study participants aged 15 to 60 years. Three blood pressure readings were obtained by trained observers using random-zero and standard mercury sphygmomanometers, respectively, in a random order. Overall, blood pressure readings obtained using the random-zero device were significantly lower than those obtained with the standard mercury sphygmomanometer, with a mean difference ranging from -3.0 to -2.7 mm Hg for systolic and -1.4 to -0.9 mm Hg for diastolic blood pressure (all P < 0.01). Correlation coefficients between mean blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers were high (0.90 for systolic and 0.85 for diastolic blood pressure, both P < 0.0001). In conclusion, our study indicated that there was strong agreement between blood pressure measurements obtained using the random-zero and standard mercury sphygmomanometers although blood pressure values were on average lower with the random-zero sphygmomanometer. C1 [Yang, Wenjie; Chen, Jing; Hixson, James E.; Kelly, Tanika N.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. [Chen, Jing; Hamm, L. Lee; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Gu, Dongfeng; Wu, Xigui; Duan, Xiufang] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China. [Gu, Dongfeng; Wu, Xigui; Duan, Xiufang] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China. Peking Union Med Coll, Beijing 100021, Peoples R China. Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China. [Jaquish, Cashell E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol, Houston, TX USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave SL18, New Orleans, LA 70112 USA. EM jhe@tulane.edu FU National Institutes of Health, Bethesda, Maryland [U01HL072507] FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by a cooperative agreement project grant (U01HL072507) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. NR 34 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2008 VL 336 IS 5 BP 373 EP 378 DI 10.1097/MAJ.0b013e31816956ac PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 375NY UT WOS:000261121800001 PM 19011391 ER PT J AU McArthur, JH Durbin, AP Marron, JA Wanionek, KA Thumar, B Pierro, DJ Schmidt, AC Blaney, JE Murphy, BR Whitehead, SS AF McArthur, Julie H. Durbin, Anna P. Marron, Jennifer A. Wanionek, Kimberli A. Thumar, Bhavin Pierro, Dennis J. Schmidt, Alexander C. Blaney, Joseph E., Jr. Murphy, Brian R. Whitehead, Stephen S. TI Phase I Clinical Evaluation of rDEN4 Delta 30-200,201: A Live Attenuated Dengue 4 Vaccine Candidate Designed for Decreased Hepatotoxicity SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VIRUS-VACCINE; HEMORRHAGIC-FEVER; VOLUNTEERS; IMMUNOGENICITY; INFECTIONS; HUMANS; STRAIN; SAFE AB The rDEN4A/30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4 Delta 30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 105 plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for safety every other day for 16 days. Serum neutralizing antibody titer against DEN4 was determined at study day 28, 42, and 180. The vaccine infected all vaccinees and was well tolerated without inducing alanine aminotransferase (ALT) elevations. Although virus was not recovered from the serum of any vaccinee, moderate levels of neutralizing antibody were induced in all volunteers. Thus the restricted replication of rDEN4 Delta 30-200,201 previously documented in animal models was confirmed in humans. The rDEN4 Delta 30-200,201 is a promising candidate and can be considered for inclusion in a tetravalent dengue virus (DENV) vaccine. C1 [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD 21205 USA. [Pierro, Dennis J.; Schmidt, Alexander C.; Blaney, Joseph E., Jr.; Murphy, Brian R.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, 624 N Broadway,Room 251, Baltimore, MD 21205 USA. EM jmcarthu@jhsph.edu; adurbin@jhsph.edu; jmarron@jhsph.edu; kwanione@jhsph.edu; bthumar@jhsph.edu; pierrod@mail.nih.gov; as337y@nih.gov; jblaney@niaid.nih.gov; bmurphy@niaid.nih.gov; swhitehead@niaid.nih.gov FU NIAID; National Institutes of Health FX This research was supported by the Intramural Research Program of the NIAID, National Institutes of Health. NR 27 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2008 VL 79 IS 5 BP 678 EP 684 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 373BD UT WOS:000260945100010 PM 18981503 ER PT J AU Hu, CAA Phang, JM Valle, D AF Hu, Chien-an A. Phang, James M. Valle, David TI Proline metabolism in health and disease SO AMINO ACIDS LA English DT Editorial Material C1 [Hu, Chien-an A.] Univ New Mexico, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. [Phang, James M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Valle, David] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. RP Hu, CAA (reprint author), Univ New Mexico, Dept Biochem & Mol Biol, MSC08 4670,BMSB-258,915 Camino Salud, Albuquerque, NM 87131 USA. EM ahu@salud.unm.edu FU NCI NIH HHS [R01 CA106644-04, R01 CA106644, R01 CA106644-03]; NCRR NIH HHS [P20 RR016480, P20 RR016480-086585] NR 0 TC 14 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 651 EP 652 DI 10.1007/s00726-008-0102-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800001 PM 18504525 ER PT J AU Phang, JM AF Phang, James M. TI Introduction to second proline symposium SO AMINO ACIDS LA English DT Editorial Material C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Phang, JM (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. EM phang@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010743-02] NR 0 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 653 EP 654 DI 10.1007/s00726-008-0103-0 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800002 PM 18491029 ER PT J AU Phang, JM Donald, SP Pandhare, J Liu, YM AF Phang, James M. Donald, Steven P. Pandhare, Jui Liu, Yongmin TI The metabolism of proline, a stress substrate, modulates carcinogenic pathways SO AMINO ACIDS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Proline Metabolism in Health and Disease CY SEP 10-11, 2007 CL Frederick, MD DE proline oxidase; proline dehydrogenase; mTOR; PPAR gamma; apoptosis; bioenergetics ID ACTIVATED-RECEPTOR-GAMMA; MATRIX METALLOPROTEINASES; COLORECTAL-CANCER; LUNG-CANCER; PPAR-GAMMA; OXIDASE; APOPTOSIS; CELLS; GENE; COLLAGEN AB The resurgence of interest in tumor metabolism has led investigators to emphasize the metabolism of proline as a "stress substrate" and to suggest this pathway as a potential anti-tumor target. Proline oxidase, a.k.a. proline dehydrogenase (POX/PRODH), catalyzes the first step in proline degradation and uses proline to generate ATP for survival or reactive oxygen species for programmed cell death. POX/PRODH is induced by p53 under genotoxic stress and initiates apoptosis by both mitochondrial and death receptor pathways. Furthermore, POX/PRODH is induced by PPAR gamma and its pharmacologic ligands, the thiazolidinediones. The anti-tumor effects of PPAR gamma may be critically dependent on POX/PRODH. In addition, it is upregulated by nutrient stress through the mTOR pathway to maintain ATP levels. We propose that proline is made available as a stress substrate by the degradation of collagen in the microenvironmental extracellular matrix by matrix metalloproteinases. In a manner analogous to autophagy, this proline-dependent process for bioenergetics from collagen in extracellular matrix can be designated "ecophagy". C1 [Phang, James M.; Donald, Steven P.; Pandhare, Jui] NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Liu, Yongmin] NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Ctr Canc Res, Comparat Carcinogenesis Lab, Bldg 538,Room 115, Frederick, MD 21702 USA. EM phang@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 64 TC 100 Z9 106 U1 1 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 681 EP 690 DI 10.1007/s00726-008-0063-4 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800006 PM 18401543 ER PT J AU Surazynski, A Miltyk, W Palka, J Phang, JM AF Surazynski, A. Miltyk, W. Palka, J. Phang, J. M. TI Prolidase-dependent regulation of collagen biosynthesis SO AMINO ACIDS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Proline Metabolism in Health and Disease CY SEP 10-11, 2007 CL Frederick, MD DE prolidase; collagen metabolism; beta(1)-integrin signaling ID HUMAN SKIN FIBROBLASTS; HUMAN-ERYTHROCYTE PROLIDASE; HUMAN DERMAL FIBROBLASTS; EXTRACELLULAR-MATRIX; L-PROLINE; GENE-TRANSCRIPTION; CLINICAL SYMPTOMS; MOLECULAR-CLONING; ACTIVE-SITE; PEPTIDASE-D AB Prolidase [EC.3.4.13.9] is a cytosolic imidodipeptidase, which specifically splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme plays an important role in the recycling of proline from imidodipeptides (mostly derived from degradation products of collagen) for resynthesis of collagen and other proline-containing proteins. The enzyme activity is up-regulated by beta(1)-integrin receptor stimulation. The increase in the enzyme activity is due to its phosphorylation on serine/threonine residues. Collagen is not only structural component of extracellular matrix. It has been recognized as a ligand for integrin receptors, which play an important role in signaling that regulate ion transport, lipid metabolism, kinase activation and gene expression. Therefore, changes in the quantity, structure and distribution of collagens in tissues may affect cell signaling, metabolism and function. Several line of evidence suggests that prolidase activity may be a step-limiting factor in the regulation of collagen biosynthesis. It has been shown in different physiologic and pathologic conditions. It is of great importance during wound healing, inflammation, aging, tissue fibrosis and possibly skeletal abnormalities seen in Osteogenesis Imperfecta. The mechanism of prolidase-dependent regulation of collagen biosynthesis was found at both transcriptional and post-transcriptional levels. In this study, we provide evidence for prolidase-dependent transcriptional regulation of collagen biosynthesis. The mechanism was found at the level of NF-kB, known inhibitor of type I collagen gene expression. Modulation of integrin-dependent signaling by stimulatory (i.e. thrombin) or inhibitory (i.e. echistatin) beta(1)-integrin ligands or by nitric oxide donors (i.e. DETA/NO) affect prolidase at post-transcriptional level. All those factors may represent novel approach to pharmacotherapy of connective tissue disorders. C1 [Surazynski, A.; Miltyk, W.; Palka, J.] Med Univ Bialystok, Dept Med Chem, PL-15089 Bialystok, Poland. [Phang, J. M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Palka, J (reprint author), Med Univ Bialystok, Dept Med Chem, Ul Kilinskiego 1, PL-15089 Bialystok, Poland. EM pal@amb.edu.pl NR 74 TC 63 Z9 67 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 731 EP 738 DI 10.1007/s00726-008-0051-8 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800011 PM 18320291 ER PT J AU Liao, XH Majithia, A Huang, XL Kimmel, AR AF Liao, Xin-Hua Majithia, Amit Huang, Xiuli Kimmel, Alan R. TI Growth control via TOR kinase signaling, an intracellular sensor of amino acid and energy availability, with crosstalk potential to proline metabolism SO AMINO ACIDS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Proline Metabolism in Health and Disease CY SEP 10-11, 2007 CL Frederick, MD DE TORC1; rapamycin; Raptor; FKBP12; S6K; 4E-BP ID CAP-DEPENDENT TRANSLATION; MESSENGER-RNA TRANSLATION; RICTOR-MTOR COMPLEX; P70 S6 KINASE; SACCHAROMYCES-CEREVISIAE; CELL-GROWTH; MAMMALIAN TARGET; NUCLEAR-LOCALIZATION; BINDING PARTNER; GENE-EXPRESSION AB The TOR (Target of Rapamycin) protein kinase pathway plays a central role in sensing and responding to nutrients, stress, and intracellular energy state. TOR complex 1 (TORC1) is comprised of TOR, Raptor, and Lst8 and its activity is sensitive to inhibition by the macrolide antibiotic rapamycin. TORC1 regulates protein synthesis, ribosome biogenesis, autophagy, and ultimately cell growth through the phosphorylation of S6 K, 4E-BP, and other substrates. As TORC1 activity is positively or negatively modulated in response to upstream regulators, cellular growth rate is, respectively, enhanced or suppressed. A separate multiprotein TOR complex, TORC2, is insensitive to direct inhibition by rapamycin and does not regulate growth patterns directly; TORC2 can, however, impact certain aspects of TORC1 signaling and cell survival. TOR signaling is an ancient pathway, conserved among the yeasts, Dictyostelium, C. elegans, Drosophila, mammals, and Arabidopsis. This review will focus on the regulation of TORC1 in mammalian cells in the context of amino acid sensing/regulation and intracellular ATP homeostasis, but will also include comparisons among other organisms. C1 [Liao, Xin-Hua; Majithia, Amit; Huang, Xiuli; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Majithia, Amit] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Bethesda, MD 20817 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU Intramural NIH HHS NR 68 TC 58 Z9 62 U1 3 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 761 EP 770 DI 10.1007/s00726-008-0100-3 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800014 PM 18651095 ER PT J AU Kempf, L AF Kempf, Lucas TI POX imaging genetics: Proline oxidase's impact on brain structure and function SO AMINO ACIDS LA English DT Meeting Abstract C1 [Kempf, Lucas] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 773 EP 773 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800021 ER PT J AU Drgonova, J Liu, QR Hall, FS Uhl, GR AF Drgonova, Jana Liu, Qing-Rong Hall, F. Scott Uhl, George R. TI Deletion of v7-3 (SLC6A15) transporter improves motor performance in aging female mice SO AMINO ACIDS LA English DT Meeting Abstract C1 [Drgonova, Jana; Liu, Qing-Rong; Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Intramural Res Program,DHHS, Baltimore, MD 21224 USA. RI Drgonova, Jana/B-2903-2008; Liu, Qing-Rong/A-3059-2012; Hall, Frank/C-3036-2013 OI Liu, Qing-Rong/0000-0001-8477-6452; Hall, Frank/0000-0002-0822-4063 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 774 EP 774 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800025 ER PT J AU Sun, XB Li, Q Veeramani, S Wan, GH Phang, J Lin, MF Hu, CAA AF Sun, Xiaobo Li, Qian Veeramani, Suresh Wan, Guanghua Phang, James Lin, Ming-Fong Hu, Chien-an A. TI Interactive role of POX and p66(Shc) in oxidative stress-induced cell death in cancer cells SO AMINO ACIDS LA English DT Meeting Abstract C1 [Sun, Xiaobo; Li, Qian; Wan, Guanghua; Hu, Chien-an A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA. [Veeramani, Suresh; Lin, Ming-Fong] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. [Phang, James] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 774 EP 774 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800024 ER PT J AU Alvord, WG Roayaei, JA Reinhold, WC Quinones, OA Weinstein, JN AF Alvord, W. Gregory Roayaei, Jean A. Reinhold, William C. Quinones, Octavio A. Weinstein, John N. TI A microarray analysis for differential gene expression for two cancer cell lines, DU145 non-drug resistant and RC.01 drug-resistant using R & bioconductor SO AMINO ACIDS LA English DT Meeting Abstract C1 [Alvord, W. Gregory; Roayaei, Jean A.; Quinones, Octavio A.] NCI, DMS Inc, Frederick, MD 21701 USA. [Reinhold, William C.; Weinstein, John N.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 775 EP 776 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800030 ER PT J AU Velazquez, C Knaus, E Chen, QH Citro, M Keefer, L AF Velazquez, Carlos Knaus, Edward Chen, Quiao-Hong Citro, Michael Keefer, Larry TI NONO-NSAIDS possessing a PROLI/NO moiety: The new anti-inflammatory, analgesic, and potentially chemopreventive prodrugs SO AMINO ACIDS LA English DT Meeting Abstract C1 [Velazquez, Carlos; Keefer, Larry] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. [Knaus, Edward; Chen, Quiao-Hong] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada. [Citro, Michael] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. RI Velazquez, Carlos/C-4224-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD NOV PY 2008 VL 35 IS 4 BP 776 EP 776 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355NE UT WOS:000259714800031 ER PT J AU Kacinko, SL Concheiro-Guisan, M Shakleya, DM Huestis, MA AF Kacinko, Sherri L. Concheiro-Guisan, Marta Shakleya, Diaa M. Huestis, Marilyn A. TI Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of buprenorphine, norbuprenorphine, and metabolites in human urine SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the German-Society-for-Mass-Spectrometry CY MAR 02-05, 2008 CL Giessen, GERMANY SP German Soc Mass Spectrometry DE Buprenorphine; Norbuprenorphine; Buprenorphine glucuronide; Norbuprenorphine glucuronide; Urine; Liquid chromatography-tandem mass spectrometry ID SAMPLES; HAIR; PLASMA; MISUSE; BLOOD; MS AB A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in human urine was developed and fully validated. Extensive endogenous and exogenous interferences were evaluated and limits of quantification were identified empirically. Analytical ranges were 5-1,000 ng/mL for BUP and BUP-Gluc and 25-1,000 ng/mL for NBUP and NBUP-Gluc. Intra-assay and interassay imprecision were less than 17% and recovery was 93-116%. Analytes were stable at room temperature, at 4 degrees C, and for three freeze-thaw cycles. This accurate and precise assay has sufficient sensitivity and specificity for urine analysis of specimens collected from individuals treated with BUP for opioid dependence. C1 [Kacinko, Sherri L.; Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Suite 200,Room 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10] NR 23 TC 13 Z9 14 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD NOV PY 2008 VL 392 IS 5 BP 903 EP 911 DI 10.1007/s00216-008-2326-z PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 362SV UT WOS:000260218300017 PM 18758763 ER PT J AU Brooks, BD Albertson, AE Jones, JA Speare, JO Lewis, RV AF Brooks, Benjamin D. Albertson, Amy E. Jones, Justin A. Speare, Jonathan O. Lewis, Randolph V. TI Efficient screening of high-signal and low-background antibody pairs in the bio-bar code assay using prion protein as the target SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DISEASE AB The bio-bar code assay is an assay for ultrasensitive detection of proteins. The main technical hurdle in bio-bar code assay development is achieving a dose-dependent, reproducible signal with low background. We report on a magnetic bead ELISA screening mechanism for characterizing antibody pairs that are effective for use in the bio-bar code assay. The normal isoform of prion protein was utilized as the target protein as dozens of antibodies have been developed against it. The development of an ultrasensitive assay for the detection of the various isoforms of PrP has the potential to enable significant advances in the diagnosis and understanding of transmissible spongiform encephalopathies, including transmission mechanisms, disease pathology, and potential therapeutics. With prion protein as the target, the magnetic bead ELISA identified pairs with high background and low signal in the bio-bar code assay. The magnetic bead ELISA was effective as a screening mechanism because it reduced assay time and cost and allowed for understanding of pair characteristics such as development times and signal-to-noise ratios. (C) 2008 Elsevier Inc. All rights reserved. C1 [Brooks, Benjamin D.; Albertson, Amy E.; Jones, Justin A.; Lewis, Randolph V.] Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. [Speare, Jonathan O.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Brooks, BD (reprint author), Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. EM bbrooks@uwyo.edu FU Department of Defense and a US Department of Agriculture CSREES FX The authors acknowledge Phil Lefebvre, Paul Bao, Uwe Mueller, and Liangxiu He from Nanosphere, Inc., for technical training, reagents, and advice. The authors also acknowledge Jan Langeveld of the Central Institute for Animal Disease Control in the Netherlands, Kathryn O'Rourke of the USDA, Greg Raymond of the NIH Rocky Mountain Labs, and Man-Sun Sy of Case University, who provided antibodies and excellent advice during the study. The authors also acknowledge Amanda Brooks, Holly Steinkraus, and Erin Shefferly for their technical support. This research was funded by the Department of Defense and a US Department of Agriculture CSREES nanotechnology grant. NR 10 TC 7 Z9 7 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 2008 VL 382 IS 1 BP 60 EP 62 DI 10.1016/j.ab.2008.07.009 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 409OZ UT WOS:000263517000010 PM 18694717 ER PT J AU Mussolino, ME Gillum, RF AF Mussolino, Michael E. Gillum, R. F. TI Low Bone Mineral Density and Mortality in Men and Women: The Third National Health and Nutrition Examination Survey Linked Mortality File SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Bone Density; Follow-up Studies; Longitudinal Studies; Mortality; Proportional Hazards Models; Men; Women ID ELDERLY-WOMEN; FRACTURES; STROKE AB PURPOSE: The aim of this study is to determine the association of bone mineral density and mortality over a median follow-up of 9 years. METHODS: The baseline data used are from the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative sample of non-institutionalized civilians. A cohort of 5,769 non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged 50 years and older at baseline (1988-1994) was followed through 2000 for overall mortality using the restricted-Use NHANES III Linked Mortality File (1,741 deaths). Total proximal femoral bone mineral density was measured by dual-energy x-ray absorptiometry and categorized into quartiles. Cox proportional hazards models were used to estimate the relative risk of death after adjusting for multiple risk factors. RESULTS: Compared with subjects in the highest quartile of bone mineral density, those in the lowest quartile had greater risk of death (relative risk, 1.53; 95% confidence interval: 1.08-2.18; P 0.02). There was no significant interaction of bone mineral density with race or ethnicity. CONCLUSION: Low bone mineral density was associated with increased risk of death. C1 [Mussolino, Michael E.; Gillum, R. F.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Mussolino, ME (reprint author), NHLBI, Div Prevent & Populat Sci, NIH, 6701 Rockledge Dr,Suite 10018, Bethesda, MD 20892 USA. EM mussolinom@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 15 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2008 VL 18 IS 11 BP 847 EP 850 DI 10.1016/j.annepidem.2008.07.003 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 369PG UT WOS:000260705800004 PM 18809342 ER PT J AU Gail, MH Pfeiffer, RM Wheeler, W Pee, D AF Gail, M. H. Pfeiffer, R. M. Wheeler, W. Pee, D. TI Probability that a Two-Stage Genome-Wide Association Study will Detect a Disease-Associated SNP and Implications for Multistage Designs SO ANNALS OF HUMAN GENETICS LA English DT Article DE case-control association study; detection probability; power; proportion positive; ranking and selection; SNP chip ID SAMPLE-SIZE; GENE; GENOTYPES; SCANS AB Large two-stage genome-wide association studies (GWASs) have been shown to reduce required genotyping with little loss of power, compared to a one-stage design, provided a substantial fraction of cases and controls, pi(sample), is included in stage 1. However, a number of recent GWASs have used pi(sample) < 0.2. Moreover, standard power calculations are not applicable because SNPs are selected in stage 1 by ranking their p-values, rather than comparing each SNP's statistic to a fixed critical value. We define the detection probability (DP) of a two-stage design as the probability that a given disease-associated SNP will have a p-value among the lowest ranks of p-values at stage 1, and, among those SNPs selected at stage 1, at stage 2. For 8000 cases and 8000 controls available for study and for odds ratios per allele in the range 1.1-1.3, we show that DP is substantially reduced for designs with pi(sample) <= 0.25, and that DP cannot be appreciably increased by analyzing the stage 1 and stage 2 data jointly. These results suggest that multistage designs with small first stages (e.g. pi(sample) <= 0.25) should be avoided, and that additional genotyping in earlier studies with small first stages will yield previously unselected disease-associated SNPs. C1 [Gail, M. H.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wheeler, W.; Pee, D.] Informat Management Serv Inc, Rockville, MD 20852 USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS [Z01 CP010181-05] NR 17 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2008 VL 72 BP 812 EP 820 DI 10.1111/j.1469-1809.2008.00467.x PN 6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 358SB UT WOS:000259936700011 PM 18652601 ER PT J AU Zheng, G AF Zheng, Gang TI Can the Allelic Test be Retired from Analysis of Case-Control Association Studies? SO ANNALS OF HUMAN GENETICS LA English DT Article DE Allele-based test; trend test; disequilibrium coefficient; genetic model; robust tests ID HARDY-WEINBERG EQUILIBRIUM; SAMPLE-SIZE AB It has been stated that, when Hardy-Weinberg equilibrium (HWE) holds in the combined case-control samples, the allelic test is asymptotically equivalent to the trend test (for the additive model) for testing genetic association, and hence the allelic test should not be used. A recent publication shows that the allelic test and the trend test are asymptotically equivalent when HWE holds in the population. It is known that, when HWE does not hold, the trend test can still be used while the allelic test is no longer valid. Therefore, the allelic test is either not valid or is asymptotically equivalent to the trend test. It appears that the allelic test is a nuisance test. Can it be retired from the analysis of case-control association studies ? It all depends on data and model assumptions. We give conditions under which the allelic test and the trend test are asymptotically equivalent under both null and alternative hypotheses. C1 NHLBI, Off Biostat Res, DPPS, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, DPPS, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 16 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2008 VL 72 BP 848 EP 851 DI 10.1111/j.1469-1809.2008.00466.x PN 6 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 358SB UT WOS:000259936700014 PM 18652599 ER PT J AU Ay, H Arsava, EM Gungor, L Greer, D Singhal, AB Furie, KL Koroshetz, WJ Sorensen, AG AF Ay, Hakan Arsava, Ethem Murat Gungor, Levent Greer, David Singhal, Aneesh B. Furie, Karen L. Koroshetz, Walter J. Sorensen, A. Gregory TI Admission International Normalized Ratio and Acute Infarct Volume in Ischemic Stroke SO ANNALS OF NEUROLOGY LA English DT Article ID ATRIAL-FIBRILLATION; ENDOTHELIAL FUNCTION; ANTICOAGULATION; TRIAL; THROMBOLYSIS; ASSOCIATION; PREVENTION; REGRESSION; SEVERITY; THROMBUS AB Objective: The level of anticoagulation at the time of stroke onset may influence the size, composition, and dissolution rate of the occlusive clot. We explored the relation between admission international normalized ratio (INR) and acute infarct volume in patients with ischemic stroke. Methods: We studied 93 consecutive patients with preadmission warfarin use who had INR measurement and diffusion-weighted imaging performed within 24 hours of stroke onset. Ninety-three etiologic stroke subtype-matched patients without prior warfarin use served as control patients. Linear regression analysis was used to test for independence of INR as a predictor of infarct volume. Results: In patients with preadmission warfarin use, admission INR was inversely correlated with lesion volume oil diffusion-weighted imaging (r = -0-38). This relation was retained after adjustment for potential covariates (p = 0.014). INR less than 2.0 was associated with 3.5-fold (95% confidence interval, 2.9-4.2) greater lesion volume on diffusion-weighted imaging as compared with INR of 2.0 or more. Patients who were on therapeutic INR ( :2.0) had smaller infarcts compared with patients without preadmission warfarin use (p = 0.001). Admission INR was inversely correlated with acute perfusion defect (r = -0.33), chronic infarct volume (r = -0.42), National Institutes of Health Stroke Scale score at admission (r = -0.27), and modified Rankin score at discharge (r = -0.28). Interpretation: These results suggest that preadmission warfarin use associated with therapeutic level of anticoagulation can offer a benefit in limiting the extent of ischemic injury in an event of acute stroke. C1 [Ay, Hakan; Greer, David; Singhal, Aneesh B.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Boston, MA USA. [Ay, Hakan; Arsava, Ethem Murat; Gungor, Levent; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol,Sch Med, Boston, MA USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Ay, H (reprint author), Harvard Univ, Sch Med, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013 OI Arsava, Ethem Murat/0000-0002-6527-4139 FU NIH (National Institute of Neurological Disorders and Stroke) [R01-NS038477, R01NS051412, P50-NS051343] FX This work was Supported by NIH (National Institute of Neurological Disorders and Stroke) grants R01-NS038477 (AGS), R01NS051412 (ABS) and P50-NS051343 (KLF). NR 27 TC 37 Z9 39 U1 0 U2 3 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 NOV PY 2008 VL 64 IS 5 BP 499 EP 506 DI 10.1002/ana.21456 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700009 PM 18661516 ER PT J AU Cushman, M Cantrell, RA McClure, LA Howard, G Prineas, RJ Moy, CS Temple, EM Howard, VJ AF Cushman, Mary Cantrell, Ronald A. McClure, Leslie A. Howard, George Prineas, Ronald J. Moy, Claudia S. Temple, Ella M. Howard, Virginia J. TI Estimated 10-Year Stroke Risk by Region and Race in the United States: Geographic and Racial Differences in Stroke Risk SO ANNALS OF NEUROLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; BLACK-WHITE DIFFERENCES; LEFT-VENTRICULAR MASS; FOLLOW-UP; ATHEROSCLEROSIS RISK; NATIONAL-HEALTH; HYPERTENSION; MORTALITY; COMMUNITIES; DISPARITIES AB Objective: Black individuals younger than 75 years have more than twice the risk for stroke death than whites in the United States. Regardless of race, stroke death is approximately 50% greater in the "stroke belt" and "stroke buckle" states of the Southeastern United States. We assessed geographic and racial differences in estimated 10-year stroke risk. Methods: The Reasons for Geographic and Racial Differences in Stroke study is a population-based cohort of men and women 45 years or older, recruited February 2003 to September 2007 at this report, with oversampling of stroke belt/buckle residents and blacks. Racial and regional differences in the Framingham Stroke Risk Score were Studied in 23,940 participants without previous stroke or transient ischemic attack. Results: The mean age-, race-, and sex-adjusted 10-year predicted stroke probability differed slightly across regions: 10.7% in the belt, 10.4% in the buckle, and 10.1% elsewhere (p < 0.001). Geographic differences were largest for the score components of diabetes and use of antihypertensive therapy. Blacks had a greater age- and sex-adjusted mean 10-year predicted stroke probabilicy than whites: 12.0 versus 9.2%, respectively (p < 0.001). Race differences were largest for the score components of hypertension, systolic blood pressure, diabetes, smoking, and left ventricular hypertrophy. Interpretation. Although blacks had a greater predicted stroke probability than whites, regional differences were small. Results suggest that interventions to reduce racial disparities in stroke risk factors hold promise to reduce the racial disparity in stroke mortality. The same may not be true regarding geographic disparities in stroke mortality. C1 [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Cantrell, Ronald A.; Howard, Virginia J.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [McClure, Leslie A.; Howard, George; Temple, Ella M.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Prineas, Ronald J.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Cushman, M (reprint author), Univ Vermont, Dept Med, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA. EM mary.cushman@uvm.edu RI McClure, Leslie/P-2929-2015 FU NINDS NIH HHS [U01 NS041588-03, R01 NS041588, R01 NS041588-01, U01 NS041588, U01 NS041588-02, U01 NS041588-04, U01 NS041588-05, U01 NS041588-06, U01 NS041588-08] NR 31 TC 60 Z9 61 U1 0 U2 4 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 NOV PY 2008 VL 64 IS 5 BP 507 EP 513 DI 10.1002/ana.21493 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700010 PM 19067365 ER PT J AU Schiffmann, R Fitzgibbon, EJ Harris, C DeVile, C Davies, EH Abel, L van Schaik, IN Benko, W Timmons, M Ries, M Vellodi, A AF Schiffmann, Raphael Fitzgibbon, Edmond J. Harris, Chris DeVile, Catherine Davies, Elin H. Abel, Larry van Schaik, Ivo N. Benko, William Timmons, Margaret Ries, Markus Vellodi, Ashok TI Randomized, Controlled Trial of Miglustat in Gaucher's Disease Type 3 SO ANNALS OF NEUROLOGY LA English DT Article ID ENZYME REPLACEMENT THERAPY; N-BUTYLDEOXYNOJIRIMYCIN; INVOLVEMENT; IDENTIFICATION; BIOSYNTHESIS; INHIBITOR; EFFICACY; OGT-918 AB Objective: To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3). Methods: This 24-month, phase II, open-label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or "no miglustat treatment." The randomized phase was followed by an optional 12-month extension phase in which all patients received miglustat. All patients received ERT during the 24-month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations. Results: Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to "no miglustat treatment." Twenty-eight patients entered the 12-month extension phase. No significant between-group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone. Interpretation: Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustar may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3. C1 [Schiffmann, Raphael; Benko, William; Timmons, Margaret; Ries, Markus] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Bethesda, MD USA. [Fitzgibbon, Edmond J.] NEI, NIH, Bethesda, MD 20892 USA. [Harris, Chris] Univ Plymouth, Ctr Theoret & Computat Neurosci, Plymouth PL4 8AA, Devon, England. [DeVile, Catherine; Davies, Elin H.; Vellodi, Ashok] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Abel, Larry] Univ Melbourne, Dept Optometry & Vis Sci, Melbourne, Vic, Australia. [van Schaik, Ivo N.] Univ Amsterdam, Acad Med Ctr, Dept Neurol & Clin Neurophysiol, NL-1105 AZ Amsterdam, Netherlands. RP Schiffmann, R (reprint author), Baylor Inst Metab Dis, 3812 Elm St, Dallas, TX 75226 USA. EM raphael.schiffmann@baylorhealth.edu RI Abel, Larry/D-9915-2012; OI Abel, Larry/0000-0002-2393-0644; Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS [Z01 NS002984-09, Z99 NS999999] NR 27 TC 82 Z9 82 U1 0 U2 2 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 NOV PY 2008 VL 64 IS 5 BP 514 EP 522 DI 10.1002/ana.21491 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700011 PM 19067373 ER PT J AU Mortiboys, H Thomas, KJ Koopman, WJH Klaffke, S Abou-Sleiman, P Olpin, S Wood, NW Willems, PHGM Smeitink, JAM Cookson, MR Bandmann, O AF Mortiboys, Heather Thomas, Kelly Jean Koopman, Werner J. H. Klaffke, Stefanie Abou-Sleiman, Patrick Olpin, Simon Wood, Nicholas W. Willems, Peter H. G. M. Smeitink, Jan A. M. Cookson, Mark R. Bandmann, Oliver TI Mitochondrial Function and Morphology Are Impaired in parkin-Mutant Fibroblasts SO ANNALS OF NEUROLOGY LA English DT Article ID COMPLEX-I DEFICIENCY; SKIN FIBROBLASTS; DISEASE; MUTATIONS; PATHOLOGY; MUSCLE; PINK1; CELLS; DEGENERATION; ASSOCIATION AB Objective: There are marked mitochondrial abnormalities in parkin-knock-out Drosophila and other model systems. The aim of Our Study was to determine mitochondrial function and morphology in parkin-mutant patients. We also investigated whether pharmacological rescue of impaired mitochondrial function may be possible in parkin-mutant human tissue. Methods: We used three sets of techniques, namely, biochemical measurements of mitochondrial function, quantitative morphology, and live cell imaging of functional connectivity to assess the mitochondrial respiratory chain, the outer shape and connectivity of the mitochondria, and their functional inner connectivity in fibroblasts from patients with homozygous or compound heterozygous parkin Mutations. Results. Parkin-mutant cells had lower mitochondrial complex I activity and complex I-linked adenosine triphosphate production, which correlated with a greater degree of mitochondrial branching, suggesting that the functional and morphological effects of Parkin are related. Knockdown of parkin in control fibroblasts confirmed chat Parkin deficiency is sufficient to explain these mitochondrial effects. In contrast, 50% knockdown of parkin, mimicking haploinsufficiency in human patient tissue, did not result in impaired mitochondrial function or morphology. Fluorescence recovery after photobleaching assays demonstrated a lower level of functional connectivity of the mitochondrial matrix, which further worsened after rotenone exposure. Treatment with experimental neuroprotective compounds resulted in a rescue of the mitochondrial membrane potential. Interpretation: Our Study demonstrates marked abnormalities of mitochondrial function and morphology in parkin-mutant patients and provides proof-of-principle data for the potential usefulness of this new model system as a tool to screen for disease-modifying compounds in genetically homogenous parkinsonian disorders. C1 [Mortiboys, Heather; Klaffke, Stefanie; Bandmann, Oliver] Univ Sheffield, Sch Med, Acad Neurol Unit, Sheffield S10 2RX, S Yorkshire, England. [Thomas, Kelly Jean; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Koopman, Werner J. H.; Willems, Peter H. G. M.] Radboud Univ Nijmegen, Ctr Med, Dept Biochem, Nijmegen Cencre Mol Life Sci, Nijmegen, Netherlands. [Abou-Sleiman, Patrick; Wood, Nicholas W.] Inst Neurol, London WC1N 3BG, England. [Olpin, Simon] Sheffield Childrens Hosp, Sheffield S10 2TH, S Yorkshire, England. [Smeitink, Jan A. M.] Radboud Univ Nijmegen, Dept Pediat, Nijmegen Ctr Mitochondrial Disorders, Nijmegen, Netherlands. RP Bandmann, O (reprint author), Univ Sheffield, Sch Med, Acad Neurol Unit, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM o.bandmann@sheffield.ac.uk RI Smeitink, Jan/D-6064-2011; Smeitink, Jan/C-1351-2013; Koopman, Werner/N-3586-2014; Mortiboys, Heather/E-8838-2010; Wood, Nicholas/C-2505-2009; Koopman, Werner/D-3592-2009; Willems, P.H.G.M./L-4759-2015; OI Wood, Nicholas/0000-0002-9500-3348; Koopman, Werner/0000-0002-5340-6747; Willems, P.H.G.M./0000-0002-0915-1599; olpin, simon/0000-0001-9018-5173 FU Parkinson's Disease Society (UK) [G-0715]; University of Sheffield; NIH; National Institute on Aging [Z01 AG000953-07] FX This work was supported by the Parkinson's Disease Society (UK) (G-0715, H.M., O.B.), the Sheila McKenzie Fund of the University of Sheffield (H.M., O.B.), the Intramural Research Program of the NIH (National Institute on Aging, Z01 AG000953-07, K.J.T., M.R.C.), and an Innovative Research Projects (IOP)-genomics project entitled "New tools for the identification of nutritional modulators of mitochondrial activity: small molecules that promote health and combat disease" (IGE05003, W.J.H.K., P.H.G.M.W., J.A.M.S.). NR 33 TC 170 Z9 172 U1 1 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2008 VL 64 IS 5 BP 555 EP 565 DI 10.1002/ana.21492 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700015 PM 19067348 ER PT J AU Pierson, TM Bonnemann, CG Finkel, RS Bunin, N Tennekoon, GI AF Pierson, Tyler Mark Bonnemann, Carsten G. Finkel, Richard S. Bunin, Nancy Tennekoon, Gihan I. TI Umbilical Cord Blood Transplantation for Juvenile Metachromatic Leukodystrophy SO ANNALS OF NEUROLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CELL TRANSPLANTATION; METABOLIC DISEASES; NERVE-CONDUCTION; LYSOSOMAL-ENZYME; GENETICS; OUTCOMES; CHILDREN; HURLER AB Three siblings with metachromatic leukodystrophy underwent umbilical cord blood transplantation at different stages of disease. Neuroimaging, nerve conduction studies, neurological examinations, and neuropsychological examinations were used to measure Outcome over 2 years. After transplant, the oldest sibling experienced disease progression. His two siblings had near or total resolution of signal abnormalities on neuroimaging. Their neuropsychological testing remained stable, and nerve conduction studies have shown improvement. These results indicate pretransplantation neurological examinations may be the most significant predictor of outcome after transplant. To our knowledge, this report is the first to document neurological outcome of metachromatic leukodystrophy treated by umbilical cord blood transplantation. C1 [Pierson, Tyler Mark; Bonnemann, Carsten G.; Finkel, Richard S.; Tennekoon, Gihan I.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Bunin, Nancy] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Pierson, TM (reprint author), NINDS, Nenrogenet Branch, Porter Neurosci Res Ctr, Bldg 35,Room 2A-1000,35 Convent Dr,MSC 3705, Bethesda, MD 20892 USA. EM piersonty@ninds.nih.gov FU NIH [T32-HD043021-04] FX This work was supported by, the NIH (T32-HD043021-04, T. M. P.). NR 23 TC 24 Z9 24 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2008 VL 64 IS 5 BP 583 EP 587 DI 10.1002/ana.21522 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 383BS UT WOS:000261649700018 PM 19067349 ER PT J AU Villalona-Calero, MA Otterson, GA Wientjes, MG Weber, F Bekaii-Saab, T Young, D Murgo, AJ Jensen, R Yeh, TK Wei, Y Zhang, Y Eng, C Grever, M Au, JLS AF Villalona-Calero, M. A. Otterson, G. A. Wientjes, M. G. Weber, F. Bekaii-Saab, T. Young, D. Murgo, A. J. Jensen, R. Yeh, T. -K. Wei, Y. Zhang, Y. Eng, C. Grever, M. Au, J. L. -S. TI Noncytotoxic suramin as a chemosensitizer in patients with advanced non-small-cell lung cancer: a phase II study SO ANNALS OF ONCOLOGY LA English DT Article DE chemosensitization; drug resistance; FGF; lung cancer; suramin ID FIBROBLAST-GROWTH-FACTOR; FACTOR RECEPTOR-BINDING; HUMAN BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; PLUS CARBOPLATIN; POTENT INHIBITOR; ENHANCE ACTIVITY; FACTOR BFGF; PACLITAXEL; GEFITINIB AB Background: The purpose of this study was to evaluate the potential of noncytotoxic doses of suramin to reverse chemotherapy resistance in advanced chemonaive and chemoresistant non-small-cell lung cancer patients. Patients and methods: Patients received paclitaxel (Taxol) (200 mg/m(2)) and carboplatin (area under the concentration-time curve 6 mg/ml/min) every 3 weeks. The total suramin per cycle dose was calculated using a nomogram derived from the preceding phase I trial to obtain the desirable plasma concentration range of 10-50 mu M. Results: Thirty-nine response-assessable chemonaive patients (arm A) received 213 cycles. Thirty-eight cycles were administered to 15 patients with demonstrated resistance to paclitaxel and carboplatin (arm B). The pattern/frequency of toxic effects was similar to those expected for paclitaxel/carboplatin, and pharmacokinetic analyses (199 cycles) showed suramin plasma concentrations maintained between 10 and 50 mu M in 94% of cycles. In arm A, response evaluation criteria in solid tumors (RECIST) response rate was 36% (95% confidence interval 22% to 54%; two complete, 12 partial); 15 patients (38%) had disease stabilization for >= 4 months; median progression-free survival (intention to treat) was 6.4 months; median overall survival (OS) 10.4 months and 1-year survival rate 38%. In arm B, no RECIST responses occurred; four patients had disease stabilization for >= 4 months; median OS was 132 days and 1-year survival rate 7%. Plasma basic fibroblast growth factor levels were higher in chemopretreated/refractory patients compared with chemonaive patients (P = 0.05). Sequence analysis of the EGFR tyrosine kinase domain in a long-term disease-free survivor revealed an ATP-binding pocket mutation (T790M). Conclusions: Noncytotoxic suramin did not increase paclitaxel/carboplatin's toxicity and the suramin dose was predicted from clinical parameters. No clinically significant reversal of primary resistance was documented, but a modulatory effect in chemotherapy-naive patients cannot be excluded. Controlled randomization is planned for further evaluation of this treatment strategy. C1 [Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Ohio State Univ, Dept Med, Arthur G James Canc Hosp, Columbus, OH 43210 USA. [Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Ohio State Univ, Coll Pharm, Arthur G James Canc Hosp, Columbus, OH 43210 USA. [Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] Richard J Solove Res Inst, Columbus, OH USA. [Villalona-Calero, M. A.; Otterson, G. A.; Wientjes, M. G.; Bekaii-Saab, T.; Young, D.; Murgo, A. J.; Jensen, R.; Yeh, T. -K.; Wei, Y.; Zhang, Y.; Grever, M.; Au, J. L. -S.] NCI, Bethesda, MD 20892 USA. [Weber, F.; Eng, C.] Cleveland Clin Fdn, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44195 USA. [Weber, F.; Eng, C.] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. RP Villalona-Calero, MA (reprint author), Ohio State Univ, B406 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM miguel.villalona@osumc.edu RI Weber, Frank/A-1883-2012; Bekaii-Saab, Tanios/E-2733-2011; OI Weber, Frank/0000-0002-0995-667X; Eng, Charis/0000-0002-3693-5145 FU National Cancer Institute, DHHS [R37CA49816, R21CA91547, R01CA97067, U01CA76576]; NCI Merit Award; Doris Duke Distinguished Clinical Scientist Award FX R37CA49816 (JLSA), R21CA91547 (JLSA), R01CA97067 (JLSA), and U01CA76576 (MG) from the National Cancer Institute, DHHS; NCI Merit Award to JLSA; Doris Duke Distinguished Clinical Scientist Award to CE. NR 57 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2008 VL 19 IS 11 BP 1903 EP 1909 DI 10.1093/annonc/mdn412 PG 7 WC Oncology SC Oncology GA 365BO UT WOS:000260381100013 PM 18632723 ER PT J AU Bishop, MR Dean, RM Steinberg, SM Odom, J Pavletic, SZ Chow, C Pittaluga, S Sportes, C Hardy, NM Gea-Banacloche, J Kolstad, A Gress, RE Fowler, DH AF Bishop, M. R. Dean, R. M. Steinberg, S. M. Odom, J. Pavletic, S. Z. Chow, C. Pittaluga, S. Sportes, C. Hardy, N. M. Gea-Banacloche, J. Kolstad, A. Gress, R. E. Fowler, D. H. TI Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation SO ANNALS OF ONCOLOGY LA English DT Article DE allogeneic; diffuse large B-cell lymphoma; graft-versus-lymphoma ID NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; EUROPEAN GROUP; CHEMOTHERAPY; LEUKEMIA; BLOOD; EFFICACY; REGISTRY; DISEASE AB Background: A graft-versus-lymphoma effect against diffuse large B-cell lymphoma (DLBCL) is inferred by sustained relapse-free survival after allogeneic stem-cell transplantation; however, there are limited data on a direct graft-versus-lymphoma effect against DLBCL following immunotherapeutic intervention by either withdrawal of immunosuppression or donor lymphocyte infusion (DLI). Materials and methods: An analysis was carried out to determine whether a direct graft-versus-lymphoma effect exists against DLBCL. The analysis was restricted to patients with DLBCL, who were either not in complete remission at day +100 after allogeneic stem-cell transplantation or subsequently relapsed beyond this time point. Results: Fifteen patients were identified as either not in complete remission (n = 13) at their day +100 evaluation or subsequently relapsed (n = 2) and were assessed for subsequent responses after withdrawal of immunosuppression or DLI. Eleven patients were treated with either withdrawal of immunosuppression (n = 10) or a DLI (n = 1) alone; four patients received chemotherapy with DLI to reduce tumor bulk. Nine (60%) patients subsequently responded (complete = 8, partial = 1). Six responses occurred after withdrawal of immunosuppression alone. Six patients are alive (range 42-83+ months) in complete remission without further treatment. Conclusion: The demonstration of sustained complete remission following immunotherapeutic intervention provides direct evidence of a graft-versus-lymphoma effect against DLBCL. C1 [Bishop, M. R.; Dean, R. M.; Odom, J.; Pavletic, S. Z.; Sportes, C.; Hardy, N. M.; Gea-Banacloche, J.; Gress, R. E.; Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Dean, R. M.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Steinberg, S. M.] Natl Canc Inst, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD USA. [Chow, C.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Pittaluga, S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kolstad, A.] Norwegian Radium Hosp, Oslo, Norway. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,CRC Room 4-3152,10 Ctr Dr, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov FU The Center for Cancer Research, National Cancer Institute. FX The Center for Cancer Research, National Cancer Institute. NR 31 TC 38 Z9 41 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2008 VL 19 IS 11 BP 1935 EP 1940 DI 10.1093/annonc/mdn404 PG 6 WC Oncology SC Oncology GA 365BO UT WOS:000260381100018 PM 18684698 ER PT J AU Hoffer, LJ Levine, M Assouline, S Melnychuk, D Padayatty, SJ Rosadiuk, K Rousseau, C Robitaille, L Miller, WH AF Hoffer, L. J. Levine, M. Assouline, S. Melnychuk, D. Padayatty, S. J. Rosadiuk, K. Rousseau, C. Robitaille, L. Miller, W. H., Jr. TI Phase I clinical trial of i.v. ascorbic acid in advanced malignancy SO ANNALS OF ONCOLOGY LA English DT Article DE antioxidants; vitamin C ID VITAMIN-C; DEHYDROASCORBIC ACID; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CANCER-THERAPY; LUNG-CANCER; CELLS; INHIBITION; CHEMOTHERAPY; TOXICITY AB Background: Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies. Patients and methods: Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly. Results: Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response. Conclusions: High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules. C1 [Levine, M.; Padayatty, S. J.] NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Hoffer, L. J.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal Ctr Expt Therapeut Canc, Montreal, PQ H3T 1E2, Canada. RP Hoffer, LJ (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal Ctr Expt Therapeut Canc, 3755 Cote Ste Catherine Rd, ANNALS ONCO Montreal, PQ H3T 1E2, Canada. EM l.hoffer@mcgill.ca RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 FU Lotte and John Hecht Memorial Foundation FX Lotte and John Hecht Memorial Foundation. NR 33 TC 110 Z9 112 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2008 VL 19 IS 11 BP 1969 EP 1974 DI 10.1093/annonc/mdn377 PG 6 WC Oncology SC Oncology GA 365BO UT WOS:000260381100023 PM 18544557 ER PT J AU Shanti, RM Janjanin, S Li, WJ Nesti, LJ Mueller, MB Tzeng, MB Tuan, RS AF Shanti, Rabie M. Janjanin, Sasa Li, Wan-Ju Nesti, Leon J. Mueller, Michael B. Tzeng, Megan B. Tuan, Rocky S. TI In Vitro Adipose Tissue Engineering Using an Electrospun Nanofibrous Scaffold SO ANNALS OF PLASTIC SURGERY LA English DT Article DE adipose tissue engineering; electrospinning; nanofibers; mesechymal stem cells; tissue engineering ID MESENCHYMAL STEM-CELLS; COLLAGEN IMPLANT; AUGMENTATION; VIVO; PREADIPOCYTES; MATRIX; DIFFERENTIATION; TRANSPLANTATION; PROLIFERATION; LIPOSUCTION AB Electrospun 3-dimensional nanofibrous scaffolds share morphologic similarities to collagen fibrils, and promote favorable biologic responses of seeded cells. In this Study, we have fabricated a 3-dimensional nanofibrous scaffold made of poly L-lactic acid, and examined its ability to support and maintain the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro. After a 21-day incubation, on red O staining of constructs treated with adipogenic supplements revealed positive adipose-like staining, compared with lack of staining in untreated cultures. Semi-quantitative RT-PCR analysis of human bone marrow-derived mesenchymal stern Cells Cultured in adipogenic medium revealed highly elevated levels of adipogenesis-associated genes (1797-fold for lipoprotein lipase, and 5.6-fold for peroxisome proliferator-activated receptor gamma). Immunofluorescence staining of cellular constructs in adipogenic culture media showed the presence of lipoprotein lipase vesicles, a characteristic feature of adipose tissue. These results suggest that the poly L-lactic acid-based nanofibrous scaffold is a promising candidate for adult stern cell-based engineering of adipose tissue. C1 [Shanti, Rabie M.; Janjanin, Sasa; Li, Wan-Ju; Mueller, Michael B.; Tzeng, Megan B.; Tuan, Rocky S.] NIAMSD, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. [Shanti, Rabie M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Nesti, Leon J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. RP Tuan, RS (reprint author), NIAMSD, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1523,MSC 8022, Bethesda, MD 20892 USA. EM shanti.rabie@gmail.com FU Intramural Research Program of NIAMS [NIH Z01 AR 41131] FX The authors thank the Light Imaging Section of the Intramural Research National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Dr. James A. Cooper for aid in confocal laser scanning microscopy and scanning electron microscopy, respectively. This work is supported by the Intramural Research Program of NIAMS (NIH Z01 AR 41131). NR 43 TC 23 Z9 25 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD NOV PY 2008 VL 61 IS 5 BP 566 EP 571 DI 10.1097/SAP.0b013e31816d9579 PG 6 WC Surgery SC Surgery GA 364VP UT WOS:000260363800022 PM 18948788 ER PT J AU Zeitoun, G Mourra, N Blanche-Koch, H Thomas, G Olschwang, S AF Zeitoun, Guy Mourra, Najat Blanche-Koch, Helene Thomas, Gilles Olschwang, Sylviane TI Genomic Profile of Colon Cancer Metastases SO ANTICANCER RESEARCH LA English DT Article DE Colon cancer; metastasis; genomic profiling; dormancy; clonal expansion; microsatellite stability ID COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; DORMANCY; APC; MUTATIONS; SURVIVAL; CELLS; SEED AB Background: In colon cancer, the occurrence of metastases is associated with microsatellite stability. As metastatic cells derive from a clonal expansion of primary tumor cells, specific genomic alterations are expected in addition to the common genomic profile. Patients and Methods: Genome-wide allelotyping was performed on 75 liver metastases samples from sporadic colon cancer. Results: No microsatellite instability was observed. Allelic loss on 5q in metastases was significantly different from that of non metastatic primary tumors (16/58 vs. 43/75, p=0.0008). Four additional chromosomes, 4, 7, 8 and 19, were more frequently lost in liver metastases, but statistical significance was reached only for 19q (14/63 versus 2/68 in primary tumors; p=0.033 after Dunn-Sidak adjustment). Conclusion: This study, confirms that liver metastasis is rather restricted to patients with microsatellite stable colon cancer and these retain the 5q arm with high frequency. In addition, it suggests that loss of 19q may be critical for one of the steps involved in the development of liver metastases. C1 [Olschwang, Sylviane] Inst J Paoli I Calmettes, CRCM, INSERM, U891, F-13009 Marseille, France. [Zeitoun, Guy] Gen Hosp, Dept Surg, F-78000 Mantes La Jolie, France. [Mourra, Najat] Hop St Antoine, Dept Pathol, F-75012 Paris, France. [Blanche-Koch, Helene] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. [Olschwang, Sylviane] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Olschwang, Sylviane] Univ Aix Marseille 2, F-13007 Marseille, France. [Thomas, Gilles] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. RP Olschwang, S (reprint author), Inst J Paoli I Calmettes, CRCM, INSERM, U891, 232 Blvd St Marguerite, F-13009 Marseille, France. EM sylviane.olschwang@inserm.f2r RI Olschwang, Sylviane/G-2716-2013 FU Ligue Nationale Contre le Cancer and Association pour la Recherche contre le Cancer FX This work was supported by grants from Ligue Nationale Contre le Cancer and Association pour la Recherche contre le Cancer. The French Association for Surgical Research is gratefully acknowledged for its collaboration with patient recruitment. NR 22 TC 6 Z9 7 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2008 VL 28 IS 6A BP 3609 EP 3612 PG 4 WC Oncology SC Oncology GA 388VW UT WOS:000262049100007 PM 19189641 ER PT J AU Petraitiene, R Petraitis, V Hope, WW Mickiene, D Kelaher, AM Murray, HA Mya-San, C Hughes, JE Cotton, MP Bacher, J Walsh, TJ AF Petraitiene, Ruta Petraitis, Vidmantas Hope, William W. Mickiene, Diana Kelaher, Amy M. Murray, Heidi A. Mya-San, Christine Hughes, Johanna E. Cotton, Margaret P. Bacher, John Walsh, Thomas J. TI Cerebrospinal Fluid and Plasma (1 -> 3)-beta-D-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BIRTH-WEIGHT INFANTS; BETA-D-GLUCAN; AMPHOTERICIN-B; INVASIVE CANDIDIASIS; FUNGAL-INFECTIONS; MICAFUNGIN FK463; BLOOD CULTURES; RISK-FACTORS; ANTIFUNGAL AB The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1 -> 3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously obtained CSF (P < 0.05). CSF beta-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r = 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF beta-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME. C1 [Petraitiene, Ruta; Petraitis, Vidmantas; Hope, William W.; Mickiene, Diana; Kelaher, Amy M.; Murray, Heidi A.; Mya-San, Christine; Hughes, Johanna E.; Cotton, Margaret P.; Walsh, Thomas J.] Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Petraitiene, Ruta; Petraitis, Vidmantas; Mickiene, Diana] SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD USA. [Bacher, John] Off Res Serv, Surg Serv, Div Vet Resources, Bethesda, MD USA. RP Walsh, TJ (reprint author), Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,CRC,Rm 1W-5740,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 35 TC 28 Z9 29 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2008 VL 52 IS 11 BP 4121 EP 4129 DI 10.1128/AAC.00674-08 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 363ZI UT WOS:000260305600041 PM 18779361 ER PT J AU Ostrosky-Zeichner, L Rex, JH Pfaller, MA Diekema, DJ Alexander, BD Andes, D Brown, SD Chaturvedi, V Ghannoum, MA Knapp, CC Sheehan, DJ Walsh, TJ AF Ostrosky-Zeichner, Luis Rex, John H. Pfaller, Michael A. Diekema, Daniel J. Alexander, Barbara D. Andes, David Brown, Steven D. Chaturvedi, Vishnu Ghannoum, Mahmoud A. Knapp, Cindy C. Sheehan, Daniel J. Walsh, Thomas J. TI Rationale for Reading Fluconazole MICs at 24 Hours Rather than 48 Hours When Testing Candida spp. by the CLSI M27-A2 Standard Method SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLORIMETRIC ANTIFUNGAL PANEL; INTERPRETIVE BREAKPOINTS; EMPIRIC TREATMENT; AMPHOTERICIN-B; ITRACONAZOLE; MORTALITY; COMMITTEE; ALBICANS; THERAPY AB We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata. C1 [Ostrosky-Zeichner, Luis; Rex, John H.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA. [Rex, John H.] AstraZeneca, Macclesfield, Cheshire, England. [Pfaller, Michael A.; Diekema, Daniel J.] Univ Iowa, Iowa City, IA USA. [Alexander, Barbara D.] Duke Univ, Durham, NC USA. [Andes, David] Univ Wisconsin, Madison, WI USA. [Brown, Steven D.] Inst Clin Microbiol, Wilsonville, OR USA. [Chaturvedi, Vishnu] New York State Dept Hlth, Albany, NY USA. [Ghannoum, Mahmoud A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Knapp, Cindy C.] TREK Diagnost Syst, Cleveland, OH USA. [Sheehan, Daniel J.] Pfizer Inc, New York, NY USA. [Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. RP Ostrosky-Zeichner, L (reprint author), Univ Texas Houston, Sch Med, 6431 Fannin,MSB 2-112, Houston, TX 77030 USA. EM Luis.Ostrosky-Zeichner@uth.tmc.edu OI Diekema, Daniel/0000-0003-1273-0724 NR 17 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2008 VL 52 IS 11 BP 4175 EP 4177 DI 10.1128/AAC.00420-08 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 363ZI UT WOS:000260305600053 PM 18809944 ER PT J AU Baker, R Peacock, S AF Baker, Robert Peacock, Susan TI BEI Resources: Supporting antiviral research SO ANTIVIRAL RESEARCH LA English DT Article DE Biodefense; Emerging infectious disease; Repository; Reagents; Culture collection; Antiviral therapy AB The Biodefense and Emerging Infections Research Resources Repository (BEI Resources) provides unique, quality-assured reagents to the scientific community for use in basic research and product development involving biodefense and emerging infectious diseases. These include microorganisms (up to Biosafety Level-3) on the National Institute of Allergy and Infectious Diseases (NIAID)and Centers for Disease Control and Prevention (CDC) lists of Category A, B and C priority pathogens. In addition to live microorganisms, related products such as polyclonal antisera, monoclonal antibodies, isolated nucleic acid preparations, overlapping peptide arrays, purified proteins, and assay kits are also available. Many of these materials have direct or indirect applications in antiviral research. These reagents are available free of charge to all registered investigators, regardless of funding source or affiliation. Acquisition of new reagents for the repository is one of the critically necessary and challenging tasks for BEI Resources. Therefore, investigators are encouraged to deposit relevant items, so as to provide access to materials, relief from the burden of distribution, protection of intellectual property rights, and secure storage. In addition, BEI Resources has the capability of contracting for the preparation of specific reagents. If there is a resource needed to advance a specific research area, contact an NIAID program officer or use the "suggest a reagent" option on the BEI Resources homepage, www.beiresources.org. (C) 2008 Elsevier B.V. All rights reserved. C1 [Peacock, Susan] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. [Baker, Robert] BEI Resources, Amer Type Culture Collect, Manassas, VA USA. RP Peacock, S (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. EM peacocksusan@niaid.nih.gov FU NIAID NIH HHS [N01 AI030067] NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2008 VL 80 IS 2 BP 102 EP 106 DI 10.1016/j.antiviral.2008.07.003 PG 5 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 371FX UT WOS:000260818300003 PM 18675849 ER PT J AU Silverman, JEY Ciustea, M Shudofsky, AMD Bender, F Shoemaker, RH Ricciardi, RP AF Silverman, Janice Elaine Y. Ciustea, Mihai Shudofsky, Abigail M. Druck Bender, Florent Shoemaker, Robert H. Ricciardi, Robert P. TI Identification of polymerase and processivity inhibitors of vaccinia DNA synthesis using a stepwise screening approach SO ANTIVIRAL RESEARCH LA English DT Article DE Poxvirus; Vaccinia virus; DNA polymerase; Processivity factor; Antiviral inhibitors; High-throughput screening; Rapid plate assay; Smallpox ID ANTIBACTERIAL AGENT FENTICHLOR; ANTIPOXVIRUS COMPOUND ST-246; TRITYL-L-CYSTEINE; STAPHYLOCOCCUS-AUREUS; SMALLPOX VACCINATION; ESCHERICHIA-COLI; PROTEIN INTERACTIONS; ANTI-MICROBIALS; SLIDING CLAMPS; UNITED-STATES AB Nearly all DNA polymerases require processivity factors to ensure continuous incorporation of nucleotides. Processivity factors are specific for their cognate DNA polymerases. For this reason, the vaccinia DNA polymerase (E9) and the proteins associated with processivity (A20 and D4) are excellent therapeutic targets. In this study, we show the utility of stepwise rapid plate assays that (i) screen for compounds that block vaccinia DNA synthesis, (ii) eliminate trivial inhibitors, e.g. DNA intercalators, and (iii) distinguish whether inhibitors are specific for blocking DNA polymerase activity or processivity. The sequential plate screening of 2222 compounds from the NO Diversity Set library yielded a DNA polymerase inhibitor (NSC 55636) and a processivity inhibitor (NSC 123526) that were capable of reducing vaccinia viral plaques with minimal cellular cytotoxicity. These compounds are predicted to block cellular infection by the smallpox virus, variola, based on the very high sequence identity between A20, D4 and E9 of vaccinia and the corresponding proteins of variola. (C) 2008 Elsevier B.V. All rights reserved. C1 [Silverman, Janice Elaine Y.; Ciustea, Mihai; Bender, Florent; Ricciardi, Robert P.] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Shudofsky, Abigail M. Druck] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21701 USA. [Ricciardi, Robert P.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Ricciardi, RP (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. EM ricciardi@biochem.dental.upenn.edu FU NIH [EID T32]; NIAID [U54-AI057168 MARCE] FX The authors thank Dr. G.H. Cohen and Dr. R.J. Eisenberg (University of Pennsylvania) for kindly providing the viral stocks and HSV antibodies, Dr. S.N. Isaac (University of Pennsylvania) for helpful advice on the plaque assay and Dr. M.J. Currens (NCI) for helping to obtain compounds from the NCI Diversity Set library. A.M.D.S.was supported by an NIH EID T32 training grant. This study was supported by NIAID U54-AI057168 MARCE grant. NR 66 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2008 VL 80 IS 2 BP 114 EP 123 DI 10.1016/j.antiviral.2008.05.010 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 371FX UT WOS:000260818300005 PM 18621425 ER PT J AU Krajewski, P Ammann, M Bartuskova, M Duffa, C Filistovic, V Homma, T Kanyar, B Malatova, I Nedveckaite, T Simon, S Vlasov, O Webbe-Wood, D Zvonova, I AF Krajewski, P. Ammann, M. Bartuskova, M. Duffa, C. Filistovic, V. Homma, T. Kanyar, B. Malatova, I. Nedveckaite, T. Simon, S. Vlasov, O. Webbe-Wood, D. Zvonova, I. TI Validation of environmental transfer models and assessment of the effectiveness of countermeasures using data on I-131 releases from Chernobyl SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT International Conference on Environmental Radioactivity - From Measurements and Assessments to Regulation CY APR 23-27, 2007 CL Vienna, AUSTRIA SP IAEA, Dept Nucl Sci & Applicat, Dept Nucl Safety & Secur DE environmental assessment modelling; iodine-131; Chernobyl releases; thyroid doses; dose reconstruction; effectiveness of countermeasures ID THYROID-CANCER; RECONSTRUCTION; ACCIDENT; BYELARUS; POPULATION; FALLOUT; RUSSIA AB The studies undertaken by the I-131 Working Group, part of the International Atomic Energy Agency's EMRAS (Environmental Modelling for Radiation Safety) programme, were focused primarily on evaluating the predictive capability of environmental models. Particular emphasis was placed on applying models to evaluate the effectiveness of countermeasures. (C) 2008 IAEA. Published by Elsevier Ltd. All rights reserved. C1 [Krajewski, P.] Cent Lab Radiol Protect, Warsaw, Poland. [Ammann, M.; Homma, T.] Radiat & Nucl Safety Author STUK, Helsinki, Finland. [Bartuskova, M.] Natl Radiat Protect Inst SURO, Ostrava, Czech Republic. [Duffa, C.] IRSN, Fontenay Aux Roses, France. [Filistovic, V.; Nedveckaite, T.] Lithuania Acad Sci, Inst Phys, LT-232600 Vilnius, Lithuania. [Kanyar, B.] Univ Pannonia, Veszprem, Hungary. [Malatova, I.] Natl Radiat Protect Inst SURO, Prague, Czech Republic. [Simon, S.] NCI, Bethesda, MD 20892 USA. [Vlasov, O.] RAMS, MRRC, Obninsk, Russia. [Webbe-Wood, D.] FSA, London, England. [Zvonova, I.] Minist Publ Hlth, Inst Radiat Hyg, St Petersburg, Russia. RP Krajewski, P (reprint author), Cent Lab Radiol Protect, Warsaw, Poland. EM krajewski@clor.waw.pl FU PHS HHS [263-MQ-408981] NR 14 TC 2 Z9 3 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD NOV PY 2008 VL 66 IS 11 BP 1730 EP 1735 DI 10.1016/j.apradiso.2007.11.022 PG 6 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 357GK UT WOS:000259834100044 PM 18541435 ER PT J AU Schultz, ZD Stranick, SJ Levin, IW AF Schultz, Zachary D. Stranick, Stephan J. Levin, Ira W. TI Tip-Enhanced Raman Spectroscopy and Imaging: An Apical Illumination Geometry SO APPLIED SPECTROSCOPY LA English DT Article DE Tip-enhanced Raman spectroscopy; TERS; Raman spectroscopy; Near field; Microscopy; Imaging; Vibrational spectroscopy; Radial polarization ID FIELD; MICROSCOPY; SURFACE; SCATTERING; NANOSCALE; AU(111); PROBES; BEAMS AB Results are presented illustrating the use of tip-enhanced Raman spectroscopy (TERS) and imaging in a top-illumination geometry. A radially polarized beam is used to generate an electric field component in the direction of beam propagation, normal to the surface, resulting in a 5X increased enhancement compared to a linearly polarized beam. This multiplicative enhancement facilitates a discrimination of tile near-field signal from the far-field Raman background. The top illumination configuration facilitates the application of TERS for investigating molecules on a variety of surfaces, such as All, glass, and Si. The near-field Raman spectra of Si(100), rhodamine B, brilliant cresyl blue, and single wall carbon nanotubes are presented. Sufficient enhancement is obtained to permit a sub-diffraction-limited resolution Raman imaging of the surface distribution of large bundles of carbon nanotubes of various diameters. C1 [Schultz, Zachary D.; Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Stranick, Stephan J.] Natl Inst Stand & Technol, Surface & Microanal Sci Div, Gaithersburg, MD 20899 USA. RP Levin, IW (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX We acknowledge support from the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 28 TC 15 Z9 15 U1 2 U2 20 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD NOV PY 2008 VL 62 IS 11 BP 1173 EP 1179 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 376QO UT WOS:000261198300003 PM 19007457 ER PT J AU Guyer, AE Lau, JYF McClure-Tone, EB Parrish, J Shiffrin, ND Reynolds, RC Chen, G Blair, RJR Leibenluft, E Fox, NA Ernst, M Pine, DS Nelson, EE AF Guyer, Amanda E. Lau, Jennifer Y. F. McClure-Tone, Erin B. Parrish, Jessica Shiffrin, Nina D. Reynolds, Richard C. Chen, Gang Blair, R. J. R. Leibenluft, Ellen Fox, Nathan A. Ernst, Monique Pine, Daniel S. Nelson, Eric E. TI Amygdala and Ventrolateral Prefrontal Cortex Function During Anticipated Peer Evaluation in Pediatric Social Anxiety SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MASKED ANGRY FACES; FACIAL EXPRESSIONS; DISORDERS; PHOBIA; ADOLESCENTS; ACTIVATION; BEHAVIOR; CHILDREN; HUMANS; FMRI AB Context: Amygdala and ventrolateral prefrontal cortex (vlPFC) dysfunction manifests in adolescents with anxiety disorders when they view negatively valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening. Objective: To determine whether photographs of negatively evaluated smiling peers viewed during anticipated social evaluation engage the amygdala and vlPFC differentially in adolescents with and without social anxiety. Design: Case-control study. Setting: Government clinical research institute. Participants: Fourteen adolescents with anxiety disorders associated with marked concerns of social evaluation and 14 adolescents without a psychiatric diagnosis matched on sex, age, intelligence quotient, and socioeconomic status. Main Outcome Measures: Blood oxygenation level dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants' ratings of specific peers. Results: Participants classified 40 pictures of same-age peers as ones with whom they did or did not want to engage in a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers previously rated as undesired for an interaction. Psychophysiological interaction connectivity analyses also revealed a significant positive association between amygdala and vlPFC activation in anxious vs healthy adolescents in response to these stimuli. Conclusions: Anticipating social evaluation from negatively perceived peers modulates amygdala and vlPFC engagement differentially in anxious and healthy adolescents. Amygdala and vlPFC dysfunction manifests in adolescent anxiety disorders in specific contexts of anticipated peer evaluation. C1 [Guyer, Amanda E.; Lau, Jennifer Y. F.; Shiffrin, Nina D.; Blair, R. J. R.; Leibenluft, Ellen; Ernst, Monique; Pine, Daniel S.; Nelson, Eric E.] NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. [McClure-Tone, Erin B.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Parrish, Jessica] Catholic Univ, Dept Psychol, Washington, DC USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Guyer, AE (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K N Dr,Room 208, Bethesda, MD 20892 USA. EM amandaguyer@mail.nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU Intramural NIH HHS [Z01 MH002781-06]; NIMH NIH HHS [R29 MH057503-03, K99 MH080076, R00 MH080076, R29 MH057503-04] NR 49 TC 151 Z9 154 U1 15 U2 41 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2008 VL 65 IS 11 BP 1303 EP 1312 DI 10.1001/archpsyc.65.11.1303 PG 10 WC Psychiatry SC Psychiatry GA 368DA UT WOS:000260600300008 PM 18981342 ER PT J AU Murphy, AJ Woollard, KJ Hoang, A Mukhamedova, N Stirzaker, RA McCormick, SPA Remaley, AT Sviridov, D Chin-Dusting, J AF Murphy, Andrew J. Woollard, Kevin J. Hoang, Anh Mukhamedova, Nigora Stirzaker, Roslynn A. McCormick, Sally P. A. Remaley, Alan T. Sviridov, Dmitri Chin-Dusting, Jaye TI High-Density Lipoprotein Reduces the Human Monocyte Inflammatory Response SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apolipoprotein A-I; CD11b; monocyte; ABCA1; Tangier ID APOLIPOPROTEIN-A-I; HUMAN ENDOTHELIAL-CELLS; CASSETTE TRANSPORTER A1; CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; CHOLESTEROL EFFLUX; ADHESION MOLECULES; HELICAL PEPTIDES; LIPID EFFLUX; ICAM-1 CD54 AB Objective-Whereas the anti-inflammatory effects of high-density lipoprotein (HDL) on endothelial cells are well described, such effects on monocytes are less studied. Methods and Results-Human monocytes were isolated from whole blood followed by assessment of CD11b activation/expression and cell adhesion under shear-flow. HDL caused a dose-dependent reduction in the activation of CD11b induced by PMA or receptor-dependent agonists. The constituent of HDL responsible for the antiinflammatory effects on CD11b activation was found to be apolipoprotein A-I (apoA-I). Cyclodextrin, but not cyclodextrin/cholesterol complex, also inhibited PMA-induced CD11b activation implicating cholesterol efflux as the main mechanism. This was further confirmed with the demonstration that cholesterol content of lipid rafts diminished after treatment with the cholesterol acceptors. Blocking ABCA1 with an anti-ABCA1 antibody abolished the effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient definitively confirmed the requirement of ABCA1 in apoA-I mediated CD11b inhibition. The antiinflammatory effects of apoA-I were also observed in functional models including cell adhesion to an endothelial cell monolayer, monocytic spreading under shear flow, and transmigration. Conclusions-HDL and apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through several receptors. (Arterioscler Thromb Vasc Biol. 2008; 28: 2071-2077) C1 [Murphy, Andrew J.; Woollard, Kevin J.; Chin-Dusting, Jaye] Baker Heart Res Inst, Labs Vasc Pharmacol, Melbourne, Vic 8008, Australia. [Hoang, Anh; Mukhamedova, Nigora; Sviridov, Dmitri] Baker Heart Res Inst, Lab Lipoprot & Atherosclerosis, Melbourne, Vic 8008, Australia. [Stirzaker, Roslynn A.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [McCormick, Sally P. A.] Univ Otago, Dept Biochem, Dunedin, Otago, New Zealand. [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA. RP Chin-Dusting, J (reprint author), Baker Heart Res Inst, Labs Vasc Pharmacol, POB 6492, Melbourne, Vic 8008, Australia. EM jaye.chin-dusting@baker.edu.au RI Sviridov, Dmitri/E-7943-2010; OI Woollard, Kevin/0000-0002-9839-5463 FU Actelion Ltd, Sydney; Australian National Heart Foundation Research Fellow; Australian National Health; Medical Research Council FX A.J.M. is supported by an industry scholarship form Actelion Ltd, Sydney. K.J.W. is an Australian National Heart Foundation Research Fellow. D. S. and J.C.-D. are Senior Research Fellows of the Australian National Health and Medical Research Council. NR 51 TC 167 Z9 174 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2008 VL 28 IS 11 BP 2071 EP U313 DI 10.1161/ATVBAHA.108.168690 PG 23 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 363NK UT WOS:000260273800030 PM 18617650 ER PT J AU Fujimura, Y Hwang, PM Trout, H Kozloff, L Imaizumi, M Innis, RB Fujita, M AF Fujimura, Yota Hwang, Paul M. Trout, Hugh, III Kozloff, Louis Imaizumi, Masao Innis, Robert B. Fujita, Masahiro TI Increased peripheral benzodiazepine receptors in arterial plaque of patients with atherosclerosis: An autoradiographic study with [(3)H]PK 11195 SO ATHEROSCLEROSIS LA English DT Article DE Atherosclerosis; Macrophage; Peripheral benzodiazepine receptor; [(3)H]PK 11195; Imaging; Nuclear medicine; CD68 ID BRAIN; MACROPHAGES; INFLAMMATION; BINDING AB Inflammation in atherosclerotic plaques makes them unstable and can cause thrombosis. Therefore, it is important to detect macrophage activity for clinical management of atherosclerosis. Peripheral benzodiazepine receptor (PBR) is expressed in various tissue and organs including macrophages. In this study, we tested whether inflammation characterized by macrophage infiltration can be detected by PBR binding. Six patients diagnosed as carotid atherosclerosis underwent endarterectomy. Using the fresh frozen sections, presence of PBRs and macrophages was examined by in vitro autoradiography using [(3)H]PK 11195 and immunohistochemical staining of CD68, respectively. All sections showed specific binding of [(3)H]PK 11195, and the staining with CD68 indicating macrophage infiltration. Density and distribution of PBR detected by [(3)H]PK 11195 autoradiography were consistent with those of the immunohistochemical staining. In conclusion, this Study demonstrated that macrophage and inflammatory activity in atherosclerotic plaque can be imaged specifically by the binding of PBR indicating future application of PET imaging for PBR. Published by Elsevier Ireland Ltd. C1 [Fujimura, Yota; Imaizumi, Masao; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hwang, Paul M.] NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. [Trout, Hugh, III; Kozloff, Louis] Suburban Hosp, Bethesda, MD USA. RP Fujimura, Y (reprint author), NIMH, Mol Imaging Branch, Bldg 31,Room B2-B37,31 Ctr Dr, Bethesda, MD 20892 USA. EM fujimuray@mail.nih.gov FU NIMH [Z01-MH-002852-03] FX This research was supported by the Intramural Program of NIMH (project # Z01-MH-002852-03). We thank David Mozley, MD (Merck Research Laboratory) for suggesting the potential utility of PBR imaging as a marker of inflammation in vulnerable plaque. NR 16 TC 34 Z9 34 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2008 VL 201 IS 1 BP 108 EP 111 DI 10.1016/j.atherosclerosis.2008.02.032 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377QN UT WOS:000261265800013 PM 18433754 ER PT J AU Levitzky, YS Guo, CY Rong, J Larson, MG Walter, RE Keaney, JF Sutherland, PA Vasan, A Lipinska, I Evans, JC Benjamin, EJ AF Levitzky, Yamini S. Guo, Chao-Yu Rong, Jian Larson, Martin G. Walter, Robert E. Keaney, John F., Jr. Sutherland, Patrice A. Vasan, Aditi Lipinska, Izabella Evans, Jane C. Benjamin, Emelia J. TI Relation of smoking status to a panel of inflammatory markers: The Framingham offspring SO ATHEROSCLEROSIS LA English DT Article DE Smoking; Inflammation; Cardiovascular disease; Epidemiology ID CARDIOVASCULAR-DISEASE RISK; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; CIGARETTE-SMOKING; OXIDATIVE STRESS; EXPOSURE; ATHEROSCLEROSIS; POLYMORPHISMS; ASSOCIATIONS; INEQUALITIES AB Aims: We sought to investigate the hypothesis that smoking is accompanied by systemic inflammation. Methods and results: We examined the relation of smoking to 11 systemic inflammatory markers in Framingham Study participants (n = 2944) mean age 60 years, 55% women, 12% ethnic minorities) examined from 1998-2001. The cohort was divided into never (n = 1149), former (n = 1424), and current smokers with last cigarette >6 h (n = 134) or <= 6 h (n = 237) prior to phlebotomy. In multivariable-adjusted models there were significant overall between-smoking group differences (defined as p < 0.0045 to account for multiple testing) for every inflammatory 9 C marker tested, except for serum CD40 ligand (CD40L), myeloperoxidase (MPO) and tumor necrosis factor receptor-2 (TNFR2). With multivariable-adjustment, pair-wise comparisons with never smokers revealed that former smokers had significantly lower concentrations of plasma CD40L (p < 0.0001) and higher concentrations of (CRP) C-reactive protein (p = 0.002). Conclusions: As opposed to never smokers, those with acute cigarette smoke exposure (<= 6h) had significantly higher concentrations of all markers p < 0.0001) except serum CD40L, MPO, and TNFR2; plasma CD40L were significantly lower. Compared with never smokers, cigarette snickers have significantly elevated concentrations of most circulating inflammatory markers, consistent with the hypothesis that smoking is associated with a systemic inflammatory state. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Benjamin, Emelia J.] Boston Univ, NHLBI, Framingham Heart Study, Sch Med, Framingham, MA 01702 USA. [Guo, Chao-Yu; Larson, Martin G.; Evans, Jane C.] Boston Univ, Sch Med, Dept Math Stat & Consulting, Boston, MA 02118 USA. [Keaney, John F., Jr.; Lipinska, Izabella; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Keaney, John F., Jr.; Benjamin, Emelia J.] Boston Med Ctr, Div Cardiol, Boston, MA USA. [Walter, Robert E.] Boston Med Ctr, Div Pulm & Crit Care, Boston, MA USA. [Levitzky, Yamini S.] Case Western Reserve Univ, Heart & Vasc Ctr, Cleveland, OH 44106 USA. RP Benjamin, EJ (reprint author), Boston Univ, NHLBI, Framingham Heart Study, Sch Med, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Larson, Martin/0000-0002-9631-1254; Walter, Robert/0000-0003-4931-5049; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute's Framingham Heart [N01-HC 25195, RO1 HL076784, RO1 HL064753, RO1 AG028321]; Flight Attendants Medical Research Institute's Young Clinical Scientist Award FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC 25195; RO1 HL076784; RO1 HL064753, RO1 AG028321; and the Flight Attendants Medical Research Institute's Young Clinical Scientist Award (Dr. Walter). NR 43 TC 43 Z9 44 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2008 VL 201 IS 1 BP 217 EP 224 DI 10.1016/j.atherosclerosis.2007.12.058 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377QN UT WOS:000261265800029 PM 18289552 ER PT J AU Evrony, HK Ganiban, JM Ulbricht, J Haddad, SK Lichtenstein, P Spotts, EL Reiss, D Neiderhiser, JM AF Evrony, Hilah K. Ganiban, Jody M. Ulbricht, J. Haddad, Suzanne K. Lichtenstein, Paul Spotts, Erica L. Reiss, David Neiderhiser, Jenae M. TI Retrospective Perceptions of Parenting and Marital Satisfaction: Genetic and Environmental Influences SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 38th Annual Meeting of the Behavior-Genetics-Association CY JUN 28, 2008 CL Louisville, KY SP Behav Genet Assoc C1 [Evrony, Hilah K.; Ganiban, Jody M.; Ulbricht, J.; Haddad, Suzanne K.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Lichtenstein, Paul] Karolinska Inst, Stockholm, Sweden. [Spotts, Erica L.] NIA, Bethesda, MD 20892 USA. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, College Stn, TX USA. [Reiss, David] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2008 VL 38 IS 6 BP 625 EP 626 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 367FX UT WOS:000260539000058 ER PT J AU Ganiban, JM Jacobs, T Spotts, EL Lichtenstein, P Reiss, D Neiderhiser, J AF Ganiban, Jody M. Jacobs, Tova Spotts, Erica L. Lichtenstein, Paul Reiss, David Neiderhiser, Jenae TI Family Influences on Personality SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 38th Annual Meeting of the Behavior-Genetics-Association CY JUN 28, 2008 CL Louisville, KY SP Behav Genet Assoc C1 [Ganiban, Jody M.; Jacobs, Tova] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIA, Behav & Social Sci Res Program, Bethesda, MD 20892 USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Stat, Stockholm, Sweden. [Reiss, David] Yale Univ, New Haven, CT USA. [Neiderhiser, Jenae] Penn State Univ, Dept Psychol, State Coll, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2008 VL 38 IS 6 BP 628 EP 628 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 367FX UT WOS:000260539000066 ER PT J AU Grassmann, R Jeang, KT AF Grassmann, Ralph Jeang, Kuan-Teh TI The roles of microRNAs in mammalian virus infection SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Review DE MicroRNA; Virus replication; Innate immunity; Post-transcriptional regulation; Viral gene expression; Virus-host interaction ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; SMALL INTERFERING RNAS; VIRAL GENE-EXPRESSION; HIV-1 TAR ELEMENT; ANTIVIRAL DEFENSE; ENCODED MICRORNAS; ANTISENSE TRANSCRIPTS; CELLULAR MICRORNAS; SILENCING PATHWAY AB MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that are important for the control of a multitude of critical processes in mammalian cells. Increasing evidence supports that miRNAs also have important functions in viral replication and may be used by host cells to control viral infection. Expression of miRNAs has been reported for various groups of viruses including herpesviruses, small DNA viruses and retroviruses. The recent identification of target genes regulated by some of these viral miRNAs suggests that they may function in the control of lytic and latent viral replication, in the limitation of antiviral responses, in the inhibition of apoptosis, and in the stimulation of cellular growth. In this review, we summarize in brief recent findings on the antiviral activities of cellular miRNAs and the viral counter-responses to the cell's RNAi restriction. Published by Elsevier B.V. C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Grassmann, Ralph] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM grassmann@viro.med.uni-erlangen.de; kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU EU; INCA [LSHC-CF-2005-018704]; Deutsche Forschungsgemeinschaft [DFG-GRK1071, GR 1224/3-1]; MAID; NIH; Intramural AIDS Targeted Antiviral Program FX Work in RG's laboratory is supported by grants from Wilhelm Sander-Stiftung, EU (INCA, LSHC-CF-2005-018704) and by Deutsche Forschungsgemeinschaft (DFG-GRK1071, GR 1224/3-1). Work in KTj's laboratory is supported by intramural funding from MAID, NIH; and by the Intramural AIDS Targeted Antiviral Program from the Office of the Director, NIH. NR 100 TC 76 Z9 80 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD NOV PY 2008 VL 1779 IS 11 BP 706 EP 711 DI 10.1016/j.bbagrm.2008.05.005 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 377UF UT WOS:000261275500010 PM 18549828 ER PT J AU Voss, TC Hager, GL AF Voss, Ty C. Hager, Gordon L. TI Visualizing chromatin dynamics in intact cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Chromatin Nuclear receptor; Dynamics; Living cells; Hit-and-run; Transcription ID MAMMARY-TUMOR VIRUS; ESTROGEN-RECEPTOR-ALPHA; RNA-POLYMERASE-II; GREEN FLUORESCENT PROTEIN; LIGAND-SPECIFIC DYNAMICS; INTERACTIONS IN-VIVO; GLUCOCORTICOID-RECEPTOR; LIVING CELLS; MOLECULAR CHAPERONES; NUCLEAR RECEPTORS AB Chromatin and associated regulatory proteins regulate gene expression in the natural environment of the intact cell nucleus. Specific combinations of DNA-binding transcription factors and recruited coregulatory proteins alter the conformation of chromatin at promoters and enhancers of target genes to stimulate or repress transcription. The dynamic nature of the regulatory proteins active in these processes allows the cell to modulate gene expression very rapidly, an important feature in many physiological processes. Live cell imaging and photobleaching studies of fluorescently-tagged proteins reveal that many transcription factors and other chromatin-associated proteins rapidly move through the nucleoplasm. Transcription factors also transiently interact with specific regulatory sequences in chromatin, suggesting that gene activation does not require the formation of stable long-lived regulatory complexes on the chromatin. In this review we discuss how dynamic interactions allow transcriptional regulatory proteins find their targets within the nucleus, alter target chromatin structure, and modulate physiological gene expression. Published by Elsevier B.V. C1 [Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We would like to acknowledge the assistance of Tatiana Karpova, manager of the LRBGE Fluorescence Imaging Facility. NR 77 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV PY 2008 VL 1783 IS 11 SI SI BP 2044 EP 2051 DI 10.1016/j.bbamcr.2008.06.022 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 372PD UT WOS:000260912600002 PM 18675855 ER PT J AU Dowd, TL Li, L Gundberg, CM AF Dowd, T. L. Li, L. Gundberg, C. M. TI The H-1 NMR structure of bovine Pb2+-osteocalcin and implications for lead toxicity SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE Osteocalcin; NMR; Pb2+; Lead toxicity ID GAMMA-CARBOXYGLUTAMIC ACID; OSTEOCALCIN-DEFICIENT MICE; OSTEOBLASTIC BONE-CELLS; X-RAY-FLUORESCENCE; BINDING-PROPERTIES; CRYSTAL-STRUCTURE; CHEMICAL-SHIFT; ELDERLY-MEN; NMR-SPECTRA; PROTEIN AB Structural information on the effect of Pb2+ on proteins under physiologically relevant conditions is largely unknown. We have previously shown that low levels of lead increased the amount of osteocalcin bound to hydroxyapatite (BBA 1535:153). This suggested that lead induced a more compact structure in the protein. We have determined the 3D structure of Pb2+-osteocalcin (49 amino acids), a bone protein from a target tissue, using H-1 2D NMR techniques. Lead, at a stoichiometry of only 1:1, induced a similar fold in the protein as that induced by Ca2+ at a stoichiometry of 3:1. The structure consisted of an unstructured N-terminus and an ordered C-terminal consisting of a hydrophobic core (residues 16-49). The genetic algorithm-molecular dynamics simulation predicted the lead ion was coordinated by the Gla 24 and Gla 21 residues. It is proposed that mineral binding occurs via uncoordinated Gla oxygen ions binding to calcium in hydroxyapatite. A comparison of Pb2+- and Ca2+-osteocalcin suggests Pb2+, at a lower stoichiometry, may induce similar conformational changes in proteins and subsequent molecular processes normally controlled by calcium alone. This may contribute to a molecular mechanism of lead toxicity for calcium binding proteins. Lead exposure may alter the amount of mineral bound osteocalcin and contribute to abnormal bone remodeling. (C) 2008 Elsevier B.V. All rights reserved. C1 [Dowd, T. L.] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA. [Li, L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Gundberg, C. M.] Yale Univ, Sch Med, Dept Orthoped, New Haven, CT USA. RP Dowd, TL (reprint author), CUNY Brooklyn Coll, Dept Chem, Room 359 NE,2900 Bedford Ave, Brooklyn, NY 11210 USA. EM TDowd@brooklyn.cuny.edu FU NIH [ES-9032, AR-38460] FX The authors would like to thank Drs. Mark Girvin, Sean Cahill and John Rosen for their technical advice and helpful discussions. Support for this project was provided by NIH grant ES-9032 to T.D., and NIH grant AR-38460 to C.G. The authors would also like to thank the Analytical Ultracentrifugation Facility of the Albert Einstein College of Medicine for conducting the sedimentation equilibrium experiments. NR 70 TC 5 Z9 5 U1 5 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD NOV PY 2008 VL 1784 IS 11 BP 1534 EP 1545 DI 10.1016/j.bbapap.2008.08.010 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 374CC UT WOS:000261019000007 PM 18793762 ER PT J AU Roy, SW Irimia, M AF Roy, Scott William Irimia, Manuel TI Comment on "When good transcripts go bad: artifactual RT-PCR 'splicing' and genome analysis" response SO BIOESSAYS LA English DT Letter ID INTRON GAIN C1 [Roy, Scott William] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain. RP Roy, SW (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM scottwroy@gmail.com; mirimia@gmail.com RI Irimia, Manuel/E-3040-2010 NR 10 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV-DEC PY 2008 VL 30 IS 11-12 BP 1257 EP 1258 DI 10.1002/bies.20841 PG 2 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 372PF UT WOS:000260912800026 ER PT J AU de Souza, RF Anantharaman, V de Souza, SJ Aravind, L Gueiros, FJ AF de Souza, Robson Francisco Anantharaman, Vivek de Souza, Sandro Jose Aravind, L. Gueiros-Filho, Frederico J. TI AMIN domains have a predicted role in localization of diverse periplasmic protein complexes SO BIOINFORMATICS LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; ESCHERICHIA-COLI; ARCHITECTURE; SECRETIN; KALIGN; FTSN AB We describe AMIN (Amidase N-terminal domain), a novel protein domain found specifically in bacterial periplasmic proteins. AMIN domains are widely distributed among peptidoglycan hydrolases and transporter protein families. Based on experimental data, contextual information and phyletic profiles, we suggest that AMIN domains mediate the targeting of periplasmic or extracellular proteins to specific regions of the bacterial envelope. C1 [de Souza, Robson Francisco; Gueiros-Filho, Frederico J.] Univ Sao Paulo, Dept Bioquim, Sao Paulo, Brazil. [de Souza, Robson Francisco; de Souza, Sandro Jose] Ludwig Inst Canc Res, Sao Paulo Branch, Sao Paulo, Brazil. [Anantharaman, Vivek; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Gueiros, FJ (reprint author), Univ Sao Paulo, Dept Bioquim, Sao Paulo, Brazil. RI Gueiros-Filho, Frederico/D-2160-2013; OI Gueiros-Filho, Frederico/0000-0001-5425-2439; Anantharaman, Vivek/0000-0001-8395-0009 FU FAPESP [02/10616-4]; National Library of Medicine; CNPq (Brazil) FX FAPESP 02/10616-4 (to F. J. G.-F.); National Library of Medicine [Intramural funds. National Institutes of Health (to V. A. and L. A.)]. R. F. de. S. was a recipient of a doctoral fellowship from CNPq (Brazil). NR 19 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2008 VL 24 IS 21 BP 2423 EP 2426 DI 10.1093/bioinformatics/btn449 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 365BP UT WOS:000260381200001 PM 18723522 ER PT J AU La Camera, G Giugliano, M Senn, W Fusi, S AF La Camera, Giancarlo Giugliano, Michele Senn, Walter Fusi, Stefano TI The response of cortical neurons to in vivo-like input current: theory and experiment SO BIOLOGICAL CYBERNETICS LA English DT Review DE Integrate-and-fire; Mean field; Population density; Collective dynamics; Attractor; Pyramidal; Fast spiking ID INTEGRATE-AND-FIRE; SPIKE-FREQUENCY ADAPTATION; NEOCORTICAL PYRAMIDAL NEURONS; PRIMATE TEMPORAL CORTEX; MULTIPLE TIME SCALES; WORKING-MEMORY; IN-VIVO; SYNAPTIC INPUT; PERSISTENT ACTIVITY; PREFRONTAL CORTEX AB The study of several aspects of the collective dynamics of interacting neurons can be highly simplified if one assumes that the statistics of the synaptic input is the same for a large population of similarly behaving neurons (mean field approach). In particular, under such an assumption, it is possible to determine and study all the equilibrium points of the network dynamics when the neuronal response to noisy, in vivo-like, synaptic currents is known. The response function can be computed analytically for simple integrate-and-fire neuron models and it can be measured directly in experiments in vitro. Here we review theoretical and experimental results about the neural response to noisy inputs with stationary statistics. These response functions are important to characterize the collective neural dynamics that are proposed to be the neural substrate of working memory, decision making and other cognitive functions. Applications to the case of time-varying inputs are reviewed in a companion paper (Giugliano et al. in Biol Cybern, 2008). We conclude that modified integrate-and-fire neuron models are good enough to reproduce faithfully many of the relevant dynamical aspects of the neuronal response measured in experiments on real neurons in vitro. C1 [La Camera, Giancarlo] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Giugliano, Michele] Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, Lausanne, Switzerland. [Giugliano, Michele] Univ Antwerp, Antwerp, Belgium. [Senn, Walter] Univ Bern, Inst Physiol, Bern, Switzerland. [Fusi, Stefano] Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, New York, NY 10032 USA. [Fusi, Stefano] Univ Zurich, ETH, Inst Neuroinformat, Zurich, Switzerland. RP La Camera, G (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr,Rm 1B80, Bethesda, MD 20892 USA. EM lacamerag@gmail.com RI Giugliano, Michele/A-5666-2012; Senn, Walter/D-6308-2014; Fusi, Stefano/E-9109-2011 OI Giugliano, Michele/0000-0003-2626-594X; Senn, Walter/0000-0003-3622-0497; Fusi, Stefano/0000-0002-3035-6652 FU National Institute of Mental Health; European Commission [FP6-2004-IST-FETPI-015879, LSHM-CT-2005-019055]; Swiss National Science Foundation [3152A0-105966, PP00A-106556] FX G. La Camera is supported by the Intramural Research Program of the National Institute of Mental Health. M. Giugliano is supported by the European Commission (FACETS Project FP6-2004-IST-FETPI-015879, EUSynapse Project LSHM-CT-2005-019055). W. Senn is supported by the Swiss National Science Foundation, grant No. 3152A0-105966. S. Fusi is supported by the Swiss National Science Foundation, grant PP00A-106556. The views expressed in this article do not necessarily represent the views of the NIMH, NIH, or the US Government. NR 155 TC 18 Z9 18 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD NOV PY 2008 VL 99 IS 4-5 BP 279 EP 301 DI 10.1007/s00422-008-0272-7 PG 23 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 372YL UT WOS:000260938100005 PM 18985378 ER PT J AU Giugliano, M La Camera, G Fusi, S Senn, W AF Giugliano, Michele La Camera, Giancarlo Fusi, Stefano Senn, Walter TI The response of cortical neurons to in vivo-like input current: theory and experiment: II. Time-varying and spatially distributed inputs SO BIOLOGICAL CYBERNETICS LA English DT Review DE Populations of spiking neurons; Dynamics; Integrate-and-fire model; Patch clamp; Calcium spikes ID SPIKE-FREQUENCY ADAPTATION; POPULATION-DENSITY APPROACH; PRIMARY VISUAL-CORTEX; PYRAMIDAL NEURONS; NEOCORTICAL NEURONS; FIRE NEURONS; SHUNTING INHIBITION; SENSORY ADAPTATION; GAIN MODULATION; NEURAL-NETWORKS AB The response of a population of neurons to time-varying synaptic inputs can show a rich phenomenology, hardly predictable from the dynamical properties of the membrane's inherent time constants. For example, a network of neurons in a state of spontaneous activity can respond significantly more rapidly than each single neuron taken individually. Under the assumption that the statistics of the synaptic input is the same for a population of similarly behaving neurons (mean field approximation), it is possible to greatly simplify the study of neural circuits, both in the case in which the statistics of the input are stationary (reviewed in La Camera et al. in Biol Cybern, 2008) and in the case in which they are time varying and unevenly distributed over the dendritic tree. Here, we review theoretical and experimental results on the single-neuron properties that are relevant for the dynamical collective behavior of a population of neurons. We focus on the response of integrate-and-fire neurons and real cortical neurons to long-lasting, noisy, in vivo-like stationary inputs and show how the theory can predict the observed rhythmic activity of cultures of neurons. We then show how cortical neurons adapt on multiple time scales in response to input with stationary statistics in vitro. Next, we review how it is possible to study the general response properties of a neural circuit to time-varying inputs by estimating the response of single neurons to noisy sinusoidal currents. Finally, we address the dendrite-soma interactions in cortical neurons leading to gain modulation and spike bursts, and show how these effects can be captured by a two-compartment integrate-and-fire neuron. Most of the experimental results reviewed in this article have been successfully reproduced by simple integrate-and-fire model neurons. C1 [Giugliano, Michele] Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, CH-1015 Lausanne, Switzerland. [Giugliano, Michele] Univ Antwerp, Antwerp, Belgium. [La Camera, Giancarlo] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Fusi, Stefano] Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, New York, NY 10032 USA. [Fusi, Stefano] Univ Zurich, ETH, Inst Neuroinformat, Zurich, Switzerland. [Senn, Walter] Univ Bern, Dept Physiol, CH-3012 Bern, Switzerland. RP Giugliano, M (reprint author), Ecole Polytech Fed Lausanne, Lab Neural Microcircuitry, Stn 15, CH-1015 Lausanne, Switzerland. EM michele.giugliano@epfl.ch; michele.giugliano@ua.ac.be RI Giugliano, Michele/A-5666-2012; Senn, Walter/D-6308-2014; Fusi, Stefano/E-9109-2011 OI Giugliano, Michele/0000-0003-2626-594X; Senn, Walter/0000-0003-3622-0497; Fusi, Stefano/0000-0002-3035-6652 FU European Commission; Intramural Research Program; NIMH; Swiss National Science Foundation [PP00A-106556, 3152A0-105966] FX M. Giugliano acknowledges support from the European Commission (FACETS and EUSynapse Project). G. La Camera is supported by the Intramural Research Program, NIMH. S. Fusi is supported by the Swiss National Science Foundation, grant PPP00A-106556. W. Senn is supported by the Swiss National Science Foundation, grant no. 3152A0-105966. The views expressed in this article do not necessarily repesent the views of the NIMH, NIH, or the United States Government. NR 93 TC 9 Z9 9 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD NOV PY 2008 VL 99 IS 4-5 BP 303 EP 318 DI 10.1007/s00422-008-0270-9 PG 16 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 372YL UT WOS:000260938100006 PM 19011920 ER PT J AU Ceaser, AE Goldberg, TE Egan, MF McMahon, RP Weinberger, DR Gold, JM AF Ceaser, Alan E. Goldberg, Terry E. Egan, Michael F. McMahon, Robert P. Weinberger, Daniel R. Gold, James M. TI Set-Shifting Ability and Schizophrenia: A Marker of Clinical Illness or an Intermediate Phenotype? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE CANTAB; cognition; executive function; intermediate phenotype; schizophrenia; set-shifting; working memory ID EXECUTIVE FUNCTION; 1ST-EPISODE SCHIZOPHRENIA; PREPULSE INHIBITION; PARKINSONS-DISEASE; COGNITIVE DEFICITS; HEALTHY-VOLUNTEERS; WORKING-MEMORY; LIFE-SPAN; PERFORMANCE; RELATIVES AB Background: Impairments of executive functioning, such as set-shifting ability, are seen as core deficits of schizophrenia and are of interest as candidate intermediate phenotype markers. The lntradimensional/Extradimensional (ID/ED) shift task offers a differentiated assessment of shifting from previously reinforced stimuli as well as shifting from previously reinforced features and has proven to be sensitive to the impairment seen in patients with schizophrenia. Methods: We examined ID/ED performance in 147 patients with schizophrenia, 131 of their healthy siblings, and 303 healthy control subjects. Participants were recruited from local and national sources as volunteers for the Clinical Brain Disorders Branch/National Institute of Mental Health "sibling study". Results: Nearly all control subjects (87%) finished the task successfully, as did 80% of siblings. In contrast only 54% of patients with schizophrenia were able to complete the task. Despite the apparent similarity of performance across the sibling and healthy comparison group, the two groups differed significantly in terms of the number of stages until failure. This difference, however, was not present at any particular stage or any other measure of performance. Conclusions: Patients demonstrated robust ID/ED deficits. However, their siblings were minimally impaired, and this impairment did not seem to run in families. These results suggest that impairments on attentional set shifting assessed by ID/ED task are strongly associated with clinical illness, but these impairments are not a promising intermediate phenotype. C1 [Ceaser, Alan E.; Goldberg, Terry E.; Egan, Michael F.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [McMahon, Robert P.; Gold, James M.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RP Weinberger, DR (reprint author), 10 Ctr Dr,MSC 1379,CRC Bldg,10 Bethesda, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI McMahon, Robert/C-5462-2009; OI Ceaser, Alan/0000-0002-1554-6693 FU Intramural NIH HHS [Z01 MH002712-13] NR 41 TC 46 Z9 46 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2008 VL 64 IS 9 BP 782 EP 788 DI 10.1016/j.biopsych.2008.05.009 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 364WD UT WOS:000260365300007 PM 18597738 ER PT J AU Karlsson, RM Tanaka, K Heilig, M Holmes, A AF Karlsson, Rose-Marie Tanaka, Kohichi Heilig, Markus Holmes, Andrew TI Loss of Glial Glutamate and Aspartate Transporter (Excitatory Amino Acid Transporter 1) Causes Locomotor Hyperactivity and Exaggerated Responses to Psychotomimetics: Rescue by Haloperidol and Metabotropic Glutamate 2/3 Agonist SO BIOLOGICAL PSYCHIATRY LA English DT Article DE GLAST; glutamate; mGlu2/3; NMDA; schizophrenia ID PREFRONTAL CORTEX; RECEPTOR AGONIST; SCHIZOPHRENIA; KETAMINE; MICE; PHENCYCLIDINE; TRANSMISSION; EXPRESSION; RAT AB Background: Recent data suggest that excessive glutamatergic signaling in the prefrontal cortex may contribute to the pathophysiology of schizophrenia and that promoting presynaptic glutamate modulation via group II metabotropic glutamate 2/3 (mGlu2/3) receptor activation can exert antipsychotic efficacy. The glial glutamate and aspartate transporter (GLAST) (excitatory amino acid transporter 1 [EAAT1]) regulates extracellular glutamate levels via uptake into glia, but the consequences of GLAST dysfunction for schizophrenia are largely unknown. Methods: We examined GLAST knockout mice (KO) for behaviors thought to model positive symptoms in schizophrenia (locomotor hyperactivity to novelty, exaggerated locomotor response to N-methyl-D-aspartate receptor [NMDAR] antagonism) and the ability of haloperidol and the mGlu2/3 agonist LY379268 to normalize novelty-induced hyperactivity. Results: Glial glutamate and aspartate transporter KO consistently showed locomotor hyperactivity to a novel but not familiar environment, relative to wild-type (WT) mice. The locomotor hyperactivity-inducing effects of the NMDAR antagonist MK-801 was exaggerated in GLAST KO relative to WT. Treatment with haloperidol or LY379268 normalized novelty-induced locomotor hyperactivity in GLAST KO. Conclusions: Schizophrenia-related abnormalities in GLAST KO raise the possibility that loss of GLAST-mediated glutamate clearance could be a pathophysiological risk factor for the disease. Our findings provide novel support for the hypothesis that glutamate dysregulation contributes to the pathophysiology of schizophrenia and for the antipsychotic potential of mGlu2/3 agonists. C1 [Karlsson, Rose-Marie; Heilig, Markus] Natl Inst Alcohol Abuse & Alcoholism, Lab Clin & Translat Studies, Natl Inst Hlth, Bethesda, MD 20892 USA. [Tanaka, Kohichi] Tokyo Med & Dent Univ, Lab Mol Neurosci, Sch Biomed Sci, Bunkyo Ku, Tokyo, Japan. [Tanaka, Kohichi] Tokyo Med & Dent Univ, Med Res Inst, Bunkyo Ku, Tokyo, Japan. [Holmes, Andrew] Natl Inst Alcoholism & Alcohol Abuse, NIH, Lab Integrat Neurosci, Sect Behav Sci & Genet, Rockville, MD USA. RP Karlsson, RM (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Lab Clin & Translat Studies, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 1-5330, Bethesda, MD 20892 USA. EM karlssonr@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 FU National Institute on Alcohol Abuse and Alcoholism (AMAA)-Intramural Research Program (IRP); The Novartis Foundation (Japan); The Tokyo Biochemical Research Foundation; Research Foundation of Opto-Science and Technology; Ministry of Education, Culture, Sports, Science, and Technology of Japan [20022013, 18053006] FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism (AMAA)-Intramural Research Program (IRP). Tanaka was supported by The Novartis Foundation (Japan) for the Promotion of Science, Takeda Science Foundation, The Tokyo Biochemical Research Foundation, Research Foundation of Opto-Science and Technology, and Grants-in-Aids for Scientific Research on Prioriy Area (20022013 and 18053006) provided by the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 23 TC 50 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2008 VL 64 IS 9 BP 810 EP 814 DI 10.1016/j.biopsych.2008.05.001 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 364WD UT WOS:000260365300011 PM 18550032 ER PT J AU Petricciani, J Sheets, R AF Petricciani, John Sheets, Rebecca TI An overview of animal cell substrates for biological products SO BIOLOGICALS LA English DT Article DE Cell substrates; Vaccines; Biological products AB The issue of which cells to use as substrates for the production of biological products, and especially vaccines, has been with us in one form or another ever since the development of cell cultures in the 1950s. The major cell substrate events that occurred over the past 50 years are reviewed briefly. Although numerous conferences were held during that period, incomplete resolution of some cell substrate issues has remained. Specifically, the potential oncogenicity of cellular DNA derived from continuous cell lines, and the tests that are used to rule out the presence of adventitious agents have been recognized as areas that could benefit greatly from studies using state-of-the-art techniques. A collaborative effort involving WHO, NIAID, and IABS resulted from consensus recommendations of a 2004 conference, and the prospects for revised guidance in the near future on the characterization and use of animal cell substrates are bright. (C) 2008 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 [Petricciani, John] John Wayne Canc Inst, Santa Monica, CA 90404 USA. [Sheets, Rebecca] NIAID, US PHS, NIH, Bethesda, MD 20892 USA. RP Petricciani, J (reprint author), John Wayne Canc Inst, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. EM jpmdpsca@aol.com NR 8 TC 14 Z9 15 U1 2 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD NOV PY 2008 VL 36 IS 6 BP 359 EP 362 DI 10.1016/j.biologicals.2008.06.004 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 389BY UT WOS:000262066300005 PM 18674929 ER PT J AU Lee, SJ Astigarraga, CC Eapen, M Artz, AS Davies, SM Champlin, R Jagasia, M Kernan, NA Loberiza, FR Bevans, M Soiffer, RJ Joffe, S AF Lee, Stephanie J. Astigarraga, Claudia C. Eapen, Mary Artz, Andrew S. Davies, Stella M. Champlin, Richard Jagasia, Madan Kernan, Nancy A. Loberiza, Fausto R., Jr. Bevans, Margaret Soiffer, Robert J. Joffe, Steven TI Variation in Supportive Care Practices in Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Practice variation; Supportive care; Autologous stem cell transplantation; Allogeneic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; RANDOMIZED CONTROLLED-TRIALS; URSODEOXYCHOLIC ACID; PROTECTIVE ISOLATION; INFORMED-CONSENT; CLINICAL-TRIALS; EUROPEAN-GROUP; ACUTE GVHD; BLOOD AB Hematopoietic cell transplantation is an elective procedure that results in prolonged immune suppression and high treatment-related morbidity and mortality. Transplant centers and physicians use a variety of prophylaxis and monitoring strategies to prevent or minimize complications. Little is known about the variability in these practices. We conducted an international Internet-based survey of 526 physicians to describe the spectrum of supportive care practices employed. Consistency in pretransplant cardiac (96%) and pulmonary (95%) screening, informed consent documentation (93%), and use of antifungal prophylaxis (92%) was observed. Greater heterogeneity was seen in use of myelogenous growth factors, empiric antibiotic therapy, protective isolation procedures, posttransplant monitoring, and environmental and social restrictions. Although some practice differences were associated with physician characteristics and transplant type, most practice variation remained unexplained. These results suggest a need for well-designed observational and interventional studies to provide data about which supportive care practices improve outcomes. For practices proved to be beneficial, publication of guidelines and incorporation of monitoring into quality improvement initiatives may help standardize practices. C1 [Lee, Stephanie J.; Astigarraga, Claudia C.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Artz, Andrew S.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Davies, Stella M.] Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. [Champlin, Richard] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Jagasia, Madan] Vanderbilt Univ, Ctr Med, Div Hematol Oncol, Nashville, TN 37232 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, Pediat Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Loberiza, Fausto R., Jr.] Univ Nebraska, Dept Med, Omaha, NE 68182 USA. [Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Joffe, Steven] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Joffe, Steven] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA. EM sjlee@fhcrc.org OI Kernan, Nancy/0000-0003-1417-1823; Joffe, Steven/0000-0002-0667-7384 FU Intramural NIH HHS [Z99 CL999999]; NCI NIH HHS [U24 CA076518] NR 34 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2008 VL 14 IS 11 BP 1231 EP 1238 DI 10.1016/j.bbmt.2008.08.008 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 367DY UT WOS:000260533900005 PM 18940677 ER PT J AU Allen, D Herbert, DC McMahan, CA Rotrekl, V Sobol, RW Wilson, SH Walter, CA AF Allen, Diwi Herbert, Damon C. McMahan, C. Alex Rotrekl, Vladimir Sobol, Robert W. Wilson, Samuel H. Walter, Christi A. TI Mutagenesis Is Elevated in Male Germ Cells Obtained from DNA Polymerase-beta Heterozygous Mice SO BIOLOGY OF REPRODUCTION LA English DT Article DE base excision repair; DNA repair; gamete biology; gametogenesis; lacl; mutagenesis; POLB; spermatogenesis; spermatogenic cells ID BASE EXCISION-REPAIR; LIGASE-III; NUCLEAR EXTRACTS; MAMMALIAN-CELLS; POLY(ADP-RIBOSE) POLYMERASE; MEIOTIC RECOMBINATION; SPERMATOGENIC CELLS; MUTATION FREQUENCY; BINDING ACTIVITY; TRANSGENIC MICE AB Gametes carry the DNA that will direct the development of the next generation. By compromising genetic integrity, DNA damage and mutagenesis threaten the ability of gametes to fulfill their biological function. DNA repair pathways function in germ cells and serve to ameliorate much DNA damage and prevent mutagenesis. High base excision repair (BER) activity is documented for spermatogenic cells. DNA polymerase-beta (POLB) is required for the short-patch BER pathway. Because mice homozygous null for the Polb gene die soon after birth, mice heterozygous for Polb were used to examine the extent to which POLB contributes to maintaining spermatogenic genomic integrity in vivo. POLB protein levels were reduced only in mixed spermatogenic cells. In vitro short-patch BER activity assays revealed that spermatogenic cell nuclear extracts obtained from Polb heterozygous mice had one third the BER activity of age-matched control mice. Polb heterozygosity had no effect on the BER activities of somatic tissues tested. The Polb heterozygous mouse line was crossed with the lacl transgenic Big Blue mouse line to assess mutant frequency. The spontaneous mutant frequency for mixed spermatogenic cells prepared from Polb heterozygous mice was 2-fold greater than that of wild-type controls, but no significant effect was found among the somatic tissues tested. These results demonstrate that normal POLB abundance is necessary for normal BER activity, which is critical in maintaining a low germline mutant frequency. Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency. C1 [Allen, Diwi; Herbert, Damon C.; Rotrekl, Vladimir; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [McMahan, C. Alex] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. [Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Sobol, Robert W.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. [Wilson, Samuel H.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Walter, Christi A.] Audie Murphy Mem Vet Affairs Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Mail Code 7762, San Antonio, TX 78229 USA. EM walter@uthscsa.edu RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU Elsa U. Pardee Foundation [P20 CA103730]; National Institutes of Health [1 R01 AG24364-01, AG21163]; National Institute of Environmental Health Sciences FX Supported by grant P20 CA103730 from the Elsa U. Pardee Foundation and the National Institutes of Health to R.W.S. and by grants 1 R01 AG24364-01 and AG21163 from the National Institutes of Health to C.A.W. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The contents are solely the responsibility of the authors and do not necessarily reflect the views of the funding agencies. NR 73 TC 15 Z9 17 U1 0 U2 8 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 2008 VL 79 IS 5 BP 824 EP 831 DI 10.1095/biolreprod.108.069104 PG 8 WC Reproductive Biology SC Reproductive Biology GA 364FJ UT WOS:000260321300005 PM 18650495 ER PT J AU Han, YM Romero, R Kim, JS Tarca, AL Kim, SK Draghici, S Kusanovic, JP Gotsch, F Mittal, P Hassan, SS Kim, CJ AF Han, Yu Mi Romero, Roberto Kim, Jung-Sun Tarca, Adi L. Kim, Sun Kwon Draghici, Sorin Kusanovic, Juan Pedro Gotsch, Francesca Mittal, Pooja Hassan, Sonia S. Kim, Chong Jai TI Region-Specific Gene Expression Profiling: Novel Evidence for Biological Heterogeneity of the Human Amnion SO BIOLOGY OF REPRODUCTION LA English DT Article DE IL1B; lipopolysaccharide; microarray; parturition; placenta; pregnancy ID OCULAR SURFACE RECONSTRUCTION; HUMAN GESTATIONAL TISSUES; FETAL MEMBRANES; PREMATURE RUPTURE; HLA-G; SPONTANEOUS LABOR; EPITHELIAL-CELLS; HUMAN PLACENTA; TERM; PRETERM AB The amnion plays an important role during pregnancy and parturition. Though referred to as a single structure, this fetal tissue is regionally divided into placental amnion, reflected amnion, and umbilical amnion. Histological differences between placental amnion and reflected amnion led us to hypothesize that the amnion is biologically heterogeneous. The gene expression profiles of placental amnion and reflected amnion were compared in patients at term with no labor (TNL; n = 10) and in labor (TIL; n = 10). Real-time quantitative RTPCR revealed a higher expression of IL1B mRNA in reflected amnion than in placental amnion in TNL cases but not in TIL cases. Extended screening using microarrays showed differential expression of 17 genes in labor, regardless of the region. Interestingly, 839 genes were differentially expressed between placental amnion and reflected amnion. Pathway analysis identified 19 signaling pathways, such as mitogen-activated protein kinase and transforming growth factor beta pathways, associated with region. Lipopolysaccharide (LPS) treatment of the amnion explants showed more robust activation of mitogen-activated protein kinase 3/1 (extracellular signal-regulated kinase 1/2) in placental amnion of TNL but not in TIL cases. Placental amnion from TNL and TIL cases showed a significant difference in the amplitude of IL1B mRNA induction by LPS. We report that the anatomical region has a substantial impact on the transcriptional program and the biological properties of the amnion. Labor-associated switching to a proinflammatory signature is a feature particular to placental amnion. The novel observations herein strongly suggest that the seemingly homogeneous amnion is biologically heterogeneous and compartmentalized, with implications for the physiology of pregnancy and parturition. C1 [Han, Yu Mi; Romero, Roberto; Kim, Jung-Sun; Kim, Sun Kwon; Kusanovic, Juan Pedro; Gotsch, Francesca; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Han, Yu Mi; Romero, Roberto; Kim, Jung-Sun; Tarca, Adi L.; Kim, Sun Kwon; Kusanovic, Juan Pedro; Gotsch, Francesca; Mittal, Pooja; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Kim, Jung-Sun; Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 36 TC 29 Z9 30 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 2008 VL 79 IS 5 BP 954 EP 961 DI 10.1095/biolreprod.108.069260 PG 8 WC Reproductive Biology SC Reproductive Biology GA 364FJ UT WOS:000260321300020 PM 18685129 ER PT J AU Kuznetsov, SA Huang, KE Marshall, GW Robey, PG Mankani, MH AF Kuznetsov, Sergei A. Huang, Katherine E. Marshall, Grayson W. Robey, Pamela G. Mankani, Mahesh H. TI Long-term stable canine mandibular augmentation using autologous bone marrow stromal cells and hydroxyapatite/tricalcium phosphate SO BIOMATERIALS LA English DT Article DE Autologous cell; Bone tissue engineering; Hydroxyapatite composite; Stem cell; Transplantation ID TISSUE-ENGINEERED BONE; MESENCHYMAL STEM-CELLS; TRICALCIUM PHOSPHATE; IN-VIVO; RECONSTRUCTION; DEFECTS; REGENERATION; REPAIR AB Transplants of culture-expanded bone marrow stromal cells (BMSCs) combined with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds successfully form cortico-cancellous bone to reconstruct the dog craniofacial skeleton. Yet, these transplants' long-term stability in large animal models has not been evaluated. This study's purpose was the evaluation of long-term BMSC transplant stability when used to augment the mandible. Here, autologous BMSC-HA/TCP transplants were introduced onto the unilateral dog mandible as onlay grafts, while contralateral control mandibles received HA/TCP onlays alone. Quantitative CT (qCT) scans were obtained both early and late after transplantation. Transplants were harvested up to 19 months later for histologic and mechanical analyses. In all dogs, BMSC transplants formed significantly greater amounts of bone over their control counterparts. The new bone formed an extensive union with the underlying mandible. BMSC transplants retained the majority of their initial volume, while control (HA/TCP only) transplants were nearly completely resorbed. By qCT, the extent of newly formed bone could be determined non-invasively. In summary, HA/TCP particles alone undergo a high degree of resorption, while autologous cultured BMSC-HA/TCP transplants provide long-term bony augmentation of the mandible. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Huang, Katherine E.; Mankani, Mahesh H.] Univ Calif San Francisco, Dept Surg, Div Plast Surg, San Francisco, CA 94143 USA. [Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, Dept Surg, Div Plast Surg, 1001 Potrero Ave,Box 0807, San Francisco, CA 94143 USA. EM mahesh.mankani@ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU University of California- San Francisco Research Evaluation and Allocation Committee; National Institute of Dental and Craniofacial Research, NIH, DHHS FX The authors are indebted to Zimmer (Warsaw, IN) for its gift of HA/TCP, to Mindways Software (San Francisco, CA) and Dr. Chris Cann for technical assistance, and to Dr. Nilo Avila, Mr. Dennis Johnson, Mr. David Williams, and Mr. Ronald Norman (Department of Radiology, Clinical Center, National Institutes of Health, Bethesda, MD) for assistance with the imaging. Mr. Kent Yamaguchi Jr. provided additional technical assistance. This research was supported in part by the University of California- San Francisco Research Evaluation and Allocation Committee and in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH, DHHS. NR 12 TC 23 Z9 23 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD NOV PY 2008 VL 29 IS 31 BP 4211 EP 4216 DI 10.1016/j.biomaterials.2008.07.013 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 359BG UT WOS:000259960600009 PM 18687465 ER PT J AU Thomas, JD Hofer, T Rader, C Burke, TR AF Thomas, Joshua D. Hofer, Thomas Rader, Christoph Burke, Terrence R., Jr. TI Application of a trifunctional reactive linker for the construction of antibody-drug hybrid conjugates SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE LLP2A; Immunoconjugate; Fc; IgG1; Peptidomimetic; Integrin ID ALPHA(4)BETA(1) INTEGRIN; CANCER-THERAPY; SOLID-PHASE AB A flexible, trifunctional poly(ethylene glycol)-succinamide-Lysine-Lysine-maleimide (PEG-SU-Lys-Lysmal) linker was employed to simultaneously allow biotin tagging and cell-surface targeting through an integrin alpha(4)beta(1)-binding peptidomimetic that was regiospecifically conjugated to an IgG1-derived Fc fragment with an engineered C-terminal selenocysteine residue. The resulting antibody derivative mediates Fc receptor binding by virtue of the Fc protein and selectively targets cancer cells expressing human integrin alpha(4)beta(1). The PEG-SU-Lys-Lys-mal linker may have general utility as an organic tether for the construction of antibody-drug conjugates. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA. [Hofer, Thomas; Rader, Christoph] NCI, NIH, Expt Transplantat & Immunol Branch, CCR, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, NIH, Med Chem Lab, CCR, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU Intramural Research Program of the Center for Cancer Research; NCI-Frederick; NCI; NIH FX This work was supported by the Intramural Research Program of the Center for Cancer Research, NCI-Frederick and NCI, NIH. NR 17 TC 7 Z9 7 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2008 VL 18 IS 21 BP 5785 EP 5788 DI 10.1016/j.bmcl.2008.09.078 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 362WH UT WOS:000260227400019 PM 18922692 ER PT J AU Chong, HS Lim, S Baidoo, KE Milenic, DE Ma, X Jia, F Song, HA Brechbiel, MW Lewis, MR AF Chong, Hyun-Soon Lim, Sooyoun Baidoo, Kwamena E. Milenic, Diane E. Ma, Xiang Jia, Fang Song, Hyun A. Brechbiel, Martin W. Lewis, Michael R. TI Synthesis and biological evaluation of a novel decadentate ligand DEPA SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Radioimmunotherapy; DEPA; (177)Lu; (212)Bi; (213)Bi; Bimodal ligand ID AGENTS; RADIOIMMUNOTHERAPY; RADIONUCLIDES; CHELATORS; COMPLEXES; COPPER; ACID AB An efficient and short synthetic route to a novel decadentate ligand 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-bis-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid (DEPA) with both macrocyclic and acyclic binding moieties is reported. A reproducible and scalable synthetic method to a precursor molecule of DEPA, 1,4,7-tris(tert-butoxycarbonylmethyl) tetraazacyclododecane was developed. DEPA was evaluated as a chelator of (177)Lu, (212)Bi, and (213)Bi for potential use in an antibody-targeted cancer therapy, radioimmunotherapy (RIT) using Arsenazo III based spectroscopic complexation kinetics, in vitro serum stability, and in vivo biodistribution studies. (C) 2008 Published by Elsevier Ltd. C1 [Chong, Hyun-Soon; Lim, Sooyoun; Ma, Xiang; Song, Hyun A.] IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. [Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Jia, Fang; Lewis, Michael R.] Univ Missouri, Nucl Sci & Engn Inst, Dept Radiol, Dept Vet Med & Surg, Columbia, MO USA. RP Chong, HS (reprint author), IIT, Div Chem, Biol Chem & Phys Sci Dept, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA. EM Chong@iit.edu FU National Institutes of Health [R01CA112503-01A2]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; Office of Research and Development (Medical Research Service); Department of Veterans Affairs FX This research is supported by the National Institutes of Health (R01CA112503-01A2 to C. H. S.). This material is in part based upon work supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (M. W. B.) and by the Office of Research and Development (Medical Research Service), Department of Veterans Affairs, through a Merit Review Type I Award (M. R. L.). NR 18 TC 11 Z9 11 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2008 VL 18 IS 21 BP 5792 EP 5795 DI 10.1016/j.bmcl.2008.09.063 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 362WH UT WOS:000260227400021 PM 18845437 ER PT J AU Damjanovic, A Wu, XW Garcia-Moreno, B Brooks, BR AF Damjanovic, Ana Wu, Xiongwu Garcia-Moreno E., Bertrand Brooks, Bernard R. TI Backbone Relaxation Coupled to the Ionization of Internal Groups in Proteins: A Self-Guided Langevin Dynamics Study SO BIOPHYSICAL JOURNAL LA English DT Article ID PH MOLECULAR-DYNAMICS; SECONDARY STRUCTURE ASSIGNMENT; PHOTOACTIVE YELLOW PROTEIN; CONSTANT-PH; STAPHYLOCOCCAL NUCLEASE; WATER PENETRATION; FREE-ENERGY; CONFORMATIONAL-CHANGES; STRUCTURAL-CHANGES; HYDROGEN-EXCHANGE AB Pathways of structural relaxation triggered by ionization of internal groups in staphylococcal nuclease ( SNase) were studied through multiple self-guided Langevin dynamics ( SGLD) simulations. Circular dichroism, steady-state Trp fluorescence, and nuclear magnetic resonance spectroscopy have shown previously that variants of SNase with internal Glu, Asp, and Lys at positions 66 or 92, and Arg at position 66, exhibit local reorganization or global unfolding when the internal ionizable group is charged. Except for Arg-66, these internal ionizable groups have unusual pK(a) values and are neutral at physiological pH. The structural trends observed in the simulations are in general agreement with experimental observations. The I92D variant, which unfolds globally upon ionization of Asp-92, in simulations often exhibits extensive hydration of the protein core, and sometimes also significant perturbations of the beta-barrel. In the crystal structure of the V66R variant, the beta 1 strand from the beta-barrel is domain-swapped; in the simulations, the beta 1 strand is sometimes partially released. The V66K variant, which in solutions shows reorganization of six residues at the C-terminus of helix alpha 1 and perturbations in the beta-barrel structure, exhibits fraying of three residues of helix a1 in one simulation, and perturbations and partial unfolding of three beta-strands in a few other simulations. In sharp contrast, very small structural changes were observed in simulations of the wild-type protein. The simulations indicate that charging of internal groups frequently triggers penetration of water into the protein interior. The pK(a) values of Asp-92 and Arg-66 calculated with continuum methods on SGLD-relaxed structures reached the normal values in most simulations. Detailed analysis of accuracy and performance of SGLD demonstrates that SGLD outperforms LD in sampling of alternative protein conformations without loss of the accuracy and level of detail characteristic of regular LD. C1 [Damjanovic, Ana; Garcia-Moreno E., Bertrand] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21205 USA. [Damjanovic, Ana; Wu, Xiongwu; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA. RP Damjanovic, A (reprint author), Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21205 USA. EM ad@jhu.edu FU National Institutes of Health [R01 GM061597]; National Heart, Lung, and Blood Institute FX This work was supported by a National Institutes of Health grant (No. R01 GM061597) to B. G. M. E. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 60 TC 36 Z9 36 U1 1 U2 10 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 1 PY 2008 VL 95 IS 9 BP 4091 EP 4101 DI 10.1529/biophysj.108.130906 PG 11 WC Biophysics SC Biophysics GA 360QO UT WOS:000260072600003 PM 18641078 ER PT J AU Low, C Weininger, U Lee, H Schweimer, K Neundorf, I Beck-Sickinger, AG Pastor, RW Balbach, J AF Low, Christian Weininger, Ulrich Lee, Hwankyu Schweimer, Kristian Neundorf, Ines Beck-Sickinger, Annette G. Pastor, Richard W. Balbach, Jochen TI Structure and Dynamics of Helix-0 of the N-BAR Domain in Lipid Micelles and Bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; MEMBRANE CURVATURE; MOLECULAR-DYNAMICS; AMPHIPHYSIN-2 BIN1; VESICLE; NMR; SIMULATIONS; PROTEINS; ENVIRONMENTS; RECOGNITION AB Bin/Amphiphysin/Rvs-homology (BAR) domains generate and sense membrane curvature by binding the negatively charged membrane to their positively charged concave surfaces. N-BAR domains contain an N-terminal extension (helix-0) predicted to form an amphipathic helix upon membrane binding. We determined the NMR structure and nano-to-picosecond dynamics of helix-0 of the human Bin1/Amphiphysin II BAR domain in sodium dodecyl sulfate and dodecylphosphocholine micelles. Molecular dynamics simulations of this 34-amino acid peptide revealed electrostatic and hydrophobic interactions with the detergent molecules that induce helical structure formation from residues 8-10 toward the C-terminus. The orientation in the micelles was experimentally confirmed by backbone amide proton exchange. The simulation and the experiment indicated that the N-terminal region is disordered, and the peptide curves to adopted the micelle shape. Deletion of helix-0 reduced tubulation of liposomes by the BAR domain, whereas the helix-0 peptide itself was fusogenic. These findings support models for membrane curving by BAR domains in which helix-0 increases the binding affinity to the membrane and enhances curvature generation. C1 [Balbach, Jochen] Univ Halle Wittenberg, Fachgrp Biophys, Inst Phys, D-06120 Halle, Saale, Germany. [Lee, Hwankyu] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA. [Schweimer, Kristian; Pastor, Richard W.] Univ Bayreuth, Lehrstuhl Biopolymere, D-95447 Bayreuth, Germany. [Neundorf, Ines; Beck-Sickinger, Annette G.] Univ Leipzig, Fak Biowissensch Pharm & Psychol, Inst Biochem, D-04103 Leipzig, Germany. [Balbach, Jochen] Univ Halle Wittenberg, Mitteldeutsch Zentrum Struktur & Dynam Prot MZP, D-4010 Halle, Germany. RP Balbach, J (reprint author), Univ Halle Wittenberg, Fachgrp Biophys, Inst Phys, D-06120 Halle, Saale, Germany. EM jochen.balbach@physik.uni-halle.de OI Weininger, Ulrich/0000-0003-0841-8332 FU Deutsche Forschungsgemeinschaft [Ba 1821/3-1, GRK 1026]; Excellence Initiative of the State Sachsen-Anhalt; National Institutes of Health (NIH); National Heart, Lung and Blood Institute; CIT [Biowulf/LoBoS3] FX This research was supported in part by a grant from the Deutsche Forschungsgemeinschaft (Ba 1821/3-1 and GRK 1026); the Excellence Initiative of the State Sachsen-Anhalt; the Intramural Research Program of the National Institutes of Health (NIH), National Heart, Lung and Blood Institute; and the CIT Biowulf/LoBoS3 cluster at the NIH for use of the high-performance computational capabilities. NR 52 TC 30 Z9 31 U1 0 U2 14 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV 1 PY 2008 VL 95 IS 9 BP 4315 EP 4323 DI 10.1529/biophysj.108.134155 PG 9 WC Biophysics SC Biophysics GA 360QO UT WOS:000260072600024 PM 18658220 ER PT J AU Phue, JN Lee, SJ Trinh, L Shiloach, J AF Phue, Je-Nie Lee, Sang Jun Trinh, Loc Shiloach, Joseph TI Modified Escherichia coli B (BL21), a Superior Producer of Plasmid DNA Compared With Escherichia coli K (DH5 alpha) SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE pDNA: E. coli B; high density ID DIRECT GENE-TRANSFER; VACCINE; IMMUNOGENICITY; FERMENTATION; PROTECTION; INVIVO; GROWTH; SAFETY AB Plasmid DNA (pDNA) is an emerging experimental vaccine, Produced in E. coli, initially targeted for viral diseases. Unlike traditional protein vaccines whose average dose is micrograms, the average dose of pDNA is on the scale of milligrams. Production yields are, therefore, important for the future development of this vaccine. The E. coli strains currently used for pDNA production, JM109 and DH5 alpha, are both suitable for production of stable pDNA due to the deletion of recA and endA, however, these two E. coli K strains are sensitive to growth conditions such as high glucose concentration. On the other hand E. coli BL21 is less sensitive to growth conditions than E. coli JM109 or DH5a, this strain grows to higher densities and due to its active glyoxylate shunt and anaplerotic pathways is not sensitive to high glucose concentration. This strain is used for recombinant protein production but not for pDNA production because of its inability to produce stable pDNA. To adapt E. coli BL21 for stable pDNA production, the strain was mutated by deleting both recA and endA, and a proper growth and production strategy was developed. Production values, reaching 2 g/L were obtained using glucose as a carbon source. The produced plasmid, which was constructed for HIV clinical study, was found to halve identical properties to the plasmid currently produced by E. coli DH5u. C1 [Phue, Je-Nie; Trinh, Loc; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Lee, Sang Jun] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A Room 173, Bethesda, MD 20892 USA. EM yossi@nih.gov FU NIDDK; NIH FX Funding was provided by the intramural program at the NIDDK, NIH. NR 26 TC 36 Z9 38 U1 1 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD NOV 1 PY 2008 VL 101 IS 4 BP 831 EP 836 DI 10.1002/bit.21973 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 360AY UT WOS:000260030600018 PM 18814292 ER PT J AU Holmes, MK Erickson, K Luckenbaugh, DA Drevets, WC Bain, EE Cannon, DM Snow, J Sahakian, BJ Manji, HK Zarate, CA AF Holmes, M. Kathleen Erickson, Kristine Luckenbaugh, David A. Drevets, Wayne C. Bain, Earle E. Cannon, Dara M. Snow, Joseph Sahakian, Barbara J. Manji, Husseini K. Zarate, Carlos A., Jr. TI A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; cognition; depression; lithium; valproate ID SUSTAINED ATTENTION-DEFICIT; AFFECTIVE-DISORDER; EUTHYMIC PATIENTS; MOOD DISORDERS; DOUBLE-BLIND; IMPAIRMENT; MEMORY; LITHIUM; UNIPOLAR; MANIA AB Objective: Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These. findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects. Method: Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable. Results: With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory. Conclusions: Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety. C1 [Holmes, M. Kathleen; Erickson, Kristine; Luckenbaugh, David A.; Drevets, Wayne C.; Bain, Earle E.; Cannon, Dara M.; Snow, Joseph; Manji, Husseini K.; Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Sahakian, Barbara J.] Univ Cambridge, Dept Psychiat, Cambridge, England. RP Zarate, CA (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 10 Ctr Dr,Mark O Hatfield CRC,Unit 7 SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 FU Stanley Medical Research Institute; NARSAD FX This study was completed within the Intramural Research Program at the National Institutes of Health, Bethesda, MD, USA. We thank the participating subjects, their families, and the nursing and research staff.. We also acknowledge the support of the Stanley Medical Research Institute and NARSAD. NR 43 TC 49 Z9 52 U1 3 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2008 VL 10 IS 7 BP 806 EP 815 DI 10.1111/j.1399-5618.2008.00628.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 394TZ UT WOS:000262472900006 PM 19032712 ER PT J AU Deep-Soboslay, A Iglesias, B Hyde, TM Bigelow, LB Imamovic, V Herman, MM Kleinman, JE AF Deep-Soboslay, Amy Iglesias, Bianca Hyde, Thomas M. Bigelow, Llewelyn B. Imamovic, Vesna Herman, Mary M. Kleinman, Joel E. TI Evaluation of tissue collection for postmortem studies of bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; brain; Harvard Brain Tissue Resource Center; NIMH Brain Collection; postmortem; Stanley Array Collection; Stanley Foundation Neuropathology Consortium ID FOUNDATION BRAIN COLLECTION; GENE-EXPRESSION; MENTAL-ILLNESS; SCHIZOPHRENIA; CORTEX; NEUROPATHOLOGY; COMORBIDITY AB Objectives: Postmortem human brain is a valuable resource for studying the neuropathology, neurochemistry, and molecular pathways of genes associated with bipolar disorder (BPD), yet available, well-characterized BPD brain tissue appears scarce. We set out to evaluate BPD postmortem brain collections in order to identify both successful methods as well as barriers to collection. Methods: We conducted a literature review of postmortem studies of BPD over the past 30 years, compared and contrasted characteristics of established BPD collections, and identified possible barriers specific to BPD brain collection based on our experience at the NIMH Brain Collection. Results: Currently, 80% of postmortem BPD studies were derived from just two brain repositories worldwide: the Stanley Brain Collection (69%) and Harvard Brain Tissue Resource Center (HBTRC) (11%) (combined subjects n = 72). The NIMH Brain Collection collected BPD cases four times less frequently than cases with schizophrenia, despite similar prevalence rates for these disorders. Only 53% of cases referred to the NIMH collection as BPD met DSM-IV criteria, with inadequate documentation and comorbid substance abuse as primary confounds for diagnosis in the remaining 47% of cases. Conclusions: Accurate identification and diagnosis of BPD is a central obstacle to BPD brain collection. Comorbid substance abuse and manner of death are two of many critical factors to consider in BPD postmortem studies. Difficulties in BPD brain collection, coupled with the cessation of brain collection by the Stanley Brain Collection, make the need for alternative BPD brain sources imperative. Recommendations for future BPD tissue collection are offered. C1 [Deep-Soboslay, Amy; Iglesias, Bianca; Hyde, Thomas M.; Bigelow, Llewelyn B.; Imamovic, Vesna; Herman, Mary M.; Kleinman, Joel E.] NIMH, Sect Neuropathol, CBDB, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. RP Kleinman, JE (reprint author), NIMH, Sect Neuropathol, CBDB, Div Intramural Res Programs,NIH, 10 Ctr Dr,MSC 1385, Bethesda, MD 20892 USA. EM joel.kleinman@mail.nih.gov FU NIMH Intramural Research Programs; National Institutes of Health FX This research was supported by the NIMH Intramural Research Programs, National Institutes of Health. We thank the families of the individuals who generously donated tissue for this research. We acknowledge the Offices of the Chief Medical Examiner of the District of Columbia and Northern Virginia, USA, for their collaboration. We also thank Yeva Snitkovsky and Jewell King for their efforts in tissue collection and processing, and John Meyers and Tianzhang Ye for data management. NR 35 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD NOV PY 2008 VL 10 IS 7 BP 822 EP 828 DI 10.1111/j.1399-5618.2008.00607.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 394TZ UT WOS:000262472900008 PM 19032714 ER PT J AU Kristinsson, SY Fears, TR Gridley, G Turesson, I Mellqvist, UH Bjorkholm, M Landgren, O AF Kristinsson, Sigurdur Y. Fears, Thomas R. Gridley, Gloria Turesson, Ingemar Mellqvist, Ulf-Henrik Bjoerkholm, Magnus Landgren, Ola TI Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma SO BLOOD LA English DT Article ID PROTHROMBOTIC COAGULATION ABNORMALITIES; PULMONARY-EMBOLISM; VENOUS THROMBOSIS; INCREASED RISK; THALIDOMIDE; THROMBOEMBOLISM; CANCER; POPULATION; THERAPY; DISEASE AB Patients with multiple myeloma ( MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT ( crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively ( crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P <.01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 ( 95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS ( RR = 8.4; 95% CI, 5.7-12.2) and MM ( RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM. (Blood. 2008; 112: 3582-3586) C1 [Landgren, Ola] NCI, DCEG, GEB, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjoerkholm, Magnus] Karolinska Univ Hosp & Inst, Div Hematol, Dept Med, Stockholm, Sweden. [Turesson, Ingemar] Lund Univ, Malmo Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden. [Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Dept Med, Gothenburg, Sweden. RP Landgren, O (reprint author), NCI, DCEG, GEB, US Dept HHS,NIH, 6120 Execut Blvd,Bldg EPS,Rm 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics (DCEG); Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations FX We thank the Medical Administration Service of the Veterans Health Services and Research Administration, which provided the data on which this study is based, and Ms Heather Morris of Information Management Services (Silver Spring, MD) for computer programming support.; This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (DCEG) and by grants from the Swedish Cancer Society, Stockholm County Council, and Karolinska Institutet Foundations. NR 33 TC 68 Z9 69 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2008 VL 112 IS 9 BP 3582 EP 3586 DI 10.1182/blood-2008-04-151076 PG 5 WC Hematology SC Hematology GA 363XW UT WOS:000260301800016 PM 18559977 ER PT J AU Yu, CI Gallegos, M Marches, F Zurawski, G Ramilo, O Garcia-Sastre, A Banchereau, J Palucka, AK AF Yu, Chun I. Gallegos, Michael Marches, Florentina Zurawski, Gerard Ramilo, Octavio Garcia-Sastre, Adolfo Banchereau, Jacques Palucka, A. Karolina TI Broad influenza-specific CD8(+) T-cell responses in humanized mice vaccinated with influenza virus vaccines SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; IN-VIVO; SMALLPOX VACCINATION; IMMUNE PROTECTION; DNA VACCINES; SUBSETS; IMMUNOLOGY; ANTIGEN; IMMUNODEFICIENCY AB The development of novel human vaccines would be greatly facilitated by the development of in vivo models that permit preclinical analysis of human immune responses. Here, we show that nonobese diabetic severe combined immunodeficiency (NOD/SCID) beta(2) microglobulin(-/-) mice, engrafted with human CD34(+) hematopoietic progenitors and further reconstituted with T cells, can mount specific immune responses against influenza virus vaccines. Live attenuated trivalent influenza virus vaccine induces expansion of CD8(+) T cells specific to influenza matrix protein (FluM1) and nonstructural protein 1 in blood, spleen, and lungs. On ex vivo exposure to influenza antigens, antigen-specific CD8(+) T cells produce IFN-gamma and express cell-surface CD107a. FluM1-specific CD8(+) T cells can be also expanded in mice vaccinated with inactivated trivalent influenza virus vaccine. Expansion of antigen-specific CD8(+) T cells is dependent on reconstitution of the human myeloid compartment. Thus, this humanized mouse model permits preclinical testing of vaccines designed to induce cellular immunity, including those against influenza virus. Furthermore, this work sets the stage for systematic analysis of the in vivo functions of human DCs. This, in turn, will allow a new approach to the rational design and preclinical testing of vaccines that cannot be tested in human volunteers. (Blood. 2008; 112: 3671-3678) C1 [Yu, Chun I.; Gallegos, Michael; Marches, Florentina; Zurawski, Gerard; Ramilo, Octavio; Banchereau, Jacques; Palucka, A. Karolina] Baylor Inst Immunol Res, Baylor Natl Inst Allergy & Infect Dis NIAID, Cooperat Ctr Translat Res Human Immunol, INSERM,U899, Dallas, TX 75204 USA. [Yu, Chun I.] Baylor Univ, Waco, TX 76798 USA. [Ramilo, Octavio] Univ Texas SW, Dallas, TX USA. [Garcia-Sastre, Adolfo] Emerging Pathogens Inst, Dept Microbiol, New York, NY USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, NIAID, Ctr Investigating Virus Immun & Antagonism, New York, NY USA. RP Palucka, AK (reprint author), Baylor Inst Immunol Res, Baylor Natl Inst Allergy & Infect Dis NIAID, Cooperat Ctr Translat Res Human Immunol, INSERM,U899, 3434 Live Oak St, Dallas, TX 75204 USA. EM karolinp@baylorhealth.edu FU BHCS Foundation; DANA Foundation; National Institutes of Health [U19 AI057234, U19 AI062623, AIO56001, CA78846] FX The authors thank volunteers for participation in our studies; Dr Joseph Fay and the clinical group as well as Lynette Walters and the personnel at Cell and Tissue Procurement core at Baylor Institute for Immunology Research; Albert Barnes and the personnel at Bioscience Center at BRI; Flow cytometry and Luminex Core at Baylor Institute for Immunology Research; Anne-Laure Flamar, Dr Xiao-Hua Li, Sandra Zurawski, and Dr Gouchen He for FLT3 Ligand; Dr SangKon Oh and Dr Hideki Ueno for discussion; Cindy Samuelsen, Dr Carson Harrod, and Nicolas Taquet for administrative and facility support; and Dr Michael Ramsay and Dr William Duncan for continuous support.; This work was supported by BHCS Foundation, DANA Foundation, and National Institutes of Health (U19 AI057234, U19 AI062623, AIO56001, and CA78846). J.B. holds the Caruth Chair for Transplant Immunology Research. A. K. P. holds the Ramsay Chair for Cancer Immunology Research. NR 38 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2008 VL 112 IS 9 BP 3671 EP 3678 DI 10.1182/blood-2008-05-157016 PG 8 WC Hematology SC Hematology GA 363XW UT WOS:000260301800026 PM 18713944 ER PT J AU Jeker, LT Barthlott, T Keller, MP Zuklys, S Hauri-Hohl, M Deng, CX Hollander, GA AF Jeker, Lukas T. Barthlott, Thomas Keller, Marcel P. Zuklys, Saulius Hauri-Hohl, Mathias Deng, Chu-Xia Hollaender, Georg A. TI Maintenance of a normal thymic microenvironment and T-cell homeostasis require Smad4-mediated signaling in thymic epithelial cells SO BLOOD LA English DT Article ID EARLY THYMOCYTE DEVELOPMENT; TGF-BETA SUPERFAMILY; TRANSCRIPTION FACTORS; LINEAGE COMMITMENT; C-KIT; DIFFERENTIATION; PROGENITORS; SMAD4/DPC4; RECEPTOR; RECRUITMENT AB Signals mediated by the transforming growth factor-beta superfamily of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis, and function, but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical transforming growth factor-beta signaling by the loss of Smad4 expression in TECs leads to qualitative changes in TEC function and a progressively disorganized thymic microenvironment. Moreover, the number of thymus resident early T-lineage progenitors is severely reduced in the absence of Smad4 expression in TECs and directly correlates with extensive thymic and peripheral lymphopenia. Our observations hence place Smad4 within the signaling events in TECs that determine total thymus cellularity by controlling the number of early T-lineage progenitors. (Blood. 2008; 112:3688-3695) C1 [Jeker, Lukas T.; Barthlott, Thomas; Keller, Marcel P.; Zuklys, Saulius; Hauri-Hohl, Mathias; Hollaender, Georg A.] Univ Basel, Lab Pediat Immunol, Dept Biomed, CH-4058 Basel, Switzerland. [Jeker, Lukas T.; Barthlott, Thomas; Keller, Marcel P.; Zuklys, Saulius; Hauri-Hohl, Mathias; Hollaender, Georg A.] Univ Childrens Hosp, Basel, Switzerland. [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. RP Hollander, GA (reprint author), Univ Basel, Lab Pediat Immunol, Dept Biomed, Mattenstr 28, CH-4058 Basel, Switzerland. EM georg-a.hollaender@unibas.ch RI deng, chuxia/N-6713-2016; OI Jeker, Lukas/0000-0002-3359-8796 FU Swiss National Science Foundation [3100-68310.02, 3235062696.00]; European Community 6th Framework Programme Euro-Thymide Integrated Project; National Institutes of Health [ROI-A105747701]; Roche Research Foundation FX The authors thank Thomas Boulay, Katrin Hafen, and Annick Peter for expert technical help, Angelika Offinger and Rodrigo Recinos for excellent animal care, and Ed Palmer, Willem van Ewijk, and Hamish Scott for providing reagents.; This work was supported by the Swiss National Science Foundation (grant 3100-68310.02, G. A. H.; and grant 3235062696.00, L. T. J.), the European Community 6th Framework Programme Euro-Thymide Integrated Project (G. A. H.), the National Institutes of Health (Besthesda, MD; grant ROI-A105747701, G. A. H.), and the Roche Research Foundation (M. H.-H.). NR 50 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2008 VL 112 IS 9 BP 3688 EP 3695 DI 10.1182/blood-2008-04-150532 PG 8 WC Hematology SC Hematology GA 363XW UT WOS:000260301800028 PM 18695001 ER PT J AU Calvo, KR Dabir, B Kovach, A Devor, C Bandle, R Bond, A Shih, JH Jaffe, ES AF Calvo, Katherine R. Dabir, Bhavana Kovach, Alexandra Devor, Christopher Bandle, Russell Bond, Amelia Shih, Joanna H. Jaffe, Elaine S. TI IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; GENE-EXPRESSION; TUMOR-DEVELOPMENT; GERMINAL CENTER; T-CELLS; INTERLEUKIN-4-INDUCED TRANSCRIPTION; MEK INHIBITORS; KINASE CASCADE; STAT6 AB Follicular lymphoma (FL) is characterized by constitutive expression of Bcl-2 as a consequence of t(14;18). Evidence suggests factors in the lymph node microenvironment, related to intratumoral T cells, macrophages, and dendritic cells, play a role in the disease process. We generated proteomic cytokine profiles of FL (N=50) and follicular hyperplasia (FH; N=23). A total of 10 cytokines were assayed using ultrasensitive multiplex enzyme-linked immunosorbent assays: IL-1 beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-13, IL-12p70, tumor necrosis factor-alpha, and interferon-gamma. Each cytokine showed overall lower protein concentrations in FL, with the exception of IL-4, which was nearly 5 times higher in FL than FH (P= .005). Using reverse-phase protein microarrays (RPMAs), we evaluated the activation state of several intracellular signaling proteins downstream of cytokine receptors. Basal Erk phosphorylation was approximately 4 times greater in FL than FH (P <.001), with similar findings for Mek; Stat-6 showed weak basal phosphorylation that was approximately twice as high in FL than in FH (P=.012). In conclusion, the FL microenvironment contains increased levels of IL-4, with prominent tumor basal phosphorylation of Erk. These findings suggest IL-4, Erk, and possibly Stat-6 may play a role in the biology of FL and may serve as targets for future therapies. (Blood. 2008; 112:3818-3826) C1 [Calvo, Katherine R.] NCI, NIH, Ctr Clin, Dept Lab Med,Hematopathol Sect,Lab Pathol, Bethesda, MD 20892 USA. [Devor, Christopher; Bandle, Russell; Bond, Amelia] NCI, NIH, Clin Prote Core Lab, LP, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, NIH, Div Canc Treatment, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, NIH, Diag Biometr Res Branch, Bethesda, MD 20892 USA. RP Calvo, KR (reprint author), NCI, NIH, Ctr Clin, Dept Lab Med,Hematopathol Sect,Lab Pathol, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA. EM calvok@mail.nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191 FU NIH, National Cancer Institute FX We thank Dr Liang Cao for use of the SECTOR Imager 6000, Adnan Siddiqui for assistance in lysate preparation, and Dr David Levens and Dr Hye-Jung Chung for invaluable discussions.; This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 60 TC 29 Z9 31 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 NOV 1 PY 2008 VL 112 IS 9 BP 3818 EP 3826 DI 10.1182/blood-2008-02-138933 PG 9 WC Hematology SC Hematology GA 363XW UT WOS:000260301800042 PM 18682601 ER PT J AU Zoueva, OP Garrett, LJ Bodine, D Rodgers, GP AF Zoueva, Olga P. Garrett, Lisa J. Bodine, David Rodgers, Griffin P. TI BP1 motif in the human beta-globin promoter affects beta-globin expression during embryonic/fetal erythropoiesis in transgenic mice bearing the human beta-globin gene SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Human beta-globin promoter; BP1 binding site; Human beta-globin expression; Transcription factor; Transgenic mice ID REGULATORY ELEMENTS AB The binding of the transcription factor BP1 (beta protein 1) to its site on the promoter of the adult beta-globin gene has a silencing effect on beta-globin transcription in vitro. To better understand the mechanism of BP1's negative regulation of p-globin expression, we developed transgenic mice bearing a human beta-globin locus-containing cosmid. Specifically, we introduced a mutated BP1 binding site (mtBP1) into the promoter of the beta-globin gene sequence of this cosmid construct. In the mtBP1 mice, we detected a more than a 20-fold increase in human beta-globin expression in the yolk sac-derived blood at E10.5, a 3-fold increase in fetal livers at E13.5, and an approximately 1.4-fold increase in adult reticulocytes compared with control mice bearing the human beta-globin gene with the wild-type BP1 binding site sequence (wtBP1). Our in vivo observations support the contention that the BP1 binding site of the beta-globin promoter plays an important role in the regulation of transcription of the adult beta-globin gene. Published by Elsevier Inc. C1 [Zoueva, Olga P.; Rodgers, Griffin P.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Garrett, Lisa J.; Bodine, David] Natl Human Genome Res Inst, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, 9000 Rockville Pike,Bldg 31,Room 9A52, Bethesda, MD 20892 USA. EM gprod@helix.nih.gov FU Intramural NIH HHS [Z01 DK027008-10] NR 12 TC 2 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2008 VL 41 IS 3 BP 244 EP 251 DI 10.1016/j.bcmd.2008.05.008 PG 8 WC Hematology SC Hematology GA 361TT UT WOS:000260150700002 PM 18656399 ER PT J AU Yang, H Dixit, VD Patel, K Vandanmagsar, B Collins, G Sun, YX Smith, RG Taub, DD AF Yang, Hyunwon Dixit, Vishwa D. Patel, Kalpesh Vandanmagsar, Bolormaa Collins, Gary Sun, Yuxiang Smith, Roy G. Taub, Dennis D. TI Reduction in hypophyseal growth hormone and prolactin expression due to deficiency in ghrelin receptor signaling is associated with Pit-1 suppression: Relevance to the immune system SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Ghrelin; GHS-R; Aging; Pituitary; GH; IGF-1; Prolactin; Pit-1; Thymus ID GH SECRETAGOGUE MK-677; SOMATOSTATIN SECRETION; PITUITARY; STIMULATION; RELEASE; MICE AB In mice and in rats, reduced levels of the growth hormone secretagogue receptor (GHS-R1a) results in reduced body weight and lower levels of serum insulin-like growth factor I (IGF-1). However, the mechanism leading to these impairments has not been elucidated. Studies in primary cultures of pituitary cells from very young mice have shown that GHS-R1a agonists, including ghrelin, increase expression of the pituitary-specific transcription factor (Pit-1) that is critical for differentiation of pituitary cells into somatotrophs, lactotrophs, and thyrotrophs. Hence, we hypothesized that ablation of Ghsr would reduce Pit-1 expression and as a consequence reduce growth hormone (GH) production explaining the lower body weight of Ghsr-/- mice. Here, we now show that Pit-1 mRNA levels are significantly lower in the pituitary gland of Ghsr-/- mice compared to wild-type littermates and also with advancing age. This Pit-1 loss is associated with reduced GH mRNA and fewer GH producing cells. To determine whether reduced GH is caused by reduced expression of Pit-1 in Ghsr-/- mice, we also measured prolactin (PRL) expression in the pituitary gland and in the circulation. PRL mRNA was significantly reduced in Ghsr-/- mice compared to wild-type littermates and fewer cells expressed PRL. The reduction in expression of both GH and PRL is consistent with a Pit-1 regulated pathway and demonstrates that the GHS-R has an important role in the pituitary gland as a modulator of Pit-1 expression and provides a possible mechanism to explain the lower plasma IGF-1 and modestly reduced body weight exhibited by Ghsr-/ - mice. We also believe that lower systemic and lymphoid hormone expression may also account, in part, for the enhanced thymic involution and reduced thymic output in Ghsr-/- mice. Published by Elsevier Inc. C1 [Yang, Hyunwon; Dixit, Vishwa D.; Patel, Kalpesh; Vandanmagsar, Bolormaa; Collins, Gary; Taub, Dennis D.] NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Sun, Yuxiang; Smith, Roy G.] Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Sun, Yuxiang; Smith, Roy G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rsmith@bcm.edu; taubd@grc.nia.nih.gov RI Patel, Kalpesh/G-6685-2012 OI Patel, Kalpesh/0000-0002-2952-6773 FU Intramural Research Program of the National Institute on Aging; National Institutes of Health [R01 AG19230-01, R01 AG18895-02]; NIH FX We thank the staff of the Comparative Medicine Section of the NIA animal facility for their support in maintaining and monitoring our animals. We would also like to thank Drs. Dan L. Longo, Mark Mattson, and Arya Biragyn for reviewing this manuscript and Mrs. Dawn Tripp for her administrative assistance with the manuscript. This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health and R01 AG19230-01 and R01 AG18895-02 NIH grants to R.G.S. NR 24 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD NOV PY 2008 VL 22 IS 8 BP 1138 EP 1145 DI 10.1016/j.bbi.2008.06.003 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 360UM UT WOS:000260083400004 PM 18602461 ER PT J AU Wayne, SJ Neuhouser, ML Ulrich, CM Koprowski, C Baumgartner, KB Baumgartner, RN McTiernan, A Bernstein, L Ballard-Barbash, R AF Wayne, Sharon J. Neuhouser, Marian L. Ulrich, Cornelia M. Koprowski, Carol Baumgartner, Kathy B. Baumgartner, Richard N. McTiernan, Anne Bernstein, Leslie Ballard-Barbash, Rachel TI Dietary fiber is associated with serum sex hormones and insulin-related peptides in postmenopausal breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer outcomes; dietary fiber; serum hormones; serum peptides ID CARDIOVASCULAR-DISEASE RISK; PHYSICAL-ACTIVITY LEVELS; GROWTH-FACTOR-I; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; C-PEPTIDE; ESTROGEN CONCENTRATIONS; PLASMA-INSULIN; WEIGHT-GAIN; WHEAT BRAN AB Objective To measure the association between dietary fiber intake and eleven hormones and peptides in postmenopausal breast cancer survivors. Methods Intake of fiber from food and supplements was measured two to three years after breast cancer diagnosis in 493 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-1 (IGF1), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of fiber intake. Results High intake of dietary fiber was significantly (P <= 0.05) associated with low serum levels of estradiol and free estradiol and with high serum levels of IGF1. The combination of high dietary fiber intake and use of fiber supplements was additionally associated with low serum levels of C-peptide. The magnitude of the difference in hormone/peptide values, comparing high fiber intake to low fiber intake, varied from 16 to 28%, and the associations were independent of multiple confounding variables. Conclusion High fiber diets may be beneficial to postmenopausal breast cancer survivors due to fiber's favorable influence on sex hormones and peptides known to affect breast cancer prognosis. C1 [Wayne, Sharon J.] 1 Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. [Neuhouser, Marian L.; Ulrich, Cornelia M.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Koprowski, Carol] Univ So Calif, Inst Hlth Promot & Dis Prevent, Alhambra, CA 91803 USA. [Baumgartner, Kathy B.; Baumgartner, Richard N.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40202 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Wayne, SJ (reprint author), 1 Univ New Mexico, New Mexico Tumor Registry, MSC 11 620, Albuquerque, NM 87131 USA. EM swayne@salud.unm.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010/N01PC-35139, N01-PC-67007/N01-PC-35138, N01-PC-67009/N01PC-35142, T32 CA09661]; NIH [M01-RR-00037]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228, N01-PC-67010/N01PC-35139, N01-PC-67007/N01-PC-35138 and N01-PC-67009/N01PC-35142, and training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the NIH grant M01-RR-00037. Data collection for the Women's Contraceptive and Reproductive Experiences Study at the University of Southern California was supported by the National Institute of Child Health and Human Development contract N01-HD-3-3175. Patient identification was supported in part by the California Department of Health Services grant 050Q-8709-S1528. NR 48 TC 5 Z9 5 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2008 VL 112 IS 1 BP 149 EP 158 DI 10.1007/s10549-007-9834-y PG 10 WC Oncology SC Oncology GA 355GD UT WOS:000259696500018 PM 18058020 ER PT J AU Pro, B Leber, B Smith, M Fayad, L Romaguera, J Hagemeister, F Rodriguez, A McLaughlin, P Samaniego, F Zwiebel, J Lopez, A Kwak, L Younes, A AF Pro, Barbara Leber, Brian Smith, Mitchell Fayad, Luis Romaguera, Jorge Hagemeister, Fredrick Rodriguez, Alma McLaughlin, Peter Samaniego, Felipe Zwiebel, James Lopez, Adriana Kwak, Larry Younes, Anas TI Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE non-Hodgkin lymphoma; oblimersen sodium; rituximab; recurrent B-cell NHL ID ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; PROTEIN EXPRESSION; THERAPY; CYCLOPHOSPHAMIDE; APOPTOSIS; EFFICACY AB Oblimersen sodium plus rituximab was evaluated in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) patients. Oblimersen was administered as a continuous intravenous infusion at a daily dose of 3 mg/kg/d for 7 d on alternate weeks for 3 weeks. Rituximab was given at a weekly dose of 375 mg/m(2) for six doses. Patients with stable disease or objective response were allowed to receive a second course of treatment. The overall response rate (ORR) was 42% with 10 complete responses (CR) and eight partial responses (PR). Twelve (28%) patients achieved a minimal response or stable disease. Among the 20 patients with follicular lymphoma the ORR was 60% (eight CR, four PR). Three of the responders were refractory to prior treatment with rituximab, and two of the responses occurred in patients who had failed an autologous stem cell transplant. Median duration of response was 12 months. Most toxicities were low grade and reversible. In conclusion, oblimersen sodium can be safely combined with rituximab. The combination appears to be most beneficial in patients with indolent NHL and warrants further investigation in a large randomized trial. C1 [Pro, Barbara] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Unit 429, Houston, TX 77030 USA. [Leber, Brian] McMaster Univ, Hamilton, ON, Canada. [Smith, Mitchell] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Zwiebel, James] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Lopez, Adriana] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. RP Pro, B (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Unit 429, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM bpro@mdanderson.org OI Smith, Mitchell/0000-0003-1428-8765 FU National Cancer Institute [01/CM17003] FX This study was supported by the National Cancer Institute Grant No 01/CM17003. NR 14 TC 65 Z9 66 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 3 BP 355 EP 360 DI 10.1111/j.1365-2141.2008.07353.x PG 6 WC Hematology SC Hematology GA 361HC UT WOS:000260117300005 PM 18764869 ER PT J AU Chin, KL Aerbajinai, WL Zhu, JQ Drew, L Chen, L Liu, WL Rodgers, GP AF Chin, Kyung L. Aerbajinai, Wulin Zhu, Jiangqiong Drew, LaShawn Chen, Ling Liu, Wenli Rodgers, Griffin P. TI The regulation of OLFM4 expression in myeloid precursor cells relies on NF-kappa B transcription factor SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE olfactomedin 4 gene; human G-CSF-stimulated clone-1; NF-kappa B; activator protein 1; GW112 ID SIGNAL-TRANSDUCTION; REDOX-REGULATION; TYROSINE PHOSPHORYLATION; GENE-EXPRESSION; RECEPTOR; PROTEIN; GROWTH; PROLIFERATION; ANTIOXIDANT; TRANSITION AB The human olfactomedin 4 gene (OLFM4, also known as hGC-1, GW112) is thought to be a useful marker for early myeloid development. To understand the molecular mechanisms underlying granulocyte colony-stimulating factor (G-CSF)-stimulated OLFM4 expression, we characterized the promoter region of OLFM4. The 35-bp region (-101 to -66) of the proximal promoter regulated reporter gene expression, and mutation of the nuclear factor (NF)-kappa B binding site within the promoter abolished the binding of the transcription factor and the ability to regulate OLFM4 expression. G-CSF increased reactive oxygen species (ROS) production in human CD34(+) cells, which was abrogated by inhibition of phosphatidylinositol 3-kinase (PI3K) or NADPH oxidase. Phosphorylation of ERK1/2 mitogen-activated protein kinase (MAPK) induced by G-CSF inhibited by the antioxidant N-acetyl-L-cysteine (NAC), ERK1/2 inhibitor PD98059, or U0126. However, phosphorylation of signal transducer and activator of transcription (STAT)3 was only partially inhibited by NAC, but not by PD98059 or U0126. Inhibition of the ERK pathway remarkably decreased OLFM4 expression and this inhibition required NF-kappa B transcription factor. Inhibition of ROS or the ERK pathway remarkably decreased G-CSF-induced OLFM4 expression. Our results suggest that G-CSF-induced expression of OLFM4 is regulated by the transcription factor NF-kappa B, and that this induction is mediated by the ERK1/2 MAPK signaling pathway through PI3K-driven ROS production. C1 [Chin, Kyung L.; Aerbajinai, Wulin; Zhu, Jiangqiong; Drew, LaShawn; Chen, Ling; Liu, Wenli; Rodgers, Griffin P.] NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM gprod@helix.nih.gov NR 30 TC 24 Z9 24 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2008 VL 143 IS 3 BP 421 EP 432 DI 10.1111/j.1365-2141.2008.07368.x PG 12 WC Hematology SC Hematology GA 361HC UT WOS:000260117300015 PM 18764868 ER PT J AU Latimer, AE Rench, TA Rivers, SE Katulak, NA Materese, SA Cadmus, L Hicks, A Hodorowski, JK Salovey, P AF Latimer, Amy E. Rench, Tara A. Rivers, Susan E. Katulak, Nicole A. Materese, Stephanie A. Cadmus, Lisa Hicks, Althea Hodorowski, Julie Keany Salovey, Peter TI Promoting participation in physical activity using framed messages: An application of prospect theory SO BRITISH JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article ID MASS-MEDIA CAMPAIGNS; PLANNED BEHAVIOR; SELF-EFFICACY; ACTIVITY QUESTIONNAIRE; SOURCE CREDIBILITY; HEALTHY BEHAVIOR; LOW-INCOME; FAT INTAKE; INTERVENTION; PERCEPTIONS AB Objectives. Messages designed to motivate participation in physical activity usually emphasize the benefits of physical activity (gain-framed) as well as the costs of inactivity (loss-framed). The framing implications of prospect theory suggest that the effectiveness of these messages could be enhanced by providing gain-framed information only. We compared the effectiveness of gain-, loss-, and mixed-framed messages for promoting moderate to vigorous physical activity. Design. Randomized trial. Method. Sedentary, healthy callers to the US National Cancer Institute's Cancer Information Service (N = 322) received gain-, loss-, or mixed-framed messages on three occasions (baseline, Week 1, and Week 5). Social cognitive variables and self-reported physical activity were assessed at baseline, Week 2, and Week 9. Separate regression analyses were conducted to examine message effects at each assessment point. Results. At Week 2, gain-and mixed-framed messages resulted in stronger intentions and greater self-efficacy than loss-framed messages. At Week 9, gain-framed messages resulted in greater physical activity participation than loss-or mixed-framed messages. Social cognitive variables at Week 2 did not mediate the Week 9 framing effects on physical activity participation. Conclusions. Using gain-framed messages exclusively may be a means of increasing the efficacy of physical activity materials. C1 [Latimer, Amy E.; Rench, Tara A.; Rivers, Susan E.; Katulak, Nicole A.; Cadmus, Lisa; Salovey, Peter] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Materese, Stephanie A.; Cadmus, Lisa] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Hicks, Althea; Hodorowski, Julie Keany] Mem Sloan Kettering Canc Ctr, Natl Canc Inst, Canc Informat Serv, New York, NY 10021 USA. RP Latimer, AE (reprint author), Queens Univ, Sch Kinesiol & Hlth Studies, 69 Union St, Kingston, ON K7L 3N6, Canada. EM amy.latimer@queensu.ca OI Hodorowski, Julie/0000-0003-3587-2135 FU NCI NIH HHS [R01-CA68427, N02-CO-51101, R01 CA068427]; PHS HHS [HHSN261200511001C] NR 56 TC 43 Z9 43 U1 2 U2 15 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 1359-107X J9 BRIT J HEALTH PSYCH JI Br. J. Health Psychol. PD NOV PY 2008 VL 13 BP 659 EP 681 DI 10.1348/135910707X246186 PN 4 PG 23 WC Psychology, Clinical SC Psychology GA 366DG UT WOS:000260460200006 PM 17925060 ER PT J AU McLaren, GD McLaren, CE Adams, PC Barton, JC Reboussin, DM Gordeuk, VR Acton, RT Harris, EL Speechley, MR Sholinsky, P Dawkins, FW Snively, BM Vogt, TM Eckfeldt, JH AF McLaren, Gordon D. McLaren, Christine E. Adams, Paul C. Barton, James C. Reboussin, David M. Gordeuk, Victor R. Acton, Ronald T. Harris, Emily L. Speechley, Mark R. Sholinsky, Phyliss Dawkins, Fitzroy W. Snively, Beverly M. Vogt, Thomas M. Eckfeldt, John H. CA HEIRC Study Res Invest TI Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Complications; Cross-sectional study; Hemochromatosis; FIFE; Iron overload; Prevalence ID PRIMARY-CARE PATIENTS; HEREDITARY HEMOCHROMATOSIS; IRON-OVERLOAD; GENETIC HEMOCHROMATOSIS; TRANSFERRIN SATURATION; GENERAL-POPULATION; AMERICAN-COLLEGE; LIVER-DISEASES; SERUM FERRITIN; PREVALENCE AB BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study. C1 [McLaren, Gordon D.] Dept Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [McLaren, Gordon D.] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA. [McLaren, Christine E.] Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. [Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada. [Barton, James C.] So Iron Disorders Ctr, Birmingham, AL USA. [Reboussin, David M.; Snively, Beverly M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. [Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20059 USA. [Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Acton, Ronald T.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Acton, Ronald T.] Univ Alabama, Dept Genet & Epidemiol, Birmingham, AL USA. [Acton, Ronald T.] Univ Alabama, Dept Int Hlth, Birmingham, AL USA. [Harris, Emily L.] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. [Speechley, Mark R.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Sholinsky, Phyliss] NHLBI, Epidemiol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Vogt, Thomas M.] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP McLaren, GD (reprint author), VA Long Beach Healthcare Syst, Hematol Oncol Sect, 11-111-H,5901 E 7th St, Long Beach, CA 90822 USA. EM gordon.mclaren@va.gov FU NHLBI,; NHGRI; University of Minnesota [N01-HC-05185]; Howard University [NO1-HC-05186]; University of Alabama at Birmingham [NO1-HC-05188]; Kaiser Permanente Centre for Health Research [N01-HC-05189]; University of California, Irvine [N01-HC-05190]; London Health Sciences Centre [N01-HC-05191]; Wake Forest University [N01-HC-05192]; General Clinical Research Center, School of Medicine, University of California, Irvine; National Center for Research Resources [5M01RR 00827-29]; U.S. Public Health Service; GCRC [M01-RR00032]; Howard University General Clinical Research Center (GCRC) [M01-RR10284]; NHLBI and the Office of Minority Health [UH1-HL03679-05] FX The HEIRS study was initiated and funded by NHLBI, in conjunction with NHGRI. The study was supported by contracts N01-HC-05185 (University of Minnesota), NO1-HC-05186 (Howard University), NO1-HC-05188 (University of Alabama at Birmingham), N01-HC-05189 (Kaiser Permanente Centre for Health Research), N01-HC-05190 (University of California, Irvine), N01-HC-05191 (London Health Sciences Centre), and N01-HC-05192 (Wake Forest University). Additional support was provided by the General Clinical Research Center, School of Medicine, University of California, Irvine, with funds provided by the National Center for Research Resources, 5M01RR 00827-29, U.S. Public Health Service; GCRC grant #M01-RR00032 (University of Alabama at Birmingham); and the Howard University General Clinical Research Center (GCRC) grant, M01-RR10284 and from the NHLBI and the Office of Minority Health UH1-HL03679-05. The work was independent of the funding. NR 52 TC 30 Z9 31 U1 1 U2 1 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD NOV PY 2008 VL 22 IS 11 BP 923 EP 930 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 378XX UT WOS:000261359500008 PM 19018338 ER PT J AU Figueroa, JD Sakoda, LC Graubard, BI Chanock, S Rubertone, MV Erickson, RL McGlynn, KA AF Figueroa, Jonine D. Sakoda, Lori C. Graubard, Barry I. Chanock, Stephen Rubertone, Mark V. Erickson, R. Loren McGlynn, Katherine A. TI Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors SO CANCER CAUSES & CONTROL LA English DT Article DE testicular cancer; hormone metabolism; genetic polymorphisms ID BREAST-CANCER RISK; POLYCHLORINATED-BIPHENYLS; ANDROGEN RECEPTOR; CYP1A1 POLYMORPHISMS; CYTOCHROME-P450 1A1; HSD17B1 GENE; IN-UTERO; ESTROGEN; WOMEN; EXPOSURE AB Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma. C1 [Figueroa, Jonine D.; Graubard, Barry I.; Chanock, Stephen; McGlynn, Katherine A.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Figueroa, Jonine D.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Chanock, Stephen] NCI, Dept Hlth & Human Serv, Core Genotyping Facil, Adv Technol Ctr, Bethesda, MD 20892 USA. [Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD USA. [Erickson, R. Loren] Walter Reed Army Inst Res, Global Emerging Infect Syst, Silver Spring, MD USA. RP Figueroa, JD (reprint author), NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM figueroaj@mail.nih.gov FU NCI Cancer Prevention Fellowship program FX The authors wish to thank Emily Steplowski of IMS for her contributions to data management and Sabah Quraishi for her contributions to data analysis. In addition, Jonine Figueroa would like to thank Victoria Chia and Michael Cook for discussions about data presentation and the NCI Cancer Prevention Fellowship program for their support. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. NR 60 TC 20 Z9 23 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2008 VL 19 IS 9 BP 917 EP 929 DI 10.1007/s10552-008-9153-6 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 351WR UT WOS:000259457100003 PM 18415690 ER PT J AU Howard, RA Freedman, DM Park, Y Hollenbeck, A Schatzkin, A Leitzmann, MF AF Howard, Regan A. Freedman, D. Michal Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur Leitzmann, Michael F. TI Physical activity, sedentary behavior, and the risk of colon and rectal cancer in the NIH-AARP Diet and Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE colon cancer; rectal cancer; physical activity; cohort studies ID MIDDLE-AGED MEN; COLORECTAL-CANCER; LEISURE-TIME; UNITED-STATES; FOLLOW-UP; ACTIVITY PATTERNS; WOMEN; COHORT; NUTRITION; OBESITY AB Objective: In order to prospectively investigate physical activity at varying intensities and sedentary behavior in relation to colorectal cancer. Methods: We considered 488,720 participants of the NIH-AARP Diet and Health Study who were aged 50-71 years at baseline in 1995-1996. Through 31 December, 2003, we identified 3,240 and 1,482 colorectal cancers among men and women, respectively. We estimated multivariable relative risks (RR) and 95% confidence intervals (CI) of colorectal cancer using Cox regression. Results: Engaging in exercise/sports five or more times per week compared to never or rarely exercising was associated with a reduced risk of colon cancer among men (p = 0.001; RR = 0.79, 95% CI = 0.68-0.91) and a suggestive decrease in risk among women (p = 0.376; RR = 0.85, 95% CI = 0.70-1.04). Engaging in exercise/sports was also associated with a decreased risk of rectal cancer in men (P = 0.074; RR comparing extreme categories = 0.76, 95% CI = 0.61-0.94). In men, we observed inverse relations of both low intensity (p = 0.017; RR = 0.81, 95% CI = 0.65-1.00 for >= 7 h/week) and moderate to vigorous intensity activity (p = 0.037; RR = 0.82, 95% CI = 0.67-0.99 for >= 7 h/week) to colon cancer risk. In contrast, sedentary behavior (time spent watching television/videos) was positively associated with colon cancer (p < 0.001; RR = 1.61, 95% CI = 1.14-2.27 for >= 9 h/day) among men. Similar, but less pronounced relations were observed in women. Conclusion: Engaging in physical activity of any intensity is associated with reductions in colon and rectal cancer risk. Conversely, time spent sedentary is associated with increased colon cancer risk. C1 [Howard, Regan A.; Freedman, D. Michal] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Park, Yikyung; Schatzkin, Arthur; Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Howard, RA (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH,DHHS, Execut Plaza S,Suite 7091, Bethesda, MD 20892 USA. EM reganho@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS [Z01 CP010196-01] NR 55 TC 73 Z9 75 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2008 VL 19 IS 9 BP 939 EP 953 DI 10.1007/s10552-008-9159-0 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 351WR UT WOS:000259457100005 PM 18437512 ER PT J AU Liang, XJ Yin, JJ Taylor, B Winkovitch, SM Garfield, SH Shen, DW Gottesman, MM Aszalos, A AF Liang, Xing-Jie Yin, Jun-Jie Taylor, Barbara Winkovitch, Stephen M. Garfield, Susan H. Shen, Ding-Wu Gottesman, Michael M. Aszalos, Adorjan TI Disruption of microfilaments by cytochalasin B decreases accumulation of cisplatin in human epidermal carcinoma and liver carcinoma cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cisplatin; electron spin resonance; cytochalasin B; carcinoma cell lines; microfilaments ID RESISTANT CELLS; PLEIOTROPIC DEFECT; CROSS-RESISTANCE; PLASMA-MEMBRANES; CANCER-CELLS; ACTIN; PROTEINS; MICROTUBULES; ENDOCYTOSIS; METALS AB Background Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification. Results We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 mu M). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells. Conclusion Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells. C1 [Liang, Xing-Jie; Shen, Ding-Wu; Gottesman, Michael M.; Aszalos, Adorjan] Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Yin, Jun-Jie] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Taylor, Barbara] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Winkovitch, Stephen M.; Garfield, Susan H.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM aszalosa@nih.gov RI Yin, Jun Jie /E-5619-2014 FU Intramural Research Program of the NIH; Center for Cancer Research, National Cancer Institute FX We would like to thank George Leiman for his assistance with the text and figures. This research was funded by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. NR 25 TC 6 Z9 6 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2008 VL 62 IS 6 BP 977 EP 984 DI 10.1007/s00280-008-0687-9 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 348CR UT WOS:000259189100006 PM 18274748 ER PT J AU White, DB Bonham, VL Jenkins, J Stevens, N McBride, CM AF White, Della Brown Bonham, Vence L. Jenkins, Jean Stevens, Nancy McBride, Colleen M. TI Too Many Referrals of Low-Risk Women for BRCA1/2 Genetic Services by Family Physicians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OVARIAN-CANCER SUSCEPTIBILITY; RANDOMIZED CONTROLLED-TRIAL; MANAGED CARE ORGANIZATION; BREAST-CANCER; INFORMATION-SERVICE; PUBLIC-HEALTH; TASK-FORCE; KNOWLEDGE; IMPACT; GUIDELINES AB The increasing availability and public awareness of BRCA1/2 genetic testing will increase women's self-referrals to genetic services. The objective of this study was to examine whether patient characteristics influence the referral decisions of family physicians when a patient requests BRCA1/2 genetic testing. Family physicians (n = 284) completed a Web-based survey in 2006 to assess their attitudes and practices related to the use of genetics in their clinical practice. Using a 2 x 2 x 2 factorial design, we tested the effects of a hypothetical patient's race, level of worry, and insurance status on the decisions of family physicians to refer her for BRCA1/2 testing. The patient was not appropriate for referral based on U.S. Preventive Services Task Force guidelines. No patient characteristics were associated with the family physicians' referral decisions. Although referral was not indicated, only 8% did not refer to genetic services; 92% referred for genetic services, and 50% referred to genetic counseling. Family physicians regarded it unlikely that the patient carried a mutation, but 65% of family physicians believed that if they refused to refer for genetic services it would harm their relationship with the patient. Despite scarce and costly genetic services, family physicians were likely to inappropriately refer a low-risk patient who requested BRCA1/2 testing. The implications of this inappropriate referral on women's screening behavior, genetic services, and health care costs are unknown. Clinicians and patients could benefit from education about the appropriate use of genetic services so that both are more comfortable with a decision against referral. (Cancer Epidemiol Biomarkers Prev 2008;17(11):2980-6) C1 [White, Della Brown; Bonham, Vence L.; McBride, Colleen M.] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Jenkins, Jean] NHGRI, NIH, Off Director, Bethesda, MD 20892 USA. [Stevens, Nancy] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP White, DB (reprint author), NHGRI, NIH, Social & Behav Res Branch, 31 Ctr Dr,Bldg 31,Room B1B54G, Bethesda, MD 20892 USA. EM whitede@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, NIH FX Grant support: Intramural Research Program of the National Human Genome Research Institute, NIH. NR 41 TC 25 Z9 25 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 2980 EP 2986 DI 10.1158/1055-9965.EPI-07-2879 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500012 PM 18990739 ER PT J AU Fatima, N Yi, M Ajaz, S Stephens, RM Stauffer, S Greenwald, P Munroe, DJ Ali, IU AF Fatima, Naheed Yi, Ming Ajaz, Sadia Stephens, Robert M. Stauffer, Stacey Greenwald, Peter Munroe, David J. Ali, Iqbal Unnisa TI Altered Gene Expression Profiles Define Pathways in Colorectal Cancer Cell Lines Affected by Celecoxib SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INHIBITOR CELECOXIB; DNA-DAMAGE; COX-2; SUPPRESSION; APOPTOSIS; CARCINOMA; PROTEIN; TARGET; GROWTH; TRANSCRIPTION AB It is well established that celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) and a tested chemopreventive agent, has several COX-2-independent activities. In an attempt to better understand COX-2-independent molecular mechanisms underlying the chemopreventive activity of celecoxib, we did global transcription profiling of celecoxib-treated COX-2-positive and COX-2-deficient colorectal cancer cell lines. Celecoxib treatment resulted in significantly altered expression levels of over 1,000 to 3,000 transcripts in these cell lines, respectively. A pathway/functional analysis of celecoxib-affected transcripts, using Gene Ontology and Biocarta Pathways and exploring biological association networks, revealed that celecoxib modulates expression of numerous genes involved in a variety of cellular processes, including metabolism, cell proliferation, apoptotic signaling, cell cycle check points, lymphocyte activation, and signaling pathways. Among these processes, cell proliferation and apoptotic signaling consistently ranked as the highest-scoring Gene Ontology terms and Biocarta Pathways in both COX-2 expresser and nonexpresser cell lines. Altered expression of many of the genes by celecoxib was confirmed by quantitative PCR and at the protein level by Western blotting. Many novel genes emerged from our analysis of global transcription patterns that were not previously reported to be affected by celecoxib. In the future, in-depth work on selected genes will determine if these genes may serve as potential molecular targets for more effective chemopreventive strategies. (Cancer Epidemiol Biomarkers Prev 2008; 17(11):3051-61) C1 [Fatima, Naheed; Stauffer, Stacey; Greenwald, Peter; Ali, Iqbal Unnisa] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Yi, Ming; Stephens, Robert M.] Sci Applicat Int Corp Inc, Adv Biomed Comput Ctr, Frederick, MD USA. [Fatima, Naheed] Sci Applicat Int Corp Inc, Basic Res Program, Frederick, MD USA. [Munroe, David J.] Sci Applicat Int Corp Inc, Lab Mol Technol, Frederick, MD USA. [Ajaz, Sadia] Univ Karachi, Panjwani Ctr Mol Med, Karachi 75270, Pakistan. RP Ali, IU (reprint author), Univ Karachi, Int Ctr Chem Biol Sci, Panjwani Ctr Mol Med & Drug Res, Mol Oncol Program, Karachi 75270, Pakistan. EM iuali@cyber.net.pk OI Ajaz, Sadia/0000-0003-3940-1269 FU National Cancer Institute, NIH [N01-C0-12400] FX Grant support: National Cancer Institute, NIH, under contract N01-C0-12400. NR 42 TC 7 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3051 EP 3061 DI 10.1158/1055-9965.EPI-08-0261 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500021 PM 18957522 ER PT J AU Abnet, CC Kamangar, F Islami, F Nasrollahzadeh, D Brennan, P Aghcheli, K Merat, S Pourshams, A Marjani, HA Ebadati, A Sotoudeh, M Boffetta, P Malekzadeh, R Dawsey, SM AF Abnet, Christian C. Kamangar, Farin Islami, Farhad Nasrollahzadeh, Dariush Brennan, Paul Aghcheli, Karim Merat, Shahin Pourshams, Akram Marjani, Haj Amin Ebadati, Abdolhakim Sotoudeh, Masoud Boffetta, Paolo Malekzadeh, Reza Dawsey, Sanford M. TI Tooth Loss and Lack of Regular Oral Hygiene Are Associated with Higher Risk of Esophageal Squamous Cell Carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MALE HEALTH-PROFESSIONALS; NORTHEASTERN IRAN; GASTROINTESTINAL-TRACT; PERIODONTAL-DISEASE; PANCREATIC-CANCER; GOLESTAN COHORT; GASTRIC CANCERS; POPULATION; CHINA; RELIABILITY AB We tested the association between tooth loss and oral hygiene and the risk of esophageal squamous cell carcinoma (ESCC) in people living in a high-risk area of Iran. We used a case-control study of pathologically confirmed ESCC cases (n = 283) and controls (n = 560) matched on sex, age, and neighborhood. Subjects with ESCC had significantly more decayed, missing, or filled teeth (DMFT) with a median (interquartile range) of 31 (23-32) compared with controls 28 (16-32; P = 0.0045). Subjects with ESCC were significantly more likely than controls to fail to practice regular oral hygiene (78% versus 58%). In multivariate-adjusted conditional logistic regression models, having 32 DMFT compared with <= 15 conferred an odds ratio (95% confidence interval) of 2.10 (1.19-3.70). Compared with daily tooth brushing, practicing no regular oral hygiene conferred an odds ratio (95% confidence interval) of 2.37 (1.42-3.97). Restricting the analysis to subjects that had never smoked tobacco did not materially alter these results. We found significant associations between two markers of poor oral hygiene, a larger number of DMFT and lack of daily tooth brushing, and risk of ESCC in a population at high risk for ESCC where many cases occur in never smokers. Our results are consistent with several previous analyses in other high-risk populations. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3062-8) C1 [Abnet, Christian C.; Kamangar, Farin; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD 20852 USA. [Islami, Farhad; Aghcheli, Karim; Merat, Shahin; Pourshams, Akram; Marjani, Haj Amin; Ebadati, Abdolhakim; Sotoudeh, Masoud; Malekzadeh, Reza] IARC, Lyon, France. [Islami, Farhad; Nasrollahzadeh, Dariush; Brennan, Paul; Boffetta, Paolo] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Execut Plaza S,Room 320,6120 Execut Blvd,MSC 7232, Rockville, MD 20852 USA. EM abnetc@mail.nih.gov RI Abnet, Christian/C-4111-2015; OI Abnet, Christian/0000-0002-3008-7843; Malekzadeh, Reza/0000-0003-1043-3814 FU Digestive Disease Research Center of Tehran University of Medical Sciences [82-603]; National Cancer Institute, NIH intramural funds FX Grant support: Digestive Disease Research Center of Tehran University of Medical Sciences grant 82-603 and National Cancer Institute, NIH intramural funds. NR 31 TC 65 Z9 66 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3062 EP 3068 DI 10.1158/1055-9965.EPI-08-0558 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500022 PM 18990747 ER PT J AU Anderson, LA Pfeiffer, R Warren, JL Landgren, O Gadalla, S Berndt, SI Ricker, W Parsons, R Wheeler, W Engels, EA AF Anderson, Lesley A. Pfeiffer, Ruth Warren, Joan L. Landgren, Ola Gadalla, Shahinaz Berndt, Sonja I. Ricker, Winnie Parsons, Ruth Wheeler, William Engels, Eric A. TI Hematopoietic Malignancies Associated with Viral and Alcoholic Hepatitis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKINS-LYMPHOMA; C-VIRUS-INFECTION; B-VIRUS; UNITED-STATES; EPIDEMIOLOGY CONSORTIUM; CYTOTOXIC THERAPY; BURKITTS-LYMPHOMA; RISK; PREVALENCE; CONSUMPTION AB Hepatitis C virus (HCV) and hepatitis B virus (HBV) have been associated with hematopoietic malignancies, but data for many subtypes are limited. From the U.S. Surveillance, Epidemiology, and End Results-Medicare database, we selected 61,464 cases ( >= 67 years) with hematopoietic malignancies and 122,531 population-based controls, frequency-matched by gender, age, and year (1993-2002). Logistic regression was used to compare the prevalence of HCV, HBV, and alcoholic hepatitis in cases and controls, adjusted for matching factors, race, duration of Medicare coverage, and number of physician claims. HCV, HBV, and alcoholic hepatitis were reported in 195 (0.3%), 111 (0.2%), and 404 (0.7%) cases and 264 (0.2%), 242 (0.2%), and 798 (0.7%) controls, respectively. HCV was associated with increased risk of diffuse large B-cell lymphoma [odds ratio (OR) 1.52,95% confidence interval (95% CI) 1.05-2.18], Burkitt lymphoma (OR 5.21, 95% CI 1.62-16.8), follicular lymphoma (OR 1.88, 95% CI 1.17-3.02), marginal zone lymphoma (OR 2.20, 95% Cl 1.22-3.95), and acute myeloid leukemia (OR 1.54, 95% Cl 1.00-2.37). In contrast, HBV was unrelated to any hematopoietic malignancies. Alcoholic hepatitis was associated with decreased risk of non-Hodgkin lymphoma overall, but increased risk of Burkitt lymphoma. In summary, HCV, but not other causes of hepatitis, was associated with the elevated risk of non-Hodgkin lymphoma and acute myeloid leukemia. HCV may induce lymphoproliferative malignancies through chronic immune stimulation. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3069-75) C1 [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Warren, Joan L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Anderson, Lesley A.] Queens Univ Belfast, Ctr Clin & Populat Sci, Belfast, Antrim, North Ireland. [Ricker, Winnie; Parsons, Ruth; Wheeler, William] Informat Management Serv Inc, Rockville, MD USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Execut Blvd,EPS 7076, Bethesda, MD 20892 USA. EM engelse@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Anderson, Lesley/0000-0002-1000-3649 FU National Cancer Institute; Research and Development Office, Northern Ireland FX The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsiblity of the authors. The authors acknowledge the effort of the Applied Research Program, National Cancer Institute (NCI); the Office of research, Development, and Information, Centres for Medicare and Medicaid Services; Information Management Services (IMS), Inc; and the Surveillance, Epidemiology, and End Result (SEER) Program tumour registries in the creation of the SEER-Medicare database. This research was supported by the Intramural Research Program of the National Cancer Institute. The Research and Development Office, Northern Ireland, funded Dr. Lesley Anderson to participate in the Cancer Prevention Felllowship Program, Office of Preventive Oncology, NCI. NR 49 TC 49 Z9 52 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3069 EP 3075 DI 10.1158/1055-9965.EPI-08-0408 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500023 PM 18957521 ER PT J AU Hung, RJ Christiani, DC Risch, A Popanda, O Haugen, A Zienolddiny, S Benhamou, S Bouchardy, C Lan, Q Spitz, MR Wichmann, HE LeMarchand, L Vineis, P Matullo, G Kiyohara, C Zhang, ZF Pezeshki, B Harris, C Mechanic, L Seow, A Ng, DPK Szeszenia-Dabrowska, N Zaridze, D Lissowska, J Rudnai, P Fabianova, E Mates, D Foretova, L Janout, V Bencko, V Caporaso, N Chen, C Duell, EJ Goodman, G Field, JK Houlston, RS Hong, YC Landi, MT Lazarus, P Muscat, J McLaughlin, J Schwartz, AG Shen, H Stucker, I Tajima, K Matsuo, K Thun, M Yang, P Wiencke, J Andrew, AS Monnier, S Boffetta, P Brennan, P AF Hung, Rayjean J. Christiani, David C. Risch, Angela Popanda, Odilia Haugen, Aage Zienolddiny, Shan Benhamou, Simone Bouchardy, Christine Lan, Qing Spitz, Margaret R. Wichmann, H. -Erich LeMarchand, Loic Vineis, Paolo Matullo, Giuseppe Kiyohara, Chikako Zhang, Zuo-Feng Pezeshki, Benhnaz Harris, Curtis Mechanic, Leah Seow, Adeline Ng, Daniel P. K. Szeszenia-Dabrowska, Neonila Zaridze, David Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Mates, Dana Foretova, Lenka Janout, Vladimir Bencko, Vladimir Caporaso, Neil Chen, Chu Duell, Eric J. Goodman, Gary Field, John K. Houlston, Richard S. Hong, Yun-Chul Landi, Maria Teresa Lazarus, Philip Muscat, Joshua McLaughlin, John Schwartz, Ann G. Shen, Hongbing Stucker, Isabelle Tajima, Kazuo Matsuo, Keitaro Thun, Michael Yang, Ping Wiencke, John Andrew, Angeline S. Monnier, Stephanie Boffetta, Paolo Brennan, Paul TI International Lung Cancer Consortium: Pooled Analysis of Sequence Variants in DNA Repair and Cell Cycle Pathways SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; SUSCEPTIBILITY LOCUS; RISK; METAANALYSIS; XRCC3; ASSOCIATION; SMOKING; GENES; P53; EPIDEMIOLOGY AB Background: The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies. Methods: Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects. Results: Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% Cl, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% Cl, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% Cl, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk. Discussion: In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3081-9) C1 [Hung, Rayjean J.; Duell, Eric J.; Monnier, Stephanie; Boffetta, Paolo; Brennan, Paul] IARC, F-69008 Lyon, France. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [Christiani, David C.] Harvard Univ, Boston, MA 02115 USA. [Risch, Angela; Popanda, Odilia] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Haugen, Aage; Zienolddiny, Shan] Natl Inst Occupat Hlth, Oslo, Norway. [Benhamou, Simone] Fdn Jean Dausset CEPH, INSERM U794, Paris, France. [Benhamou, Simone] Inst Gustave Roussy, CNRS FRE2939, Villejuif, France. [Bouchardy, Christine] Canc Registry, Geneva, Switzerland. [Lan, Qing; Harris, Curtis; Mechanic, Leah; Caporaso, Neil; Landi, Maria Teresa] NCI, Rockville, MD USA. [Spitz, Margaret R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wichmann, H. -Erich] GSF Natl Res Ctr Environm & Hlth, Neuherberg, Germany. [Wichmann, H. -Erich] Univ Munich, IBE, D-80539 Munich, Germany. [LeMarchand, Loic] Univ Hawaii, Honolulu, HI 96822 USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Matullo, Giuseppe] Univ Turin, Turin, Italy. [Kiyohara, Chikako] Kyushu Univ, Fukuoka 812, Japan. [Zhang, Zuo-Feng; Pezeshki, Benhnaz] Univ Calif Los Angeles, Los Angeles, CA USA. [Seow, Adeline; Ng, Daniel P. K.] Natl Univ Singapore, Singapore 117548, Singapore. [Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Rudnai, Peter] Fodor Jozsef Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Budapest, Hungary. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Mates, Dana] Inst Publ Hlth, Bucharest, Romania. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Field, John K.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England. [Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Lazarus, Philip; Muscat, Joshua] Penn State Coll Med, Hershey, PA USA. [Schwartz, Ann G.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Peoples R China. [Stucker, Isabelle] INSERM U754, Villejuif, France. [Stucker, Isabelle] UMR S754, Villejuif, France. [Tajima, Kazuo; Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Aichi, Japan. [Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA. [Yang, Ping] Mayo Clin, Ctr Canc, Rochester, MI USA. [Wiencke, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Andrew, Angeline S.] Dartmouth Med Sch, Lebanon, NH USA. RP Boffetta, P (reprint author), IARC, 150 Cours Albert Thomas, F-69008 Lyon, France. EM boffetta@iarc.fr RI Hong, Yun-Chul/J-5725-2012; Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013; Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Zienolddiny, Shanbeh/O-7392-2015; Benhamou, Simone/K-6554-2015; Matullo, Giuseppe/K-6383-2016; Risch, Angela/H-2669-2013; OI Field, John/0000-0003-3951-6365; Matsuo, Keitaro/0000-0003-1761-6314; Houlston, Richard/0000-0002-5268-0242; mates, dana/0000-0002-6219-9807; Lissowska, Jolanta/0000-0003-2695-5799; Risch, Angela/0000-0002-8026-5505; Duell, Eric J/0000-0001-5256-0163; MATULLO, Giuseppe/0000-0003-0674-7757 FU National Cancer Institute [CA119704] FX Grant support: National Cancer Institute R03 grant CA119704. NR 36 TC 58 Z9 68 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3081 EP 3089 DI 10.1158/1055-9965.EPI-08-0411 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500025 PM 18990748 ER PT J AU Brinton, LA Richesson, D Leitzmann, MF Gierach, GL Schatzkin, A Mouw, T Hollenbeck, AR Lacey, JV AF Brinton, Louise A. Richesson, Douglas Leitzmann, Michael F. Gierach, Gretchen L. Schatzkin, Arthur Mouw, Traci Hollenbeck, Albert R. Lacey, James V., Jr. TI Menopausal Hormone Therapy and Breast Cancer Risk in the NIH-AARP Diet and Health Study Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGESTIN-REPLACEMENT THERAPY; ESTROGEN PLUS PROGESTIN; CONJUGATED EQUINE ESTROGENS; RANDOMIZED CONTROLLED-TRIAL; WOMENS HEALTH; POSTMENOPAUSAL WOMEN; UNITED-STATES; DIFFERENT REGIMENS; PROGNOSTIC-FACTORS; RECEPTOR STATUS AB Background: Results from the Women's Health Initiative trial raise new questions regarding the effects of estrogen therapy (ET) and estrogen plus progestin therapy (EPT) on breast cancer risk. Methods: We analyzed data from 126,638 females, ages 50 to 71 years at baseline, who completed two questionnaires (1995-1996 and 1996-1997) as part of the NIH-AARP Diet and Health Cohort Study and in whom 3,657 incident breast cancers were identified through June 30, 2002. Hormone-associated relative risks (RR) and 95% confidence intervals (CI) of breast cancer were estimated via multivariable regression models. Results: Among thin women (body mass index <25 kg/m(2)), ET use was associated with a significant 60% excess risk after 10 years of use. EPT was associated with a significantly increased risk among women with intact uteri, with the highest risk among current, long-term (>= 10 years) users (RR, 2.44; 95% Cl, 2.13-2.79). These risks were slightly higher when progestins were prescribed continuously than sequentially (<15 days/mo; respective RRs of 2.76 versus 2.01). EPT associations were strongest in thin women, but elevated risks persisted among heavy women. EPT use was strongly related to estrogen receptor (ER)-positive tumors, requiring consideration of this variable when assessing relationships according to other clinical features. For instance, ER- ductal tumors were unaffected by EPT use, but all histologic subgroups of ER+ tumors were increased, especially low-grade and mixed ductal-lobular tumors. Conclusions: Both ET and EPT were associated with breast cancer risks with the magnitude of increase varying according to body mass and clinical characteristics of the tumors. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3150-60) C1 [Brinton, Louise A.; Richesson, Douglas; Gierach, Gretchen L.; Lacey, James V., Jr.] NCI, Hormonal & Reprod Epidemiol Branch, Washington, DC USA. [Leitzmann, Michael F.; Schatzkin, Arthur; Mouw, Traci] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Washington, DC USA. [Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC USA. RP Brinton, LA (reprint author), 6120 Execut Blvd,Suite 550,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU NIH, National Cancer Institute; Department of Health; Louisiana by the Louisiana Tumor Registry; Louisiana State University Medical Center; New Orleans; New Jersey by the New Jersey State Cancer Registry; Cancer Epidemiology Services; New Jersey State Department of Health and Senior Services; North Carolina by the North Carolina Central Cancer Registry; Pennsylvania by the Division of Health Statistics and Research; Pennsylvania Department of Health, Harrisburg, PA FX Intramural Research Program of the NIH, National Cancer Institute. Cancer incidence data were collected for the Atlanta metropolitan area by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University; for California by the California Department of Health Services, Cancer Surveillance Section; for the Detroit metropolitan area by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan; for Florida by the Florida Cancer Data Svstem under contract to the Department of Health; for Louisiana by the Louisiana Tumor Registry, Louisiana State University Medical Center, New Orleans; for New Jersey by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services; for North Carolina by the North Carolina Central Cancer Registry; and for Pennsylvania by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, PA. NR 56 TC 48 Z9 48 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3150 EP 3160 DI 10.1158/1055-9965.EPI-08-0435 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500034 PM 18990757 ER PT J AU Wayne, S Neuhouser, ML Ulrich, CM Koprowski, C Wiggins, C Baumgartner, KB Bernstein, L Baumgartner, RN Gilliland, F McTiernan, A Ballard-Barbash, R AF Wayne, Sharon Neuhouser, Marian L. Ulrich, Cornelia M. Koprowski, Carol Wiggins, Charles Baumgartner, Kathy B. Bernstein, Leslie Baumgartner, Richard N. Gilliland, Frank McTiernan, Anne Ballard-Barbash, Rachel TI Association between Alcohol Intake and Serum Sex Hormones and Peptides Differs by Tamoxifen Use in Breast Cancer Survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHYSICAL-ACTIVITY LEVELS; GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN; DEHYDROEPIANDROSTERONE-SULFATE; INSULIN-RESISTANCE; MESSENGER-RNA; LEPTIN LEVELS; DHEA SULFATE; RISK; CONSUMPTION AB Objective: To measure the association between alcohol intake and 11 hormones and peptides in postmenopausal breast cancer survivors and to evaluate whether this association differs by tamoxifen use. Methods: Self-reported alcohol intake was assessed via food frequency questionnaire on average 30 months post-breast cancer diagnosis in 490 postmenopausal women from three western states. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, C-peptide, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Adjusted means of these hormones and peptides were calculated for categories of alcohol intake, overall and stratified by tamoxifen use. Results: The association between alcohol intake and serum hormone and peptide levels differed by tamoxifen use. We found statistically significant inverse associations between alcohol intake and both leptin and SHBG values but only among tamoxifen users. In women not using tamoxifen, we found a positive association between alcohol intake and DHEAS but no association in tamoxifen users. Conclusion: Tamoxifen may modify the association between alcohol intake and serum hormones and peptides. The significant associations found for DHEAS and SHBG are in a direction considered unfavorable for breast cancer prognosis. Postmenopausal breast cancer survivors may benefit from decreasing their alcohol intake. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3224-32) C1 [Wayne, Sharon; Wiggins, Charles] Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. [Neuhouser, Marian L.; Ulrich, Cornelia M.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Koprowski, Carol; Gilliland, Frank] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Baumgartner, Kathy B.; Baumgartner, Richard N.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Wayne, S (reprint author), Univ New Mexico, New Mexico Tumor Registry, MSC 11 6020, Albuquerque, NM 87131 USA. EM swayne@salud.unm.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, N01-PC-35139, N01-PC-67007, N01-PC-35138, N01-PC-67009, N01-PC-35142, T32 CA09661]; University of Washington; NIH [M01-RR-00037]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528]; University of New Mexico Cancer Center; National Cancer Institute cancer [P30-CA118100] FX National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228, N01-PC-67010/N01-PC-35139, N01-PC-67007/N01-PC-35138, and N01-PC-67009/N01-PC-35142 and training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the NIH grant M01-RR-00037. Data collection for the Women's Contraceptive and Reproductive Experiences Study at the University of Southern California was supported by the National Institute of Child Health and Human Development contract N01-HD-3-3175. Patient identification was supported in part by the California Department of Health Services grant 050Q-8709-Sl528. Preparation of this article was supported, in part, by the University of New Mexico Cancer Center, a recipient of National Cancer Institute cancer support grant P30-CA118100. NR 55 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3224 EP 3232 DI 10.1158/1055-9965.EPI-08-0171 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500043 PM 18957523 ER PT J AU Weinstein, SJ Albanes, D Selhub, J Graubard, B Lim, U Taylor, PR Virtamo, J Stolzenberg-Solomon, R AF Weinstein, Stephanie J. Albanes, Demetrius Selhub, Jacob Graubard, Barry Lim, Unhee Taylor, Philip R. Virtamo, Jarmo Stolzenberg-Solomon, Rachael TI One-Carbon Metabolism Biomarkers and Risk of Colon and Rectal Cancers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NESTED CASE-CONTROL; COLORECTAL-CANCER; FOLATE LEVELS; CELL-PROLIFERATION; TOTAL HOMOCYSTEINE; PLASMA FOLATE; FOLIC-ACID; VITAMIN-B-6; COHORT; WOMEN AB Background: Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers. Methods: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression. Results: Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk. Conclusions: Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3233-40) C1 [Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Ser, Bethesda, MD 20892 USA. [Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Weinstein, SJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Ser, Suite 320,6120 Execut Blvd, Bethesda, MD 20892 USA. EM weinstes@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU NIH National Cancer Institute Intramural Research Program and Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National Cancer Institute, Department of Health and Human Services FX NIH National Cancer Institute Intramural Research Program and Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute, Department of Health and Human Services. NR 50 TC 43 Z9 44 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3233 EP 3240 DI 10.1158/1055-9965.EPI-08-0459 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500044 PM 18990766 ER PT J AU Chu, LW Zhu, Y Yu, K Zheng, TZ Chokkalingam, AP Stanczyk, FZ Gao, YT Hsing, AW AF Chu, Lisa W. Zhu, Yong Yu, Kai Zheng, Tongzhang Chokkalingam, Anand P. Stanczyk, Frank Z. Gao, Yu-Tang Hsing, Ann W. TI Correlation between Circadian Gene Variants and Serum Levels of Sex Steroids and Insulin-like Growth Factor-I SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EXTREME DIURNAL PREFERENCE; FACTOR BINDING PROTEIN-3; FACTOR (IGF)-I; PROSTATE-CANCER; BREAST-CANCER; ELDERLY MEN; IGF-II; HORMONE; TESTOSTERONE; POLYMORPHISM AB A variety of biological processes, including steroid hormone secretion, have circadian rhythms, which are influenced by nine known circadian genes. Previously, we reported that certain variants in circadian genes were associated with risk for prostate cancer. To provide some biological insight into these findings, we examined the relationship of five variants of circadian genes, including NPAS2 (rs2305160:G>A), PER1 (rs2585405:G>C), CSNK1E (rs1005473:A>C), PER3 (54-bp repeat length variant), and CRY2 (rs1401417:G>C), with serum levels of sex steroids and insulin-like growth factor (IGF)-I and IGF-binding protein 3 (IGFBP3) in 241 healthy elderly Chinese men (mean age of 71.5). Age-adjusted and waist-to-hip ratio-adjusted ANOVA followed by likelihood ratio tests (LRT) showed that the NPAS2 variant A allele was associated with lower free and bioavailable testosterone (P-LRT = 0.02 and 0.01, respectively) compared with the GG genotype. In addition, the PER1 variant was associated with higher serum levels of sex hormonebinding globulin levels (P-trend = 0.03), decreasing 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide levels (P-trend = 0.02), and decreasing IGFBP3 levels (P-trend = 0.05). Furthermore, the CSNK1E variant C allele was associated with higher testosterone to dihydrotestosterone ratios (P-LRT = 0-01) compared with the AA genotype, whereas the longer PER3 repeat was associated with higher serum levels of IGF-I (P-LRT = 0.03) and IGF-I to IGFBP3 ratios (P-LRT = 0.04). The CRY2 polymorphism was not associated with any biomarkers analyzed. Our findings, although in need of confirmation, suggest that variations in circadian genes are associated with serum hormone levels, providing biological support for the role of circadian genes in hormone-related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3268-73) C1 [Chu, Lisa W.; Yu, Kai; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chu, Lisa W.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Zhu, Yong; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Chokkalingam, Anand P.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Chu, LW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM chulisa@mail.nih.gov NR 35 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2008 VL 17 IS 11 BP 3268 EP 3273 DI 10.1158/1055-9965.EPI-08-0073 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 372IY UT WOS:000260896500048 PM 18990770 ER PT J AU Berzofsky, JA Terabe, M AF Berzofsky, Jay A. Terabe, Masaki TI A novel immunoregulatory axis of NKT cell subsets regulating tumor immunity SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT Progress in Vaccination Against Cancer 7 (PIVAC 7) CY SEP 10-11, 2007 CL Stockholm, SWEDEN DE tumor immunosurveillance; immunoregulation; NKT cells; tumor immunity ID KILLER T-CELLS; ANTITUMOR IMMUNITY; IN-VIVO; IMMUNOSURVEILLANCE; ACTIVATION; IL-13; AUTOIMMUNITY; RECOGNITION; SUFFICIENT; SULFATIDE AB There are many mechanisms that regulate and dampen the immune response to cancers, including several types of regulatory T cells. Besides the T reg cell, we have identified another immunoregulatory circuit initiated by NKT cells that produce IL-13 in response to tumor growth and this IL-13 then induces myeloid cells to make TGF-beta that inhibits cytotoxic T cell-mediated tumor immunosurveillance in several mouse tumor models. This finding created a paradox in the role of NKT cells in tumor immunity, in that they can also contribute to protection. We resolve this paradox by the finding that the suppressive NKT cell is a type II NKT cell that lacks the canonical invariant T cell receptor, whereas the protective cell is a type I NKT cell that expresses the invariant receptor. Further, we see that these two subsets of NKT cells counter-regulate each other, defining a new immunoregulatory axis. The balance along this axis may determine the outcome of tumor immunosurveillance as well as influence the efficacy of anti-cancer vaccines and immunotherapy. C1 [Berzofsky, Jay A.; Terabe, Masaki] Natl Canc Inst, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), Natl Canc Inst, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov; terabe@mail.nih.gov NR 31 TC 35 Z9 38 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2008 VL 57 IS 11 BP 1679 EP 1683 DI 10.1007/s00262-008-0495-4 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA 341MC UT WOS:000258717600011 PM 18369622 ER PT J AU Rowland, JH AF Rowland, Julia H. TI What Are Cancer Survivors Telling Us? SO CANCER JOURNAL LA English DT Article DE cancer survivors; lessons learned; cancer survivorship research; quality of care; cancer control ID BREAST-CANCER; PHYSICAL-ACTIVITY; PSYCHOSOCIAL FACTORS; TEACHABLE MOMENT; PEDIATRIC CANCER; DIAGNOSIS; HEALTH; CARE; MECHANISMS; CHALLENGE AB Among the great medical success stories of the 20th century was our ability to turn cancer. once almost uniformily fatal into an illness that was curable for more people, and could be controlled in most. As a result of advances in screening and early detection, the development of effective treatments and the delivery of better supportive care, the population of those living long term with a history of cancer continues to grow. The field of cancer survivorship research, now entering its adolescence, has developed to help us better understand the human and social challenges of living long term after cancer. Estimated at approaching 12 million, cancer survivors have taught us a number of important lessons about what it means to live beyond a cancer diagnosis. In this article, 7 of these lessons will be discussed along with their implications for current clinical practice and future directions in cancer survivorship research. C1 [Rowland, Julia H.] NCI, Off Canc Survivorship, NIH, DHHS, Bethesda, MD 20892 USA. RP Rowland, JH (reprint author), 6116 Execut B,Blvd,Suite 404, Bethesda, MD 20892 USA. EM rowland.j@mail.nih.gov NR 56 TC 32 Z9 32 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2008 VL 14 IS 6 BP 361 EP 368 DI 10.1097/PPO.0b013e31818ec48e PG 8 WC Oncology SC Oncology GA 382IY UT WOS:000261600700004 PM 19060600 ER PT J AU Fall-Dickson, JM Mock, V Berk, RA Grimm, PM Davidson, N Gaston-Johansson, F AF Fall-Dickson, Jane M. Mock, Victoria Berk, Ronald A. Grimm, Patricia M. Davidson, Nancy Gaston-Johansson, Fannie TI Stomatitis-Related Pain in Women With Breast Cancer Undergoing Autologous Hematopoietic Stem Cell Transplant SO CANCER NURSING LA English DT Article DE Acute oral pain; Autologous hematopoietic stem cell transplantation; Stomatitis ID BONE-MARROW-TRANSPLANTATION; ORAL MUCOSITIS; DEPRESSION; COMPLICATIONS; PATHOBIOLOGY; MANAGEMENT AB The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. The hypotheses that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing were tested. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two women were recruited at 2 East Coast comprehensive cancer centers. Data were collected on bone marrow transplantation day +7 +/- 24 hours using Painometer, Oral Mucositis Index-20, Oral Assessment Guide, State-Trait Anxiety Inventory, and Beck Depression Inventory. Data analysis included descriptive statistics, correlations, and stepwise multiple regression. All participants had stomatitis; 47% had oral pain, with a subset reporting continuous moderate to severe oral pain despite pain management algorithms. Significant, positive associations were seen between oral pain, stomatitis, and alteration in swallowing and between oral pain with swallowing and alteration in swallowing. Oral pain was not significantly correlated with state anxiety and depression. Oral sensory and affective pain Intensity most accurately predicted oral pain overall intensity. Future research needs to explore factors that affect perception and response to stomatitis-related oropharyngeal pain and individual patient response to opioid treatment. C1 [Fall-Dickson, Jane M.] NINR, Symptom Management Branch, NIH, Bethesda, MD 20892 USA. [Mock, Victoria] Johns Hopkins Univ, Ctr Nursing Res, Baltimore, MD USA. [Berk, Ronald A.; Grimm, Patricia M.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Davidson, Nancy] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Gaston-Johansson, Fannie] Johns Hopkins Univ, Acute & Chron Care Dept, Baltimore, MD USA. RP Fall-Dickson, JM (reprint author), NINR, Symptom Management Branch, NIH, CRC 2NE 1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM dicksonj@mail.nih.gov FU American Cancer Society Doctoral Scholarship in Cancer Nursing (Atlanta, Georgia); Sigma Theta Tau; Nu Beta Chapter; Johns Hopkins University School of Nursing; Nursing Research Award FX This work was supported by an American Cancer Society Doctoral Scholarship in Cancer Nursing (Atlanta, Georgia) and a Sigma Theta Tau, Nu Beta Chapter, Johns Hopkins University School of Nursing, Nursing Research Award for Outstanding Research Proposal. NR 43 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD NOV-DEC PY 2008 VL 31 IS 6 BP 452 EP 461 DI 10.1097/01.NCC.0000339244.58914.4a PG 10 WC Oncology; Nursing SC Oncology; Nursing GA 371GU UT WOS:000260820600006 PM 18987512 ER PT J AU Sigurdson, AJ Bhatti, P Preston, DL Doody, MM Karnpa, D Alexander, BH Petibone, D Yong, LC Edwards, AA Ron, E Tucker, JD AF Sigurdson, Alice J. Bhatti, Parveen Preston, Dale L. Doody, Michele Morin Karnpa, Diane Alexander, Bruce H. Petibone, Dayton Yong, Lee C. Edwards, Alan A. Ron, Elaine Tucker, James D. TI Routine Diagnostic X-ray Examinations and Increased Frequency of Chromosome Translocations among US Radiologic Technologists SO CANCER RESEARCH LA English DT Article ID RADIATION-INDUCED TRANSLOCATIONS; SELLAFIELD NUCLEAR FACILITY; BIOLOGICAL DOSIMETRY; CANCER INCIDENCE; UNITED-STATES; ABERRATION ANALYSIS; MEDICAL RADIATION; SMOKING-HABITS; EXPOSURE; FISH AB The U.S. population has nearly one radiographic examination per person per year, and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to. diagnostic X-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U.S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and,were interviewed about past X-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range, 0-303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval, 0.002-0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice X-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine X-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data. [Cancer lies 2008;68(21):8825-31] C1 [Sigurdson, Alice J.; Bhatti, Parveen; Doody, Michele Morin; Ron, Elaine] Natl Canc Inst, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA. [Karnpa, Diane; Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. [Petibone, Dayton; Tucker, James D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Yong, Lee C.] NIOSH, Cincinnati, OH 45226 USA. [Edwards, Alan A.] Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England. RP Sigurdson, AJ (reprint author), Natl Canc Inst, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute, NIH, Department Health and Human Services,; National Institute for Occupational Safety and Health [Y1-CP-9012]; National Institute for Occupational Safety and Health FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, the National Cancer Institute, NIH, Department Health and Human Services, and by all interagency agreement with the National Institute for Occupational Safety and Health contract Y1-CP-9012. The findings and Conclusions ill this report are those of the author(s) and do not necessarily represent the views of the National Institute for Occupational Safety and Health. NR 45 TC 10 Z9 11 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2008 VL 68 IS 21 BP 8825 EP 8831 DI 10.1158/0008-5472.CAN-08-1691 PG 7 WC Oncology SC Oncology GA 369MP UT WOS:000260698900023 PM 18974125 ER PT J AU Yeung, ML Yasunaga, JI Bennasser, Y Dusetti, N Harris, D Ahmad, N Matsuoka, M Jeang, KT AF Yeung, Man Lung Yasunaga, Jun-ichirou Bennasser, Yamina Dusetti, Nelson Harris, David Ahmad, Nafees Matsuoka, Masao Jeang, Kuan-Teh TI Roles for MicroRNAs, miR-93 and miR-130b, and Tumor Protein 53-induced Nuclear Protein 1 Tumor Suppressor in Cell Growth Dysregulation by Human T-Cell Lymphotrophic Virus 1 SO CANCER RESEARCH LA English DT Article ID P53-INDUCED NUCLEAR-PROTEIN-1; TRANSCRIPTION FACTOR; GENE-REGULATION; TAX GENE; I TAX; EXPRESSION; CANCER; LEUKEMIA; RNA; TRANSFORMATION AB A role for microRNAs (miRNA) in human T-cell leukemia virus 1 (HTLV-1)-mediated cellular transformation has not been described. Here, we profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. Analyses of I I different profiles revealed six miRNAs that were consistently up-regulated. Two of the up-regulated miRNAs (miR-93 and miR-130b) target the 3' untranslated region (3'UTR) of the mRNA for a tumor suppressor protein, tumor protein 53-induced nuclear protein 1 (TP53INP1). A low expression level of TP53INP1 protein was found in HTLV-1-transformed cells. Additionally, when antagomirs were used to knock down miR-93 and miR-130b in these cells, the expression of TP53INP1 was increased, suggesting that the latter is regulated inside cells by the former. A role for TP53INP1 in regulating cell growth was established by experiments that showed that enhanced TP53INP1 expression increased apoptosis. Collectively, the findings implicate a miR-93/miR-130b-TP53INP1 axis that affects the proliferation and survival of HTLV-1-infected/transformed cells. [Cancer Res 2008;68(21):8976-85] C1 [Yeung, Man Lung; Yasunaga, Jun-ichirou; Bennasser, Yamina; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Yasunaga, Jun-ichirou; Matsuoka, Masao] Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Sakyo Ku, Kyoto 606, Japan. [Dusetti, Nelson] Univ Mediterrance, INSERM, IFR 137, Inst Cancerol & Immunol Marseille,U624, Marseille, France. [Bennasser, Yamina] CNRS, Mol Virol Lab, Inst Genet Humaine, UPR 1142, Montpellier, France. [Harris, David; Ahmad, Nafees] Univ Arizona, Dept Microbiol & Immunol, Hlth Sci Ctr, Tucson, AZ 85721 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Matsuoka, Masao/0000-0002-0473-754X; Yasunaga, Jun-ichirou/0000-0002-7939-2080 FU National Institute of Allergy and Infectious Diseases/NIH; NIH FX Work in K-T. Jeang's laboratory is supported by intramural National Institute of Allergy and Infectious Diseases/NIH funds and funding from the NIH IATAP program. NR 49 TC 117 Z9 125 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2008 VL 68 IS 21 BP 8976 EP 8985 DI 10.1158/0008-5472.CAN-08-0769 PG 10 WC Oncology SC Oncology GA 369MP UT WOS:000260698900040 PM 18974142 ER PT J AU Neklason, DW Kerber, RA Nilson, DB Anton-Culver, H Schwartz, AG Griffin, CA Lowery, JT Schildkraut, JM Evans, JP Tomlinson, GE Strong, LC Miller, AR Stopfer, JE Finkelstein, DM Nadkarni, PM Kasten, CH Mineau, GP Burt, RW AF Neklason, Deborah W. Kerber, Richard A. Nilson, David B. Anton-Culver, Hoda Schwartz, Ann G. Griffin, Constance A. Lowery, Jan T. Schildkraut, Joellen M. Evans, James P. Tomlinson, Gail E. Strong, Louise C. Miller, Alexander R. Stopfer, Jill E. Finkelstein, Dianne M. Nadkarni, Prakash M. Kasten, Carol H. Mineau, Geraldine P. Burt, Randall W. TI Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis SO CANCER RESEARCH LA English DT Article ID SUSCEPTIBILITY LOCUS; ASSOCIATION SCAN; LINKAGE; GENES; KINDREDS; ERBB4; TESTS; RISK; 8Q24; MAP AB Present investigations suggest that similar to 30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores >= 2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (+/- 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993-7] C1 [Neklason, Deborah W.; Kerber, Richard A.; Nilson, David B.; Mineau, Geraldine P.; Burt, Randall W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Anton-Culver, Hoda] Univ Calif Irvine, Irvine, CA USA. [Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Griffin, Constance A.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Griffin, Constance A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Lowery, Jan T.] Colorado Sch Publ Hlth, Denver, CO USA. [Schildkraut, Joellen M.] Duke Univ, Durham, NC USA. [Evans, James P.] Univ N Carolina, Chapel Hill, NC USA. [Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Miller, Alexander R.] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. [Miller, Alexander R.] Univ Texas San Antonio, San Antonio, TX USA. [Stopfer, Jill E.] Univ Penn, Philadelphia, PA 19104 USA. [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Stat Coordinating Ctr, Boston, MA 02114 USA. [Nadkarni, Prakash M.] Yale Ctr Informat, New Haven, CT USA. [Kasten, Carol H.] NCI, Rockville, MD USA. RP Neklason, DW (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope, Salt Lake City, UT 84112 USA. EM Deb.neklason@hci.utah.edu RI Kerber, Richard/B-8038-2009 FU NIH [U24-CA78174, P01-CA073992, U24-CA78134, U01-CA78285, N01-PC35145, U24-CA78148, CA74799, U24-CA78142, CA78157-05S1, U01-CA078284]; University of Utah General Clinical Research Center [M01-RR00064, N01-PC-67000]; National Cancer Institute Surveillance, Epidemiology, and End Results; Utah State Department of Health; University of Utah; Huntsman Cancer Foundation FX NIH grants U24-CA78174 (G.P. Mineau), P01-CA073992 (RAV. Burt), U24-CA78134 (H. Anton-Culver), U01-CA78285 (H. Anton-Culver), N01-PC35145 (A.G. Schwartz), U24-CA78148 (C.A. Griffin), CA74799 (J.T. Lowery), U24-CA78142 (I-C. Strong), CA78157-05S1 (J.E. Stopfer), and U01-CA078284 (D.M. Finkelstein); University of Utah General Clinical Research Center grants M01-RR00064 and N01-PC-67000; Utah Cancer Registry grant. N01-PC-35141 from the National Cancer Institute Surveillance, Epidemiology, and End Results program; the Utah State Department of Health; and the University of Utah, Huntsman Cancer Foundation. NR 26 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2008 VL 68 IS 21 BP 8993 EP 8997 DI 10.1158/0008-5472.CAN-08-1376 PG 5 WC Oncology SC Oncology GA 369MP UT WOS:000260698900042 PM 18974144 ER PT J AU Kim, HH Yang, X Kuwano, Y Gorospe, M AF Kim, Hyeon Ho Yang, Xiaoling Kuwano, Yuki Gorospe, Myriam TI Modification at HuR(S242) alters HuR localization and proliferative influence SO CELL CYCLE LA English DT Article DE cell cycle; cyclins; RNA-binding protein; post-transcriptional gene expression; ribonucleoprotein complex; mRNA turnover ID RNA-BINDING PROTEIN; AU-RICH ELEMENT; MESSENGER-RNA; NUCLEAR IMPORT; PHOSPHORYLATION; ALPHA; STABILIZATION; EXPRESSION; STABILITY; TRANSLATION AB HuR is predominantly nuclear but following exposure to stress and mitogens, it can translocate to the cytoplasm where it stabilizes target mRNAs and/or modulates their translation. Several phosphorylation sites in a central 'hinge' region of HuR have been reported to affect its nucleocytoplasmic shuttle: phosphorylation by PKC at serine (S) 221 and by Cdk1 at S202. Here, we investigated if there are additional putative phosphorylation sites within the HuR hinge region capable of influencing its cytoplasmic abundance. We systematically mutated all seven serine residues within the shuttling hinge domain to the nonphosphorylatable residue alanine (A), S197A, S202A, S221A, S229A, S232A, S241A and S242A. Using HeLa cells as the study system, we found that the HuR(S242A) mutant was more abundant in the cytoplasm in both untreated cells and in cells treated with short-wavelength ultraviolet light or with an inhibitor of Cdk1. Conversely, mutation of S242 to aspartic acid (D), rendered the phosphomimetic HuR(S242D) nuclear under all treatment conditions. S242 mutations did not influence HuR stability, but HuR(S242A) showed increased association with target cyclin A2 and cyclin B1 mRNAs. Accordingly, expression of HuR(S242A) led to increased cyclin mRNA stability and heightened cell proliferation rates. Our findings suggest that HuR phosphorylation at S242 hinders its cytoplasmic localization, its function as a posttranscriptional regulator, and its proliferative influence. C1 [Kim, Hyeon Ho; Yang, Xiaoling; Kuwano, Yuki; Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU National Institute on Aging, National Institutes of Health FX This work was supported entirely by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 49 TC 39 Z9 40 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2008 VL 7 IS 21 BP 3371 EP 3377 PG 7 WC Cell Biology SC Cell Biology GA 368AS UT WOS:000260594300019 PM 18948743 ER PT J AU Eiden, MV AF Eiden, M. V. TI Endogenous retroviruses - Aiding and abetting genomic plasticity SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Editorial Material DE Endogenous retrovirus; exogenous retrovirus; retroelements; symbionts; insertional mutagenesis; evolution; germ line ID KOALA RETROVIRUS; VIRUS; SYNCYTIN; RECEPTOR; GENE C1 NIH, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIH, Bldg 49,MSC 4483, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov FU Intramural NIH HHS [Z01 MH002592-17, ZIA MH002592-19, ZIA MH002592-20] NR 16 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2008 VL 65 IS 21 BP 3327 EP 3328 DI 10.1007/s00018-008-8493-4 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 369HC UT WOS:000260684200001 PM 18818876 ER PT J AU Stocking, C Kozak, CA AF Stocking, C. Kozak, C. A. TI Murine endogenous retroviruses SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Virus restriction factors; retroviral receptors; Env-receptor interactions; murine ERV classification ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; CELL-SURFACE RECEPTOR; MOUSE LEUKEMIA VIRUS; WILD-DERIVED MICE; DNA-SEQUENCES; MUERV-L; MUS-MUSCULUS; Y-CHROMOSOME; HOST-RANGE AB Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV) sequences, and most represent the remains of ancient germ line infections. Our knowledge of the three distinct classes of ERVs is inversely correlated with their copy number, and their characterization has benefited from the availability of divergent wild mouse species and subspecies, and from ongoing analysis of the Mus genome sequence. In contrast to human ERVs, which are nearly all extinct, active mouse ERVs can still be found in all three ERV classes. The distribution and diversity of ERVs has been shaped by host-virus interactions over the course of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral resistance genes. We review mechanisms by which an adaptive coexistence has evolved. (Part of a Multiauthor Review). C1 [Stocking, C.] Heinrich Pette Inst, D-20251 Hamburg, Germany. [Kozak, C. A.] NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Stocking, C (reprint author), Heinrich Pette Inst, Martinistr 52, D-20251 Hamburg, Germany. EM stocking@hpi.uni-hamburg.de; ckozak@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000300-26, Z99 AI999999] NR 150 TC 93 Z9 94 U1 3 U2 23 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2008 VL 65 IS 21 BP 3383 EP 3398 DI 10.1007/s00018-008-8497-0 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 369HC UT WOS:000260684200005 PM 18818872 ER PT J AU Luo, R Jenkins, LMM Randazzo, PA Gruschus, J AF Luo, Ruibai Jenkins, Lisa M. Miller Randazzo, Paul A. Gruschus, James TI Dynamic interaction between Arf GAP and PH domains of ASAP1 in the regulation of GAP activity SO CELLULAR SIGNALLING LA English DT Article DE ADP-ribosylation factor; GTPase-activating protein; Pleckstrin homology domain; Nuclear Magnetic Resonance spectrometry ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; PLECKSTRIN HOMOLOGY DOMAIN; ACTIN CYTOSKELETON; N-TERMINUS; COMPLEX; AGAP1; HYDROLYSIS; ACID; PHOSPHOLIPIDS AB ASAP family Arf GAPs induce the hydrolysis of GTP bound to the Ras superfamily protein Arf1, regulate cell adhesion and migration and have been implicated in carcinogenesis. The ASAP proteins have a core catalytic domain of PH, Arf GAP and Ank repeat domains. The PH domain is necessary for both biological and catalytic functions of ASAP1 and has been proposed to be integrally folded with the Arf GAP domain. Protection studies and analytical ultracentrifugation studies previously reported indicated that the domains are, at least partly, folded together. Here, using NMR spectroscopy and biochemical analysis, we have further tested this hypothesis and characterized the interdomain interaction. A comparison of NMR spectra of three recombinant proteins comprised of either the isolated PH domain of ASAP1, the Arf GAP and ankyrin repeat domain or all three domains indicated that the PH domain did interact with the Arf GAP and Ank repeat domains; however, we found a significant amount of dynamic independence between the PH and Arf GAP domains, consistent with the interactions being transient. In contrast, the Arf GAP and Ank repeat domains form a relatively rigid structure. The PH-Arf GAP domain interaction partially occluded the phosphomositide binding site in the soluble Protein, but binding studies indicated the PIP2 binding site was accessible in ASAP1 bound to a lipid bilayer Surface. Phosphomositide binding altered the conformation of the PH domain, but had little effect on the structure of the Arf GAP domain. Mutations in a loop of the PH domain that contacts the Arf GAP domain affected PIP2 binding and the K-m and k(cat) for converting Arf1.GTP to Arf1.GDP. Based on these results, we generated a homology model of a composite PH/Arf GAP/Ank repeat domain structure. We propose that the PH domain contributes to Arf GAP activity by either binding to or positioning Arf1.GTP that is simultaneously bound to the Arf GAP domain. Published by Elsevier Inc. C1 [Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Gruschus, James] NHLBI, NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Room 2042, Bethesda, MD 20892 USA. EM Randazzo@helix.nih.gov FU Intramural Research Program of the National Cancer Institute; National Heart, Lung and Blood Institute; National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Cancer Institute and the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services. NR 44 TC 10 Z9 10 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD NOV PY 2008 VL 20 IS 11 BP 1968 EP 1977 DI 10.1016/j.cellsig.2008.07.007 PG 10 WC Cell Biology SC Cell Biology GA 368QL UT WOS:000260637500007 PM 18675341 ER PT J AU Pamonsinlapatham, P Gril, B Dufour, S Hadj-Slimane, R Gigoux, V Pethe, S L'Hoste, S Camonis, J Garbay, C Raynaud, F Vidal, M AF Pamonsinlapatham, Perayot Gril, Brunilde Dufour, Sylvie Hadj-Slimane, Reda Gigoux, Veronique Pethe, Stephanie L'Hoste, Sebastien Camonis, Jacques Garbay, Christiane Raynaud, Francoise Vidal, Michel TI Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: Modulation of cell survival and migration SO CELLULAR SIGNALLING LA English DT Article DE Calpain; Migration; RasGAP; SH3 domain ID GTPASE-ACTIVATING PROTEIN; UBIQUITOUS CALPAINS PROMOTE; SH3 DOMAIN; RAS-GAP; PHOSPHORYLATION; APOPTOSIS; COMPLEX; GROWTH; SRC; DISRUPTION AB Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras Stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras. We used confocal microscopy to analyze our stably transfected cell model producing mutant Ras (PC3Ras(V12)). Staining for RasGAP-SH3/Capns1 co-localization was two-fold stronger in the protrusions of Ras(V12) cells than in PO cells. RasGAP or Capns1 knockdown in PC3Ras(V12) cells induced a two- to three-fold increase in apoptosis. Capns1 gene silencing reduced the speed and increased the persistence of movement in PC3Ras(V12) cells. In contrast, RasGAP knockdown in PC3Rasv 12 cells increased cell migration. Knockdown of both proteins altered the speed and directionality of cell Motility. Our findings Suggest that RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival. (c) 2008 Elsevier Inc. All rights reserved. C1 [Pamonsinlapatham, Perayot; Gril, Brunilde; Hadj-Slimane, Reda; Gigoux, Veronique; Pethe, Stephanie; Garbay, Christiane; Raynaud, Francoise; Vidal, Michel] Univ Paris 05, Lab Pharmacochim Mol & Cellulaire, Unites Format & Rech Biomed, F-75270 Paris 06, France. [Pamonsinlapatham, Perayot; Gril, Brunilde; Hadj-Slimane, Reda; Gigoux, Veronique; Pethe, Stephanie; Garbay, Christiane; Raynaud, Francoise; Vidal, Michel] INSERM U648, Lab Pharmacochim Mol & Cellulaire, Paris 06, France. [Gril, Brunilde] NCI, NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Dufour, Sylvie] CNRS, Inst Curie, UMR144, F-75005 Paris, France. [Pethe, Stephanie; L'Hoste, Sebastien] INSERM U528, Inst Curie, Lab Transduc Signal & Oncogenese, F-75005 Paris, France. RP Raynaud, F (reprint author), Univ Paris 05, Lab Pharmacochim Mol & Cellulaire, Unites Format & Rech Biomed, 45 Rue St Peres, F-75270 Paris 06, France. EM francoise.raynaud@univ-paris5.fr; michel.vidal@univ-paris5.fr FU La Ligue Nationale contre le Cancer; Ministere de la Technologie et de la Recherche [02L0521]; Faculty of Pharmacy, Silpakorn University, Thailand; Ministere de la Technologie et de la Recherche; Association pour la Recherche contre le Cancer [3737] FX This work received financial support from La Ligue Nationale contre le Cancer, 2006 and from Ministere de la Technologie et de la Recherche, ACI 2002 Molecules et cibles therapeutiques (number 02L0521). PP Was Supported by a scholarship from the Faculty of Pharmacy, Silpakorn University, Thailand. BG received a grant from the Ministere de la Technologie et de la Recherche and SD received financial support from the Association pour la Recherche contre le Cancer (grant 3737). The authors acknowledge NIH for stylistic revision of this manuscript. They also thank Pr Marie Agnes Sari, Yves Lepelletier, William Thomas and Pierre Colas for critical reading of the manuscript, and Veronique Lenoir for her technical assistance. NR 40 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD NOV PY 2008 VL 20 IS 11 BP 2119 EP 2126 DI 10.1016/j.cellsig.2008.08.005 PG 8 WC Cell Biology SC Cell Biology GA 368QL UT WOS:000260637500023 PM 18761085 ER PT J AU Wilson, PWF Pencina, M Jacques, P Selhub, J D'Agostino, R O'Donnell, CJ AF Wilson, Peter W. F. Pencina, Michael Jacques, Paul Selhub, Jacob D'Agostino, Ralph, Sr. O'Donnell, Christopher J. TI C-Reactive Protein and Reclassification of Cardiovascular Risk in the Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE epidemiology; inflammation; risk factors; statistics AB Background-The relationship of circulating levels of high-sensitivity C-reactive protein (CRP) with cardiovascular disease (CVD) risk, particularly with consideration of effects at intermediate levels of risk, has not been fully assessed. Methods and Results-Among 3006 offspring participants in the Framingham Heart Study free of CVD (mean age, 46 years at baseline), there were 129 hard coronary heart disease (CHD) events and 286 total CVD events during 12 years of follow-up. Cox regression, discrimination with area under the receiver operating characteristic curve, and net reclassification improvement were used to assess the role of CRP on vascular risk. In an age-adjusted model that included both sexes, the hazard ratios for new hard CHD and total CVD were significantly associated with higher CRP levels. Similar analyses according to increasing homocysteine level showed significant protective associations for hard CHD but not for total CVD. In multivariable analyses that included age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes mellitus, current smoking, hypertension treatment, and homocysteine, the log CRP level remained significantly related to development of hard CHD and total CVD and provided moderate improvement in the discrimination of events. The net reclassification improvement when CRP was added to traditional factors was 5.6% for total CVD (P=0.014) and 11.8% for hard CHD (P=0.009). Conclusions-Circulating levels of CRP help to estimate risk for initial cardiovascular events and may be used most effectively in persons at intermediate risk for vascular events, offering moderate improvement in reclassification of risk. (Circ Cardiovasc Qual Outcomes. 2008;1:92-97.) C1 [Wilson, Peter W. F.] Emory Univ, Sch Med, EPICORE, Atlanta, GA 30306 USA. [Wilson, Peter W. F.] Atlanta VAMC Epidemiol & Genet Sect, Atlanta, GA USA. [Pencina, Michael; D'Agostino, Ralph, Sr.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Pencina, Michael; D'Agostino, Ralph, Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Jacques, Paul; Selhub, Jacob] Tufts USDA Nutr Ctr, Boston, MA USA. RP Wilson, PWF (reprint author), Emory Univ, Sch Med, EPICORE, Suite 1 N,1256 Briarcliff Rd, Atlanta, GA 30306 USA. EM peter.wf.wilson@emory.edu FU Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL073272, N01 HC-25195]; Boston University School of Medicine FX This study was supported by grant R01 HL073272 (to P. W. F. W.) from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01 HC-25195). NR 35 TC 147 Z9 152 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2008 VL 1 IS 2 BP 92 EP 97 DI 10.1161/CIRCOUTCOMES.108.831198 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AL UT WOS:000207504400005 PM 20031795 ER PT J AU Go, AS Magid, DJ Wells, B Sung, SH Cassidy-Bushrow, AE Greenlee, RT Langer, RD Lieu, TA Margolis, KL Masoudi, FA McNeal, CJ Murata, GH Newton, KM Novotny, R Reynolds, K Roblin, DW Smith, DH Vupputuri, S White, RE Olson, J Rumsfeld, JS Gurwitz, JH AF Go, Alan S. Magid, David J. Wells, Barbara Sung, Sue Hee Cassidy-Bushrow, Andrea E. Greenlee, Robert T. Langer, Robert D. Lieu, Tracy A. Margolis, Karen L. Masoudi, Frederick A. McNeal, Catherine J. Murata, Glen H. Newton, Katherine M. Novotny, Rachel Reynolds, Kristi Roblin, Douglas W. Smith, David H. Vupputuri, Suma White, Robert E. Olson, Jean Rumsfeld, John S. Gurwitz, Jerry H. TI The Cardiovascular Research Network A New Paradigm for Cardiovascular Quality and Outcomes Research SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiovascular disease; risk factors; outcomes; epidemiology; quality of care ID ACUTE MYOCARDIAL-INFARCTION; BARE-METAL STENTS; SIROLIMUS-ELUTING STENTS; ACUTE CORONARY SYNDROMES; CLINICAL-DATA STANDARDS; ASSOCIATION TASK-FORCE; HMO-RESEARCH-NETWORK; KEY DATA ELEMENTS; NATIONAL REGISTRY; HEART-FAILURE AB Background-A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes. Methods and Results-The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximate to 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators. Conclusions-The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases. (Circ Cardiovasc Qual Outcomes. 2008;1:138-147.) C1 [Go, Alan S.; Sung, Sue Hee] Univ Calif San Francisco, Kaiser Permanente No Calif, San Francisco, CA 94143 USA. [Magid, David J.] Univ Colorado, Kaiser Permanente Colorado, Denver, CO 80202 USA. [Wells, Barbara; Olson, Jean] NHLBI, Bethesda, MD 20892 USA. [Cassidy-Bushrow, Andrea E.] Henry Ford Hlth Syst, Detroit, MI USA. [Greenlee, Robert T.] Univ Wisconsin, Marshfield Clin Fdn Med Res & Educ, Madison, WI USA. [Langer, Robert D.] Geisinger Hlth Syst, Danville, PA USA. [Lieu, Tracy A.] Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. [Lieu, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA. [Margolis, Karen L.] Univ Minnesota, HealthPartners Res Fdn, Minneapolis, MN USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [McNeal, Catherine J.] Scott & White Mem Hosp & Clin, Temple, TX USA. [McNeal, Catherine J.] Texas A&M Univ, Texas A&M Hlth Sci Ctr, College Stn, TX USA. [Murata, Glen H.; White, Robert E.] Univ New Mexico, Albuquerque, NM 87131 USA. [Murata, Glen H.] New Mexico VA Hlth Care Syst, Albuquerque, NM USA. [Newton, Katherine M.] Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. [Newton, Katherine M.; Smith, David H.] Univ Washington, Seattle, WA 98195 USA. [Novotny, Rachel] Univ Hawaii, Kaiser Permanente Ctr Hlth Res Hawaii, Honolulu, HI 96822 USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Pasadena, CA USA. [Roblin, Douglas W.; Vupputuri, Suma] Kaiser Permanente Georgia, Atlanta, GA USA. [Roblin, Douglas W.] Emory Univ, Atlanta, GA 30322 USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Smith, David H.] Oregon State Univ, Corvallis, OR 97331 USA. [White, Robert E.] Lovelace Clin Fdn, Albuquerque, NM USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Gurwitz, Jerry H.] Meyers Primary Care Inst & Fallon Community Hlth, Worcester, MA USA. [Gurwitz, Jerry H.] Univ Massachusetts, Amherst, MA 01003 USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. EM Alan.S.Go@kp.org OI Cassidy-Bushrow, Andrea/0000-0001-8272-4448 FU National Heart, Lung, and Blood Institute [U19 HL91179-01] FX This work was supported by National Heart, Lung, and Blood Institute cooperative agreement U19 HL91179-01. NR 44 TC 49 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2008 VL 1 IS 2 BP 138 EP 147 DI 10.1161/CIRCOUTCOMES.108.801654 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V11AL UT WOS:000207504400012 PM 20031802 ER PT J AU Engelhardt, KR Woellner, C Schaffer, AA Gertz, EM Hagena, T Salzer, U Pfeifer, D Yeganeh, M Ehl, S Holland, SM Hsu, V Puck, JM Plebani, A Junker, A Niehues, T E'tzioni, A Grimbacher, B AF Engelhardt, K. R. Woellner, C. Schaffer, A. A. Gertz, E. M. Hagena, T. Salzer, U. Pfeifer, D. Yeganeh, M. Ehl, S. Holland, S. M. Hsu, V Puck, J. M. Plebani, A. Junker, A. Niehues, T. E'tzioni, A. Grimbacher, B. TI Identification of genes mutated in autosomal-recessive hyper-IgE syndrome SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 UCL, London, England. NCBI, Computat Biol Branch, NIH, Bethesda, MD USA. Univ Hosp Freiburg, Div Rheumatol & Clin Immunol, Freiburg, Germany. Univ Sherbrooke, Div Immunol, Dept Pediat, Quebec City, PQ, Canada. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Brescia, Brescia, Italy. Children & Womens Hlth Ctr, Vancouver, BC, Canada. Univ Klinikum Dusseldorf, Dusseldorf, Germany. Rappaport Sch Med, Haifa, Israel. RI Plebani, Alessandro/C-8593-2011; Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 BP 53 EP 53 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500100 ER PT J AU Lopez-Herrera, G Detkova, D Schaffer, AA Salzer, U Pfeifer, D Gertz, M Hagena, T Kesel, A Srugo, I Etzioni, A Grimbacher, B AF Lopez-Herrera, G. Detkova, D. Schaffer, A. A. Salzer, U. Pfeifer, D. Gertz, M. Hagena, T. Kesel, A. Srugo, I Etzioni, A. Grimbacher, B. TI Genetic linkage in autosomal recessive common variable immunodeficiency SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Lopez-Herrera, G.; Detkova, D.; Grimbacher, B.] Royal Free Hosp, London NW3 2QG, England. [Lopez-Herrera, G.; Detkova, D.; Grimbacher, B.] UCL, London, England. [Schaffer, A. A.] NIH, DHHS, Natl Ctr Biotechnol Infor, Bethesda, MD 20892 USA. [Salzer, U.; Pfeifer, D.; Gertz, M.; Hagena, T.] Univ Hosp Freiburg, Freiburg, Germany. [Kesel, A.; Srugo, I; Etzioni, A.] Rappaport Sch Med, Div Pediat, Haifa, Israel. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 BP 65 EP 65 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500124 ER PT J AU Woellner, C Gertz, EM Schaeffer, AA Lagos, M Perro, M Pietrogrande, MC Cossu, F Franco, JL Matamoros, N Pietrucha, B Heropolianska-Pliszka, E Yeganeh, M Espanol, T Ehl, S Gennery, AR Abinun, M Breborowicz, A Niehues, T Kilic, SS Junker, A Turvey, S Plebani, A Sanchez, B Garty, BZ Pignata, C Cancrini, C Litzman, J Sanal, O Baumann, U Bacchetta, R Hsu, A Hammarstrom, L Davies, EG Eren, E Arkwright, PD Moilanen, JS Viemann, D Khan, S Marodi, L Cant, AM Puck, JM Holland, SM Grimbacher, B AF Woellner, C. Gertz, E. M. Schaeffer, A. A. Lagos, M. Perro, M. Pietrogrande, M. C. Cossu, F. Franco, J. L. Matamoros, N. Pietrucha, B. Heropolianska-Pliszka, E. Yeganeh, M. Espanol, T. Ehl, S. Gennery, A. R. Abinun, M. Breborowicz, A. Niehues, T. Kilic, S. S. Junker, A. Turvey, S. Plebani, A. Sanchez, B. Garty, B. Z. Pignata, C. Cancrini, C. Litzman, J. Sanal, O. Baumann, U. Bacchetta, R. Hsu, A. Hammarstrom, L. Davies, E. G. Eren, E. Arkwright, P. D. Moilanen, J. S. Viemann, D. Khan, S. Marodi, L. Cant, A. M. Puck, J. M. Holland, S. M. Grimbacher, B. TI Diagnostic criteria for the hyper IgE recurrent infection syndrome/Job's syndrome/STAT3 deficiency SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Woellner, C.; Perro, M.] UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, London, England. [Gertz, E. M.; Schaeffer, A. A.] NCBI, Computat Biol Branch, NIH, Bethesda, MD USA. [Lagos, M.] Univ Valparaiso, Catedra Inmunol, Escuela Med, Valparaiso, Chile. [Pietrogrande, M. C.] Univ Milan, Dept Paediat, Milan, Italy. [Cossu, F.] Osped Microcitem, Bone Marrow Transplant Unit, Cagliari, Italy. [Franco, J. L.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia. [Matamoros, N.] Hosp Son Dureta, Serv Inmunol, Palma de Mallorca, Spain. [Pietrucha, B.; Heropolianska-Pliszka, E.] Childrens Mem Hlth Inst, Dept Immunol, Warsaw, Poland. [Yeganeh, M.] Univ Sherbrooke, Dept Pediat, Div Immunol, Quebec City, PQ, Canada. [Espanol, T.] CSI Univ, Immunol Unit, Barcelona, Spain. [Ehl, S.] Univ Freiburg Klinikum, Zentrum Kinderheilkunde & Jugendme, Freiburg, Germany. [Gennery, A. R.] Newcastle Univ, Childrens BMT Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Abinun, M.] Newcastle Gen Hosp, Dept Paediat, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Breborowicz, A.] Poznan Univ Med Sci, Dept Pediat Pulmonol, Poznan, Poland. [Niehues, T.] Univ Dusseldorf, Zentrum Kinderheilkunde, Dusseldorf, Germany. [Kilic, S. S.] Uludag Univ, Fac Med, Dept Pediat, Bursa, Turkey. [Junker, A.] Children & Womens Hlth Ctr, Div Infect & Immunol, Vancouver, BC, Canada. [Turvey, S.] BC Childrens Hosp & Child, Div Infect Dis & Immunol, Vancouver, BC, Canada. [Turvey, S.] Family Res Inst, Vancouver, BC, Canada. [Plebani, A.] Univ Brescia, Pediat Clin, Brescia, Italy. [Sanchez, B.] Hosp Virgen Rocio, Seville, Spain. [Garty, B. Z.] Schneider Childrens Med Ctr Israel, Dept Pediat B & Kipper In, Petah Tiqwa, Israel. [Pignata, C.] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Cancrini, C.] Univ Rome, Dept Pediat, Rome, Italy. [Litzman, J.] Dept Clin Immunol & Allergol, Brno, Czech Republic. [Sanal, O.] Hacettepe Univ, Div Immunol, Ankara, Turkey. [Baumann, U.] Hannover Med Sch, Abt Padiatr Pneunol & N, D-30623 Hannover, Germany. [Bacchetta, R.] Hosp San Raffaele, San Raffaele Telethon Inst Gene, I-20132 Milan, Italy. [Hsu, A.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hammarstrom, L.] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Davies, E. G.] Hosp Childrens NHS Trust, Great Ormond St Children, Ctr Immunodeficiency, London, England. [Eren, E.] Southampton Gen Hosp, Dept Immunol, Southampton SO9 4XY, Hants, England. [Arkwright, P. D.] Univ Manchester, Dept Child Hlth, Manchester, Lancs, England. [Moilanen, J. S.] Univ Tampere, IMT Bioinformat, FIN-33101 Tampere, Finland. [Moilanen, J. S.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Viemann, D.] Univ Munster, Inst Expt Dermatol, D-4400 Munster, Germany. [Khan, S.] Scunthorpe Gen Hosp, Scunthorpe, Humberside, England. [Marodi, L.] Univ Debrecen, Dept Infect Pediat, H-4012 Debrecen, Hungary. [Marodi, L.] Hlth Sci Ctr, Debrecen, Hungary. [Cant, A. M.] Newcastle Gen Hosp, Childrens BMT Unit, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. [Puck, J. M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RI Plebani, Alessandro/C-8593-2011; Moilanen, Jukka/G-2604-2012; Pignata, Claudio/O-2466-2013; Litzman, Jiri/E-2746-2012 OI Moilanen, Jukka/0000-0002-8041-3205; Pignata, Claudio/0000-0003-1568-9843; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 SU 1 BP 154 EP 155 PG 2 WC Immunology SC Immunology GA 398JD UT WOS:000262727500288 ER PT J AU Meyts, I Renard, M Uyttebroeck, A De Vos, R Freson, K Holland, S Van Geet, C AF Meyts, I Renard, M. Uyttebroeck, A. De Vos, R. Freson, K. Holland, S. Van Geet, C. TI Recurrent severe colitis in a boy with congenital neutropenia and neutrophil dysfunction SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Meyts, I; Renard, M.; Uyttebroeck, A.; De Vos, R.; Freson, K.; Van Geet, C.] Univ Hosp Leuven, Dept Pediat, Louvain, Belgium. [Holland, S.] Natl Inst Allergy & Infect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 BP 168 EP 168 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500311 ER PT J AU Boztug, K Appaswamy, G Ashikov, A Schaffer, AA Salzer, U Diestelhorst, J Germeshausen, M Brandes, G Lee-Gossler, J Noyan, F Gatzke, AK Minkov, M Greil, J Kratz, C Petropoulou, T Pellier, I Bellanne-Chantelot, C Rezaei, N Monkemoller, K Irani-Hakimeh, N Bakker, H Gerardy-Schahn, R Zeidler, C Grimbacher, B Welte, K Klein, C AF Boztug, K. Appaswamy, G. Ashikov, A. Schaeffer, A. A. Salzer, U. Diestelhorst, J. Germeshausen, M. Brandes, G. Lee-Gossler, J. Noyan, F. Gatzke, A. K. Minkov, M. Greil, J. Kratz, C. Petropoulou, T. Pellier, I Bellanne-Chantelot, C. Rezaei, N. Moenkemoeller, K. Irani-Hakimeh, N. Bakker, H. Gerardy-Schahn, R. Zeidler, C. Grimbacher, B. Welte, K. Klein, C. TI A novel clinical syndrome associating severe congenital neutropenia and complex developmental aberrations caused by deficiency of G6PC(3) SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Boztug, K.; Appaswamy, G.; Ashikov, A.; Diestelhorst, J.; Germeshausen, M.; Brandes, G.; Lee-Gossler, J.; Noyan, F.; Gatzke, A. K.; Bakker, H.; Gerardy-Schahn, R.; Zeidler, C.; Welte, K.; Klein, C.] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Schaeffer, A. A.] Natl Biotechnol Ctr, Natl Inst Hlth, Bethesda, MD USA. [Salzer, U.; Kratz, C.] Freiburg Med Ctr, Dept Rheumatol Immunol, Freiburg, Germany. [Minkov, M.] St Anna Childrens Hosp, Dept Pediat Hematol Oncol, A-1090 Vienna, Austria. [Greil, J.] Univ Heidelberg, Dept Pediat Hematol Oncol, Heidelberg, Germany. [Petropoulou, T.] Univ Athens, Sophia Childrens Hosp, Athens, Greece. [Pellier, I] CHU Angers, Dept Pediat Hematol Oncol, Angers, France. [Bellanne-Chantelot, C.] AP HP Pitie Salpetrere, Dept Genet, Paris, France. [Rezaei, N.] Univ Tehran Med Sci, Immunol Asthma & Allergy Res Inst, Tehran, Iran. [Moenkemoeller, K.] Childrens Hosp Amsterdamer Str, Cologne, Germany. [Irani-Hakimeh, N.] St Georges Univ Hosp, Beirut, Lebanon. [Grimbacher, B.] Royal Free Hosp, London NW3 2QG, England. [Grimbacher, B.] UCL, London, England. RI Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012; isabelle, pellier/L-5683-2015; Ashikov, Angel/N-7714-2015 OI Rezaei, Nima/0000-0002-3836-1827; Ashikov, Angel/0000-0001-9679-7955 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 SU 1 BP 206 EP 207 PG 2 WC Immunology SC Immunology GA 398JD UT WOS:000262727500398 ER PT J AU Grimbacher, B Hennigs, A Nabavi, M Glocker, EO Schaffer, A Woellner, C Salzer, U Pfeifer, D Tahami, F Plebani, A Amirzagar, M Rezaei, N AF Grimbacher, B. Hennigs, A. Nabavi, M. Glocker, E. O. Schaffer, A. Woellner, C. Salzer, U. Pfeifer, D. Tahami, F. Plebani, A. Amirzagar, M. Rezaei, N. TI Chronic mucocutaneous candidiasis is associated with a homozygous mutation in CARD9 SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Grimbacher, B.; Glocker, E. O.; Woellner, C.; Tahami, F.] Royal Free Hosp, Dpt Immunol, London NW3 2QG, England. [Grimbacher, B.; Glocker, E. O.; Woellner, C.] UCL, Dpt Immunol, London, England. [Hennigs, A.] Univ Hosp Freiburg, Freiburg, Germany. [Nabavi, M.] Semnan Med Univ, Amir Almomenin Hosp, Semnan, Iran. [Schaffer, A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Plebani, A.] Univ Brescia, Paediat Clin, Brescia, Italy. [Amirzagar, M.; Rezaei, N.] Univ Tehran Med Sci, Immunogenet Lab, Tehran, Iran. RI Plebani, Alessandro/C-8593-2011; Rezaei, Nima/B-4245-2008 OI Rezaei, Nima/0000-0002-3836-1827 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 BP 213 EP 213 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500412 ER PT J AU Franco, J Moncada, MA Velez-Ortega, AC Gomez-Rodriguez, J Dutra, AC Munoz, S Orrego, JC Montoya, J AF Franco, J. Moncada, M. A. Velez-Ortega, A. C. Gomez-Rodriguez, J. Dutra, A. C. Munoz, S. Orrego, J. C. Montoya, J. TI CD4 deficiency in a child with a congenital syndrome and recurrent infections SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT 13th European-Soc-for-Immunodeficiencies/10th Int-Patient-Org-for-Primary-Immunodeficiencies/8th Int-Nursing-Group-for-Immunodeficiencies Meeting CY OCT 16-19, 2008 CL Hertogenbosch, NETHERLANDS SP European Soc Immunodeficiencies, Int Patient Org Primary Immunodeficiencies, Int Nursing Grp Immunodeficiencies C1 [Franco, J.] Hosp A, Medellin, Colombia. [Moncada, M. A.; Velez-Ortega, A. C.; Munoz, S.; Orrego, J. C.] Univ Antioquia, Medellin, Colombia. [Gomez-Rodriguez, J.; Dutra, A. C.] NHGRI, Bethesda, MD 20892 USA. [Montoya, J.] Hosp Univ San Vicente Paul, Medellin, Colombia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2008 VL 154 BP 216 EP 216 PG 1 WC Immunology SC Immunology GA 398JD UT WOS:000262727500417 ER PT J AU Kinders, RJ Hollingshead, M Khin, S Rubinstein, L Tomaszewski, JE Doroshow, JH Parchment, RE AF Kinders, Robert J. Hollingshead, Melinda Khin, Sonny Rubinstein, Larry Tomaszewski, Joseph E. Doroshow, James H. Parchment, Ralph E. CA Natl Canc Inst Phase 0 Clinical Tr TI Preclinical Modeling of a Phase 0 Clinical Trial: Qualification of a Pharmacodynamic Assay of Poly (ADP-Ribose) Polymerase in Tumor Biopsies of Mouse Xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; INHIBITION; REPAIR AB Purpose: The National Cancer Institute has completed a first-in-human clinical pharmacodynamic trial of the targeted agent ABT-888, a poly (ADP-ribose) polymerase (PARP) inhibitor, under the auspices of the U.S. Food and Drug Administration's Exploratory Investigational New Drug Application. Performance of the study design, needle biopsy procedure, and validated pharmacodynamic assay were evaluated in human tumor xenograft models. Experimental Design: A validated ELISA was used to quantify PAR, a product of the PARP 1/2 enzyme activity. Sampling variability from tumor heterogeneity was determined by comparing PAR content in multiple tumors, and in different areas of the same tumor in a particular animal, collected under anesthesia by needle biopsy or resection before and after administration of nontoxic doses of ABT-888. The degree of PARP inhibition following single-dose treatment was evaluated in the time frame anticipated for biopsy in humans. Results: Sampling variability around the mean (similar to 50%) for untreated and vehicle-treated animals was random and due to specimen heterogeneity. PAR levels in initial and repeat tumor biopsies, separated by 1 week, were not altered by the stress induced by daily handling of the animals. A single ABT-888 dose (3 or 12.5 mg/kg) reduced intratumor PAR levels by >95%. ABT-888 (1.56-25 mg/kg) significantly decreased PAR levels at 2 h post-dosing. Conclusion: The detailed methodologies developed for this study facilitated the design of a phase 0, first-in-human clinical trial of ABT-888 and could serve as a model for developing proof-of-principle clinical trials of molecularly targeted anticancer agents. C1 [Kinders, Robert J.; Khin, Sonny; Parchment, Ralph E.] Natl Canc Inst Frederick, Sci Applicat Int Corp, Frederick Inc,Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, Frederick, MD 21702 USA. [Hollingshead, Melinda] NCI, Dev Therapeut Program, Biol Testing Branch, Frederick, MD 21701 USA. [Rubinstein, Larry] NCI, Biometr Res Branch, Frederick, MD 21701 USA. [Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Frederick, MD 21701 USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, Frederick, MD 21701 USA. RP Kinders, RJ (reprint author), Natl Canc Inst Frederick, Sci Applicat Int Corp, Frederick Inc,Appl Dev Res Support Directorate, Lab Human Toxicol & Pharmacol, POB B, Frederick, MD 21702 USA. EM kindersr@mail.nih.gov FU National Cancer Institute; NIH [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH under contract N01-CO-12400.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 19 TC 54 Z9 54 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2008 VL 14 IS 21 BP 6877 EP 6885 DI 10.1158/1078-0432.CCR-08-0214 PG 9 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200021 PM 18980982 ER PT J AU Jacobs, SA Swerdlow, SH Kant, J Foon, KA Jankowitz, R Land, SR DeMonaco, N Joyce, J Osborn, JL Evans, TL Schaefer, PM Luong, TM AF Jacobs, Samuel A. Swerdlow, Steven H. Kant, Jeffrey Foon, Kenneth A. Jankowitz, Rachel Land, Stephanie R. DeMonaco, Nicholas Joyce, Judith Osborn, Jennifer L. Evans, Terry L. Schaefer, Patricia M. Luong, The Minh TI Phase II Trial of Short-Course CHOP-R Followed by Y-90-ibritumomab Tiuxetan and Extended Rituximab in Previously Untreated Follicular Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; POSITRON-EMISSION-TOMOGRAPHY; LOW-GRADE; IBRITUMOMAB TIUXETAN; RESPONSE ASSESSMENT; 1ST-LINE TREATMENT; INDOLENT LYMPHOMA; I-131 TOSITUMOMAB; INITIAL TREATMENT; FREE SURVIVAL AB Purpose: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. Experimental Design: Between March 2004 and February 2007, 60 patients with stage 11 to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase 11 trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [18 F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. Results: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010). Conclusions: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse. C1 [Jacobs, Samuel A.] Univ Pittsburgh, Med Ctr, Ctr Canc, Univ Pittsburgh Med Ctr Canc Pavil,Dept Med, Pittsburgh, PA 15232 USA. [Swerdlow, Steven H.; Kant, Jeffrey] Univ Pittsburgh, Med Ctr, Ctr Canc, Dept Pathol, Pittsburgh, PA 15232 USA. [Joyce, Judith] Univ Pittsburgh, Med Ctr, Ctr Canc, Dept Radiol, Pittsburgh, PA 15232 USA. [Schaefer, Patricia M.] Univ Pittsburgh, Med Ctr, Ctr Canc, Clin Res Serv, Pittsburgh, PA 15232 USA. [Land, Stephanie R.; Luong, The Minh] NSABP, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. [Land, Stephanie R.; Luong, The Minh] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Land, Stephanie R.; Luong, The Minh] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA. [DeMonaco, Nicholas] Oncol Hematol Associates, Pittsburgh, PA USA. RP Jacobs, SA (reprint author), Univ Pittsburgh, Med Ctr, Ctr Canc, Univ Pittsburgh Med Ctr Canc Pavil,Dept Med, 5150 Ctr Ave,Suite 510, Pittsburgh, PA 15232 USA. EM jacobssa@upmc.edu FU Biogenldec Pharmaceuticals and National Cancer Institute [CCSG/IRAT P30 CA 047904] FX Biogenldec Pharmaceuticals and National Cancer Institute CCSG/IRAT P30 CA 047904. The trial is registered at http://www.clinicaltrials.gov (identifier: NCT00177554.) NR 36 TC 56 Z9 59 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2008 VL 14 IS 21 BP 7088 EP 7094 DI 10.1158/1078-0432.CCR-08-0529 PG 7 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200046 PM 18981007 ER PT J AU Odenike, OM Alkan, S Sher, D Godwin, JE Huo, D Brandt, SJ Green, M Xie, J Zhang, Y Vesole, DH Stiff, P Wright, J Larson, RA Stock, W AF Odenike, Olatoyosi M. Alkan, Serhan Sher, Dorie Godwin, John E. Huo, Dezheng Brandt, Stephen J. Green, Margaret Xie, Jingping Zhang, Yariming Vesole, David H. Stiff, Patrick Wright, John Larson, Richard A. Stock, Wendy TI Histone Deacetylase Inhibitor Romidepsin Has Differential Activity in Core Binding Factor Acute Myeloid Leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID T(8/21) FUSION PROTEIN; TRANS-RETINOIC ACID; VALPROIC ACID; DEPSIPEPTIDE FR901228; MYELODYSPLASTIC SYNDROME; GRANULOCYTIC MATURATION; DNA METHYLTRANSFERASE; MYELOGENOUS LEUKEMIA; GENE-EXPRESSION; DOWN-REGULATION AB Purpose: Recruitment of histone deacetylases (HDAC) is a mechanism of transcriptional repression implicated in the differentiation block in acute myeloid leukemia (AML). We hypothesized that the HDAC inhibitor romidepsin could cause transcriptional derepression, up-regulation of specific target genes in AML, and differentiation of the leukemic clone. The primary objectives of the study were to evaluate the safety and efficacy of romidepsin in advanced AML. Experimental Design: Twenty patients were stratified into cohort A or B based on the absence or presence of chromosomal abnormalities known to recruit HDACs, including those involving core binding factor (CBF). Romidepsin was administered i.v. at 13 mg/m(2)/d on days 1, 8, and 15 of a 28-day cycle. Pharmacodynamic endpoints were evaluated at serial time points. Results: Common adverse effects noted were grade 1 to 2 nausea, anorexia, and fatigue. No objective evidence of antileukemic activity was seen in cohort A. In cohort B, although there were no clinical responses by standard criteria, antileukemic activity was observed in 5 of 7 patients. Two patients had clearance of bone marrow blasts and 3 patients had a >50% decrease in bone marrow blasts. Furthermore, in cohort B, at 24 h, there was a significant increase in MDR1 (P = 0.005), p15 (P = 0.01), and p14 (P < 0.0001) expression. In cohort A, although there was a trend toward up-regulation of MDR1, p15, and p14 expression, these changes were not statistically significant. Conclusion: Romidepsin has differential antileukemic and molecular activity in CBF AML. Development of this agent in CBF AML should focus on combinations that target related mechanisms of gene silencing such as DNA methylation. C1 [Odenike, Olatoyosi M.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Alkan, Serhan; Godwin, John E.; Stiff, Patrick] Loyola Univ, Maywood, IL 60153 USA. [Brandt, Stephen J.; Xie, Jingping] Vanderbilt Univ, Nashville, IL USA. [Vesole, David H.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wright, John] NCI, Bethesda, MD 20892 USA. RP Odenike, OM (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM todenike@medicine.bsd.uchicago.edu OI Larson, Richard/0000-0001-9168-3203 FU National Cancer Institute/Cancer Therapy Evaluation Program [N01-CM-62201]; American Society of Oncology Career Development Award; American Cancer Society Institutional Grant; National Cancer Institute Translational Research FX National Cancer Institute/Cancer Therapy Evaluation Program contract N01-CM-62201 in collaboration with Gloucester Pharmaceuticals, American Society of Oncology Career Development Award (O.M. Odenike), American Cancer Society Institutional Grant (O.M. Odenike), and National Cancer Institute Translational Research funds (O.M. Odenike and S. Alkan). NR 43 TC 49 Z9 50 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2008 VL 14 IS 21 BP 7095 EP 7101 DI 10.1158/1078-0432.CCR-08-1007 PG 7 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200047 PM 18981008 ER PT J AU Agrawal, Y Koch, WM Xiao, W Westra, WH Trivett, AL Symer, DE Gillison, ML AF Agrawal, Yuri Koch, Wayne M. Xiao, Weihong Westra, William H. Trivett, Anna L. Symer, David E. Gillison, Maura L. TI Oral Human Papillomavirus Infection Before and After Treatment for Human Papillomavirus 16-Positive and Human Papillomavirus 16-Negative Head and Neck Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID UPPER AERODIGESTIVE TRACT; CERVICAL-CANCER PATIENTS; RISK-FACTOR; PCR; ASSOCIATION; TONSILLAR; HUSBANDS; SAMPLES; ADULTS; DNA AB Purpose: Oral human papillomavirus (HPV) infection is a risk factor for head and neck squamous cell carcinoma (HNSCC), and is a concern for patients with HPV-positive HNSCC and their partners. The prevalence of oral HPV infection before and after cancer therapy was investigated among patients with HPV16-positive and HPV16-negative HNSCC. Experimental Design: Serial oral rinse samples (ORS) were collected from a cohort of 135 HNSCC cases as frequently as every 3 months for up to 3 years. Tumor HPV status was determined by HPV16 in situ hybridization. HPV was detected in ORS by consensus PCR and line blot hybridization. The HPV16 variants in positive oral rinse - tumor pairs were determined by sequencing. The odds of oral HPV infection among HPV16-positive and HPV16-negative cases were compared by use of generalized estimating equations. Results: Patients were followed for a median of 21 months and provided a median of 4 samples. Forty-four of 135 patients had HPV16-positive tumors. HPV16-positive cases were more likely than HPV16-negative cases to have an oral HPV infection detected before (odds ratio, 8.6; 95% confidence interval, 3.5-21) and after therapy (OR, 2.9; 95% confidence interval, 1.1-7.4). Oral infections by HPV16 and other high-risk, but not low-risk, types were more common among HPV16-positive cases both before and after therapy. Most HPV16 variants in ORS were European, unique, and identical to that in the tumor. Persistence of a type-specific oral infection was demonstrable for as long as 5 years. Conclusion: Oral high-risk HPV infections are more frequent among patients with HPV16-positive than HPV16-negative HNSCC, consistent with a behavioral and/or biological disposition to infection, C1 [Agrawal, Yuri; Koch, Wayne M.] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Westra, William H.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Xiao, Weihong; Gillison, Maura L.] Johns Hopkins Kimmel Comprehens Canc Ctr, Div Viral Oncol, Baltimore, MD USA. [Trivett, Anna L.; Symer, David E.] Natl Canc Inst, Basic Res Lab, Frederick, MD USA. RP Gillison, ML (reprint author), Johns Hopkins Univ, Canc Res Bldg 1,Rm 351,1650 Orleans St, Baltimore, MD 21231 USA. EM gillima@jhmi.edu RI Symer, David/E-4173-2011 FU NIDCR [DE016631]; Oral Cancer Foundation; NIH [1 P50 CA96784-01]; Intramural Research Program of the Center for Cancer Research; National Cancer Institute FX NIDCR DE016631, Oral Cancer Foundation (M.L. Gillison) and NIH 1 P50 CA96784-01 (W. Koch). This research was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH (D. Symer). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 27 TC 41 Z9 42 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2008 VL 14 IS 21 BP 7143 EP 7150 DI 10.1158/1078-0432.CCR-08-0498 PG 8 WC Oncology SC Oncology GA 369ZK UT WOS:000260732200053 PM 18981014 ER PT J AU Goldstein, DS Holmes, C AF Goldstein, David S. Holmes, Courtney TI Neuronal Source of Plasma Dopamine SO CLINICAL CHEMISTRY LA English DT Article ID POSTURAL TACHYCARDIA SYNDROME; SYMPATHETIC-NERVE ACTIVITY; CHRONIC ORTHOSTATIC INTOLERANCE; NEURALLY-MEDIATED SYNCOPE; NOREPINEPHRINE; TYRAMINE; NORADRENALINE; RELEASE; HUMANS; CATECHOLS AB BACKGROUND: Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested ill humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves. METHODS: We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during Supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomises (SNS-x) or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not. RESULTS: Orthostasis, YOH, ISO, and TYR increased and TR1/PEN decreased plasma DA concentrations. Individual Values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%-4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%-90% of plasma DA has a sympathoneural Source. CONCLUSIONS: Plasma DA is derived Substantially from sympathetic noradrenergic nerves. (C) 2008 American Association for Clinical Chemistry C1 [Goldstein, David S.; Holmes, Courtney] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC-1620,Bldg 10 Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU NIH; National Institute of Neurological Disorders and Stroke FX Research Funding: This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 40 TC 23 Z9 23 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2008 VL 54 IS 11 BP 1864 EP 1871 DI 10.1373/clinchem.2008.107193 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 366AO UT WOS:000260452000016 PM 18801936 ER PT J AU Venditti, CP AF Venditti, Charles P. TI Increased C3-Carnitine in a Healthy Premature Infant Commentary SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Genet Dis Res Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2008 VL 54 IS 11 BP 1917 EP 1918 DI 10.1373/clinchem.2008.113449 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 366AO UT WOS:000260452000023 ER PT J AU Gennari, M Stratakis, CA Hovarth, A Pirazzoli, P Cicognani, A AF Gennari, Monia Stratakis, Constantine A. Hovarth, Anelia Pirazzoli, Piero Cicognani, Alessandro TI A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations SO CLINICAL ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-A; TISSUE-SPECIFIC EXTINGUISHER; SUBUNIT TYPE 1A; REGULATORY SUBUNIT; TSE1 ENCODES; ENDOCRINE; DISEASE; TUMORS; NEOPLASIA; GENETICS AB Context Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980). About 70% of cases are familiar; most have mutations of the PRKAR1A gene on chromosome 17q22-24. There is little phenotype-genotype correlation known to date. Objective To study the genotype-phenotype correlation in a family with newly diagnosed CNC and three generations of subjects bearing the same PRKAR1A mutation. The proband was diagnosed with hepatocellular carcinoma, a tumour that appears to be associated with CNC. Design The study consisted of clinical and genetic analysis of a total of 10 individuals belonging to a large Italian family. Patients The index case was referred for PRKAR1A gene mutation analysis because he met the diagnostic criteria for a clinical diagnosis of CNC. Results The PRKAR1A-inactivating mutation c.502 + 1G > A in the intron 5 splice-donor site was detected after bidirectional sequencing of germline DNA. The mutation causes a frameshift in the transcribed sequence and a nonsense mRNA that was shown to be degraded; this leads to PRKAR1A haploinsufficiency in all tissues. All available relatives were screened first by DNA testing and, if the latter was positive, by clinical, biochemical and imaging means. Conclusions A novel PRKAR1A mutation with an apparently low penetrance and variable expression is reported; the same mutation is also associated with a hepatocellular carcinoma. This is the first time a PRKAR1A mutation is reported in individuals who were diagnosed with CNC after retrospective family screening and following the identification of a proband; the finding has implications for genetic counselling on PRKAR1A and/or CNC. C1 [Gennari, Monia; Pirazzoli, Piero; Cicognani, Alessandro] Univ Bologna, S Orsola Hosp, I-40138 Bologna, Italy. [Stratakis, Constantine A.; Hovarth, Anelia] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NICHD,NIH, Bethesda, MD 20892 USA. [Gennari, Monia; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Program, NICHD, NIH, Bethesda, MD 20892 USA. RP Gennari, M (reprint author), Univ Bologna, S Orsola M Malpighi Hosp, Pad 13,Via Massarenti 11, I-40138 Bologna, Italy. EM monia.gennari2@unibo.it FU Department of Oncology; Hematology, Pathology Division; Felice Addarii' Institute S. Orsola-Malpighi Hospital; University of Bologna FX We thank Chiara Martini MD (General Medicine third Clinic-Hospital, Padua) for collecting blood samples of the maternal grand father (I. 2), maternal uncles (II. 1, II. 2) and their children (III. 1, III. 2, III. 3) to do genetic assay. We also thank Antonietta D'Errico MD and Barbara Corti MD (Department of Oncology and Hematology, Pathology Division, 'Felice Addarii' Institute S. Orsola-Malpighi Hospital, University of Bologna, Bologna) for liver DNA extraction. NR 20 TC 14 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 2008 VL 69 IS 5 BP 751 EP 755 DI 10.1111/j.1365-2265.2008.03286.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 361GZ UT WOS:000260117000009 PM 18445140 ER PT J AU Fitzgerald, DP Palmieri, D Hua, E Hargrave, E Herring, JM Qian, YZ Vega-Valle, E Weil, RJ Stark, AM Vortmeyer, AO Steeg, PS AF Fitzgerald, Daniel P. Palmieri, Diane Hua, Emily Hargrave, Elizabeth Herring, Jeanne M. Qian, Yongzhen Vega-Valle, Eleazar Weil, Robert J. Stark, Andreas M. Vortmeyer, Alexander O. Steeg, Patricia S. TI Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE brain metastasis; brain pathology; breast cancer; neuroinflammation; reactive glia; xenograft ID CENTRAL-NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; NUDE-MICE; ALTERED EXPRESSION; IN-VIVO; INJURY; GROWTH; MICROENVIRONMENT; MICROGLIA; STROMA AB Interactions between tumor cells and the microenvironment are crucial to tumor formation and metastasis. The central nervous system serves as a "sanctuary" site for metastasis, resulting in poor prognosis in diagnosed patients. The incidence of brain metastasis is increasing; however, little is known about interactions between the brain and metastatic cells. Brain pathology was examined in an experimental model system of brain metastasis, using a subline of MDA-MB-231 human breast cancer cells. The results were compared with an analysis of sixteen resected human brain metastases of breast cancer. Experimental metastases formed preferentially in specific brain regions, with a distribution similar to clinical cases. In both the 231-BR model, and in human specimens, Ki67 expression indicated that metastases were highly proliferative (similar to 50%). Little apoptosis was observed in either set of tumors. In the model system, metastases elicited a brain inflammatory response, with extensive reactive gliosis surrounding metastases. Similarly, large numbers of glial cells were found within the inner tumor mass of human brain metastases. In vitro co-cultures demonstrated that glia induced a similar to 5-fold increase in metastatic cell proliferation (P < 0.001), suggesting that brain tissue secretes factors conducive to tumor cell growth. Molecules used to signal between tumor cells and the surrounding glia could provide a new avenue of therapeutic targets for brain metastases. C1 [Fitzgerald, Daniel P.; Palmieri, Diane; Hua, Emily; Hargrave, Elizabeth; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Herring, Jeanne M.; Qian, Yongzhen; Vega-Valle, Eleazar] NCI, Lab Anim Sci Program, Sci Applicat Int Corp, NIH, Frederick, MD 21701 USA. [Weil, Robert J.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Dept Neurosurg, Cleveland, OH 44106 USA. [Weil, Robert J.] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Neurol Inst, Cleveland, OH 44106 USA. [Stark, Andreas M.] Schleswig Holstein Univ, Dept Neurosurg, Med Ctr, Kiel, Germany. [Vortmeyer, Alexander O.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Fitzgerald, DP (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, NIH, Bldg 37,Room 1126, Bethesda, MD 20892 USA. EM fitzgeda@mail.nih.gov RI Fitzgerald, Daniel/B-1633-2009; Palmieri, Diane/B-4258-2015 FU US Department of Defense Breast Cancer Research Program [W81 XWH-062-0033]; National Cancer Institute; CCR; NIH FX We would like to thank Hong Wang (Developmental Neurobiology Section of the NHLBI Division of Intramural Research, NIH) for providing mixed glial cultures used in the soft agar experiments. This research was supported by the US Department of Defense Breast Cancer Research Program, grant number: W81 XWH-062-0033; and the Intramural Research Program of the National Cancer Institute, CCR, NIH. NR 52 TC 90 Z9 92 U1 3 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD NOV PY 2008 VL 25 IS 7 BP 799 EP 810 DI 10.1007/s10585-008-9193-z PG 12 WC Oncology SC Oncology GA 355PG UT WOS:000259720200010 PM 18649117 ER PT J AU Loomba, R Wesley, R Pucino, F Liang, TJ Kleiner, DE Lavine, JE AF Loomba, Rohit Wesley, Robert Pucino, Frank Liang, T. Jake Kleiner, David E. Lavine, Joel E. TI Placebo in Nonalcoholic Steatohepatitis: Insight Into Natural History and Implications for Future Clinical Trials SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; URSODEOXYCHOLIC ACID; METAANALYSIS; REMISSION; RATES AB Background & Aims: Changes in biochemical and histologic parameters related to nonalcoholic steatohepatitis (NASH) in placebo-treared patients may provide an insight into the natural history and help in defining treatment end points in NASH. The aim of our study was to assess the biochemical and histologic changes seen in the placebo arm of the randomized, placebo-controlled trials in adult patients with NASH. Methods: Medline was searched (through May 2008) for studies published in the English language. Randomized, placebo-controlled trials of at least 6 months' duration in patients with NASH that provided biochemical and/or histologic data of the placebo arm were included. One investigator performed the literature search and data extraction. Two investigators independently confirmed that the studies met prespecified criteria. Pooled estimates of biochemical and histologic parameters associated with NASH were calculated. Results: Five randomized controlled trials met the predefined criteria and included 162 placebo-treated and 189 active-treatment patients. The mean serum alanine and aspartate aminotransferase levels decreased on placebo. A 1-point improvement in steatosis, ballooning degeneration, lobular inflammation, NASH fibrosis, and combined inflammation scores was seen in 31% 15%, 33%, 22%, and 32% of patients, respectively. A 2-point improvement in NASH histologic scores is rarely seen. Conclusions: Serum alanine aminotransferase levels may decrease on placebo and is not a reliable measure of treatment response. Although a 1-point improvement is seen in a third of patients, a 2-point improvement in histologic parameters is rarely seen in the placebo arm and may be more reliable in assessing treatment response. These data may have important implications in designing future clinical trials in NASH. C1 [Loomba, Rohit; Liang, T. Jake] Natl Inst Diabet & Digest Dis, Liver Dis Branch, Bethesda, MD USA. [Wesley, Robert] Hosp Epidemiol, Bethesda, MD USA. [Pucino, Frank] Ctr Clin, Dept Pharm, Bethesda, MD USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Loomba, Rohit] Univ Calif San Diego, Div Gastroenterol, Dept Med, La Jolla, CA 92093 USA. [Lavine, Joel E.] Univ Calif San Diego, Dept Pediat, Div Pediat Gastroenterol, La Jolla, CA 92093 USA. RP Loomba, R (reprint author), Univ Calif San Diego, Div Gastroenterol, Dept Med, UC 303,MC0063,9500 Gilman Dr, La Jolla, CA 92093 USA. EM roloomba@ucsd.edu OI Kleiner, David/0000-0003-3442-4453 FU National institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; National Institutes of Health. FX This study was supported by the intramural research programs of the National institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute, National Institutes of Health.; The authors thank Dr Jay H. Hoofnagle for providing helpful comments at various stages of the study. NR 17 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2008 VL 6 IS 11 BP 1243 EP 1248 DI 10.1016/j.cgh.2008.07.013 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 376VK UT WOS:000261210900018 PM 18829391 ER PT J AU Biesecker, BB Erby, L AF Biesecker, B. B. Erby, L. TI Adaptation to living with a genetic condition or risk: a mini-review SO CLINICAL GENETICS LA English DT Review DE adaptation; living with a genetic condition; genetics services; interventions ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; CYSTIC-FIBROSIS; CHRONIC ILLNESS; SOCIAL SUPPORT; RHEUMATOID-ARTHRITIS; INTERVENTION; CANCER; CHILDREN; HEALTH AB One goal of genetic counseling is to facilitate client adaptation to a genetic condition or risk. Adaptation refers to both the process of coming to terms with the implications of the condition or risk and the observable outcomes of that process. This review summarizes existing studies on how well clients adapt to living with a common chronic disease, and more specifically, a genetic condition. Overall, it appears that about one-third of clients do not adjust well to the stress of living with a genetic condition or at risk. However, the data are limited by inconsistencies in the conceptualization of adaptation, a paucity of theoretical models, poor study design and inadequate outcome measures. Well-designed studies based upon multidimensional models are needed that focus on familial as well as individual adaptation. We conclude with a summary of studies that have explored the use of interventions to enhance adaptation and suggest improved client outcomes. Further research should result in evidence-based interventions to facilitate client adaptation that can be used effectively by genetic providers within the confines of their clinical work. C1 [Biesecker, B. B.] Johns Hopkins Univ, NHGRI, Genet Counseling Program, Social & Behav Res Branch,NIH, Bethesda, MD 20892 USA. [Erby, L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. RP Biesecker, BB (reprint author), Johns Hopkins Univ, NHGRI, Genet Counseling Program, Social & Behav Res Branch,NIH, Bldg 31,Room B1B36C,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov FU National Human Genome Research Institute; National Institutes of Health FX Part of the research for this manuscript was funded by the intramural research program of the National Human Genome Research Institute, National Institutes of Health. NR 45 TC 29 Z9 29 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2008 VL 74 IS 5 BP 401 EP 407 DI 10.1111/j.1399-0004.2008.01088.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 359ST UT WOS:000260009100001 PM 18823383 ER PT J AU Young, JA Hwang, SJ Sarnak, MJ Hoffmann, U Massaro, JM Levy, D Benjamin, EJ Larson, MG Vasan, RS O'Donnell, CJ Fox, CS AF Young, Jill A. Hwang, Shih-Jen Sarnak, Mark J. Hoffmann, Udo Massaro, Joseph M. Levy, Daniel Benjamin, Emelia J. Larson, Martin G. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Association of Visceral and Subcutaneous Adiposity with Kidney Function SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SERUM CYSTATIN-C; IMPAIRED GLUCOSE-TOLERANCE; GLOMERULAR-FILTRATION-RATE; BODY-FAT DISTRIBUTION; METABOLIC SYNDROME; TISSUE VOLUMES; RENAL-FUNCTION; UNITED-STATES; RISK-FACTORS; MASS INDEX AB Background and objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations. Design, setting, participants, & measurements: Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR < 60 ml/min per 1.73 m(2), as estimated using creatinine (n = 89) in the Modification of Diet ill Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment. Results: Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m(2) and for SAT was 2.6 ml/min per 1.73 m2 in a multivariable-adjusted model. Conclusions: VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research. C1 [Young, Jill A.; Sarnak, Mark J.] Tufts Univ New England Med Ctr, Boston, MA USA. [Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Hwang, Shih-Jen; Massaro, Joseph M.; Levy, Daniel; Benjamin, Emelia J.; Larson, Martin G.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Hwang, Shih-Jen; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute/National Institutes of Health [N01-HC-25195, 2K24HL04334] FX This study was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). R.S.V. is supported in part by 2K24HL04334 (National Heart, Lung, and Blood Institute/National Institutes of Health). NR 37 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2008 VL 3 IS 6 BP 1786 EP 1791 DI 10.2215/CJN.02490508 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 366TE UT WOS:000260505500028 PM 18815239 ER PT J AU Morash, V Bai, O Furlani, S Lin, P Hallett, M AF Morash, Valerie Bai, Ou Furlani, Stephen Lin, Peter Hallett, Mark TI Classifying EEG signals preceding right hand, left hand, tongue, and right foot movements and motor imageries SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Electroencephalography (EEG); Event-related (de)synchronization (ERD/ERS); Brain-computer interface (BCI); Movement; Motor imagery ID CONTINGENT NEGATIVE-VARIATION; EVENT-RELATED DESYNCHRONIZATION; SINGLE-TRIAL EEG; BRAIN; POTENTIALS; HUMANS; CORTEX; AREA AB Objective: To use the neural signals preceding movement and motor imagery to predict which of the four movements/motor imageries is about to occur, and to access this utility for brain-computer interface (BCI) applications. Methods: Eight naive subjects performed or kinesthetically imagined four movements while electroencephalogram (EEG) was recorded from 29 channels over sensorimotor areas. The task was instructed with a specific stimulus (SI) and performed at a second stimulus (S2). A classifier was trained and tested off-line at differentiating the EEG signals from movement/imagery preparation (the 1.5-s preceding movement/imagery execution). Results: Accuracy of movement/imagery preparation classification varied between subjects. The system preferentially selected event-related (de)synchronization (ERD/ERS) signals for classification, and high accuracies were associated with classifications that relied heavily on the ERD/ERS to discriminate movement/imagery planning. Conclusions: The ERD/ERS preceding movement and motor imagery can be used to predict which of the four movements/imageries is about to Occur. Prediction accuracy depends on this signal's accessibility. Significance: The ERD/ERS is the most specific pre-movement/imagery signal to the movement/imagery about to be performed. Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, Richmond, VA 23284 USA. [Morash, Valerie; Bai, Ou; Furlani, Stephen; Lin, Peter; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, 401 W Main St Rm 1252,POB 843067, Richmond, VA 23284 USA. EM obai@vcu.edu FU NIH; National Institute of Neurological Disorders and Stroke; NINDS FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. Ms. Morash was also partly supported by NINDS Summer Intern Program. The authors thank Ms. D.G. Schoenberg for skillful editing. NR 23 TC 51 Z9 54 U1 0 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2008 VL 119 IS 11 BP 2570 EP 2578 DI 10.1016/j.clinph.2008.08.013 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 377NM UT WOS:000261257900021 PM 18845473 ER PT J AU Kubler, A Birbaumer, N AF Kuebler, A. Birbaumer, N. TI Brain-computer interfaces and communication in paralysis: Extinction of goal directed thinking in completely paralysed patients? SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Brain-computer interfaces; Brain-computer communication; Locked-in state; Consciousness; Complete locked-in state ID AMYOTROPHIC-LATERAL-SCLEROSIS; SLOW CORTICAL POTENTIALS; VEGETATIVE STATE; INFORMATION-TRANSFER; SELF-REGULATION; BCI OPERATION; EEG; TETRAPLEGIA; DISORDERS; MOVEMENT AB Objective: To investigate the relationship between physical impairment and brain-computer interface (BCI) performance. Method: We present a meta-analysis of 29 patients with amyotrophic lateral sclerosis and six patients with other severe neurological diseases in different stages of physical impairment who were trained with a BCI In most cases voluntary regulation of slow cortical potentials has been Used as input signal for BCI-control. More recently sensorimotor rhythms and the P300 event-related brain potential were recorded. Results: A strong correlation has been found between physical impairment and BCI performance, indicating that performance worsens as impairment increases. Seven patients were in the complete locked-in state (CLIS) with no communication possible. After removal of these patients from the analysis, the relationship between physical impairment and BCI performance disappeared. The lack of a relation between physical impairment and BCI performance was confirmed when adding BCI data of patients from other BCI research groups. Conclusions: Basic communication (yes/no) was not restored in any of the CLIS patients with a BCI. Whether locked-in patients can transfer learned brain control to the CLIS remains an open empirical question. Significance: Voluntary brain regulation for communication is possible in all stages of paralysis except the CLIS. (C) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Kuebler, A.] Roehampton Univ, Sch Human & Life Sci, Clin & Hlth Psychol Res Ctr, Whitelands Coll, London SW15 4JD, England. [Kuebler, A.; Birbaumer, N.] Univ Tubingen, Inst Med Psychol & Behav Neurol, Tubingen, Germany. [Birbaumer, N.] NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RP Kubler, A (reprint author), Roehampton Univ, Sch Human & Life Sci, Clin & Hlth Psychol Res Ctr, Whitelands Coll, Holybourne Ave, London SW15 4JD, England. EM a.kuebler@roehampton.ac.uk OI Kubler, Andrea/0000-0003-4876-0415 FU Deutsche Forschungsgemeinschaft [SFB 550/TB5]; National Institutes of Health NIH [HD30146]; NIBIB/National Institute of Neurologic Disorders and Stroke [EB00856] FX We are greatly indebted to our patients, who made this research possible. Particularly HPS allowed us deep insights in the psychological state of a person in the locked-in state over the past 11 years. We thank our colleagues Samuel Faran, Adrian Furdea, Sebastian Halder, Slavica von Hartlieb, Thilo Hinterberger, Miguel Jordan, Ahmed el Karim, Boris Kleber, Boris Kotchoubey, Seung-Soo Lee, Tamara Matuz, Jurgen Mellinger, Ursula Mochty, Emily Mugler, Nicola Neumann, Femke Nijboer, Ute Strehl, Tracy Trevorrow, and Barbara Wilhelm for their contribution. This study is supported by the Deutsche Forschungsgemeinschaft (SFB 550/TB5) and the National Institutes of Health NIH (NICHD, HD30146) and NIBIB/National Institute of Neurologic Disorders and Stroke (EB00856). The authors have no conflicts of interest and no financial interest. Both authors declare that they participated in data collection, data analysis, writing of the manuscript and that they have seen and approved the final version. Both authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. NR 49 TC 174 Z9 178 U1 1 U2 20 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2008 VL 119 IS 11 BP 2658 EP 2666 DI 10.1016/j.clinph.2008.06.019 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 377NM UT WOS:000261257900031 PM 18824406 ER PT J AU Kacinko, SL Jones, HE Johnson, RE Choo, RE Huestis, MA AF Kacinko, S. L. Jones, H. E. Johnson, R. E. Choo, R. E. Huestis, M. A. TI Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium With Neonatal Outcomes SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID IN-VITRO METABOLISM; ABSTINENCE SYNDROME; HUMAN PLACENTA; DRUG-USE; METHADONE; INFANTS; NEWBORN; NORBUPRENORPHINE; LOCALIZATION; GESTATION AB For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. C1 [Kacinko, S. L.; Huestis, M. A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Jones, H. E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Johnson, R. E.] Reckitt Benckiser Pharmaceut, Richmond, VA USA. [Choo, R. E.] Univ Pittsburgh, Dept Biol, Titusville, PA USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse [R01 12220, R01 DA015764, M01RR-02719]; General Clinical Research Centers Program; National Center of Research Resources; National Institutes of Health FX We thank the women who participated in this study. We also thank Paul Wakim for statistical guidance and Rosemarie Rios from the United States Drug Testing Laboratory for analyzing meconium samples for cocaine, opiates, and benzodiazepines. We thank the research and clinical staff of the Center for Addiction and Pregnancy. This study was supported by National Institute on Drug Abuse grants R01 12220 and R01 DA015764, and M01RR-02719 from the General Clinical Research Centers Program, National Center of Research Resources, National Institutes of Health. NR 39 TC 43 Z9 43 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2008 VL 84 IS 5 BP 604 EP 612 DI 10.1038/clpt.2008.156 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362PL UT WOS:000260209500018 PM 18701886 ER PT J AU Giacoia, GP Taylor-Zapata, P Mattison, D AF Giacoia, George P. Taylor-Zapata, Perdita Mattison, Donald TI Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Formulation Initiative: Selected Reports from Working Groups SO CLINICAL THERAPEUTICS LA English DT Article DE National Institute of Child Health and Human Development; Pediatric Formulation Initiative; pediatrics; extemporaneous; compounding AB Background: The Pediatric Formulation Initiative (PFI) is a project of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The PFI was established to address the issue of the lack of appropriate formulations in children and to use this activity as a means to improve pediatric formulations, as mandated by the Best Pharmaceuticals for Children Act of 2002 and 2007. The PFI began in 2005 with the formation of 3 working groups-Scientific, Economics, and Taste and Flavor. These groups began the process of identifying issues, gathering needed information, and considering possible ways to overcome barriers to the development of pediatric drug formulations. Objective: The purpose of this supplement was to provide details of the working groups' activities through presentation of full-length articles. Also presented is an article that discusses the 2007 European Union (EU) regulation on medicinal products for pediatric use. Methods: Information for this article was gathered from the proceedings of a PFI workshop, sponsored by the NICHD, that was held in Bethesda, Maryland, on December 6 and 7, 2005, as well as postworkshop discussions of the different working groups. Results: The increased awareness that the majority of medications used today have not been labeled for use in children, and have not been tested to define safety, efficacy, and appropriate dosing, has led to the passage of legislation in the United States and in the EU to create incentives to stimulate the testing of drugs in this special population. It is imperative that the problems associated with the compounding and use of extemporaneous formulations as described in this supplement be addressed. Regulatory barriers to the availability of commercially developed pediatric formulations in different countries will need to be minimized or removed. New drug delivery systems will need to be tested and made available to pediatric patients. Further research in the mediators of bitter taste and study of taste blockers, as well as newer methods for taste testing in pediatrics, should be encouraged. An overarching goal for the future is addressing the economic barriers to develop appropriate pediatric dosage forms for drugs with limited market penetration. The lack of appropriate formulations is part of a larger problem that includes limited development and manufacture of medicines tailored for pediatric patients (particularly those affected by neglected diseases), insufficient investment in drug trials, and limited research on drug disposition in various pediatric populations worldwide. Conclusion: The solution to these issues will require alignment of vision and commitment as a global priority of policy makers, regulators, scientists, pharmaceutical sponsors, academic institutions, governments, and research foundations. (Clin Ther. 2008; 30:2097-2101) (C) 2008 Excerpta Medica Inc. C1 [Giacoia, George P.; Taylor-Zapata, Perdita; Mattison, Donald] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD 20847 USA. RP Giacoia, GP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20847 USA. EM giacoiag@exchange.nih.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 7 TC 11 Z9 12 U1 1 U2 1 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD NOV PY 2008 VL 30 IS 11 BP 2097 EP 2101 DI 10.1016/j.clinthera.2008.11.017 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 385JX UT WOS:000261811600014 PM 19108797 ER PT J AU Shippenberg, TS LeFevour, A Chefer, VI AF Shippenberg, T. S. LeFevour, A. Chefer, V. I. TI Targeting Endogenous Mu- and Delta-Opioid Receptor Systems for the Treatment of Drug Addiction SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Review DE Opioid receptors; drug self-administration; enkephalin; endorphin; cocaine; ethanol; morphine ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL; EXTRACELLULAR DOPAMINE LEVELS; COCAINE-INDUCED REINSTATEMENT; CONDITIONED PLACE PREFERENCE; ANTERIOR CINGULATE CORTEX; CENTRAL AMYGDALA NEURONS; BETA-ENDORPHIN AB Drug addiction is a chronic, relapsing disorder that is characterized by a compulsion to take drug regardless of the adverse consequences that may ensue. Although the involvement of mesoaccumbal dopamine neurons in the initiation of drug abuse is well-established, neuroadaptations within the limbic cortical-striatopallidal circuit that occur as a consequence of repeated drug use are thought to lead to the behavioral dysregulation that characterizes addiction. Opioid receptors and their endogenous ligands are enriched in brain regions comprising this system and are, thus, strategically located to modulate neurotransmission therein. This article will review data suggesting an important role of mu-opioid receptor (MOPr) and delta opioid receptor (DOPr) systems in mediating the rewarding effects of several classes of abused drugs and that aberrant activity of these opioid systems may not only contribute to the behavioral dysregulation that characterizes addiction but to individual differences in addiction vulnerability. C1 [Shippenberg, T. S.; LeFevour, A.; Chefer, V. I.] NIH NIDA Intramural Res Program, Integrat Neurosci Sect, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIH NIDA Intramural Res Program, Integrat Neurosci Sect, 333 Cassell Dr, Baltimore, MD 21224 USA. EM tshippen@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999, ZIA DA000538-04] NR 195 TC 30 Z9 31 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 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD NOV PY 2008 VL 7 IS 5 BP 442 EP 453 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 397HY UT WOS:000262654700005 PM 19128202 ER PT J AU Scherma, M Fadda, P Le Foll, B Forget, B Fratta, W Goldberg, SR Tanda, G AF Scherma, Maria Fadda, Paola Le Foll, Bernard Forget, Benoit Fratta, Walter Goldberg, Steven R. Tanda, Gianluigi TI The Endocannabinoid System: A New Molecular Target for the Treatment of Tobacco Addiction SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Review DE Addiction; tobacco dependence; nicotine; endocannabinoid system; CB(1) receptors ID CANNABINOID CB1 RECEPTOR; VENTRAL TEGMENTAL AREA; ACID AMIDE HYDROLASE; NICOTINIC ACETYLCHOLINE-RECEPTORS; CENTRAL-NERVOUS-SYSTEM; N-ARACHIDONYLETHANOLAMINE ANANDAMIDE; CONDITIONED PLACE PREFERENCES; FOOD-REINFORCED BEHAVIOR; NUCLEUS-ACCUMBENS; RAT-BRAIN AB Tobacco addiction is one of the leading preventable causes of mortality in the world and nicotine appears to be the main critical psychoactive component in establishing and maintaining tobacco dependence. Several lines of evidence suggest that the rewarding effects of nicotine, which underlie its abuse potential, can be modulated by manipulating the endocannabinoid system. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors reduces or eliminates many behavioral and neurochemical effects of nicotine that are related to its addictive potential. This review will focus on the recently published literature about the role of the endocannabinoid system in nicotine addiction and on the endocannabinoid system as a novel molecular target for the discovery of medications for tobacco dependence. C1 [Tanda, Gianluigi] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Psychobiol Sect,Medicat Discovery Res Branch, Baltimore, MD USA. [Scherma, Maria; Goldberg, Steven R.] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Preclin Pharmacol Sect,Behav Neurosci Res Branch, Baltimore, MD USA. [Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy. [Le Foll, Bernard; Forget, Benoit] Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada. [Le Foll, Bernard; Forget, Benoit] Univ Toronto, Toronto, ON, Canada. RP Tanda, G (reprint author), Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv,Intramural Res Program, Psychobiol Sect,Medicat Discovery Res Branch, Baltimore, MD USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Le Foll, Bernard/K-2952-2014; OI Tanda, Gianluigi/0000-0001-9526-9878; Le Foll, Bernard/0000-0002-6406-4973; FADDA, PAOLA/0000-0002-0642-6710 FU National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services FX This research was supported in part by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, U.S. Department of Health and Human Services. NR 249 TC 19 Z9 20 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 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD NOV PY 2008 VL 7 IS 5 BP 468 EP 481 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 397HY UT WOS:000262654700007 PM 19128204 ER PT J AU Saltz, J Kurc, T Hastings, S Langella, S Oster, S Ervin, D Sharma, A Pan, T Gurcan, M Permar, J Ferreira, R Payne, P Catalyurek, U Caserta, E Leone, G Ostrowski, MC Madduri, R Foster, I Madhavan, S Buetow, KH Shanbhag, K Siegel, E AF Saltz, Joel Kurc, Tahsin Hastings, Shannon Langella, Stephen Oster, Scott Ervin, David Sharma, Ashish Pan, Tony Gurcan, Metin Permar, Justin Ferreira, Renato Payne, Philip Catalyurek, Umit Caserta, Enrico Leone, Gustavo Ostrowski, Michael C. Madduri, Ravi Foster, Ian Madhavan, Subhashree Buetow, Kenneth H. Shanbhag, Krishnakant Siegel, Eliot TI e-Science, caGrid, and Translational Biomedical Research SO COMPUTER LA English DT Article ID INFRASTRUCTURE AB Researchers are harnessing dramatic advances in many biomedical technology areas to better understand the causes of disease and to direct disease treatment. The authors' work explores the critical role e-Science plays in enabling translational biomedical research-the process of developing and applying basic science knowledge and techniques to enable new ways of diagnosing and staging, treating, or preventing diseases, as well as the adoption of best practices in the community. C1 [Saltz, Joel; Kurc, Tahsin] Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA. [Hastings, Shannon; Langella, Stephen; Oster, Scott; Ervin, David; Permar, Justin] Ohio State Univ, Software Res Inst, Columbus, OH 43210 USA. [Sharma, Ashish; Pan, Tony; Gurcan, Metin; Payne, Philip; Catalyurek, Umit] Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. [Leone, Gustavo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Ostrowski, Michael C.] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. [Ostrowski, Michael C.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Madduri, Ravi; Foster, Ian] Argonne Natl Lab, Argonne, IL 60439 USA. [Buetow, Kenneth H.] NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. [Shanbhag, Krishnakant] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA. [Siegel, Eliot] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Saltz, J (reprint author), Emory Univ, Ctr Comprehens Informat, Atlanta, GA 30322 USA. EM jhsaltz@emory.edu; tkurc@emory.edu; shannon.hastings@osumc.edu; stephen.langella@osumc.edu; oster@bmi.osu.edu; ervin@bmi.osu.edu; ashish@bmi.osu.edu; tpan@bmi.osu.edu; gurcan@bmi.osu.edu; jpermar@bmi.osu.edu; renato@dcc.ufmg.br; philip.payne@osumc.edu; umit@bmi.osu.edu; enrico.caserta@osumc.edu; gustavo.leone@osumc.edu; michael.ostrowski@osumc.edu; madduri@mcs.anl.gov; foster@ci.uchicago.edu; madhavas@mail.nih.gov; buetowk@mail.nih.gov; shanbhak@mail.nih.gov; esiegel@umaryland.edu RI Catalyurek, Umit/A-2454-2008; Ostrowski, Michael/H-3108-2011; Gurcan, Metin/F-4536-2012; InWeb, Inct/J-9839-2013 OI Catalyurek, Umit/0000-0002-5625-3758; Ostrowski, Michael/0000-0003-2948-6297; FU NCI caGrid Developer grant [79077CBS10]; State of Ohio BRTT Program [04-049, BRTT02-0003]; NHLBI [R24 HL085343]; NIH [U54 CA113001, R01 LM009239, N01-CO-12400]; NSF [CNS-0403342, CNS-0615155]; US Department of Energy [DE-AC02-06CH11357]; Children's Neuroblastoma Cancer Foundation FX We thank Laura Esserman and Nola Hylton at the University of California, San Francisco, the PIs for the I-SPY trial project; Howard Fine at the NCI, the PI for the GMDI and Rembrandt projects; and Stephen Chanock, NCI, the PI for the CGEMS (GWAS) project. Our work was supported in part by the NCI caGrid Developer grant 79077CBS10, the State of Ohio BRTT Program grants ODOD AGMT TECH 04-049 and BRTT02-0003, the NHLBI R24 HL085343 grant, the NIH U54 CA113001 and R01 LM009239 grants, and NSF grants CNS-0403342 and CNS-0615155; by the NCI and NIH under contract no. N01-CO-12400; by the US Department of Energy under contract DE-AC02-06CH11357; and by Children's Neuroblastoma Cancer Foundation. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NR 12 TC 9 Z9 9 U1 1 U2 6 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0018-9162 EI 1558-0814 J9 COMPUTER JI Computer PD NOV PY 2008 VL 41 IS 11 BP 58 EP + DI 10.1109/MC.2008.459 PG 10 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA 369VT UT WOS:000260722700014 PM 21311723 ER PT J AU Gadegbeku, CA Stillman, PK Huffman, MD Jackson, JS Kusek, JW Jamerson, KA AF Gadegbeku, Crystal A. Stillman, Phyllis Kreger Huffman, Mark D. Jackson, James S. Kusek, John W. Jamerson, Kenneth A. TI Factors associated with enrollment of African Americans into a clinical trial: Results from the African American study of kidney disease and hypertension SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE African Americans; Subject recruitment; Willingness to participate; Clinical trials ID HEALTH RESEARCH; PARTICIPATION; CANCER; RACE; WILLINGNESS; DETERMINANTS; PERCEPTIONS; DISPARITIES; PREVENTION; MINORITIES AB Recruitment of diverse populations into clinical trials remains challenging but is needed to fully understand disease processes and benefit the general public. Greater knowledge of key factors among ethnic and racial minority populations associated with the decision to participate in clinical research studies may facilitate recruitment and enhance the generalizibility of study results. Therefore, during the recruitment phase of the African American Study of Kidney Disease and Hypertension (AASK) trial, we conducted a telephone survey. using validated questions, to explore potential facilitators and barriers of research participation among eligible candidates residing in seven U.S. locations. Survey responses included a range of characteristics and perceptions among participants and non-participants and were compared using bivariate and step-wise logistic regression analyses. One-hundred forty-one respondents in the one-hundred forty (70 trial participants and 71 nonparticipants) completed the Survey. Trial participants and non-participants were similar in multiple demographic characteristics and shared similar views on discrimination, physician mistrust. and research integrity. Key group differences were related to their perceptions of the impact of their research participation. Participants associated enrollment with personal and societal health benefits. while non-participants were influenced by the health risks. In a stepwise linear regression analysis, the most powerful significant positive predictors of participation were acknowledgement of health status as important in the enrollment decision (OR = 4.54, p = 0.006), employment (OR = 3.12, p = 0.05) and healthcare satisfaction (OR = 2.12, p < 0.01). Racially-based mistrust did not emerge as a negative predictor and subjects' decisions were not influenced by the race of the research staff. In conclusion, these results suggest that health-related factors. and not psychosocial perceptions, have predominant influence on research participation among African Americans. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gadegbeku, Crystal A.; Huffman, Mark D.; Jamerson, Kenneth A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Stillman, Phyllis Kreger; Jackson, James S.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. RP Gadegbeku, CA (reprint author), Univ Michigan Hlth Syst, Dept Internal Med, Div Nephrol, 310 Simpson Mem Inst,102 Observ Rd, Ann Arbor, MI 48109 USA. EM cgadegbe@umich.edu OI Huffman, Mark/0000-0001-7412-2519 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK48682, DK45381, DK48659, DK65473, DK48669, DK48645, DK45386]; National Center for Minority Health and Health Disparities and the Office of Behavioral and Social Sciences Research; National Institutes of Health FX Supported by cooperative agreements U01 DK48682 (University of Michigan), DK45381 (Case Western Reserve), DK48659 (Medical University of South Carolina), DK65473 (Meharry Medical College), DK48669 (University of Alabama, Birminghan), DK48645 (University of California, San Diego), DK45386 (University of Texas, Southwestern) from the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support is provided by the National Center for Minority Health and Health Disparities and the Office of Behavioral and Social Sciences Research, National Institutes of Health. NR 33 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2008 VL 29 IS 6 BP 837 EP 842 DI 10.1016/j.cct.2008.06.001 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 373RO UT WOS:000260990300004 PM 18639652 ER PT J AU O'Grady, NP Barie, PS Carroll, K AF O'Grady, Naomi P. Barie, Philip S. Carroll, Karen TI Fever in critically ill patients Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PARKINSONS-DISEASE C1 [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Barie, Philip S.] Weill Cornell Med Coll, New York, NY USA. [Carroll, Karen] Johns Hopkins Sch Med, Baltimore, MD USA. RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2008 VL 36 IS 11 BP 3130 EP 3130 DI 10.1097/CCM.0b013e31818c0f23 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 369KU UT WOS:000260694200052 ER PT J AU Hayton, K Su, XZ AF Hayton, Karen Su, Xin-zhuan TI Drug resistance and genetic mapping in Plasmodium falciparum SO CURRENT GENETICS LA English DT Review DE Malaria; Genetics; Genomics; Antimalarial agents ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; TRANSMEMBRANE PROTEIN PFCRT; CHLOROQUINE-RESISTANCE; IN-VITRO; MALARIA PARASITES; MEFLOQUINE RESISTANCE; MULTIDRUG-RESISTANCE; ANTIMALARIAL-DRUGS; QUININE RESISTANCE AB Drug resistance in malaria parasites is a serious public health burden, and resistance to most of the antimalarial drugs currently in use has been reported. A better understanding of the molecular mechanisms of drug resistance is urgently needed to slow or circumvent the spread of resistance, to allow local treatments to be deployed more effectively to prolong the life span of the current drugs, and to develop new drugs. Although mutations in genes determining resistance to drugs such as chloroquine and the antifolates have been identified, we still do not have a full understanding of the resistance mechanisms, and genes that contribute to resistance to many other drugs remain to be discovered. Genetic mapping is a powerful tool for the identification of mutations conferring drug resistance in malaria parasites because most drug-resistant phenotypes were selected within the past 60 years. High-throughput methods for genotyping large numbers of single nucleotide polymorphisms (SNPs) and microsatellites (MSs) are now available or are being developed, and genome-wide association studies for malaria traits will soon become a reality. Here we discuss strategies and issues related to mapping genes contributing to drug resistance in the human malaria parasite Plasmodium falciparum. C1 [Su, Xin-zhuan] NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, Malaria Funct Genom Sect, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM KHayton@niaid.nih.gov; xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural Research Program of the Division of Intramural Research; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall for assistance. Because the authors are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMedCentral may tag or modify the work consistent with its customary practices. You can establish rights outside of the US subject to a government use license. NR 184 TC 42 Z9 42 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0172-8083 J9 CURR GENET JI Curr. Genet. PD NOV PY 2008 VL 54 IS 5 BP 223 EP 239 DI 10.1007/s00294-008-0214-x PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 366GR UT WOS:000260469100001 PM 18802698 ER PT J AU Mehta, RG Naithani, R Huma, L Hawthorne, M Moriarty, RM McCormick, DL Steele, VE Kopelovich, L AF Mehta, Rajendra G. Naithani, Rajesh Huma, Loredana Hawthorne, Michael Moriarty, Robert M. McCormick, David L. Steele, Vernon E. Kopelovich, Levy TI Efficacy of Chemopreventive Agents in Mouse Mammary Gland Organ Culture (MMOC) Model: A Comprehensive Review SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Mammary gland organ culture assay; MMOC; natural products; DMBA; chemoprevention; carcinogenesis; mammary alveolar lesions (MAL) ID CELL-CYCLE ARREST; CANCER CHEMOPREVENTION; BREAST-CANCER; VITAMIN-D; HELICOBACTER-PYLORI; INHIBITORY ACTIVITY; QUINONE REDUCTASE; DRUG DEVELOPMENT; CARCINOGENESIS; CONSTITUENTS AB Currently, breast cancer is considered as one of the leading causes for death in women in the United States. Consumption of natural products has received considerable attention in recent years as a possible approach for cancer prevention in general population. There are numerous cancer preventive agents present in the natural products, which may contribute to their chemopreventive properties. During the past two decades, numerous chemopreventive agents have been isolated and/or synthesized and evaluated for their efficacy in a variety of biological assays. To this end, we have established and utilized mouse mammary gland organ culture model (MMOC) as a bioassay for identifying chemopreventive agents. Mammary glands respond to growth promoting hormones and the physiological differentiation can be reproduced in MMOC in chemically defined medium by altering hormonal milieu. Both estrogen and progesterone dependent (mammary ductal lesions, MDL) and independent (mammary alveolar lesions, MAL) precancerous lesions can be induced in response to a 24 hour exposure to DMBA in MMOC. Suppression of the incidence and multiplicity of these lesions by a possible chemopreventive agent can serve as a tool to evaluate efficacy of potential experimental agents. Using this approach, we have evaluated more than 200 synthetic and natural product-derived chemopreventive agents in this model as a part of the National Cancer Institute-supported projects. Many of these chemopreventive agents expressing significant activity have progressed to the in vivo experimental mammary carcinogenesis studies. Thus, this bioassay has proven to be a valuable tool for screening cancer chemopreventive agents for breast cancer prevention and for understanding molecular mechanism(s) of action of these agents. In this comprehensive review, we provide a complete list of chemopreventive agents evaluated for the efficacy against development of mammary alveolar lesions (MAL) in MMOC along with the recent developments in this area. The structure-activity relationships for many chemopreventive agents evaluated in the MMOC model have been discussed. C1 [Mehta, Rajendra G.; Hawthorne, Michael; McCormick, David L.] IIT, Res Inst, Carcinogenesis & Chemoprevent Div, Chicago, IL 60616 USA. [Mehta, Rajendra G.; Naithani, Rajesh; Huma, Loredana; Moriarty, Robert M.; McCormick, David L.] IIT, Res Inst, Drug Discovery Div, Chicago, IL 60616 USA. [Moriarty, Robert M.] Univ Illinois, Dept Chem, Chicago, IL 60680 USA. [Steele, Vernon E.; Kopelovich, Levy] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Mehta, RG (reprint author), IIT, Res Inst, Carcinogenesis & Chemoprevent Div, 10 W 35th St, Chicago, IL 60616 USA. EM RMehta@iitri.org FU NCI Research Contracts, Grants and a Program Project grant FX The authors acknowledge outstanding contribution of numerous fellows, students and research technicians who have helped with the MMOC assays for the past 25 years. We are thankful to our collaborators for providing chemopreventive agents for the MMOC assays and scientific discussions over the past several years. Specifically, we would like to thank Dr. Richard Moon, Dr. John Pezzuto and Dr. A. Douglas Kinghorn for their continuous support, valuable discussions and help with various projects. Dr. Mehta is indebted to Dr. S. Nandi and late Dr. Mihir Banerjee for introducing him to mammary gland organ culture studies and for their continuous encouragement. The work was supported by the NCI Research Contracts, Grants and a Program Project grant. NR 111 TC 8 Z9 8 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD NOV PY 2008 VL 15 IS 27 BP 2785 EP 2825 DI 10.2174/092986708786242787 PG 41 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 386OF UT WOS:000261891800002 PM 18991637 ER PT J AU Vichinsky, E Rodgers, GP Rachmilewitz, E AF Vichinsky, Elliott Rodgers, Griffin P. Rachmilewitz, Eliezer TI Hot Topic: Genetic Disorders of Hemoglobin: Sickle Cell Anemia and Thalassemia SO CURRENT MOLECULAR MEDICINE LA English DT Editorial Material C1 [Vichinsky, Elliott] Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA 94609 USA. [Rodgers, Griffin P.] Natl Inst Diabet Digest & Kidney Disorders, NIH, Bethesda, MD 20892 USA. [Rachmilewitz, Eliezer] Edith Wolfson Med Ctr, Head Hematol Dept, Holon, Israel. RP Vichinsky, E (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, 747 52nd St, Oakland, CA 94609 USA. EM evichinsky@mail.cho.org; griffinr@extra.niddk.nih.gov; rachmilewitz@wolfson.health.gov.il NR 0 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD NOV PY 2008 VL 8 IS 7 BP 591 EP 591 DI 10.2174/156652408786241456 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 386OM UT WOS:000261892500001 PM 18991644 ER PT J AU Morris, CR Gladwin, MT Kato, GJ AF Morris, Claudia R. Gladwin, Mark T. Kato, Gregory J. TI Nitric Oxide and Arginine Dysregulation: A Novel Pathway to Pulmonary Hypertension in Hemolytic Disorders SO CURRENT MOLECULAR MEDICINE LA English DT Review DE Pulmonary hypertension; sickle cell disease; thalassemia; hemoglobinopathies; arginine; nitric oxide; arginase; hemolysis ID SICKLE-CELL-DISEASE; ACUTE CHEST SYNDROME; RED-BLOOD-CELLS; GLUTATHIONE-REDUCTASE ACTIVITY; CHRONIC HYPERCOAGULABLE STATE; LOWER AIRWAY-OBSTRUCTION; BETA-THALASSEMIA MAJOR; AMINO-ACID TRANSPORTER; ARTERIAL-HYPERTENSION; ARGINASE ACTIVITY AB Secondary pulmonary hypertension (PH) is emerging as one of the leading causes of mortality and morbidity in patients with hemolytic anemias such as sickle cell disease (SCD) and thalassemia. Impaired nitric oxide (NO) bioavailability represents the central feature of endothelial dysfunction, and is a major factor in the pathophysiology of PH. Inactivation of NO correlates with hemolytic rate and is associated with the erythrocyte release of cell-free hemoglobin, which consumes NO directly, and the simultaneous release of the arginine-metabolizing enzyme arginase, which limits bioavailability of the NO synthase substrate arginine during the process of intravascular hemolysis. Rapid consumption of NO is accelerated by oxygen radicals that exists in both SCD and thalassemia. A dysregulation of arginine metabolism contributes to endothelial dysfunction and PH in SCD, and is strongly associated with prospective patient mortality. The central mechanism responsible for this metabolic disorder is enhanced arginine turnover, occurring secondary to enhanced plasma arginase activity. This is consistent with a growing appreciation of the role of excessive arginase activity in human diseases, including asthma and pulmonary arterial hypertension. New treatments aimed at improving arginine and NO bioavailability through arginase inhibition, suppression of hemolytic rate, oral arginine supplementation, or use of NO donors represent potential therapeutic strategies for this common pulmonary complication of hemolytic disorders. C1 [Morris, Claudia R.] Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA. [Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15213 USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Kato, Gregory J.] NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Morris, CR (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, 747 52nd St, Oakland, CA 94609 USA. EM claudiamorris@comcast.net RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU National Institutes of Health (NIH) [UL1 RR024131]; INO Therapeutics, Inc. FX Authors declare no conflicts of interest. This study was supported in part by the NIH CTSI grant UL1 RR024131 (to CRM). GJK and MTG receive intramural support from the National Institutes of Health (NIH). MTG holds a cooperative research and development agreement (CRADA) through the NIH with INO Therapeutics, Inc. NR 215 TC 45 Z9 46 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD NOV PY 2008 VL 8 IS 7 BP 620 EP 632 DI 10.2174/156652408786241447 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 386OM UT WOS:000261892500005 PM 18991648 ER PT J AU Masdeu, JC Pascual, B AF Masdeu, Joseph C. Pascual, Belen TI Neuroimaging of Disorders Leading to Dementia SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Editorial Material ID CEREBRAL AMYLOID ANGIOPATHY; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ATROPHY; MRI; PROGRESSION; DIAGNOSIS; LESIONS; BURDEN; ONSET C1 [Masdeu, Joseph C.] NIMH, Sect Integrat Neuroimaging, NIH, CBDB,Intramural Res Program, Bethesda, MD 20892 USA. RP Masdeu, JC (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, CBDB,Intramural Res Program, 9000 Rockville Pike,Bldg 10,Room 4C101, Bethesda, MD 20892 USA. EM masdeu@nih.org NR 20 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD NOV PY 2008 VL 8 IS 6 BP 443 EP 444 DI 10.1007/s11910-008-0069-z PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 381UC UT WOS:000261560400001 PM 18957178 ER PT J AU Bondy, CA AF Bondy, Carolyn A. TI Aortic dissection in Turner syndrome SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE adult congenital heart disease; aorta; bicuspid aortic valve; coarctation; X chromosome ID MARFANS-SYNDROME; RISK-FACTOR; DILATION; DILATATION; PREVALENCE; VALVE; WOMEN; ABNORMALITIES; MORTALITY; DISEASE AB Purpose of review Turner syndrome is a relatively common disorder of female development with cardinal features of short stature and congenital cardiovascular defects (CHD). Turner syndrome is the most common established cause of aortic dissection in young women, but has received little attention outside pediatric literature. This review focuses on emerging knowledge of the characteristics of aortic disease in Turner syndrome in comparison with Marfan-like syndromes and isolated aortic valve disease. Recent findings The incidence of aortic dissection is significantly increased in individuals with Turner syndrome at all ages, highest during young adult years and in pregnancy. Pediatric patients with dissection have known congenital cardiovascular defects (CHD), but adults often have aortic valve and arch abnormalities detected only by screening cardiac magnetic resonance. Thoracic aortic dilation in Turner syndrome must be evaluated in relation to body surface area. Dilation is most prominent at the ascending aorta, similar to the pattern seen in nonsyndromic bicuspid aortic valve, is equally prevalent (20-30%) in children and adults, and does not seem to be rapidly progressive. Cardiovascular anomalies and risk for aortic dissection in Turner syndrome are strongly linked to a history of fetal lymphedema, evidenced by the presence of neck webbing and shield chest. Summary Risk for acute aortic dissection is increased by more than 100-fold in young and middle-aged women with Turner syndrome. Monitoring frequency and treatment modalities are decided on an individual basis until more information on outcomes becomes available. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS [Z01 HD000628-18] NR 29 TC 68 Z9 74 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2008 VL 23 IS 6 BP 519 EP 526 DI 10.1097/HCO.0b013e3283129b89 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 365KR UT WOS:000260405800001 PM 18839441 ER PT J AU Stenholm, S Harris, TB Rantanen, T Visser, M Kritchevsky, SB Ferrucci, L AF Stenholm, Sari Harris, Tamara B. Rantanen, Taina Visser, Marjolein Kritchevsky, Stephen B. Ferrucci, Luigi TI Sarcopenic obesity: definition, cause and consequences SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Review DE adipose tissue; body composition; disability; muscle strength; obesity; older people; sarcopenia ID BODY-MASS INDEX; HUMAN SKELETAL-MUSCLE; CARDIOVASCULAR RISK-FACTORS; LOWER-EXTREMITY PERFORMANCE; ADIPOSE-TISSUE DISTRIBUTION; INSULIN-RESISTANCE; OLDER-ADULTS; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; ELDERLY-MEN AB Purpose of review Older obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, muscle weakness should be used for the definition. Recent findings Excess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so-called 'sarcopenic obesity'. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term sarcopenic obesity' should be revisited. Summary Recognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome. C1 [Stenholm, Sari; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA. [Stenholm, Sari] Natl Publ Hlth Inst, Dept Hlth & Funct Capac, Turku, Finland. [Harris, Tamara B.] NIA, Geriatr Interdisciplinary Studies Sect, Lab Epidemiol Demog & Biometry, Baltimore, MD 21225 USA. [Rantanen, Taina] Univ Jyvaskyla, Dept Hlth Sci, Finnish Ctr Interdisciplinary Gerontol, Jyvaskyla, Finland. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,J Paul Sticht Ctr Agi, Winston Salem, NC 27103 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Stenholm, Sari/G-6940-2011; Rantanen, Taina/O-6579-2016; OI Rantanen, Taina/0000-0002-1604-1945; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural Research Program; National Institute on Aging, [263 MID 9164 13, 263 MD 821336]; NIH; Italian Ministry of Health [ICS 110.1/RS97.71]; US National Institute on Aging [N01-AG916413, N01-AG-821336]; Dutch Ministry of Public Health, Welfare and Sports; Finnish Academy [125494] FX The present research was partly supported by the Intramural Research Program, National Institute on Aging, NIH. The Baltimore Longitudinal Study of Aging was supported by the Intramural Research Program of the NIH, National Institute on Aging. The InCHIANTI Study was supported as a 'targeted project' (ICS 110.1/RS97.71) by the Italian Ministry of Health, and in part by the US National Institute on Aging (Contracts N01-AG916413 and N01-AG-821336), and by the Intramural Research Program of the NIH, National Institute on Aging (Contracts 263 MID 9164 13 and 263 MD 821336). The Longitudinal Aging Study Amsterdam is financially supported by the Dutch Ministry of Public Health, Welfare and Sports. This work was also supported by grant from the Finnish Academy (no. 125494). None of the sponsoring institutions interfered with the collection, analysis, presentation, or interpretation of the data reported here. Authors have no conflicts of interest. NR 110 TC 289 Z9 302 U1 4 U2 37 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD NOV PY 2008 VL 11 IS 6 BP 693 EP 700 DI 10.1097/MCO.0b013e328312c37d PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 368KI UT WOS:000260619600003 PM 18827572 ER PT J AU Bernstein, WB Dennis, PA AF Bernstein, Wendy B. Dennis, Phillip A. TI Repositioning HIV protease inhibitors as cancer therapeutics SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE Akt; apoptosis; autophagy; endoplasmic reticulum stress; protease inhibitors AB Purpose of review Although designed to target only the HIV protease, HIV protease inhibitors induce toxicities in patients such as insulin resistance and lipodystrophy that suggest that protease inhibitors have other targets in mammalian cells. Akt controls insulin signaling and is an important target in cancer, but no Akt inhibitors are approved as cancer therapeutics. These observations have prompted the study of HIV protease inhibitors as inhibitors of Akt and possible cancer therapeutics. This review will highlight the latest advances in repositioning HIV protease inhibitors as cancer therapeutics. Recent findings Although protease inhibitors can inhibit Akt activation and the proliferation of over 60 cancer cell lines, as well as improve sensitivity to radiation or chemotherapy, these effects do not always correlate with Akt inhibition. Other important processes, such as the induction of endoplasmic reticulum stress, appear critical to the biological activity of protease inhibitors. These impressive and surprising preclinical data have prompted clinical testing of nelfinavir as a lead HIV protease inhibitor in cancer patients. Summary Although mechanisms of action for the antitumor effects of HIV protease inhibitors are complex, their broad spectrum of activity, minimal toxicity, and wide availability make protease inhibitors ideal candidates for repositioning as cancer therapeutics. C1 [Bernstein, Wendy B.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bernstein, Wendy B.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. RP Dennis, PA (reprint author), NCI Navy Med Oncol, Room 5101 Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20899 USA. EM dennisp@mail.nih.gov FU NIH, Center for Cancer Research, National Cancer Institute FX This research was supported by the Intramural Research Programme of the NIH, Center for Cancer Research, National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or Department of Defense, nor does mention of trade names, commercial products, or organization imply endorsement by the United States Government. NR 65 TC 38 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2008 VL 3 IS 6 BP 666 EP 675 DI 10.1097/COH.0b013e328313915d PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24OC UT WOS:000208418700011 PM 19373040 ER PT J AU Lee, MJ Kim, YS Kummar, S Giaccone, G Trepel, JB AF Lee, Min-Jung Kim, Yeong Sang Kummar, Shivaani Giaccone, Giuseppe Trepel, Jane B. TI Histone deacetylase inhibitors in cancer therapy SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE cancer therapy; clinical trial; combination therapy; histone deacetylase inhibitors ID SUBEROYLANILIDE HYDROXAMIC ACID; ADVANCED SOLID TUMORS; T-CELL LYMPHOMA; ACUTE MYELOID-LEUKEMIA; ACTIVITY IN-VITRO; PHASE-I; VALPROIC ACID; HDAC INHIBITORS; RETINOIC ACID; HEMATOLOGICAL MALIGNANCIES AB Purpose of review The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer. Recent findings Recently, there has been a dramatic expansion of HDACi clinical investigation There are. now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination. Summary In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols. C1 [Lee, Min-Jung; Kim, Yeong Sang; Kummar, Shivaani; Giaccone, Giuseppe; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU Bayer Schering Pharma AG; Syndax Pharmaceuticals; Intramural Research Program; Center for Cancer Research; National Cancer Institute; National Institutes of Health FX Research funding supporting this work was received from Bayer Schering Pharma AG, Syndax Pharmaceuticals, and the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 120 TC 82 Z9 83 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2008 VL 20 IS 6 BP 639 EP 649 DI 10.1097/CCO.0b013e3283127095 PG 11 WC Oncology SC Oncology GA 369ND UT WOS:000260700300006 PM 18841045 ER PT J AU Weichel, ED Colyer, MH AF Weichel, Eric D. Colyer, Marcus H. TI Combat ocular trauma and systemic injury SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE closed-globe injury; combat ocular trauma; enucleation; intraocular foreign body; open-globe injury; traumatic brain injury ID EYE INJURIES; WAR INJURIES; IRAQI FREEDOM; DESERT-SHIELD; PROTECTION; MANAGEMENT; STORM AB Purpose of review To review the recent literature regarding combat ocular trauma during hostilities in Operations Iraqi Freedom and Enduring Freedom, describe the classification of combat ocular trauma, and offer strategies that may assist in the management of eye injuries. Recent findings Several recent publications have highlighted features of combat ocular trauma from Operation Iraqi Freedom. The most common cause of today's combat ocular injuries is unconventional fragmentary munitions causing significant blast injuries. These explosive munitions cause high rates of concomitant nonocular injuries such as traumatic brain injury, amputation, and other organ injuries. The most frequent ocular injuries include open-globe and adnexal lacerations. The extreme severity of combat-related open-globe injuries leads to high rates of primary enucleation and retained intraocular foreign bodies. Visual outcomes of intraocular foreign body injuries are similar to other series despite delayed removal, and no cases of endophthalmitis have occurred. Despite these advances, however, significant vision loss persists in cases of perforating globe injuries as well as open and closed-globe trauma involving the posterior segment. Summary This review summarizes the recent literature describing ocular and systemic injuries sustained during Operations Iraqi and Enduring Freedom. An emphasis on classification of ocular injuries as well as a discussion of main outcome measures and complications is discussed. C1 [Weichel, Eric D.] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA. [Weichel, Eric D.] NEI, NIH, Bethesda, MD 20892 USA. RP Weichel, ED (reprint author), Walter Reed Army Med Ctr, Ophthalmol Serv, 6900 Georgia Ave, Washington, DC 20307 USA. EM eweichel@hotmail.com NR 39 TC 24 Z9 24 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD NOV PY 2008 VL 19 IS 6 BP 519 EP 525 DI 10.1097/ICU.0b013e3283140e98 PG 7 WC Ophthalmology SC Ophthalmology GA 367WA UT WOS:000260582100011 PM 18854697 ER PT J AU Jiang, S Li, Z Ding, K Roller, PP AF Jiang, Sheng Li, Zheng Ding, Ke Roller, Peter P. TI Recent Progress of Synthetic Studies to Peptide and Peptidomimetic Cyclization SO CURRENT ORGANIC CHEMISTRY LA English DT Review ID SOLID-PHASE SYNTHESIS; RING-CLOSING METATHESIS; NATIVE CHEMICAL LIGATION; AZIDE-ALKYNE CYCLOADDITION; SNAR-BASED CYCLOETHERIFICATION; BIFUNCTIONAL BUILDING-BLOCKS; TYROSINE-DERIVED METABOLITE; GRB2-SH2 DOMAIN ANTAGONISTS; INTRAMOLECULAR O-ARYLATION; EFFICIENT COUPLING REAGENT AB A large number of cyclic peptides, which exhibit a range of biological activities, have been found in nature. The reason of cyclic peptides that attracted world wide attention and made them extensively studied, is their enhanced metabolic stabilities, biological specificities, bioavailability, and conformational constrained structural feature, which make them important leads for drug discovery, and as actual drugs. Many cyclic peptides show very promising biological activities, including anticancer, antibacterial, antiviral, antifungal, anti-inflammatory, and anti-clotting or anti-atherogenic properties. Peptide cyclization becomes an effective and commonly employed strategy for peptide modifications. During the past several decades, great efforts have been made to develop more efficient methods for the synthesis of cyclic peptides and peptidomimetics. This review will be focused on the major progress of the novel recently developed peptide cyclization approaches and the profitable applications since 2002. C1 [Jiang, Sheng; Ding, Ke] CAS, Guangzhou Inst Biomed & Hlth, Lab Regenerat Biol, Guangzhou 510663, Guangdong, Peoples R China. [Li, Zheng] Methodist Hosp, Res Inst, Dept Radiol, Houston, TX 77030 USA. [Roller, Peter P.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. RP Jiang, S (reprint author), CAS, Guangzhou Inst Biomed & Hlth, Lab Regenerat Biol, Guangzhou Int Business Incubator D-10,Guangzhou S, Guangzhou 510663, Guangdong, Peoples R China. EM jiang_sheng@gibh.ac.cn RI Ding, Ke/B-3257-2010; OI ding, ke/0000-0001-8167-0476 NR 298 TC 34 Z9 34 U1 3 U2 43 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 J9 CURR ORG CHEM JI Curr. Org. Chem. PD NOV PY 2008 VL 12 IS 17 BP 1502 EP 1542 DI 10.2174/138527208786241501 PG 41 WC Chemistry, Organic SC Chemistry GA 386OS UT WOS:000261893100005 ER PT J AU Appay, V van Lier, RAW Sallusto, F Roederer, M AF Appay, Victor van Lier, Rene A. W. Sallusto, Federica Roederer, Mario TI Phenotype and Function of Human T Lymphocyte Subsets: Consensus and Issues SO CYTOMETRY PART A LA English DT Review DE phenotype; function; T cells; virus ID CHEMOKINE RECEPTOR EXPRESSION; EX-VIVO; MEMORY CELLS; IN-VITRO; ANTIGENIC-STIMULATION; DISTINCT POPULATIONS; EFFECTOR FUNCTIONS; VIRUS; DIFFERENTIATION; CD4(+) AB In recent years, a tremendous effort has been devoted to the detailed characterization of the phenotype and function of distinct T cell subpopulations in humans, as well as to their pathway(s) of differentiation and role in immune responses. But these studies seem to have generated more questions than definitive answers. To clarify issues related to the function and differentiation of T cell subsets, one session of the MASIR 2008 conference was dedicated to this topic. Several points of consensus and discord were highlighted in the work presented during this session. We provide here all account of these points, including the relative heterogeneity of T cell subpopulations during infections with distinct pathogens, the relationship between phenotypic and functional T cell attributes, and the pathway(s) of T cell differentiation. Finally, we discuss the problems which still limit general agreement. Published 2008 Wiley-Liss, Inc.(dagger) C1 [Appay, Victor] Univ Paris 06, Hop La Pitie Salpetriere, INSERM,Cellular Immunol Lab, U543,Avenir Grp, F-75013 Paris, France. [van Lier, Rene A. W.] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, NL-1105 AZ Amsterdam, Netherlands. [Sallusto, Federica] Inst Res Biomed, CH-6500 Bellinzona, Switzerland. [Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Appay, V (reprint author), Univ Paris 06, Hop La Pitie Salpetriere, INSERM,Cellular Immunol Lab, U543,Avenir Grp, F-75013 Paris, France. EM appay@chups.jussieu.fr OI van Lier, Rene/0000-0002-3201-7144 NR 69 TC 335 Z9 344 U1 4 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2008 VL 73A IS 11 BP 975 EP 983 DI 10.1002/cyto.a.20643 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368LJ UT WOS:000260622300002 PM 18785267 ER PT J AU Chattopadhyay, PK Melenhorst, JJ Ladell, K Gostick, E Scheinberg, P Barrett, AJ Wooldridge, L Roederer, M Sewell, AK Price, DA AF Chattopadhyay, Pratip K. Melenhorst, J. Joseph Ladell, Kristin Gostick, Emma Scheinberg, Phillip Barrett, A. John Wooldridge, Linda Roederer, Mario Sewell, Andrew K. Price, David A. TI Techniques to Improve the Direct Ex Vivo Detection of Low Frequency Antigen-Specific CD8(+) T Cells with Peptide-Major Histocompatibility Complex Class I Tetramers SO CYTOMETRY PART A LA English DT Review DE CD8(+) T cell; peptide-major histocompatibility complex class I tetramer; polychromatic flow cytometry ID MHC CLASS-I; POLYCHROMATIC FLOW-CYTOMETRY; ALPHA-3 DOMAIN MUTANTS; EFFECTOR FUNCTION; MEMORY SUBSETS; CD8+T CELLS; BINDING; RECEPTOR; CORECEPTOR; CTL AB The ability to quantify and characterize antigen-specific CD8(+) T cells irrespective of functional readouts using fluorochrome-conjugated peptide-major histocompatibility complex class I (pMHCI) tetramers in conjunction with flow cytometry has transformed our understanding of cellular immune responses over the past decade. In the case of prevalent CD8(+) T cell populations that engage cognate pMHCI tetramers with high avidities, direct ex vivo identification and subsequent data interpretation is relatively straightforward. However, the accurate identification of low frequency antigen-specific CD8(+) T cell populations can be complicated, especially in situations where T cell receptor-mediated tetramer binding occurs at low avidities. Here, we highlight a few simple techniques that can be employed to improve the Visual resolution, and hence the accurate quantification, of tetramer binding CD8(+) T cell populations by flow cytometry. These methodological modifications enhance signal intensity, especially in the case of specific CD8(+) T cell populations that bind cognate antigen with low avidities, minimize background noise, and enable improved discrimination of true pMHCI tetramer binding events from nonspecific uptake. (C) 2008 international Society for Advancement of cytometry C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Chattopadhyay, Pratip K.; Roederer, Mario] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Chattopadhyay, Pratip K.; Roederer, Mario] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, S Glam, Wales. [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Chattopadhyay, PK (reprint author), NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pchattop@mail.nih.gov; priced6@cardiff.ac.uk RI Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Chattopadhyay, Pratip/B-9227-2008; Ladell, Kristin/C-8301-2013; OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Sewell, Andrew/0000-0003-3194-3135; Scheinberg, Phillip/0000-0002-9047-4538; Chattopadhyay, Pratip/0000-0002-5457-9666 FU National Institutes of Health; Vaccine Research Center, National Institute of Allergy and Infectious Diseases; Medical Research Council (UK) FX This work was sponsored by the Intramural Research Program of the National Institutes of Health; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and by the Medical Research Council (UK). NR 49 TC 27 Z9 27 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2008 VL 73A IS 11 BP 1001 EP 1009 DI 10.1002/cyto.a.20642 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368LJ UT WOS:000260622300005 PM 18836993 ER PT J AU Precopio, ML Butterfield, TR Casazza, JP Little, SJ Richman, DD Koup, RA Roederer, M AF Precopio, Melissa L. Butterfield, Tiffany R. Casazza, Joseph P. Little, Susan J. Richman, Douglas D. Koup, Richard A. Roederer, Mario TI Optimizing Peptide Matrices for Identifying T-Cell Antigens SO CYTOMETRY PART A LA English DT Article DE epitopes; T lymphocyte; HIV; epitope mapping ID HUMAN CYTOMEGALOVIRUS; HIV-1 INFECTION; FLOW-CYTOMETRY; VIRAL LOAD; RESPONSES; INDIVIDUALS; EPITOPES; CD4(+) AB Mapping T-cell epitopes for a pathogen or vaccine requires a complex method for screening hundreds to thousands of peptides with a limited amount of donor sample. We describe an optimized deconvolution process by which peptides are pooled in a matrix format to minimize the number of tests required to identify peptide epitopes. Four peptide pool matrices were constructed to deconvolute the HIV-specific T-cell response in three HIV-infected individuals. ELISpot assays were used to map peptide antigens. Many HIV peptides were mapped in all three individuals. However, there were several challenges and limitations associated with the deconvolution process. Peptides that induced low-frequency responses or were masked by peptide competition within a given pool were not identified, because they did not meet the threshold criteria for a positive response. Also, amino acid sequence variation limited the ability of this method to map autologous HIV peptides. Alternative analysis strategies and revisions to the original matrix optimizations are presented that address ways to increase peptide identification. This optimized deconvolution method allows for efficient mapping of T-cell peptide epitopes. It is rapid, powerful, efficient, and unrestricted by HLA type. Published 2008 Wiley-Liss, Inc.(dagger) C1 [Precopio, Melissa L.; Butterfield, Tiffany R.; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Little, Susan J.; Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Little, Susan J.; Richman, Douglas D.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Little, Susan J.; Richman, Douglas D.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Precopio, ML (reprint author), Idera Pharmaceut Inc, 167 Sidney St, Cambridge, MA 02139 USA. EM mprecopio@iderapharma.com FU UCSD Center for AIDS Research (National Institutes of Health) [AI 043638, AI 047745] FX Grant sponsor: UCSD Center for AIDS Research (National Institutes of Health); Grant numbers: AI 043638, AI 047745. NR 19 TC 16 Z9 16 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2008 VL 73A IS 11 BP 1071 EP 1078 DI 10.1002/cyto.a.20646 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368LJ UT WOS:000260622300013 PM 18781655 ER PT J AU Walker, JL Menko, AS Khalil, S Rebustini, I Hofftnan, MP Kreidberg, JA Kukuruzinska, MA AF Walker, Janice L. Menko, A. Sue Khalil, Sheede Rebustini, Ivan Hofftnan, Matthew P. Kreidberg, Jordan A. Kukuruzinska, Maria A. TI Diverse Roles of E-Cadherin in the Morphogenesis of the Submandibular Gland: Insights Into the Formation of Acinar and Ductal Structures SO DEVELOPMENTAL DYNAMICS LA English DT Article DE E-cadberin; submandibular gland; branching morphogenesis; acinar precursors; presumptive ducts; cytodifferentiation; catenins; adherens junctions ID CELL-ADHESION MOLECULES; BRANCHING MORPHOGENESIS; SALIVARY-GLAND; ALPHA-6 INTEGRIN; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; MOUSE; EXPRESSION; JUNCTIONS; CYTOSKELETON AB The formation of acinar and ductal structures during epithelial tissue branching morphogenesis is not well understood. We report that in the mouse submandibular gland (SMG), acinar and ductal cell fates are determined early in embryonic morphogenesis with E-cadherin playing pivotal roles in development. We identified two morphologically distinct cell populations at the single bud stage, destined for different functions. The outer layer of columnar cells with organized E-cadherin junctions expressed the neonatal acinar marker B1 by E13.5, demonstrating their acinar fate. The interior cells initially lacked distinct E-cadherin junctions, but with morphogenesis formed cytokeratin 7 (K7)-positive ductal structures with organized E-cadherin junctions and F-actin filaments. Inhibition of E-cadherin function with either siRNA or function blocking antibody caused extensive apoptosis of ductal cells and aberrantly dilated lumens, providing the first evidence that E-cadherin regulates ductal lumen formation during branching morphogenesis of the salivary gland. Developmental Dynamics 237.3128-3141, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Kukuruzinska, Maria A.] Boston Univ, Med Ctr, Dept Mol & Cell Biol, Sch Dent Med, Boston, MA 02118 USA. [Walker, Janice L.; Menko, A. Sue] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Rebustini, Ivan; Hofftnan, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. [Kreidberg, Jordan A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Kukuruzinska, MA (reprint author), Boston Univ, Med Ctr, Dept Mol & Cell Biol, Sch Dent Med, 715 Albany St,E428, Boston, MA 02118 USA. EM mkukuruz@bu.edu FU NIH/NIDCR [DE14437, DE 10183, EY014798] FX We thank Wellington Cardoso for helpful discussions and Mihai Nita-Lazar, Donna Afshar, and Michele Leonard for a critical reading of the manuscript. The authors also thank Ni Zhai for her technical assistance with the confocal imaging. This work was supported by Grants DE14437 and DE 10183 from the NIH/NIDCR to M.A.K. and EY014798 to A.S.M. NR 51 TC 44 Z9 45 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2008 VL 237 IS 11 BP 3128 EP 3141 DI 10.1002/dvdy.21717 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 372VP UT WOS:000260930400004 PM 18816447 ER PT J AU Wingert, JR Burton, H Sinclair, RJ Brunstrom, JE Damiano, DL AF Wingert, Jason R. Burton, Harold Sinclair, Robert J. Brunstrom, Janice E. Damiano, Diane L. TI Tactile sensory abilities in cerebral palsy: deficits in roughness and object discrimination SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID 2-POINT DISCRIMINATION; SPASTIC HEMIPLEGIA; CHILDREN; HANDS; SENSIBILITY; RELIABILITY; RECOGNITION; PREVALENCE; DISORDERS; VALIDITY AB Motor deficits in cerebral palsy (CP) have been well documented; however, associated sensory impairment in CP remains poorly understood. We examined tactile object recognition in the hands using geometric shapes, common objects, and capital letters. Discrimination of tactile roughness was tested using paired horizontal gratings of varied groove widths passively translated across the index finger. We tested 17 individuals with hemiplegia (mean 13y 9mo [SD 5y 2mo]; 6 males, 11 females), 21 with diplegia (mean 14y 10mo [SD 7y]; 10 males, 11 females), and 21 without disabilities (mean 14y 10mo [SD 5y 1mo]; 11 males, 10 females). All participants with CP fell within level I or II of the Gross Motor Function Classification System and level I or II of the Manual Abilities Classification System. Individuals with CP were significantly less accurate compared with those without disabilities on all tactile object-recognition tasks using their non-dominant hand. Both groups of patients also had significantly higher thresholds for groove-width differences with both hands compared with those without disabilities. Within the group with diplegia, only roughness discrimination differed between hands, whereas within the group with hemiplegia, significant between-limb differences were present for all tasks. Despite mild motor deficits compared with the entire population of individuals with CP, this sample demonstrated ubiquitous tactile deficits. C1 [Wingert, Jason R.] Univ N Carolina, Dept Hlth & Wellness, Asheville, NC 28804 USA. [Burton, Harold; Sinclair, Robert J.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Burton, Harold] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Brunstrom, Janice E.] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA. [Damiano, Diane L.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Wingert, JR (reprint author), Univ N Carolina, Dept Hlth & Wellness, WHC CPO 2730,1 Univ Hts, Asheville, NC 28804 USA. EM jwingert@unca.edu RI Damiano, Diane/B-3338-2010; Wingert, Jason/B-1528-2012 OI Damiano, Diane/0000-0002-2770-5356; FU United Cerebral Palsy; Foundation for Physical Therapy PODS Scholarship; Ogle family; NIH [NS054413, NS31005] FX This study was supported by grants from United Cerebral Palsy, the Foundation for Physical Therapy PODS Scholarship, funds from the Ogle family, and NIH NS054413 and NS31005. NR 26 TC 30 Z9 30 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD NOV PY 2008 VL 50 IS 11 BP 832 EP 838 DI 10.1111/j.1469-8749.2008.03105.x PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 375MU UT WOS:000261118800010 PM 18811710 ER PT J AU Narusyte, J Neiderhiser, JM D'Onofrio, BM Reiss, D Spotts, EL Ganiban, J Lichtenstein, P AF Narusyte, Jurgita Neiderhiser, Jenae M. D'Onofrio, Brian M. Reiss, David Spotts, Erica L. Ganiban, Jody Lichtenstein, Paul TI Testing Different Types of Genotype-Environment Correlation: An Extended Children-of-Twins Model SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE children-of-twins model; parenting; child adjustment; genotype-environment correlation ID ADOLESCENT ANTISOCIAL-BEHAVIOR; EXPRESSED EMOTION; GENETIC INFLUENCE; FAMILY ENVIRONMENT; CHILDHOOD; PSYCHOPATHOLOGY; DEPRESSION; INTERPLAY; SYMPTOMS; TRANSMISSION AB This study presents an extended children-of-twins model, which allowed the authors to test the direction of the association between parenting and child adjustment. Three mechanisms were examined: direct phenotypic influence of parenting on child behavior (controlling for both parental and child genotype), passive genotype-environment correlation, and evocative genotype-environment correlation. This model was tested with Monte Carlo simulations. The authors generated data sets consisting of 1,000 twin parent pairs together with their children and 1,000 twin children pairs together with their parents. These simulated data sets were then used to estimate the model, and the procedure was repeated 1,000 times. The simulation results showed that this model recovered the true values of parameters with high precision. The model was also applied to an observed data set to analyze, as a first example, the association between maternal emotional overinvolvement and child internalizing problems. The results showed that this association was best explained by evocative genotype-environment correlation. C1 [Narusyte, Jurgita; Lichtenstein, Paul] Karolinska Inst, Dept Epidemiol & Biostat, Stockholm 17177, Sweden. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [D'Onofrio, Brian M.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA. [Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Spotts, Erica L.] NIA, NIH, Bethesda, MD 20892 USA. [Ganiban, Jody] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. RP Narusyte, J (reprint author), Karolinska Inst, Dept Epidemiol & Biostat, Box 281, Stockholm 17177, Sweden. EM jurgita.narusyte@ki.se OI lichtenstein, paul/0000-0003-3037-5287 FU NIMH NIH HHS [R01 MH054610-09, R01MH54610, R01 MH054610] NR 63 TC 46 Z9 47 U1 5 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 2008 VL 44 IS 6 BP 1591 EP 1603 DI 10.1037/a0013911 PG 13 WC Psychology, Developmental SC Psychology GA 372VO UT WOS:000260930300006 PM 18999324 ER PT J AU Gaulton, KJ Willer, CJ Li, Y Scott, LJ Conneely, KN Jackson, AU Duren, WL Chines, PS Narisu, N Bonnycastle, LL Luo, JC Tong, M Sprau, AG Pugh, EW Doheny, KF Valle, TT Abecasis, GR Tuomilehto, J Bergman, RN Collins, FS Boehnke, M Mohlkel, KL AF Gaulton, Kyle J. Willer, Cristen J. Li, Yun Scott, Laura J. Conneely, Karen N. Jackson, Anne U. Duren, William L. Chines, Peter S. Narisu, Narisu Bonnycastle, Lori L. Luo, Jingchun Tong, Maurine Sprau, Andrew G. Pugh, Elizabeth W. Doheny, Kimberly F. Valle, Timo T. Abecasis, Goncalo R. Tuomilehto, Jaakko Bergman, Richard N. Collins, Francis S. Boehnke, Michael Mohlkel, Karen L. TI Comprehensive Association Study of Type 2 Diabetes and Related Quantitative Traits With 222 Candidate Genes SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; COMMON VARIANTS; RISK LOCI; SUSCEPTIBILITY; CALPAIN-10; IDENTIFICATION; POPULATION; EXPRESSION; MELLITUS AB OBJECTIVE-Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes. RESEARCH DESIGN AND METHODS-In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs, providing 99.9% coverage of common HapMap variants in the 222 candidate genes. Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant, also from Finland. RESULTS-Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility. CONCLUSIONS-Our study provides an effective gene-based approach to association study design and analysis. One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis. Analysis of additional samples will be necessary to determine their effect on susceptibility. Diabetes 57:31363144,2008 C1 [Gaulton, Kyle J.; Mohlkel, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. [Willer, Cristen J.; Li, Yun; Scott, Laura J.; Conneely, Karen N.; Jackson, Anne U.; Duren, William L.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Willer, Cristen J.; Li, Yun; Scott, Laura J.; Conneely, Karen N.; Jackson, Anne U.; Duren, William L.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Chines, Peter S.; Narisu, Narisu; Bonnycastle, Lori L.; Tong, Maurine; Sprau, Andrew G.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Luo, Jingchun] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD USA. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Valle, Timo T.; Tuomilehto, Jaakko] Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, Helsinki, Finland. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland. RP Mohlkel, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA. EM mohlke@med.unc.edu RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825 FU National Institutes of Health (NIH) [DK072193, DK062370]; American Diabetes Association; National Center for Integrative Biomedical Informatics (NCIBI) at the University of Michigan [U54 DA021519]; CIDR NIH [N01-HG-65403]; GRCF SNP Center FX Support for this research was provided by National Institutes of Health (NIH) Grants DK072193 (to K.L.M.) and DK062370 (to M.B.), a postdoctoral fellowship award from the American Diabetes Association (to C.J.W.), and the National Center for Integrative Biomedical Informatics (NCIBI) at the University of Michigan (U54 DA021519). K.L.M. and G.R.A. are Pew Scholars in the Biomedical Sciences. Genome-wide genotyping was performed by the Johns Hopkins University Genetic Resources Core Facility (GRCF) SNP Center at the Center for Inherited Disease Research (CIDR), with support from CIDR NIH contract no. N01-HG-65403 and the GRCF SNP Center.; We thank the Finnish citizens who generously participated in this study, Michael Andre and Rachana Kshatriya of the University of North Carolina Mammalian Genotyping Core for Illumina GoldenGate genotyping, Amy Swift and Mario Morken of the NHGRI for stage 2 genotyping, and Kurt Hetrick, Michael Barnhart, Craig Bark, Janet Goldstein, and Lee Watkins of the CIDR for expert technical work on genome-wide Illumina Infinium genotyping. NR 46 TC 54 Z9 58 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 3136 EP 3144 DI 10.2337/db07-1731 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800035 PM 18678618 ER PT J AU Qi, L Kang, K Zhang, CL van Dam, RM Kraft, P Hunter, D Lee, CH Hu, FB AF Qi, Lu Kang, Kihwa Zhang, Cuilin van Dam, Rob M. Kraft, Peter Hunter, David Lee, Chih-Hao Hu, Frank B. TI Fat Mass- and Obesity-Associated (FTO) Gene Variant Is Associated With Obesity Longitudinal Analyses in Two Cohort Studies and Functional Test SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; PHYSICAL-ACTIVITY; EXTREME OBESITY; ADULT OBESITY; LIFE-STYLE; RISK; WOMEN; ADIPONECTIN AB OBJECTIVE-To examine the longitudinal association of fat, mass- and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. RESEARCH DESIGN AND METHODS-We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. RESULTS-We observed a trend toward decreasing associations between rs9939609 and BMI at older age ( >= 65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]- means, 1.82 +/- 0.04, 1.73 +/- 0.03, and 1.68 +/- 0.05 for TT, TA, and AA genotypes, respectively; P for trend 0.02) and leptin (log[e]- means, 3.56 +/- 0.04, 3.63 +/- 0.04, and 3.70 +/- 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was similar to 50% lower than in those from wild-type mice. CONCLUSIONS-The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice. Diabetes 57:3145-3151, 2008 C1 [Qi, Lu; van Dam, Rob M.; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Qi, Lu; van Dam, Rob M.; Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Med & Dent, Boston, MA 02115 USA. [Qi, Lu; van Dam, Rob M.; Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kang, Kihwa; Lee, Chih-Hao] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Zhang, Cuilin] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Kraft, Peter; Hunter, David; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU American Heart Association; Boston Obesity Nutrition Research Center [DK46200]; National Institutes of Health [DK-58845, CA-87969] FX L.Q. has received an American Heart Association Scientist Development Award and was supported by the Boston Obesity Nutrition Research Center (DK46200). C.-H.L. has received an American Heart Association Scientist Development Award. F.B.H. has received an American Heart Association Established Investigator Award. This work has been supported by National Institutes of Health Grants DK-58845 and CA-87969. NR 46 TC 89 Z9 93 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 3145 EP 3151 DI 10.2337/db08-0006 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800036 PM 18647953 ER PT J AU Ma, LJ Hanson, RL Que, LN Guo, Y Kobes, S Bogardus, C Baier, LJ AF Ma, Lijun Hanson, Robert L. Que, Lorem N. Guo, Yan Kobes, Sayuko Bogardus, Clifton Baier, Leslie J. TI PCLO Variants Are Nominally Associated With Early-Onset Type 2 Diabetes and Insulin Resistance in Pima Indians SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; GRANULE EXOCYTOSIS; CA2+ SENSOR; RISK LOCI; CAMP; REPLICATION; MELLITUS; CHANNEL; SIGNALS; ATP AB OBJECTIVE-A prior genome-wide association (GWA) study in Pima Indians identified variants within PCLO that were associated with early-onset type 2 diabetes. PCLO encodes a presynaptic cytomatrix protein that functions as a Ca2+ sensor that may be involved in insulin secretion and/or insulin action. Therefore, PCLO was analyzed as a candidate gene for type 2 diabetes. RESEARCH DESIGN AND METHODS-Sequencing of PCLO identified four nonsynonymous variants and a 10-amino acid insertion. These variants, together with 100 additional variants identified by sequencing or chosen from databases, were genotyped for association analysis in the same 895 subjects analyzed in the prior GWA study (300 case subjects with diabetes onset at aged <25 years, 334 nondiabetic control subjects aged >45 years, and 261 discordant siblings of the case or control subjects for within-family analyses), as well as 415 nondiabetic Pima Indians who had been metabolically phenotyped for predictors of diabetes. Selected variants were further genotyped in a population-based sample of 3,501 Pima Indians. RESULTS-Four variants were modestly associated With early-onset type 2 diabetes in both general and within-family analyses (P = 0.004-0.04, recessive model), where the diabetes risk allele was also nominally associated with a lower insulin-mediated glucose disposal rate (P = 0.009-0.14, recessive model) in nondiabetic Pima Indians. However, their association with diabetes in the population-based sample was weaker (P = 0.02-0.20, recessive model). CONCLUSIONS-Variation within PCLO may have a modest effect on early-onset type 2 diabetes, possibly as a result of reduced insulin action, but has minimal, if any, impact on population-based risk for type 2 diabetes. Diabetes 57:31563160,2008 C1 [Ma, Lijun; Hanson, Robert L.; Que, Lorem N.; Guo, Yan; Kobes, Sayuko; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA. RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept Hlth & Human Serv, Phoenix, AZ USA. EM lbaier@phx.niddk.nih.gov FU National Institute of Digestive and Kidney Diseases (NIDDK), National Institutes of Health; American Diabetes Association FX This study was supported by the intramural research program of National Institute of Digestive and Kidney Diseases (NIDDK), National Institutes of Health. L.M. and Y.G. are supported by a grant from the American Diabetes Association.; We thank Drs. Michael Traurig and Yunhua L. Muller for critical reading of the manuscript and the staff of the Phoenix Epidemiology and Clinical Research Branch of the NIDDK for contributions to this study. We also thank the investigators from WTCCC, DGI, and DIAGRAM for making their genotypic data publicly available; this is a tremendous resource that will benefit everyone in our goal to understand the genetics of complex diseases. NR 22 TC 7 Z9 7 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2008 VL 57 IS 11 BP 3156 EP 3160 DI 10.2337/db07-1800 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PR UT WOS:000260564800038 PM 18647954 ER PT J AU Pettitt, DJ Lawrence, JM Beyer, J Hillier, TA Liese, AD Mayer-Davis, B Loots, B Imperatore, G Liu, L Dolan, LM Linder, B Dabelea, D AF Pettitt, David J. Lawrence, Jean M. Beyer, Jennifer Hillier, Teresa A. Liese, Angela D. Mayer-Davis, Beth Loots, Beth Imperatore, Giuseppina Liu, Lenna Dolan, Lawrence M. Linder, Barbara Dabelea, Dana TI Association Between Maternal Diabetes in Utero and Age at Offspring's Diagnosis of Type 2 Diabetes SO DIABETES CARE LA English DT Article ID RISK-FACTORS; BIRTH-ORDER; FETAL HYPERINSULINISM; CHILDHOOD; MELLITUS; MOTHERS; OBESITY; ENVIRONMENT; YORKSHIRE; DELIVERY AB OBJECTIVE - The purpose of this study was to examine age of diabetes diagnosis in youth who have a parent with diabetes by diabetes type and whether the parent's diabetes was diagnosed before or after the youth's birth. RESEARCH DESIGN AND METHODS - The cohort comprised SEARCH for Diabetes in Youth Study participants (diabetes diagnosis 2001-2005) with a diabetic parent. SEARCH is a multicenter survey of youth with diabetes diagnosed before age 20 years. RESULTS - Youth with type 2 diabetes were more likely to have a parent with either type I or type 2 diabetes (mother 39.3%; father 21.2%) than youth with type 1 diabetes (5.3 and 6.7%, respectively, P < 0.001 for each). Type 2 diabetes was diagnosed 1.68 years earlier among those exposed to diabetes in utero (n = 174) than among those whose mothers' diabetes was diagnosed later (P = 0.018, controlled for maternal diagnosis age, paternal diabetes, sex, and race/ethnicity). Age at diagnosis of type 1 diabetes for 269 youth with and without in utero exposure did not differ significantly (difference 0.96 year, P = 0.403 after adjustment). Controlled for the father's age of diagnosis, father's diabetes before the child's birth was not associated with age at diagnosis (P = 0.078 for type 1 diabetes; P = 0.140 for type 2 diabetes). CONCLUSIONS - Type 2 diabetes was diagnosed at younger ages among those exposed to hyperglycemia in utero. Among youth with type I diabetes, the effect of the intrauterine exposure was not significant when controlled for mother's age of diagnosis. This study helps explain why other studies have found higher age-specific rates of type 2 diabetes among offspring of women with diabetes. C1 [Pettitt, David J.] Sansum Diabet Res Inst, Santa Barbara, CA USA. [Lawrence, Jean M.] Kaiser Permanente So Calif, Pasadena, CA USA. [Beyer, Jennifer] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Hillier, Teresa A.] Kaiser Permanente, Ctr Hlth Res NW Hawaii, Honolulu, HI USA. [Liese, Angela D.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Liese, Angela D.] Univ S Carolina, Arnold Sch Publ Hlth, Ctr Res Nutr & Hlth Dispar, Columbia, SC 29208 USA. [Mayer-Davis, Beth] Univ N Carolina, Chapel Hill, NC USA. [Loots, Beth] Seattle Childrens Hosp, Seattle, WA USA. [Loots, Beth] Reg Med Ctr, Seattle, WA USA. [Imperatore, Giuseppina] Ctr Dis Control & Prevent, Atlanta, GA USA. [Liu, Lenna] Univ Washington, Seattle, WA 98195 USA. [Dolan, Lawrence M.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA. [Dabelea, Dana] Univ Colorado, Denver, CO 80202 USA. RP Pettitt, DJ (reprint author), Sansum Diabet Res Inst, Santa Barbara, CA USA. EM dpettitt@sansum.org FU Centers for Disease Control and Prevention [PA 00097, DP-05-069]; National Institute of Diabetes and Digestive and Kidney Diseases; Kaiser Permanente Southern California [U01 DP000246]; University of Colorado Health Science Center [U01 DP000247]; Pacific Health Research Institute [U01 DP000245]; Children's Hospital Medical Center (Cincinnati) [U01 DP000248]; University of South Carolina [U01 DP000254]; University of Washington School of Medicine [U01 DP000244]; Wake Forest University School of Medicine [U01 DP000250] FX SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA 00097 and DP-05-069) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Center Contract Numbers are as follows: Kaiser Permanente Southern California (U01 DP000246), University of Colorado Health Science Center (U01 DP000247), Pacific Health Research Institute (U01 DP000245), Children's Hospital Medical Center (Cincinnati) (U01 DP000248), University of South Carolina (U01 DP000254), University of Washington School of Medicine (U01 DP000244), and Wake Forest University School of Medicine (U01 DP000250).; The SEARCH for Diabetes in Youth Study is indebted to the many youth and their families and their health care providers, whose participation made this study possible. NR 25 TC 44 Z9 45 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2008 VL 31 IS 11 BP 2126 EP 2130 DI 10.2337/dc08-0769 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367PT UT WOS:000260565000012 PM 18694977 ER PT J AU Nansel, TR Weisberg-Benchell, J Wysocki, T Laffel, L Anderson, B AF Nansel, T. R. Weisberg-Benchell, J. Wysocki, T. Laffel, L. Anderson, B. CA Steering Comm Family Management Di TI Quality of life in children with Type 1 diabetes: a comparison of general and diabetes-specific measures and support for a unitary diabetes quality-of-life construct SO DIABETIC MEDICINE LA English DT Article DE children; measurement; quality of life; Type 1 diabetes ID INSULIN PUMP THERAPY; METABOLIC-CONTROL; SELF-MANAGEMENT; ADOLESCENTS; PARENTS AB Aims To assess the factor structure of the Pediatric Quality of Life Inventory (PedsQL) Diabetes Module and to compare the PedsQL general and diabetes-specific quality of life (QOL) measures regarding psychometric properties and relations to relevant outcomes. Methods The instruments were completed by 447 children age 9 to 15.5 years with Type 1 diabetes > 1 year from four US paediatric diabetes clinics; parents completed the parallel parent-proxy measures. Principal components factor analysis was used to examine the factor structure of the PedsQL diabetes module. Analyses of the generic and diabetes QOL measures included psychometric properties, parent-child correlations and correlations with depression, adherence and glycated haemoglobin (HbA(1c)). Results The factor structure of the PedsQL diabetes module did not support the original five subscales. Both one- and two-factor models were supported; however, parallel parent and child subscales did not emerge. While the generic and diabetes-specific measures of QOL were moderately to highly correlated with each other, the constructs were differentially associated with relevant diabetes outcomes. Generic QOL was more highly associated with depression than diabetes QOL. Conversely, diabetes QOL was more highly associated with adherence and HbA(1c), although this was seen to a greater extent for parent-proxy report than for child report. Conclusions Factor analysis of the PedsQL diabetes module supports the use of a total diabetes QOL score. Findings regarding the associations of the generic and diabetes modules with diabetes outcomes underscore the unique contribution provided by both generic and diabetes QOL. C1 [Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, DESPR, NIH,DHHS, Bethesda, MD USA. [Weisberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Wysocki, T.] Nemours Childrens Hosp, Jacksonville, FL USA. [Laffel, L.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Anderson, B.] Baylor Coll Med, Houston, TX 77030 USA. RP Nansel, TR (reprint author), NICHD, DESPR, PRB, 6100 Execut Blvd,Rm 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS [Z01 HD008741-06]; NICHD NIH HHS [N01-HD-3-3360, N01-HD-4-3361, N01-HD-4-3364] NR 24 TC 32 Z9 33 U1 4 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2008 VL 25 IS 11 BP 1316 EP 1323 DI 10.1111/j.1464-5491.2008.02574.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 367BT UT WOS:000260528200009 PM 19046222 ER PT J AU Tsai, HT Wang, JT Chen, CJ Chang, SC AF Tsai, Hue-Ting Wang, Jann-Tay Chen, Chien-Jen Chang, Shan-Chwen TI Association between antibiotic usage and subsequent colonization or infection of extensive drug-resistant Acinetobacter baumannii: a matched case-control study in intensive care units SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Extensive drug-resistant Acinetobacter baumannii; Infection control; Antibiotic ID RISK-FACTORS; CARBAPENEM RESISTANCE; NOSOCOMIAL OUTBREAK; MOLECULAR EPIDEMIOLOGY; NEW-YORK; ACQUISITION; EMERGENCE; SPREAD; PREVALENCE; VANCOMYCIN AB Nosocomial spreading of extensive drug-resistant Acinetobacter baumannii (EDRAB) is an emerging problem. To clarify the association between prior antibiotic usage and subsequent EDRAB acquisition, we conducted a one-to-one matched case-control study among patients in all intensive care units (ICUs) at the National Taiwan University Hospital, Taipei, Taiwan, during a 1-year period. A total of 113 pairs of patients were identified. We measured prior antibiotics exposure in 4 perspectives: usage, overall treatment duration, accumulated dosage, and treatment potency. We found positive associations between EDRAB acquisition and prior usage of imipenem and meropenem across 4 measures, especially in usage and average treatment potency (usage, odds ratio [OR](imipenem) = 3.7 with 95% confidence interval [CI] = 1.2-11.0, ORmeropenem = 5.4 with 95% CI = 1.2-20.0; average treatment potency, [OR](imipenem) = 5.3 with 95% CI = 1.3-22.0, ORmeropenem = 3.4 with 95% CI = 1.0-12.0). Ceftazidime use with stronger treatment potency was also strongly associated with subsequent nosocomial EDRAB acquisition (OR = 5.5, 95% CI = 1.5-21.0). The OR of EDRAB acquisition greatly increased in patients who had previously been exposed to any 1 (OR = 5.5, 95% CI = 2.3-13.2) or to any 2 or 3 (OR = 11.1, 95% CI = 2.7-46.4) of the abovementioned antibiotics. Based on these findings, we conclude that usage of imipenem, meropenem, and/or ceftazidime is associated with subsequent acquisition of EDRAB in critically ill patients in ICUs. (C) 2008 Elsevier Inc. All rights reserved. C1 [Wang, Jann-Tay; Chang, Shan-Chwen] Natl Taiwan Univ Hosp, Dept Internal Med, Div Infect Dis, Taipei 100, Taiwan. [Tsai, Hue-Ting; Chen, Chien-Jen] Natl Taiwan Univ Hosp, Grad Inst Epidemiol, Coll Publ Hlth, Taipei 100, Taiwan. [Tsai, Hue-Ting] NCI, Div Canc Genet & Epidemiol, NIH, Rockville, MD 20852 USA. [Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Chang, Shan-Chwen] Natl Taiwan Univ Hosp, Coll Med, Grad Inst Clin Pharm, Taipei 100, Taiwan. RP Chang, SC (reprint author), Natl Taiwan Univ Hosp, Dept Internal Med, Div Infect Dis, Taipei 100, Taiwan. EM changsc@ntu.edu.tw RI Chen, Chien-Jen/C-6976-2008; OI CHANG, SHAN-CHWEN/0000-0001-6505-4139; WANG, JANN-TAY/0000-0002-0924-3469 NR 33 TC 27 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD NOV PY 2008 VL 62 IS 3 BP 298 EP 305 DI 10.1016/j.diagmicrobio.2008.06.017 PG 8 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 370BE UT WOS:000260736900009 PM 18707839 ER PT J AU Sharif, S Ramanathan, RK Potter, D Cieply, K Krasinskas, AM AF Sharif, Saima Ramanathan, Ramesh K. Potter, Douglas Cieply, Kathleen Krasinskas, Alyssa M. TI HER2 Gene Amplification and Chromosome 17 Copy Number Do Not Predict Survival of Patients with Resected Pancreatic Adenocarcinoma SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE HER2 gene; Pancreatic cancer; Fluorescence in situ hybridization; Gene amplification; Survival rate ID EPIDERMAL-GROWTH-FACTOR; IN-SITU HYBRIDIZATION; METASTATIC BREAST-CANCER; HER-2/NEU EXPRESSION; IMMUNOHISTOCHEMICAL EVALUATION; FACTOR RECEPTOR; SOLID TUMORS; OVEREXPRESSION; ONCOGENE; CHEMOTHERAPY AB HER2 gene amplification is an established predictive and prognostic marker in breast cancer. Since there are conflicting reports as to the significance of HER2 gene amplification in pancreatic cancer, we undertook this study. We studied HER2 gene amplification, HER2 copy numbers, and chromosome 17 copy numbers using fluorescence in situ hybridization in 63 cases of resected pancreatic cancer. Sixteen tumors (25%) had HER2 gene amplification, 7 (11%) had increased HER2 copy numbers, and 11 (17%) had increased chromosome 17 copy numbers. No statistical significance was found between the genetic parameters and tumor characteristics, stage, or survival. To the best of our knowledge, this is the largest case series reporting HER2 gene amplification status and its association with tumor characteristics and survival in pancreatic cancer in the literature. Although a significant percentage (25%) of pancreatic cancers demonstrate amplification of the HER2 gene, we find no association of HER2 gene amplification or chromosome 17 hyperploidy with poorer survival. C1 [Cieply, Kathleen; Krasinskas, Alyssa M.] Univ Pittsburgh, UPMC Presbyterian Hosp, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Sharif, Saima] Allegheny Canc Ctr, Pittsburgh, PA USA. [Sharif, Saima] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Ramanathan, Ramesh K.] Translat Genom Res Inst, Phoenix, AZ USA. [Potter, Douglas] Univ Pittsburgh, Biostat Facil, Inst Canc, Pittsburgh, PA 15213 USA. [Potter, Douglas] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. RP Krasinskas, AM (reprint author), Univ Pittsburgh, UPMC Presbyterian Hosp, Sch Med, Dept Pathol, A610,200 Lothrop St, Pittsburgh, PA 15213 USA. EM krasinskasam@upmc.edu NR 40 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2008 VL 53 IS 11 BP 3026 EP 3032 DI 10.1007/s10620-008-0267-1 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 363EG UT WOS:000260250000028 PM 18463983 ER PT J AU Gore, AV Lampugnani, MG Dye, L Dejana, E Weinstein, BM AF Gore, Aniket V. Lampugnani, Maria Grazia Dye, Louis Dejana, Elisabetta Weinstein, Brant M. TI Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke SO DISEASE MODELS & MECHANISMS LA English DT Article ID CEREBRAL CAVERNOUS MALFORMATIONS; TRUNCATING MUTATIONS; EXPRESSION ANALYSIS; ZEBRAFISH; KRIT1; RAP1; HETEROGENEITY; GTPASE; FORM; HAPLOINSUFFICIENCY AB Intracranial hemorrhage (ICH) is a particularly severe form of stroke whose etiology remains poorly understood, with a highly variable appearance and onset of the disease (Felbor et al., 2006; Frizzell, 2005; Lucas et al., 2003). In humans, mutations in any one of three CCM genes causes an autosomal dominant genetic ICH disorder characterized by cerebral cavernous malformations (CCM). Recent evidence highlighting multiple interactions between the three CCM gene products and other proteins regulating endothelial junctional integrity suggests that minor deficits in these other proteins could potentially predispose to, or help to initiate, CCM, and that combinations of otherwise silent genetic deficits in both the CCM and interacting proteins might explain some of the variability in penetrance and expressivity of human ICH disorders. Here, we test this idea by combined knockdown of CCM pathway genes in zebrafish. Reducing the function of rap1b, which encodes a Ras GTPase effector protein for CCM1/Krit1, disrupts endothelial junctions in vivo and in vitro, showing it is a crucial player in the CCM pathway. Importantly, a minor reduction of Rap1b in combination with similar reductions in the products of other CCM pathway genes results in a high incidence of ICH. These findings support the idea that minor polygenic deficits in the CCM pathway can strongly synergize to initiate ICH. C1 [Gore, Aniket V.; Weinstein, Brant M.] NICHHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA. [Lampugnani, Maria Grazia; Dejana, Elisabetta] IFOM FIRC Inst Mol Oncol Fdn, Lab Vasc Biol, I-20193 Milan, Italy. [Lampugnani, Maria Grazia] Mario Negri Inst Pharmacol Res, I-20156 Milan, Italy. [Dye, Louis] NICHHD, Microscopy & Imaging Ctr, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA. EM bw96w@nih.gov OI Lampugnani, Maria Grazia/0000-0002-4802-7064 FU intramural program of National Institute of Child Health and Human Development; Associazione Italiana per la Ricerca sul Cancro; European Community (EUSTROKE consortium); Leducq Fondation FX We thank Drs I. Dawid, E. Tournier-Lasserve and K. Sampath for comments on the manuscript. We thank members of the Weinstein Lab for technical assistance and critical suggestions. This work was supported by the intramural program of National Institute of Child Health and Human Development (B.M.W.), by the Associazione Italiana per la Ricerca sul Cancro and European Community (EUSTROKE consortium; M.G.L., E.D.), and by the Leducq Fondation (B.M.W., M.G.L., E.D.). Deposited in PMC for immediate release. NR 41 TC 52 Z9 53 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 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD NOV-DEC PY 2008 VL 1 IS 4-5 BP 275 EP 281 DI 10.1242/dmm.000513 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 474AK UT WOS:000268254400016 PM 19093037 ER PT J AU Kedar, PS Stefanick, DF Horton, JK Wilson, SH AF Kedar, Padmini S. Stefanick, Donna F. Horton, Julie K. Wilson, Samuel H. TI Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by PARP inhibition SO DNA REPAIR LA English DT Article DE ATR; PARP-1; PARP inhibitor; Methylation damage ID BASE-EXCISION-REPAIR; DNA-POLYMERASE-BETA; ADP-RIBOSE POLYMERASE; CELL-CYCLE ARREST; POLY(ADP-RIBOSE) POLYMERASE; MAMMALIAN-CELLS; DEFICIENT CELLS; STRAND BREAKS; S-PHASE; DAMAGE AB Inhibition of PARP activity results in extreme sensitization to MMS-induced cell killingin cultured mouse fibroblasts. In these MMS-treated cells, PARP inhibition is accompanied by an accumulation of S-phase cells that requires signaling by the checkpoint kinase ATR [J.K. Horton, D.F. Stefanick, J.M. Naron, P.S. Kedar, S.H. Wilson, Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest following DNA methylating agent exposure, J. Biol. Chem. 280 (2005) 15773-15785]. Here, we examined mouse fibroblast extracts for formation of a complex that may reflect association between the damage responsive proteins PARP-1 and ATR. Co-immunoprecipitation of PARP-1 and ATR was observed in extracts prepared from MMS-treated cells, but not under conditions of PARP inhibition. Further, our experiments demonstrated PAR-adduction of ATR in extracts from control and MMS-treated cells. An interaction between purified ATR and PARP-1 was similarly demonstrated, suggesting that the observed co-immunoprecipitation of ATR and PARP-1 from cell extracts may be due to a direct interaction between the two enzymes. In addition, purified recombinant ATR is a substrate for poly(ADP-ribosyl)ation by PARP-1, and poly(ADP-1-ribose) adduction of PARP-1 and ATR resulted in an increase in PARP-1 and ATR co-immunoprecipitation. (C) 2008 Published by Elsevier B.V. C1 [Kedar, Padmini S.; Stefanick, Donna F.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU NIH/NIEHS [HHSN273200700046U] FX We thank Dr. William A. Beard for help with figure preparation and Jennifer Myers for editorial assistance. We thank Dr. Michael J. Carrozza for critical reading of the manuscript. We also thank Dr. Robert Petrovich for assistance with expression of Flag-tagged human ATR in 293 cells. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Dr. Kedar's contribution was funded in whole with federal funds from NIH/NIEHS, under delivery order HHSN273200700046U to Constella/SRA, LLC. NR 37 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 1 PY 2008 VL 7 IS 11 BP 1787 EP 1798 DI 10.1016/j.dnarep.2008.07.006 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 373CQ UT WOS:000260949000003 PM 18691676 ER PT J AU Cisneros, GA Perera, L Garcia-Diaz, M Bebenek, K Kunkel, TA Pedersen, LG AF Cisneros, G. Andres Perera, Lalith Garcia-Diaz, Miguel Bebenek, Katarzyna Kunkel, Thomas A. Pedersen, Lee G. TI Catalytic mechanism of human DNA polymerase lambda with Mg2+ and Mn2+ from ab initio quantum mechanical/molecular mechanical studies SO DNA REPAIR LA English DT Article DE DNA polymerase lambda; QM/MM; Molecular dynamics; Simulations; Polymerase catalysis ID MINIMUM-ENERGY PATHS; CHEMICAL-REACTIONS; ACTIVE-SITE; NUCLEOTIDYL TRANSFER; ENZYME CATALYSIS; TRANSITION-STATE; PROTON-TRANSFER; BETA; REPAIR; FIDELITY AB DNA polymerases play a crucial role in the cell cycle due to their involvement in genome replication and repair. Understanding the reaction mechanism by which these polymerases carry out their function can provide insights into these processes, Recently, the crystal structures of human DNA polymerase lambda (Pol lambda) have been reported both for pre- and post-catalytic complexes [Garcia-Diaz et al., DNA Repair 3 (2007), 1333]. Here we employ the pre-catalytic complex as a starting structure for the determination of the catalytic mechanism of Pol lambda using ab initio quantum mechanical/molecular mechanical methods. The reaction path has been calculated using Mg2+ and Mn2+ as the catalytic metals. In both cases the reaction proceeds through a two-step mechanism where the 3'-OH of the primer sugar ring is deprotonated by one of the conserved Asp residues (D490) in the active site before the incorporation of the nucleotide to the nascent DNA chain. A significant charge transfer is observed between both metals and some residues in the active site as the reaction proceeds. The optimized reactant and product structures agree with the reported crystal structures. In addition, the calculated reaction barriers for both metals are close to experimentally estimated barriers. Energy decomposition analysis to explain individual residue contributions suggests that several amino acids surrounding the active site are important for catalysis. Some of these residues, including R420, R488 and E529, have been implicated in catalysis by previous mutagenesis experiments on the homologous residues on Pol beta. Furthermore, Pol lambda residues R420 and E529 found to be important from the energy decomposition analysis, are homologous to residues R183 and E295 in Pol beta, both of which are linked to cancer. In addition, residues R386, E391, K422 and K472 appear to have an important role in catalysis and could be a potential target for mutagenesis experiments. There is partial conservation of these residues across the Pol X family of DNA polymerases. Published by Elsevier B.V. C1 [Cisneros, G. Andres; Perera, Lalith; Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.; Pedersen, Lee G.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Cisneros, GA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM cisnero1@niehs.nih.gov; pereral2@niehs.nih.gov RI Cisneros, Gerardo/B-3128-2010; perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU NIH; NIEHS FX This research was supported by the intramural research program of the NIH and NIEHS. Computing time from the NIEHS and UNC computing facilities are gratefully acknowledged. GAC would like to thank Drs. S.K. Burger, Z. Lu and Prof. W. Yang at Duke University for the QSM code and Prof. Y Zhang at NYU for enlightening discussions. We would like to thank the reviewers as well as Drs. T Darden, B. Beard and G. Muller at NIEHS for critical reading of this manuscript. NR 72 TC 38 Z9 38 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD NOV 1 PY 2008 VL 7 IS 11 BP 1824 EP 1834 DI 10.1016/j.dnarep.2008.07.007 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 373CQ UT WOS:000260949000006 PM 18692600 ER PT J AU Yeung, EYH Sueyoshi, T Negishi, M Chang, TKH AF Yeung, Eugene Y. H. Sueyoshi, Tatsuya Negishi, Masahiko Chang, Thomas K. H. TI Identification of Ginkgo biloba as a Novel Activator of Pregnane X Receptor SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CONSTITUTIVE-ANDROSTANE RECEPTOR; CYP3A GENE-EXPRESSION; NUCLEAR RECEPTORS; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; LIPID-METABOLISM; MESSENGER-RNA; MOUSE-LIVER; EXTRACT; CAR AB Pregnane X receptor (PXR; NR1/2) is a ligand-activated transcription factor that plays a role not only in drug metabolism and transport but also in various other biological processes. Ginkgo biloba is a herbal medicine commonly used to manage memory impairment. Treatment of primary cultures of rat hepatocytes with G. biloba extract increases the mRNA expression of CYP3A23, which is a target gene for rat PXR. The present study was conducted to test the hypothesis that G. biloba extract activates PXR. Treatment of mouse PXR (mPXR) or human PXR (hPXR)-transfected HepG2 cells with G. biloba extract at 200 mu g/ml increased mPXR and hPXR activation by 3.2- and 9.5-fold, respectively. Dose-response analysis showed a log-linear increase in hPXR activation by the extract over the range of 200 to 800 mu g/ml. To determine whether G. biloba extract induces hPXR target gene expression, cultured LS180 human colon adenocarcinoma cells were treated for 72 h with the extract. G. biloba extract at 200, 400, and 800 mu g/ml increased CYP3A4 mRNA expression by 1.7-, 2.4-, and 2.5-fold, respectively. The same concentrations of the extract increased CYP3A5 (1.3-3.6-fold) and P-glycoprotein (ABCB) 1 (2.7-6.4-fold) mRNA expression. At concentrations (5 and 10 mu M) that did not down-regulate PXR gene expression and were not cytotoxic, L-sulforaphane (an hPXR antagonist) decreased CYP3A4, CYP3A5, and ABCB1 gene expression in cells treated with G. biloba extract. In summary, G. biloba extract activated mPXR and hPXR in a cell-based reporter gene assay and induced CYP3A4, CYP3A5, and ABCB1 gene expression in hPXR-expressing LS180 cells. C1 [Yeung, Eugene Y. H.; Chang, Thomas K. H.] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. [Sueyoshi, Tatsuya; Negishi, Masahiko] Natl Inst Environm Hlth Sci, NIH, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. RP Chang, TKH (reprint author), Univ British Columbia, Fac Pharmaceut Sci, 2146 E Mall, Vancouver, BC V6T 1Z3, Canada. EM tchang@interchange.ubc.ca FU Canadian Institutes of Health Research [MOP-84581]; Dawson Endowment Fund in Pharmaceutical Sciences; Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences; Izaak Walton Killam Faculty Research Fellowship; Michael Smith Foundation for Health Research FX This study was supported by the Canadian Institutes of Health Research (Grant MOP-84581 to T. K. H. C.), by the Dawson Endowment Fund in Pharmaceutical Sciences (a major equipment grant to T. K. H. C.), and by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences (to T. S., M.N.). E.Y.H.Y. received a Kam Li Ma Scholarship in Pharmaceutical Sciences from the University of British Columbia and a partial graduate student traineeship in drug metabolism from Merck Research Laboratories (United States). T. K. H. C. received an Izaak Walton Killam Faculty Research Fellowship and a Senior Scholar Award from the Michael Smith Foundation for Health Research. NR 40 TC 41 Z9 45 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2008 VL 36 IS 11 BP 2270 EP 2276 DI 10.1124/dmd.108.023499 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 361MP UT WOS:000260132100015 PM 18725505 ER PT J AU Le Duc, JW Anderson, K Bloom, ME Estep, JE Feldmann, H Geisbert, JB Geisbert, TW Hensley, L Holbrook, M Jahrling, PB Ksiazek, TG Korch, G Patterson, J Skvorak, JP Weingartl, H AF Le Duc, James W. Anderson, Kevin Bloom, Marshall E. Estep, James E. Feldmann, Heinz Geisbert, Joan B. Geisbert, Thomas W. Hensley, Lisa Holbrook, Michael Jahrling, Peter B. Ksiazek, Thomas G. Korch, George Patterson, Jean Skvorak, John P. Weingartl, Hana TI Framework for Leadership and Training of Biosafety Level 4 Laboratory Workers SO EMERGING INFECTIOUS DISEASES LA English DT Article AB Construction of several new Biosafety Level 4 (BSL-4) laboratories and expansion of existing operations have created an increased international demand for well-trained staff and facility leaders. Directors of most North American BSL-4 laboratories met and agreed upon a framework for leadership and training of biocontainment research and operations staff. They agreed on essential preparation and training that includes theoretical consideration of biocontainment principles, practical hands-on training, and mentored on-the-job experiences relevant to positional responsibilities as essential preparation before a person's independent access to a BSL-4 facility. They also agreed that the BSL-4 laboratory director is the key person most responsible for ensuring that staff members are appropriately prepared for BSL-4 operations. Although standardized certification of training does not formally exist, the directors agreed that facility-specific, time-limited documentation to recognize specific skills and experiences of trained persons is needed. C1 [Le Duc, James W.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston Natl Lab, Galveston, TX 77555 USA. [Anderson, Kevin; Estep, James E.] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD USA. [Bloom, Marshall E.] Natl Inst Hlth, Hamilton, MT USA. [Feldmann, Heinz] Publ Hlth Agcy Canada, Winnipeg, MB, Canada. [Geisbert, Joan B.; Geisbert, Thomas W.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Hensley, Lisa; Korch, George; Patterson, Jean] USA, Med Res Inst Infect Dis, Frederick, MD USA. [Jahrling, Peter B.] NIH, Bethesda, MD 20892 USA. [Ksiazek, Thomas G.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Patterson, Jean] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Weingartl, Hana] Canadian Food Inspect Agcy, Winnipeg, MB, Canada. RP Le Duc, JW (reprint author), Univ Texas Med Branch, Inst Human Infect & Immun, Galveston Natl Lab, 301 Univ Blvd, Galveston, TX 77555 USA. EM jwleduc@utmb.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [UC7-AI-070083]; National Institutes of Health; NIAID Division of Intramural Research FX This study was supported by grant UC7-AI-070083 from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, and by the NIAID Division of Intramural Research. NR 5 TC 10 Z9 10 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2008 VL 14 IS 11 BP 1685 EP 1688 DI 10.3201/eid1411.080741 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 368JI UT WOS:000260617000001 PM 18976549 ER PT J AU McCutchan, TF Piper, RC Malkler, MT AF McCutchan, Thomas F. Piper, Robert C. Malkler, Michael T. TI Use of Malaria Rapid Diagnostic Test to Identify Plasmodioum knowlesi Infection SO EMERGING INFECTIOUS DISEASES LA English DT Article AB Reports of human infection with Plasmodium knowlesi, a monkey malaria, suggest that it and other nonhuman malaria species may be an emerging health problem. We report the use of a rapid test to supplement microscopic analysis in distinguishing the 5 malaria species that infect humans. C1 [McCutchan, Thomas F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA. [Piper, Robert C.] Univ Iowa, Iowa City, IA USA. [Malkler, Michael T.] Flow Inc, Portland, OR USA. RP McCutchan, TF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20892 USA. EM tmccutchan@niaid.nih.gov FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. NR 15 TC 42 Z9 43 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2008 VL 14 IS 11 BP 1750 EP 1752 DI 10.3201/eid1411.080840 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 368JI UT WOS:000260617000013 PM 18976561 ER PT J AU Briese, T Palacios, G Lipkin, WI Renwick, N Venter, M Jarman, RG Dominguez, SR Holmes, KV Holmes, EC AF Briese, Thomas Palacios, Gustavo Lipkin, W. Ian Renwick, Neil Venter, Marietjie Jarman, Richard G. Dominguez, Samuel R. Holmes, Kathryn V. Holmes, Edward C. TI Prior Evidence of Putative Novel Rhinovirus Species, Australia Response SO EMERGING INFECTIOUS DISEASES LA English DT Letter ID GENOTYPE; ILLNESS C1 [Briese, Thomas; Palacios, Gustavo; Lipkin, W. Ian] Columbia Univ, New York, NY USA. [Renwick, Neil] Rockefeller Univ, New York, NY 10021 USA. [Venter, Marietjie] Univ Pretoria, ZA-0002 Pretoria, South Africa. [Jarman, Richard G.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. [Dominguez, Samuel R.; Holmes, Kathryn V.] Univ Colorado, Denver Sch Med, Aurora, CO USA. [Holmes, Edward C.] Penn State Univ, University Pk, PA 16802 USA. [Holmes, Edward C.] Fogarty Int Ctr, Bethesda, MD USA. RP Briese, T (reprint author), Columbia Univ Epidemiol, Mailman Sch Publ Hlth, Ctr Infect & Immun, 722 W 168th St, New York, NY 10032 USA. EM thomas.briese@columbia.edu RI Venter, Marietjie/H-3032-2011; Venter, Marietjie/P-9604-2016 OI Venter, Marietjie/0000-0003-2696-824X NR 5 TC 0 Z9 0 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2008 VL 14 IS 11 BP 1824 EP 1825 DI 10.3201/eid1411.081088 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 368JI UT WOS:000260617000040 ER PT J AU Wang, XD Matsuda, H Shi, YB AF Wang, Xuedong Matsuda, Hiroki Shi, Yun-Bo TI Developmental Regulation and Function of Thyroid Hormone Receptors and 9-cis Retinoic Acid Receptors during Xenopus tropicalis Metamorphosis SO ENDOCRINOLOGY LA English DT Article ID AMPHIBIAN METAMORPHOSIS; LAEVIS METAMORPHOSIS; GENE-EXPRESSION; IN-VIVO; POSTEMBRYONIC DEVELOPMENT; COREPRESSOR COMPLEX; FROG METAMORPHOSIS; MOLECULAR-BASIS; TADPOLE TAIL; BETA GENE AB Amphibian metamorphosis serves as an excellent model to study T-3 function during postembryonic development in vertebrate due to its total dependence on T-3. Earlier molecular studies in the model species Xenopus laevis have led to a number of important in vivo findings on the function and mechanisms of T-3 receptor (TR) action during vertebrate development. However, the lack of genomic sequence information, its tetraploid genome, and lengthy developmental cycle hinder further analyses on TR functions. In this regard, the highly related species, Xenopus tropicalis, is much more advantageous. Toward developing X. tropicalis for genome-wide and genetic studies of TR function, we analyzed the expression profiles of TRs and their heterodimerization partners, retinoid X receptors (RXRs) or 9-cis retinoic acid receptors. We show that their expression correlates with transformations in different organs and that TR/RXR heterodimers are capable of repressing and activating gene expression in vivo in the absence and presence of T-3, respectively. We further demonstrate that TRs are bound to endogenous target genes in X. tropicalis tadpoles. Our results thus support a role of TRs in mediating the metamorphic effects of T-3 in X. tropicalis. More importantly, the similarities in the expression and function between X. tropicalis and X. laevis TRs and RXRs as demonstrated by our study also pave the way to take advantages of existing morphological, molecular, and cellular knowledge of X. laevis development and the genetic and sequence superiority of X. tropicalis to dissect the molecular pathways governing tissue/organ-specific transformations during vertebrate postembryonic development. (Endocrinology 149: 5610-5618, 2008) C1 [Wang, Xuedong; Matsuda, Hiroki; Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bldg 18 T,Room 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU National Institute of Child Health and Human Development; National Institutes of Health FX This work was supported by the Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health. NR 47 TC 36 Z9 36 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2008 VL 149 IS 11 BP 5610 EP 5618 DI 10.1210/en.2008-0751 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 362JM UT WOS:000260194000032 PM 18635662 ER PT J AU Huff, J Jacobson, MF Davis, DL AF Huff, James Jacobson, Michael F. Davis, Devra Lee TI The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE animal cancer tests; aspartame; bioassay designs; bisphenol A; cadmium; carcinogenicity; chemical carcinogens; genistein; toluene; toxicology ID NATIONAL TOXICOLOGY PROGRAM; SPRAGUE-DAWLEY RATS; BISPHENOL-A; RAMAZZINI-FOUNDATION; BREAST-CANCER; ASPARTAME; DIETHYLSTILBESTROL; ADENOCARCINOMA; CADMIUM; RISK AB BACKGROUND: Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. OBJECTIVES: In this Commentary,, we propose that the sensitivity of chemical carcinogenesis bioassays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at tip to about 3 years. DISCUSSION: Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. CONCLUSIONS: Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity, with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives. C1 [Jacobson, Michael F.] Ctr Sci Publ Interest, Washington, DC 20009 USA. [Huff, James] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Davis, Devra Lee] Univ Pittsburgh, Pittsburgh Canc Inst, Dept Epidemiol, Grad Sch Publ Hlth,Ctr Environm Oncol, Pittsburgh, PA USA. RP Jacobson, MF (reprint author), Ctr Sci Publ Interest, 1875 Connecticut Ave,Suite 300, Washington, DC 20009 USA. EM mjacobson@cspinet.org NR 52 TC 26 Z9 26 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1439 EP 1442 DI 10.1289/ehp.10716 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500014 PM 19057693 ER PT J AU Kan, HD Heiss, G Rose, KM Whitsel, EA Lurmann, F London, SJ AF Kan, Haidong Heiss, Gerardo Rose, Kathryn M. Whitsel, Eric A. Lurmann, Fred London, Stephanie J. TI Prospective Analysis of Traffic Exposure as a Risk Factor for Incident Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; coronary disease; traffic ID PARTICULATE AIR-POLLUTION; LONG-TERM EXPOSURE; ACUTE MYOCARDIAL-INFARCTION; ULTRAFINE PARTICLES; MAJOR HIGHWAY; MORTALITY; ASSOCIATION; HYPERTENSION; POLLUTANTS; COHORT AB BACKGROUND: For people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHID). OBJECTIVES: In this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHID in a population-based prospective cohort study. METHODS: We studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study I without previous CHD at enrollment, front 1987 to 1989 in four U.S. communities. Geographic information system-mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors. RESULTS: Over an average of 13 years of follow-tip, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06-1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one Unit increase of log-transformed density was 1.03 (95% CI, 1.01-1-05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95-1-32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity. low-density lipoprotein cholesterol level, hypertension, age, or education. CONCLUSION Higher long-term exposure to traffic is associated with incidence of CHID, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons. C1 [Kan, Haidong; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Kan, Haidong] Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Shanghai 200433, Peoples R China. [Heiss, Gerardo; Rose, Kathryn M.; Whitsel, Eric A.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Whitsel, Eric A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Lurmann, Fred] Sonoma Technol Inc, Petaluma, CA USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; National Institute of Environmental Health Sciences [Z01 ES043012] FX The Atherosclerosis Risk in Communities study is a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. This work was also supported by Z01 ES043012 from the Intramural Research Program, National Institute of Environmental Health Sciences. NR 42 TC 53 Z9 57 U1 0 U2 17 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1463 EP 1468 DI 10.1289/ehp.11290 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500018 PM 19057697 ER PT J AU van Bemmel, DM Visvanathan, K Freeman, LEB Coble, J Hoppin, JA Alavanja, MCR AF van Bemmel, Dana M. Visvanathan, Kala Freeman, Laura E. Beane Coble, Joseph Hoppin, Jane A. Alavanja, Michael C. R. TI S-Ethyl-N,N-dipropylthiocarbamate Exposure and Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study: A Prospective Cohort SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; cancer; EPTC; herbicide; neoplasms; occupational exposure; pesticides; thiocarbamates ID NON-HODGKINS-LYMPHOMA; NICOTINIC ACETYLCHOLINE-RECEPTORS; ALACHLOR MANUFACTURING WORKERS; THIOCARBAMATE HERBICIDES; CARBAMATE PESTICIDES; RISK-FACTORS; VICIA-FABA; FARMERS; EPTC; IOWA AB BACKGROUND: The Agricultural Health Study, (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled between 1993 and 1997. EPTC (S-ethyl-N,N-dipropylthiocarbamate) is a thiocarbamate herbicide used in ever), region of the United States. The U.S. Environmental Protection Agency reports that EPTC is most likely not a human carcinogen; however, the previous epidemiologic data on EPTC exposure and cancer risk were limited. OBJECTIVES: The purpose of this study was to examine cancer incidence and EPTC use in 48,378 male pesticide applicators enrolled in he AHS. METHODS: We estimated the rate ratio (RR) and 95% confidence intervals (CIs) for all cancers and selected cancer sites using Poisson regression. We assessed EPTC exposure using two quantitative metrics: lifetime exposure day's and intensity-weighted lifetime exposure days, a measure that accounts for application factors that modify personal exposure likelihood. RESULTS: Among the 9,878 applicators exposed to EPTC, 470 incident cancer cases were diagnosed during the follow-up period ending December 2004 compared with the 1,824 cases among individuals reporting no use. Although EPTC was associated with colon cancer in the highest tertile of both lifetime exposure days and intensity-weighted lifetime days (RR = 2.09; 95% Cl, 1.26-3.47 and RR = 2.05; 95% CI, 1.34-3.14, respectively) and the trend test was < 0.01 for both, the pattern of RR was not monotonic with increasing use. There was a suggestion of an association with leukemia. No other associations were observed. CONCLUSION: In this analysis, EPTC use appeared to be associated with colon cancer and leukemia. However, given the relatively small number of cases in the highest exposure tertile, results should be interpreted with caution, and further investigations are needed. C1 [van Bemmel, Dana M.; Freeman, Laura E. Beane; Coble, Joseph; Alavanja, Michael C. R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Visvanathan, Kala] Johns Hopkins Med Inst, Dept Epidemiol & Oncol, Baltimore, MD 21205 USA. [Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA. EM alavanjm@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU National Cancer Institute; Cancer Prevention Fellowship Program; NIH; National Cancer Institute Division of Cancer Epidemiol and Genetics; National Institute of Environmental Health Sciences FX D.v. B is supported by the National Cancer Institute, Cancer Prevention Fellowship Program. This research was supported by the Intramural Research Program of the NIH (National Cancer Institute Division of Cancer Epidemiol and Genetics and the National Institute of Environmental Health Sciences). NR 43 TC 19 Z9 22 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1541 EP 1546 DI 10.1289/ehp.11371 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500029 PM 19057708 ER PT J AU Rusiecki, JA Baccarelli, A Bollati, V Tarantini, L Moore, LE Bonefeld-Jorgensen, EC AF Rusiecki, Jennifer A. Baccarelli, Andrea Bollati, Valentina Tarantini, Letizia Moore, Lee E. Bonefeld-Jorgensen, Eva C. TI Global DNA Hypomethylation Is Associated with High Serum-Persistent Organic Pollutants in Greenlandic Inuit SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE DNA methylation; global methylation; Greenland; hypomethylation; Inuit; organochlorines; PCBs; persistent organic pollutants; pesticides; polychlorinated biphenyls; PoPs; serum ID ENDOCRINE-DISRUPTING CHEMICALS; NON-HODGKIN-LYMPHOMA; ORGANOCHLORINE LEVELS; PANCREATIC-CANCER; ADIPOSE-TISSUE; POLYCHLORINATED-BIPHENYLS; LIFE-STYLE; METHYLATION; DDT; NEUROTOXICITY AB BACKGROUND: Persistent organic pollutants (POPS) may influence epigenetic mechanisms; therefore, they, could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide. OBJECTIVE: Our aim in this study was to evaluate the relationship between plasma POPS concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPS. METHODS: We used pyrosequencing to estimate global DNA methylation via Alu and LINEA assays of bisulfite- treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses. RESULTS: We found inverse correlations between percents methylcytosine and many of the 13011 concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically, significant inverse linear relationships mainly, for the Alu assay for p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; beta = -0.26), p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; beta = -0.38), beta-hexachlorocyclohexane (beta = -0.48), oxychlordane (beta = -0.32), alpha-chlordane beta = -0.75), mirex (beta = -0.27), SLIM of polychlorinated biphenyls (beta = -0.56), and sum of all POPS beta = -0.48). Linear regressions for the LINE-1 assay showed beta estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant. CONCLUSIONS: This is the first study to investigate environmental exposure to POPS and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPS and merit further investigation. C1 [Rusiecki, Jennifer A.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Baccarelli, Andrea; Bollati, Valentina; Tarantini, Letizia] Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. [Baccarelli, Andrea; Bollati, Valentina; Tarantini, Letizia] Maggiore Hosp, IRCCS, Ctr Mol & Genet Epidemiol, Milan, Italy. [Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Health & Human Serv, Bethesda, MD 20892 USA. [Bonefeld-Jorgensen, Eva C.] Univ Aarhus, Unit Cellular & Mol Toxicol, Ctr Arctic Environm Med, Inst Publ Hlth, Aarhus, Denmark. RP Rusiecki, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, PMB Room A1039,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM jrusiecki@usuhs.mil RI Bonefeld-Jorgensen, Eva Cecilie/A-1682-2015; OI Baccarelli, Andrea/0000-0002-3436-0640; Bollati, Valentina/0000-0002-0370-9598 FU Uniformed Services University intramural start-up [RO87YT] FX This research was supported by a Uniformed Services University intramural start-up grant, RO87YT. NR 51 TC 157 Z9 160 U1 3 U2 31 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1547 EP 1552 DI 10.1289/ehp.11338 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500030 PM 19057709 ER PT J AU Kuniholm, MH Lesi, OA Mendy, M Akano, AO Sam, O Hall, AJ Whittle, H Bah, E Goederts, JJ Hainaut, P Kirk, GD AF Kuniholm, Mark H. Lesi, Olufunmilayo A. Mendy, Maimuna Akano, Aliu O. Sam, Omar Hall, Andrew J. Whittle, Hilton Bah, Ebrima Goederts, James J. Hainaut, Pierre Kirk, Gregory D. TI Aflatoxin Exposure and Viral Hepatitis in the Etiology of Liver Cirrhosis in The Gambia, West Africa SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aflatoxin; Africa; hepatitis B virus; liver cirrhosis; p53; The Gambia; ultrasound ID HEPATOCELLULAR-CARCINOMA PATIENTS; B-VIRUS-INFECTION; C VIRUS; P53 MUTATIONS; PLASMA DNA; DEVELOPING-COUNTRIES; ALCOHOL INTAKE; TP53 MUTATION; RISK-FACTORS; CANCER AB BACKGROUND: Cirrhosis of the liver is thought to be a major cause of morbidity and mortality in sub-Saharan Africa, but few controlled studies on the etiology of cirrhosis have been conducted in this region. OBJECTIVES: We aimed to elucidate the association between environmental and infectious exposures and cirrhosis in The Gambia. METHODS: Ninety-seven individuals were diagnosed with cirrhosis using a validated ultrasound scoring system and were compared with 397 controls. Participants reported demographic and food frequency information. Blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis C virus (HCV) antibody, HCV RNA, and the aflatoxin-associated 249(ser) TP53 mutation. RESULTS: HBsAg seropositivity was associated with a significant increase in risk of cirrhosis [odds ratio (OR) = 8.0; 95% confidence interval (Cl), 4.4-14.7] as was the presence of HBeAg (OR = 10.3; 95% CI, 2.0-53.9) and HCV infection (OR = 3.3; 95% CI, 1.2-9.5). We present novel data that exposure to aflatoxin, as assessed both by high lifetime groundnut (peanut) intake and by the presence of the 249(ser) TP53 mutation in plasma, is associated with a significant increase in the risk for cirrhosis (OR = 2.8; 95% CI, 1.1-7.7 and OR = 3.8; 95% CI, 1.5-9.6, respectively). Additionally, aflatoxin and hepatitis B virus exposure appeared to interact synergistically to substantially increase the risk of cirrhosis, although this was not statistically significant. CONCLUSIONS: Our results suggest that the spectrum of morbidity associated with aflatoxin exposure could include cirrhosis. C1 [Kuniholm, Mark H.; Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Program Infect Dis, Baltimore, MD USA. [Lesi, Olufunmilayo A.; Bah, Ebrima] Gambia Hepatitis Intervent Study, Int Agcy Res Canc, Banjul, Gambia. [Lesi, Olufunmilayo A.] Univ Lagos, Teaching Hosp, Dept Med, Lagos, Nigeria. [Mendy, Maimuna; Whittle, Hilton] MRC Labs, Banjul, Gambia. [Akano, Aliu O.; Sam, Omar] Royal Victoria Teaching Hosp, Dept Med Serv, Banjul, Gambia. [Akano, Aliu O.] Natl Hosp, Dept Radiodiag, Abuja, Nigeria. [Hall, Andrew J.] London Sch Hyg & Trop Med, London WC1, England. [Goederts, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Hainaut, Pierre] Gambia Hepatitis Intervent Study, Int Agcy Res Canc, Lyon, France. RP Kirk, GD (reprint author), 615 N Wolfe St,E-6533, Baltimore, MD 21205 USA. EM gkirk@jhsph.edu RI Kirk, Gregory/A-8484-2009; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU National Cancer Institute; National Institutes of Health [N02-CP40521] FX This work was supported by the National Cancer Institute, National Institutes of Health, contract N02-CP40521. NR 49 TC 25 Z9 25 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1553 EP 1557 DI 10.1289/ehp.11661 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500031 PM 19057710 ER PT J AU Woodruff, TJ Zeise, L Axelrad, DA Guyton, KZ Janssen, S Miller, M Miller, GG Schwartz, JM Alexeeff, G Anderson, H Birnbaum, L Bois, F Cogliano, VJ Crofton, K Euling, SY Foster, PMD Germolec, DR Gray, E Hattis, DB Kyle, AD Luebke, RW Luster, MI Portier, C Rice, DC Solomon, G Vandenberg, J Zoeller, RT AF Woodruff, Tracey J. Zeise, Lauren Axelrad, Daniel A. Guyton, Kathryn Z. Janssen, Sarah Miller, Mark Miller, Gregory G. Schwartz, Jackie M. Alexeeff, George Anderson, Henry Birnbaum, Linda Bois, Frederic Cogliano, Vincent James Crofton, Kevin Euling, Susan Y. Foster, Paul M. D. Germolec, Dori R. Gray, Earl Hattis, Dale B. Kyle, Amy D. Luebke, Robert W. Luster, Michael I. Portier, Chris Rice, Deborah C. Solomon, Gina Vandenberg, John Zoeller, R. Thomas TI Meeting Report: Moving Upstream-Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE adverse health effects; androgen antagonists; hazard identification; immunotoxicants; risk assessment; science policy; thyroid hormone; toxicologic assessments ID N-BUTYL PHTHALATE; CONGENITAL HYPOTHYROIDISM; POLYCHLORINATED-BIPHENYLS; GENE-EXPRESSION; NATIONAL-HEALTH; DISRUPTING CHEMICALS; REFERENCE RANGE; IMMUNE STATUS; EXPOSURE; POPULATION AB BACKGROUND: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links, between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment. OBJECTIVES: Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (Upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available. DISCUSSION: Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may, be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects. CONCLUSIONS: For certain classes of early perturbations, Sufficient information oil the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will Support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population. C1 [Woodruff, Tracey J.; Schwartz, Jackie M.] Univ Calif San Francisco, Dept Obstet & Gynecol, Program Reprod Hlth & Environm, San Francisco, CA 94143 USA. [Zeise, Lauren; Miller, Mark] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA. [Axelrad, Daniel A.; Miller, Gregory G.] US EPA, Off Policy Econ & Innovat, Washington, DC 20460 USA. [Guyton, Kathryn Z.; Euling, Susan Y.; Vandenberg, John] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Janssen, Sarah; Solomon, Gina] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Janssen, Sarah] Natl Resource Defense Council, San Francisco, CA USA. [Miller, Mark] Univ San Francisco, Pediat Environm Hlth Specialty Unit, San Francisco, CA 94117 USA. [Anderson, Henry] Wisconsin Div Publ Hlth, Madison, WI USA. [Birnbaum, Linda; Crofton, Kevin; Gray, Earl; Luebke, Robert W.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Bois, Frederic] Natl Inst Environm Ind & Risques, Verneuil En Halatte, France. [Cogliano, Vincent James] Int Agcy Res Canc, F-69372 Lyon, France. [Foster, Paul M. D.; Germolec, Dori R.; Portier, Chris] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Hattis, Dale B.] Clark Univ, George Perkins Marsh Inst, Worcester, MA 01610 USA. [Kyle, Amy D.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Luster, Michael I.] NIOSH, Atlanta, GA USA. [Rice, Deborah C.] Maine Ctr Dis Control & Prevent, Environm & Occupat Hlth Program, Augusta, ME USA. [Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. RP Woodruff, TJ (reprint author), Univ Calif San Francisco, Suite 1100,1330 Broadway St, Oakland, CA 94612 USA. EM woodrufft@obgyn.ucsf.edu RI Portier, Christopher/A-3160-2010; Bois, Frederic/E-9241-2012; Crofton, Kevin/J-4798-2015; OI Portier, Christopher/0000-0002-0954-0279; Bois, Frederic/0000-0002-4154-0391; Crofton, Kevin/0000-0003-1749-9971; Vandenberg, John/0000-0003-2619-9460; Miller, Mark/0000-0002-9301-0093; gray jr, leon earl/0000-0002-1111-4754 FU California Environmental Protection Agency; Office of Environmental and Health Hazar Assessment [OEHHA-06-S3]; U. S. Environmental Protection Agency; Office of Policy, Economics, and Innovation; National Center for Environmental Economics; National Center for Environmental Assessment [EP07H001060]; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH); University of California, Berkeley; NIEHS Superfund Program at Berkeley; NIH [P42 ES04705]; University of California, San Francisco FX This work was supported by California Environmental Protection Agency, Office of Environmental and Health Hazar Assessment, contract OEHHA-06-S34; the U. S. Environmental Protection Agency, Office of Policy, Economics, and Innovation, National Center for Environmental Economics and National Center for Environmental Assessment, contract EP07H001060; the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH); University of California, Berkeley, NIEHS Superfund Program at Berkeley, NIH grant P42 ES04705; and University of California, San Francisco. NR 56 TC 31 Z9 31 U1 1 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP 1568 EP 1575 DI 10.1289/ehp.11516 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500034 PM 19057713 ER PT J AU Hrynkow, SH AF Hrynkow, Sharon H. TI Climate Change and Health Research: Time for Teamwork SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Hrynkow, SH (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. EM hrynkows@niehs.nih.gov NR 2 TC 4 Z9 4 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2008 VL 116 IS 11 BP A470 EP A470 DI 10.1289/ehp.11250 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 366ZG UT WOS:000260521500001 PM 19057678 ER PT J AU Mozzachio, AM Rusiecki, JA Hoppin, JA Mahajan, R Patel, R Beane-Freeman, L Alavanja, MCR AF Mozzachio, Alicia M. Rusiecki, Jennifer A. Hoppin, Jane A. Mahajan, Rajeev Patel, Rahulkumar Beane-Freeman, Laura Alavanja, Michael C. R. TI Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study SO ENVIRONMENTAL RESEARCH LA English DT Article DE Chlorothalonil; Pesticides; Fungicides; Cancer; Agriculture AB Background: Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Methods: Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure. Results: Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers-the only cancers for which we had sufficient numbers to explore associations. Conclusion: We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer. Published by Elsevier Inc. C1 [Mozzachio, Alicia M.; Rusiecki, Jennifer A.; Patel, Rahulkumar] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Hoppin, Jane A.] NIEHS, Dept Hlth & Human Serv, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Mahajan, Rajeev; Beane-Freeman, Laura; Alavanja, Michael C. R.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Rusiecki, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd,PMB A1039, Bethesda, MD 20814 USA. EM amozzachio@att.net; jrusiecki@usuhs.mil RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU National Institutes of Health; National Institute of Environmental Health Sciences; National Cancer Institute FX This work was supported by the intramural research program of the National Institutes of Health, National Institute of Environmental Health Sciences and National Cancer Institute.; IRB approvals: All participants provided verbal informed consent prior to participation in this study, and the protocol was approved by the institutional review boards of the National Cancer Institute, Batelle, the University of Iowa, and Westat. These approvals will be provided upon request. NR 12 TC 13 Z9 16 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2008 VL 108 IS 3 BP 400 EP 403 DI 10.1016/j.envres.2008.07.018 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 368YR UT WOS:000260660000019 PM 18801479 ER PT J AU Hoover, RN AF Hoover, Robert N. TI The Sound and the Fury Was It All Worth It? SO EPIDEMIOLOGY LA English DT Editorial Material ID ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL HORMONE-THERAPY; DISEASE; TRIAL; WOMEN AB The initial report of coronary heart disease (CHD) results from the trial of menopausal hormone therapy within the Women's Health Initiative precipitated substantial surprise and concern in the epidemiology research community over the apparent differences between the trial results and those of observational studies. What followed was 6 years of discussion and debate, frequently acrimonious, along with intense methodologic and substantive research attempting to reconcile or explain the apparent differences. The results have been an impressive improvement in methods to contrast and combine studies of differing designs, dramatic illustrations of some central epidemiologic principles, insights into likely mechanisms of CHD, and increasing clarity of the public health message about menopausal hormone therapy. C1 Natl Canc Inst, Epidemiol & Biostat Program, Div Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hoover, RN (reprint author), Natl Canc Inst, Epidemiol & Biostat Program, Div Epidemiol & Genet, 6120 Execut Blvd,EPS-8094, Bethesda, MD 20892 USA. EM hooverr@mail.nih.gov NR 17 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP 780 EP 782 DI 10.1097/EDE.0b013e318188e21d PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IP UT WOS:000260191700003 PM 18813016 ER PT J AU Jukic, AMZ Weinberg, CR Baird, DD Hornsby, PP Wilcox, AJ AF Jukic, Anne Marie Zaura Weinberg, Clarice R. Baird, Donna D. Hornsby, Paige P. Wilcox, Allen J. TI Measuring Menstrual Discomfort A Comparison of Interview and Diary Data SO EPIDEMIOLOGY LA English DT Article ID PREMENSTRUAL-SYNDROME; PROSTAGLANDIN F-2ALPHA; PRIMARY DYSMENORRHEA; CYCLE SYMPTOMS; PAIN; RECALL; MEMORY; WOMEN; DISTRESS; BELIEFS AB Background: Menstrual discomfort is common among women of reproductive age and can be debilitating. The accuracy of self-report of menstrual discomfort is unknown. Methods: At enrollment into the DES Reproductive Health Study in 1990, premenopausal women classified their frequency of any menstrual discomfort as "always," "often," "sometimes," and "never." Subsequently, women provided daily diary information for up to 6 months regarding any menstrual discomfort and medication used for menstrual pain. Results: A total of 324 women contributed data on 4 or more menstrual cycles in the prospective study. At enrollment, 10% had reported never having menstrual discomfort. Of these, 65% recorded at least I day of menstrual discomfort during follow-up. For the 27% who had reported always having discomfort, 88% recorded discomfort in all cycles. The enrollment statement of discomfort was more strongly correlated with the percentage of cycles in which women took medication for menstrual pain; respondents who said they never had menstrual discomfort reported use of pain medication in 3% of cycles; sometimes, 36%; often, 67%; and always, 92%. The average number of days per cycle with prospectively recorded menstrual discomfort was also correlated with the enrollment response. Conclusions: A single question regarding frequency of menstrual discomfort was positively correlated with prospectively recorded menstrual discomfort and especially with pain requiring medication. C1 [Jukic, Anne Marie Zaura; Baird, Donna D.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Jukic, AMZ (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,MD A3-05, Res Triangle Pk, NC 27709 USA. EM jukica@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 28 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP 846 EP 850 DI 10.1097/EDE.0b013e318187ac9e PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IP UT WOS:000260191700016 PM 18854711 ER PT J AU Adar, SD Klein, R Klein, B Cotch, M Wong, T O'Neill, MS Shrager, S Siscovick, D Daviglus, M Kaufrnan, J AF Adar, S. D. Klein, R. Klein, B. Cotch, M. Wong, T. O'Neill, M. S. Shrager, S. Siscovick, D. Daviglus, M. Kaufrnan, J. TI Long-Term Exposures to Air Pollution and Retinal Micro-Vascular Caliber: The Multi-Ethnic Study of Atherosclerosis (MESA) SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Adar, S. D.; Shrager, S.; Siscovick, D.; Kaufrnan, J.] Univ Washington, Seattle, WA 98195 USA. [Klein, R.] Univ Wisconsin, Madison, WI USA. [Cotch, M.] NEI, Bethesda, MD 20892 USA. [Wong, T.] Univ Melbourne, Melbourne, Vic, Australia. [Daviglus, M.] Northwestern Univ, Chicago, IL 60611 USA. RI Adar, Sara/L-2278-2016 OI Adar, Sara/0000-0001-8383-485X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S337 EP S338 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901405 ER PT J AU Alavanja, M AF Alavanja, M. TI Cancer Risk Associated with Pesticide Exposure in the Agricultural Health Study: Introduction and Recent Findings SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Alavanja, M.] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S79 EP S79 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900243 ER PT J AU Bell, EM Ward, MH Colt, JS Nioshioka, MG Gunier, RB Riggs, PD Buffer, PA Nuckols, JR AF Bell, E. M. Ward, M. H. Colt, J. S. Nioshioka, M. G. Gunier, R. B. Riggs, P. D. Buffer, P. A. Nuckols, J. R. TI Geographic-Based Prediction of Agricultural Pesticide Exposure and Concentrations in Windowsill Dust SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Bell, E. M.] SUNY Albany, Rensselaer, NY USA. [Ward, M. H.; Colt, J. S.] NCI, Rockville, MD USA. [Nioshioka, M. G.] Battelle Mem Inst, Columbus, OH 43201 USA. [Gunier, R. B.] No Calif Canc Ctr, Berkeley, CA USA. [Riggs, P. D.; Nuckols, J. R.] Colorado State Univ, Ft Collins, CO 80523 USA. [Buffer, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S345 EP S345 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901425 ER PT J AU De Roos, AJ Davis, S Colt, JS Blair, A Airola, M Severson, RK Cozen, W Cerhan, JR Hartge, P Nuckols, JR Ward, MH AF De Roos, A. J. Davis, S. Colt, J. S. Blair, A. Airola, M. Severson, R. K. Cozen, W. Cerhan, J. R. Hartge, P. Nuckols, J. R. Ward, M. H. TI Residential Proximity to Industrial Facilities and Risk of Non-Hodgkin Lymphoma SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [De Roos, A. J.; Davis, S.] Univ Washington, Seattle, WA 98195 USA. [Colt, J. S.; Blair, A.; Airola, M.; Hartge, P.; Ward, M. H.] NCI, Rockville, MD USA. [Severson, R. K.] Wayne State Univ, Detroit, MI USA. [Cozen, W.] Univ So Calif, Los Angeles, CA USA. [Cozen, W.] Mayo Clin, Coll Med, Rochester, MN USA. [Cozen, W.] Colorado State Univ, Ft Collins, CO 80523 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S181 EP S181 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900515 ER PT J AU Dellarco, M Viet, S AF Dellarco, M. Viet, S. TI Challenges and Strategies for Exposure Measurement in the National Children's Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Dellarco, M.] NICHD, Natl Childrens Study, Bethesda, MD USA. [Viet, S.] WESTAT Corp, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S47 EP S47 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900130 ER PT J AU Engel, LS Andersen, A Barr, DB Cantor, KP Chou, J Hayes, RB Lan, Q Langseth, H Needham, LL Wacholder, S Blair, A Rothman, N AF Engel, L. S. Andersen, A. Barr, D. B. Cantor, K. P. Chou, J. Hayes, R. B. Lan, Q. Langseth, H. Needham, L. L. Wacholder, S. Blair, A. Rothman, N. TI Serum Concentrations of Organochlorines and Risk of Melanoma: Results of a Prospective Analysis SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Engel, L. S.; Chou, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Andersen, A.; Langseth, H.] Canc Registry Norway, Oslo, Norway. [Barr, D. B.; Needham, L. L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Cantor, K. P.; Hayes, R. B.; Lan, Q.; Wacholder, S.; Blair, A.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S195 EP S196 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901031 ER PT J AU Fenton, SE Mendola, P Sjodin, A Patterson, DG Needham, LL Hines, EP AF Fenton, S. E. Mendola, P. Sjodin, A. Patterson, D. G. Needham, L. L. Hines, E. P. TI Brominated Flame Retardant Levels in Human Milk and Serum from MAMA Study Participants: Preliminary Findings from Correlations over Time and Matrix, and with Questionnaire Results SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Fenton, S. E.; Hines, E. P.] US EPA, Res Triangle Pk, NC USA. [Mendola, P.] NICHHD, CDC, Rockville, MD USA. [Sjodin, A.; Patterson, D. G.; Needham, L. L.] NCEH, DLS, CDC, Atlanta, GA USA. RI Needham, Larry/E-4930-2011; Sjodin, Andreas/F-2464-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S330 EP S330 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901385 ER PT J AU Fleischman, A AF Fleischman, A. TI Practical Considerations of Privacy and Confidentiality: The National Childrens Study As A Case Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Fleischman, A.] NIH, Natl Childrens Study, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S22 EP S23 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900043 ER PT J AU Gunier, RB Riggs, P Ward, MH Reynolds, P Rull, RP Hertz, A Colt, JS Metayer, C Nishioka, M Buffler, PA Nuckols, JR AF Gunier, R. B. Riggs, P. Ward, M. H. Reynolds, P. Rull, R. P. Hertz, A. Colt, J. S. Metayer, C. Nishioka, M. Buffler, P. A. Nuckols, J. R. TI Proximity to Agricultural Pesticide Use and Concentrations in Carpet Dust SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Gunier, R. B.; Reynolds, P.; Rull, R. P.; Hertz, A.] No Calif Canc Ctr, Berkeley, CA USA. [Riggs, P.; Nuckols, J. R.] Colorado State Univ, Ft Collins, CO 80523 USA. [Ward, M. H.; Colt, J. S.] Natl Canc Inst, Bethesda, MD USA. [Metayer, C.; Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Nishioka, M.] Battelle Mem Inst, Columbus, OH 43201 USA. RI Rull, Rudolph/B-8121-2013 OI Rull, Rudolph/0000-0003-0989-3629 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S269 EP S270 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901225 ER PT J AU Hoppin, JA AF Hoppin, J. A. TI AHS Exposure Assessment Strategies: Questionnaires, Intensity Metrics, and Validation Studies SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Hoppin, J. A.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S79 EP S80 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900244 ER PT J AU Kamel, F AF Kamel, F. TI Organophosphate Insecticides and Neurologic Dysfunction in the Agricultural Health Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Kamel, F.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900245 ER PT J AU Kan, H London, SJ Chen, G Zhang, Y Song, G Jiang, L Zhao, N Chen, B AF Kan, H. London, S. J. Chen, G. Zhang, Y. Song, G. Jiang, L. Zhao, N. Chen, B. TI Season, Gender, Age, and Education as Modifiers of the Effects of Outdoor Air Pollution on Daily Mortality in Shanghai, China: The Public Health and Air Pollution in Asia (PAPA) Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Kan, H.; Zhang, Y.; Zhao, N.; Chen, B.] Fudan Univ, Shanghai 200433, Peoples R China. [London, S. J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Chen, G.] Shanghai Environm Monitoring Ctr, Shanghai, Peoples R China. [Song, G.; Jiang, L.] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S92 EP S92 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900278 ER PT J AU Nuckols, JR Riggs, PD Gunier, RB Roll, RP Bell, EM Nishioka, M Hertz, A Reynolds, P Buffler, PA Ward, MH AF Nuckols, J. R. Riggs, P. D. Gunier, R. B. Roll, R. P. Bell, E. M. Nishioka, M. Hertz, A. Reynolds, P. Buffler, P. A. Ward, M. H. TI Geographic-Based Prediction of Agricultural Pesticides in Household Carpet Dust in the Central Valley of California SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Nuckols, J. R.; Riggs, P. D.] Colorado State Univ, Ft Collins, CO 80523 USA. [Gunier, R. B.; Roll, R. P.; Hertz, A.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA. [Bell, E. M.] SUNY Albany, Rensselaer, NY USA. [Nishioka, M.] Battelle Labs, Columbus, OH USA. [Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Ward, M. H.] NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S320 EP S320 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901360 ER PT J AU Nuckols, JR Beane-Freeman, L Baris, D Lubin, JH Ayotte, JDJ Schwenn, M Johnson, A Karagas, M Colt, J Silverman, DT Cantor, KP AF Nuckols, J. R. Beane-Freeman, L. Baris, D. Lubin, J. H. Ayotte, J. D. J. Schwenn, M. Johnson, A. Karagas, M. Colt, J. Silverman, D. T. Cantor, K. P. TI Arsenic Exposure Assessment in the New England Bladder Cancer Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Nuckols, J. R.; Beane-Freeman, L.; Baris, D.; Lubin, J. H.; Colt, J.; Silverman, D. T.; Cantor, K. P.] NCI, Bethesda, MD 20892 USA. [Ayotte, J. D. J.] US Geol Survey, Pembroke, NH USA. [Schwenn, M.] Maime Canc Registry, Augusta, GA USA. [Johnson, A.] Vermont Canc Registry, Burlington, VT USA. [Karagas, M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S23 EP S24 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900046 ER PT J AU Rull, RP Gunier, RB Reynolds, P Colt, JS Nishicka, M Metayer, C Buffer, PA Ward, MH AF Rull, R. P. Gunier, R. B. Reynolds, P. Colt, J. S. Nishicka, M. Metayer, C. Buffer, P. A. Ward, M. H. TI Residential Concentrations of Polycyclic Aromatic Hydrocarbons and Childhood Leukemia Risk SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Rull, R. P.; Gunier, R. B.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA. [Colt, J. S.; Ward, M. H.] NCI, Bethesda, MD 20892 USA. [Nishicka, M.] Battelle Mem Inst, Columbus, OH 43201 USA. [Metayer, C.; Buffer, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. RI Rull, Rudolph/B-8121-2013 OI Rull, Rudolph/0000-0003-0989-3629 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S275 EP S275 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901239 ER PT J AU Sandler, DP AF Sandler, D. P. TI Remote Data Collection Devices for Exposure Measurement in Large Scale Epidemiologic Studies SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Sandler, D. P.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S53 EP S53 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900148 ER PT J AU Stefaniak, AB Virji, M Day, G Schuler, C Tinkle, S AF Stefaniak, A. B. Virji, M. Day, G. Schuler, C. Tinkle, S. TI A Simple Biologically-Based Dynamic Model for Beryllium Sensitization SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Stefaniak, A. B.; Virji, M.; Day, G.; Schuler, C.] NIOSH, Morgantown, WV USA. [Tinkle, S.] NIEHS, Res Triangle Pk, NC 27709 USA. RI Stefaniak, Aleksandr/I-3616-2012 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S104 EP S104 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900310 ER PT J AU Von Ehrenstein, OS Hines, EP Kato, K Kuklenyik, Z Calafat, AM Fenton, SE AF Von Ehrenstein, O. S. Hines, E. P. Kato, K. Kuklenyik, Z. Calafat, A. M. Fenton, S. E. TI Perfluoroalkyl Acids in the Serum and Milk of Breastfeeding North Carolina Women SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Von Ehrenstein, O. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Hines, E. P.; Fenton, S. E.] US EPA, ORD, NHEERL, RTD, Res Triangle Pk, NC USA. [Kato, K.; Kuklenyik, Z.; Calafat, A. M.] CDC, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S338 EP S339 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901407 ER PT J AU von Ehrenstein, OS Sundaram, R Nansel, T Gabhainn, SN Lannotti, RJ AF von Ehrenstein, O. S. Sundaram, R. Nansel, T. Gabhainn, Nic S. Lannotti, R. J. TI Self-reported Child Hunger in Relation to Socioeconomic Status in the US and Across 36 Countries in the Health Behavior in School-Children Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [von Ehrenstein, O. S.; Sundaram, R.; Nansel, T.; Lannotti, R. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Gabhainn, Nic S.] Natl Univ Ireland, Dept Hlth Promot, Galway, Ireland. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S270 EP S271 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901228 ER PT J AU Ward, MH Colt, JS Metayer, C Gunier, RB Lubin, J Nishioka, MG Reynolds, P Buffler, PA AF Ward, M. H. Colt, J. S. Metayer, C. Gunier, R. B. Lubin, J. Nishioka, M. G. Reynolds, P. Buffler, P. A. TI Residential Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Childhood Leukemia SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Ward, M. H.; Colt, J. S.; Lubin, J.] NCI, Bethesda, MD 20892 USA. [Metayer, C.; Buffler, P. A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Gunier, R. B.; Reynolds, P.] No Calif Canc Ctr, Berkeley, CA USA. [Nishioka, M. G.] Battelle Mem Inst, Columbus, OH 43201 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S206 EP S206 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191901060 ER PT J AU Weyer, PJ Kantamneni, JR Lu, X Ward, MH Cerhan, JR AF Weyer, P. J. Kantamneni, J. R. Lu, X. Ward, M. H. Cerhan, J. R. TI Nitrate Ingestion from Drinking Water and Diet and Cancer Risk SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Weyer, P. J.; Kantamneni, J. R.; Lu, X.] Univ Iowa, Ctr Hlth Effects Environm Contaminat, Iowa City, IA USA. [Ward, M. H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cerhan, J. R.] Mayo Clin, Coll Med, Rochester, MN USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S55 EP S55 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900156 ER PT J AU Winseck, K AF Winseck, K. TI Community Outreach and Engagement for the National Children's Study SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Winseck, K.] NICHD, Natl Childrens Study, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S46 EP S47 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900129 ER PT J AU Theodore, WH Epstein, L Gaillard, WD Shinnar, S Wainwright, MS Jacobson, S AF Theodore, William H. Epstein, Leon Gaillard, William D. Shinnar, Shlomo Wainwright, Mark S. Jacobson, Steven TI Human herpes virus 6B: A possible role in epilepsy ? SO EPILEPSIA LA English DT Review DE Human herpes virus; Temporal lobe; Mesial temporal sclerosis; Febrile seizures; Epilepsy ID TEMPORAL-LOBE EPILEPSY; HUMAN HERPESVIRUS-6 INFECTION; CENTRAL-NERVOUS-SYSTEM; POLYMERASE-CHAIN-REACTION; INDUCED HYPERSENSITIVITY SYNDROME; BONE-MARROW-TRANSPLANTATION; MULTIPLE-SCLEROSIS PATIENTS; FEBRILE STATUS EPILEPTICUS; STEM-CELL TRANSPLANTATION; CYTOKINE UP-REGULATION AB Human herpes virus 6 (HHV6) infection is nearly ubiquitous in childhood and may include central nervous system invasion. There are two variants, HHV6A and HHV6B. Usually asymptomatic, it is associated with the common, self-limited childhood illness roseola infantum and rarely with more severe syndromes. In patients with immune compromise, subsequent reactivation of viral activity may lead to severe limbic encephalitis. HHV6 has been identified as a possible etiologic agent in multiple sclerosis, myocarditis, and encephalitis. A preponderance of evidence supports an association between HHV6 and febrile seizures. An ongoing multicenter study is investigating possible links between HHV6 infection, febrile status epilepticus, and development of mesial temporal sclerosis (MTS). Investigation of temporal lobectomy specimens showed evidence of active HHV6B but not HHV6A replication in hippocampal astrocytes in about two-thirds of patients with MTS but not other causes of epilepsy. It has been suggested that HHV6B may cause "excitotoxicity" by interfering with astrocyte excitatory amino acid transport. Although conventional inflammatory changes are not found in most MTS specimens, inflammatory modulators may play a role in neuronal injury leading to MTS as well. If the link between early viral infection, complex or prolonged febrile seizures, and later development of intractable temporal lobe epilepsy is confirmed, new therapeutic approaches to a common intractable epilepsy syndrome may be possible. C1 [Theodore, William H.; Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Epstein, Leon; Wainwright, Mark S.] Northwestern Univ, Feinberg Sch Med, Div Child Neurol, Chicago, IL 60611 USA. [Gaillard, William D.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Shinnar, Shlomo] Albert Einstein Coll Med, Dept Neurol, New York, NY USA. [Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov FU NINDS [NS 43209] FX This work was supported by the NINDS Division of Intramural Research (to W. D. G., S. J., and W. H. T.) and NINDS NS 43209 (to L. E. and S. S.). We thank Jenny Ahlqvist and the NINDS EM facility for Figure 2. NR 115 TC 57 Z9 58 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2008 VL 49 IS 11 BP 1828 EP 1837 DI 10.1111/j.1528-1167.2008.01699.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 370DZ UT WOS:000260744200002 PM 18627418 ER PT J AU Mayer, AMS Gustafson, KR AF Mayer, Alejandro M. S. Gustafson, Kirk R. TI Marine pharmacology in 2005-2006: Antitumour and cytotoxic compounds SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Marine; Antitumour; Drugs; Agents; Antineoplastic; Cancer; Chemotherapy; Pharmacology; Review; Screening ID ADVANCED SOLID TUMORS; NEW-GUINEA COLLECTION; MULTICENTER PHASE-II; SOFT-TISSUE SARCOMAS; CYANOBACTERIUM LYNGBYA-MAJUSCULA; CUCUMBER PENTACTA-QUADRANGULARIS; SULFATED TRITERPENE GLYCOSIDES; ENDOPLASMIC-RETICULUM STRESS; SPONGE THEONELLA-SWINHOEI; ADVANCED BREAST-CANCER AB During 2005 and 2006, marine pharmacology research directed towards the discovery and development of novel antitumour agents was reported in 171 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumour and cytotoxic properties of 136 marine natural products, many of which are novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive marine compounds included invertebrate animals, algae, fungi and bacteria. Antitumour pharmacological studies were conducted with 42 structurally defined marine natural products in a number of experimental and clinical models which further defined their mechanisms of action. Particularly potent in vitro cytotoxicity data generated with murine and human tumour cell lines were reported for 94 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anticancer research was sustained by a global collaborative effort, involving researchers from Australia, Belgium, Benin, Brazil, Canada, China, Egypt, France, Germany, India, Indonesia, Italy, Japan, Mexico, the Netherlands, New Zealand, Panama, the Philippines, Slovenia, South Korea, Spain, Sweden, Taiwan, Thailand, United Kingdom (UK) and the United States of America (USA). Finally, this 2005-2006 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumour agents continued at the same active pace as during 1998-2004. (C) 2008 Elsevier Ltd. All rights reserved, C1 [Mayer, Alejandro M. S.] Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, Downers Grove, IL 60515 USA. [Gustafson, Kirk R.] NCI Frederick, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. RP Mayer, AMS (reprint author), Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA. EM amayer@midwestern.edu OI Mayer, Alejandro /0000-0002-8358-4528 FU NIH; National Cancer Institute; Center for Cancer Research; Midwestern University's office of Research and Sponsored Programs FX This publication was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Additional support to AMSM from Midwestern University's office of Research and Sponsored Programs is gratefully acknowledged. The excellent support for literature searches and article retrieval by library staff members as well as medical and pharmacy students of Midwestern University is most gratefully recognised. The authors wish to specially thank Mrs. Victoria Sears and Ms. Mary Hall for careful and dedicated assistance in the preparation of this manuscript. NR 174 TC 69 Z9 72 U1 5 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2008 VL 44 IS 16 BP 2357 EP 2387 DI 10.1016/j.ejca.2008.07.001 PG 31 WC Oncology SC Oncology GA 376ZM UT WOS:000261221500011 PM 18701274 ER PT J AU Blumenthal, GM Dennis, PA AF Blumenthal, Gideon M. Dennis, Phillip A. TI PTEN hamartoma tumor syndromes SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RILEY-RUVALCABA-SYNDROME; BANNAYAN-ZONANA-SYNDROME; LHERMITTE-DUCLOS-DISEASE; SYNDROME PLEASE STAND; COWDEN-SYNDROME; BREAST-CANCER; PROTEUS-SYNDROME; SUPPRESSOR PTEN; GERMLINE MUTATION; PHOSPHOINOSITOL-3-KINASE/AKT PATHWAY AB The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22-23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist. C1 [Dennis, Phillip A.] NCI, Signal Transduct Sect, Navy Med Oncol, Med Oncol Branch,Ctr Canc Res, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Signal Transduct Sect, Navy Med Oncol, Med Oncol Branch,Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 77 TC 99 Z9 102 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2008 VL 16 IS 11 BP 1289 EP 1300 DI 10.1038/ejhg.2008.162 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 363JL UT WOS:000260263500001 PM 18781191 ER PT J AU Wolf, RC Sambataro, F Vasic, N Schonfeldt-Lecuona, C Ecker, D Landwehrmeyer, B AF Wolf, R. C. Sambataro, F. Vasic, N. Schoenfeldt-Lecuona, C. Ecker, D. Landwehrmeyer, B. TI Altered frontostriatal coupling in pre-manifest Huntington's disease: effects of increasing cognitive load SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE cognition; Huntington's disease; prefrontal cortex; pre-symptomatic; psychophysiological interactions ID WORKING-MEMORY; BASAL GANGLIA; GLUCOSE CONSUMPTION; PREFRONTAL CORTEX; BLOOD-FLOW; FMRI; DYSFUNCTION; PET; MORPHOMETRY; DEPRESSION AB Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals. Methods: Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand. C1 [Wolf, R. C.; Vasic, N.; Schoenfeldt-Lecuona, C.] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89075 Ulm, Germany. [Sambataro, F.] NIMH, Clin Brain Disorders Branch, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Ecker, D.; Landwehrmeyer, B.] Univ Ulm, Dept Neurol, D-89075 Ulm, Germany. RP Wolf, RC (reprint author), Univ Ulm, Dept Psychiat & Psychotherapy 3, Leimgrubenweg 12-14, D-89075 Ulm, Germany. EM christian.wolf@uni-ulm.de RI Sambataro, Fabio/E-3426-2010; OI Sambataro, Fabio/0000-0003-2102-416X; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X FU Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Bethesda, MD; European Huntington's Disease Network (EHDN) FX The authors would like to thank Georg Gron ( Department of Psychiatry III, Ulm) for valuable comments during data evaluation and Qiang Chen (Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Bethesda, MD) for technical support with the PPI analysis. We are grateful to Beate Englet and Sebastian Satzinger for their assistance with data collection. This study was supported by the European Huntington's Disease Network (EHDN). NR 51 TC 41 Z9 41 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD NOV PY 2008 VL 15 IS 11 BP 1180 EP 1190 DI 10.1111/j.1468-1331.2008.02253.x PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 357BR UT WOS:000259821800012 PM 18754766 ER PT J AU Di Giorgio, A Blasi, G Sambataro, F Rampino, A Papazacharias, A Gambi, F Romano, R Caforio, G Rizzo, M Latorre, V Popolizio, T Kolachana, B Callicott, JH Nardini, M Weinberger, DR Bertolino, A AF Di Giorgio, Annabella Blasi, Giuseppe Sambataro, Fabio Rampino, Antonio Papazacharias, Apostolos Gambi, Francesco Romano, Raffaella Caforio, Grazia Rizzo, Miriam Latorre, Valeria Popolizio, Teresa Kolachana, Bhaskar Callicott, Joseph H. Nardini, Marcello Weinberger, Daniel R. Bertolino, Alessandro TI Association of the Ser(704)Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE DISC1; fMRI; gray matter; hippocampus; memory encoding; phenotypic variance ID MEDIAL TEMPORAL-LOBE; PREFRONTAL CORTEX; NEURITE OUTGROWTH; NUCLEUS-ACCUMBENS; CEREBRAL-CORTEX; RHESUS-MONKEY; ADULT RATS; SCHIZOPHRENIA; DISRUPTED-IN-SCHIZOPHRENIA-1; BINDING AB A common nonsynonymous single nucleotide polymorphism leading to a serine-to-cysteine substitution at amino acid 704 (Ser(704)Cys) in the DISC1 protein sequence has been recently associated with schizophrenia and with specific hippocampal abnormalities. Here, we used multimodal neuroimaging to investigate in a large sample of healthy subjects the putative association of the Ser(704)Cys DISC1 polymorphism with in vivo brain phenotypes including hippocampal formation (HF) gray matter volume and function (as assessed with functional MRI) as well as HF functional coupling with the neural network engaged during encoding of recognition memory. Individuals homozygous for DISC1 Ser allele relative to carriers of the Cys allele showed greater gray matter volume in the HF. Further, Ser/Ser subjects exhibited greater engagement of the HF together with greater HF-dorsolateral prefrontal cortex functional coupling during memory encoding, in spite of similar behavioral performance. These findings consistently support the notion that Ser(704)Cys DISC1 polymorphism is physiologically relevant. Moreover, they support the hypothesis that genetic variation in DISC1 may affect the risk for schizophrenia by modifying hippocampal gray matter and function. C1 [Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Rampino, Antonio; Papazacharias, Apostolos; Gambi, Francesco; Romano, Raffaella; Caforio, Grazia; Rizzo, Miriam; Latorre, Valeria; Nardini, Marcello; Bertolino, Alessandro] Univ Bari, Psychiat Neurosci Grp, Sect Mental Disorders, Dept Neurol & Psychiat Sci, I-70124 Bari, Italy. [Sambataro, Fabio; Kolachana, Bhaskar; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Popolizio, Teresa; Bertolino, Alessandro] IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. RP Bertolino, A (reprint author), Univ Bari, Psychiat Neurosci Grp, Sect Mental Disorders, Dept Neurol & Psychiat Sci, Piazza Giulio Cesare 9, I-70124 Bari, Italy. EM a.bertolino@psichiat.uniba.it RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016; Rampino, Antonio/Q-4465-2016; Di Giorgio, Annabella /D-7353-2017; OI Sambataro, Fabio/0000-0003-2102-416X; Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380; Rampino, Antonio/0000-0002-9654-3266; Di Giorgio, Annabella /0000-0001-7876-3495; Papazacharias, Apostolos/0000-0001-5470-1601 FU Intramural NIH HHS [Z01 MH002734-12] NR 48 TC 54 Z9 54 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2008 VL 28 IS 10 BP 2129 EP 2136 DI 10.1111/j.1460-9568.2008.06482.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 371HQ UT WOS:000260822800018 PM 19046394 ER PT J AU Fejzo, MS Ingles, SA Wilson, M Wang, W MacGibbon, K Romero, R Goodwin, TM AF Fejzo, Marlena S. Ingles, Sue Ann Wilson, Melissa Wang, Wei MacGibbon, Kimber Romero, Roberto Goodwin, Thomas M. TI High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE Hyperemesis gravidarum; Nausea; Vomiting; Pregnancy; Genetic ID THYROTROPIN RECEPTOR; EPIDEMIOLOGY; POPULATION; EXPOSURE; OUTCOMES; DISEASE; RISK AB Objective: The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals. Study design: Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006. Results: Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s). Conclusion: There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Fejzo, Marlena S.; Wilson, Melissa; Wang, Wei; Goodwin, Thomas M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Ingles, Sue Ann; Wilson, Melissa; Wang, Wei] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [MacGibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA. [Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. RP Fejzo, MS (reprint author), 5535 MRL,675 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM mfejzo@mednet.ucla.edu OI MacGibbon, Kimber/0000-0002-6534-3114 FU Intramural Research Program of the National Institute of Child Health and Human Development; NIH; DHHS FX We thank Dr. Frederic Paik Schoenberg, UCLA Department of Statistics, for his valuable contribution to the creation and implementation of the original survey instrument. This research was supported (in part) by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS. NR 32 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD NOV PY 2008 VL 141 IS 1 BP 13 EP 17 DI 10.1016/j.ejogrb.2008.07.003 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 378CD UT WOS:000261297800004 PM 18752885 ER PT J AU Loeb, S Kettermann, A Ferrucci, L Landis, P Metter, EJ Carter, HB AF Loeb, Stacy Kettermann, Anna Ferrucci, Luigi Landis, Patricia Metter, E. Jeffrey Carter, H. Ballentine TI PSA Doubling Time Versus PSA Velocity to Predict High-Risk Prostate Cancer: Data from the Baltimore Longitudinal Study of Aging SO EUROPEAN UROLOGY LA English DT Article DE PSA kinetics; PSA doubling time; PSA velocity; Prostate cancer; Prognosis ID RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; RADIATION-THERAPY; ANTIGEN VELOCITY; MORTALITY; DEATH; AREAS; MEN AB Background: Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness. Objective: To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer. Design, setting, and participants: From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements. Measurements: Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease. Results and limitations: Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p < 0.001), whereas PSA DT did not. Conclusions: These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Loeb, Stacy; Kettermann, Anna; Landis, Patricia; Carter, H. Ballentine] Johns Hopkins Univ, Sch Med, Dept Urol, James Buchanan Brady Urol Inst,Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Ferrucci, Luigi; Metter, E. Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA. RP Loeb, S (reprint author), Johns Hopkins Sch Med, Dept Urol, Marburg 100,600 N Wolfe St, Baltimore, MD 21287 USA. EM stacyloeb@gmail.com OI Loeb, Stacy/0000-0003-3933-9207 FU US National Institutes of Health; National institute on Aging FX This research was supported by the Intramural Research Program of the US National Institutes of Health, National institute on Aging. NR 18 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD NOV PY 2008 VL 54 IS 5 BP 1073 EP 1080 DI 10.1016/j.eururo.2008.06.076 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 368YO UT WOS:000260659600013 PM 18614274 ER PT J AU Di Lorenzo, G Figg, WD Fossa, SD Mirone, V Autorino, R Longo, N Imbimbo, C Perdona, S Giordano, A Giuliano, M Labianca, R De Placido, S AF Di Lorenzo, Giuseppe Figg, William D. Fossa, Sophie D. Mirone, Vincenzo Autorino, Riccardo Longo, Nicola Imbimbo, Ciro Perdona, Sisto Giordano, Antonio Giuliano, Mario Labianca, Roberto De Placido, Sabino TI Combination of Bevacizumab and Docetaxel in Docetaxel-Pretreated Hormone-Refractory Prostate Cancer: A Phase 2 Study SO EUROPEAN UROLOGY LA English DT Article DE Bevacizumab; Chemotherapy; Docetaxel; Hormone-refractory; prostate cancer ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; II TRIAL; CHEMOTHERAPY; MITOXANTRONE; THALIDOMIDE; PREDNISONE AB Objective: Although the taxanes represent the most active agents for the first-line treatment of metastatic hormone-refractory prostate cancer (HRPC), most patients eventually progress while receiving taxane-based treatments. No agents are approved for second-line therapy in HRPC, but common standard practice for the oncologists is to treat patients also after docetaxel failure. Methods: Twenty highly pretreated patients with HRPC received bevacizumab (10 mg/kg) and docetaxel (60 mg/m(2)) every 3 wk, All patients had bone metastases and eight had measurable lesions. Results: Eleven patients (55%) had major prostate-specific antigen (PSA) responses, and 3 (37.5%) had objective responses. Seven major PSA responses were recorded in the same patients who had reported a >50% PSA decrease after first-line docetaxel. However, four major PSA responses were observed in patients previously nonresponsive to docetaxel alone. The treatment was well tolerated. Conclusions: Our results show that the combination of bevacizumab and docetaxel is active and well tolerated. Continued investigation of bevacizumab with cytotoxic chemotherapy is warranted in HRPC. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Di Lorenzo, Giuseppe; Giordano, Antonio; Giuliano, Mario; De Placido, Sabino] Univ Naples Federico 2, Dept Clin & Mol Oncol, Naples, Italy. [Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Fossa, Sophie D.] Univ Oslo, Rikshosp, Canc Clin, N-0316 Oslo, Norway. [Mirone, Vincenzo; Longo, Nicola; Imbimbo, Ciro] Univ Naples Federico 2, Urol Clin, Naples, Italy. [Autorino, Riccardo] Seconda Univ, Urol Clin, Naples, Italy. [Perdona, Sisto] Fdn G Pascale IRCSS Napoli, Ist Nazl Tumori, UO Urol, Naples, Italy. [Labianca, Roberto] Osped Riuniti Bergamo, Oncol Sect, I-24100 Bergamo, Italy. RP Di Lorenzo, G (reprint author), Univ Naples Federico 2, Dept Clin & Mol Oncol, Naples, Italy. EM giuseppedilorenzoncol@hotmail.com RI Figg Sr, William/M-2411-2016; Labianca, Roberto/N-1847-2016; OI Labianca, Roberto/0000-0001-7149-822X; MIRONE, Vincenzo/0000-0002-7639-2560 NR 22 TC 88 Z9 88 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD NOV PY 2008 VL 54 IS 5 BP 1089 EP 1096 DI 10.1016/j.eururo.2008.01.082 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 368YO UT WOS:000260659600015 PM 18276061 ER PT J AU Yamaguchi, Y Coelho, SG Zmudzka, BZ Takahashi, K Beer, JZ Hearing, VJ Miller, SA AF Yamaguchi, Yuji Coelho, Sergio G. Zmudzka, Barbara Z. Takahashi, Kaoruko Beer, Janusz Z. Hearing, Vincent J. Miller, Sharon A. TI Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV irradiation SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE apoptosis; p53; pigmentation; skin cancer; UV ID DNA-DAMAGE; ULTRAVIOLET-RADIATION; TANNING DEVICES; MELANIN CONTENT; HUMAN EPIDERMIS; BASAL-CELL; IN-VIVO; EXPOSURE; RISK; RESPONSES AB Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation. C1 [Yamaguchi, Yuji; Coelho, Sergio G.; Takahashi, Kaoruko; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Coelho, Sergio G.; Zmudzka, Barbara Z.; Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,room 2132,MSC 4256, Bethesda, MD 20892 USA. EM hearingv@nih.gov FU Office of Science and the Center for Devices and Radiological Health; Food and Drug Administration (FDA); NIH; Ministry of Education, Culture, Sports, and Technology of Japan; FDA Office of Women's Health FX This research was supported by the Office of Science and the Center for Devices and Radiological Health, Food and Drug Administration (FDA), by the Intramural Research Program of the National Cancer Institute at NIH, by a grant-in-aid from the Ministry of Education, Culture, Sports, and Technology of Japan, and by the FDA Office of Women's Health. The opinions and conclusions stated in this paper are those of the authors and do not represent the official position of the U. S. Department of Health and Human Services. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the U. S. Department of Health and Human Services. NR 41 TC 23 Z9 23 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2008 VL 17 IS 11 BP 916 EP 924 DI 10.1111/j.1600-0625.2008.00722.x PG 9 WC Dermatology SC Dermatology GA 358RV UT WOS:000259936100003 PM 18363705 ER PT J AU Klitten, LL Rath, MF Coon, SL Kim, JS Klein, DC Moller, M AF Klitten, Laura L. Rath, Martin F. Coon, Steven L. Kim, Jong-So Klein, David C. Moller, Morten TI Localization and regulation of dopamine receptor D4 expression in the adult and developing rat retina SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retina; diurnal rhythm; dopamine; Drd4; development; triiodothyronine ID SEROTONIN N-ACETYLTRANSFERASE; MT1 MELATONIN RECEPTOR; PINEAL-GLAND; CIRCADIAN CLOCK; PHOTORECEPTOR CELLS; CHICK RETINA; AMPHIBIAN RETINA; MAMMALIAN RETINA; GENE-EXPRESSION; AMACRINE CELLS AB Levels of dopamine and melatonin exhibit diurnal rhythms in the rat retina. Dopamine is high during daytime adapting the retina to light, whereas melatonin is high during nighttime participating in the adaptation of the retina to low light intensities. Dopamine inhibits the synthesis of melatonin in the photoreceptors via Drd4 receptors located on the cell membrane of these cells. In this study, we show by semiquantitative in situ hybridization a prominent day/night variation in Drd4 expression in the retina of the Sprague-Dawley rat with a peak during the nighttime. Drd4 expression is seen in all retinal layers but the nocturnal increase is confined to the photoreceptors. Retinal Drd4 expression is not affected by removal of the sympathetic input to the eye, but triiodothyronine treatment induces Drd4 expression in the photoreceptors. In a developmental series, we show that the expression of Drd4 is restricted to postnatal stages with a peak at postnatal day 12. The high Drd4 expression in the rat retinal photoreceptors during the night supports physiological and pharmacologic evidence that the Drd4 receptor is involved in the dopaminergic inhibition of melatonin synthesis upon light stimulation. The sharp increase of Drd4 expression at a specific postnatal time suggests that dopamine is involved in retinal development. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Klitten, Laura L.; Rath, Martin F.; Moller, Morten] Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst, DK-2200 Copenhagen, Denmark. [Coon, Steven L.; Kim, Jong-So; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Moller, M (reprint author), Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst 24 3 43, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM morm@sund.ku.dk OI Rath, Martin/0000-0002-4047-6324 FU Lundbeck Foundation; Danish Medical Research Council [271-06-0754]; Novo Nordisk Foundation; Carlsberg Foundation; Simon Fougner Hartmann's Family Foundation; Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH FX This study was supported by the Lundbeck Foundation, the Danish Medical Research Council (grant number 271-06-0754), the Novo Nordisk Foundation, the Carlsberg Foundation, the Simon Fougner Hartmann's Family Foundation, the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. We wish to thank Mrs. Ursula Rentzmann for expert histological assistance. NR 59 TC 26 Z9 26 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2008 VL 87 IS 5 BP 471 EP 477 DI 10.1016/j.exer.2008.08.004 PG 7 WC Ophthalmology SC Ophthalmology GA 374CT UT WOS:000261020700010 PM 18778704 ER PT J AU Huey, ED Armstrong, N Momeni, P Grafman, J AF Huey, Edward D. Armstrong, Nicole Momeni, Parastoo Grafman, Jordan TI Challenges and new opportunities in the investigation of new drug therapies to treat frontotemporal dementia SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE frontotemporal dementia; medication treatment; neurodegenerative disorders; neuroprotection ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRANULIN MUTATION CARRIERS; PRIMARY PROGRESSIVE APHASIA; LOBAR DEGENERATION; ALZHEIMERS-DISEASE; TAU GENE; BEHAVIORAL-CHARACTERISTICS; FTDP-17 MUTATIONS; SEMANTIC DEMENTIA; TEMPORAL VARIANT AB Background: Frontotemporal dementia spectrum disorders are a set of neurodegenerative disorders affecting the frontal and anterior temporal lobes. They are often fatal, and currently no medications have been shown to slow their progression. Recent developments in understanding these disorders may aid in developing treatments. Objective: To discuss the development of drug therapies for frontotemporal dementia spectrum disorders, both those under current investigation and those that could be targets for future investigation. Methods: This review is divided into four sections: First, a brief review of frontotemporal dementia spectrum disorders; second, a discussion of the challenges in the development of drug therapies third, a review of the current clinical trials; and finally a discussion of some recent discoveries, which have sparked new areas of investigation. Conclusions: Hopefully, advances in understanding of frontotemporal dementia spectrum disorders and clinical trial design will aid the development of new treatments. C1 [Huey, Edward D.; Armstrong, Nicole; Grafman, Jordan] NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. [Huey, Edward D.; Armstrong, Nicole] Lirwin Zucker Ctr Res Alzheimers Dis, Manhasset, NY 11030 USA. [Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Neurol, Lubbock, TX 79430 USA. RP Huey, ED (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM hueye@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 FU National Institutes of Health/The National Institute of Neurological Disorders and Stroke FX This study was supported by the intramural program of The National Institutes of Health/The National Institute of Neurological Disorders and Stroke. NR 110 TC 6 Z9 6 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD NOV PY 2008 VL 12 IS 11 BP 1367 EP 1376 DI 10.1517/14728220802482148 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 368JT UT WOS:000260618100005 PM 18851693 ER PT J AU Archer, TK AF Archer, Trevor K. TI Chromatin-modifying enzymes as therapeutic targets - Part 2 SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE chromatin; chromatin-modifying enzymes; epigenetics; histones; nucleosome remodelling; phosphorylation; ribosylation; SUMOylation; ubiquitylation ID MITOTIC CHROMOSOME CONDENSATION; HISTONE H3 PHOSPHORYLATION; PROTEIN TRIPLE KINASE; EARLY GENE INDUCTION; AURORA KINASES; POLY(ADP-RIBOSE) POLYMERASE; TRANSCRIPTIONAL ELONGATION; MOUSE FIBROBLASTS; ADP-RIBOSYLATION; CANCER-THERAPY AB Background: Part 1 of this review described the importance of histone acetylases, cleacetylases, methylases and demethylases in transcriptional control and their potential as therapeutic targets. However precise gene regulation requires the involvement of more than just the addition or removal of acetyl and methyl groups on histories. Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity. Accordingly, the enzymes responsible for these modifications are also misregulated in various disease states. Objective: To review the complex roles of chromatin-modifying enzymes in gene regulation and to highlight their potential as therapeutic targets. Methods: This review is based on recent published literature and online resources. Results/conclusion: In this second and final part of the review, we discuss the importance of these other histone and nucleosome modifying enzymes in gene transcription as well as their therapeutic potential. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 65 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 EI 1744-7631 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD NOV PY 2008 VL 12 IS 11 BP 1457 EP 1466 DI 10.1517/14728220802384047 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 368JT UT WOS:000260618100012 ER PT J AU Szklarczyk, A Ewaleifoh, O Beique, JC Wang, Y Knorr, D Haughey, N Malpica, T Mattson, MP Huganir, R Conant, K AF Szklarczyk, Arek Ewaleifoh, Osefame Beique, Jean-Claude Wang, Yue Knorr, David Haughey, Norman Malpica, Tanya Mattson, Mark P. Huganir, Richard Conant, Katherine TI MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor function SO FASEB JOURNAL LA English DT Article DE matrilysin; glutamate; synapse; proteolysis ID MATRIX-METALLOPROTEINASE ACTIVITY; AMYLOID PROTEIN-PRECURSOR; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; SPINAL-CORD; CELL-DEATH; CALCIUM DYSREGULATION; HIPPOCAMPAL SYNAPSES; SYNAPTIC PLASTICITY AB Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that play a role in the inflammatory response. These enzymes have been well studied in the context of cancer biology and inflammation. Recent studies, however, suggest that these enzymes also play roles in brain development and neurodegenerative disease. Select MMPs can target proteins critical to synaptic structure and neuronal survival, including integrins and cadherins. Here, we show that one member of the MMP family, MMP-7, which may be released from cells, including microglia, can target a protein critical to synaptic function. Through analysis of extracts from murine cortical slice preparations, we show that MMP-7 cleaves the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor to generate an N-terminal fragment of similar to 65 kDa. Moreover, studies with recombinant protein show that MMP-7-mediated cleavage of NR1 occurs at amino acid 517, which is extracellular and just distal to the first transmembrane domain. Data suggest that NR2A, which shares sequence homology with NR1, is also cleaved following treatment of slices with MMP-7, while select AMPA receptor subunits are not. Consistent with a potential effect of MMP-7 on ligand binding, additional experiments demonstrate that NMDA-mediated calcium flux is significantly diminished by MMP-7 pretreatment of cultures. In addition, the AMPA/NMDA ratio is increased by MMP-7 pretreatment. These data suggest that synaptic function may be altered in neurological conditions associated with increased levels of MMP-7.-Szklarczyk, A., Ewaleifoh, O., Beique, J.-C., Wang, Y., Knorr, D., Haughey, N., Malpica, T., Mattson, M. P., Huganir, R., Conant, K. MMP-7 cleaves the NR1 NMDA receptor subunit and modifies NMDA receptor function. FASEB J. 22, 3757-3767 (2008) C1 [Conant, Katherine] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. [Beique, Jean-Claude; Mattson, Mark P.; Huganir, Richard] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21287 USA. [Beique, Jean-Claude; Huganir, Richard] Howard Hughes Med Inst, Chevy Chase, MD USA. [Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Conant, K (reprint author), Johns Hopkins Univ, Dept Neurol, Sch Med, Pathol Bldg Rm 625,600 N Wolfe St, Baltimore, MD 21287 USA. EM kconant@mail.jhmi.edu RI Mattson, Mark/F-6038-2012 FU National Institutes of Health [NS052580, DA024447]; Alzheimer's Association; Howard Hughes Medical Institute; NARSAD; National Institute on Aging Intramural Research Program FX We thank Jenny Ryu and Jackie Mann for expert technical assistance. We also thank Dr. Yuri Kim and Kee Jun Kim for helpful comments. And we thank Marc Mayer and Yongneng Yao for the NR1 S1/S2 construct. This work was supported, in part, by the National Institutes of Health (NS052580 and DA024447 to K. C.), the Alzheimer's Association (K.C.), the Howard Hughes Medical Institute (J.C.B. and R.H.), NARSAD (J.C.B.), and the National Institute on Aging Intramural Research Program. NR 66 TC 27 Z9 29 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD NOV PY 2008 VL 22 IS 11 BP 3757 EP 3767 DI 10.1096/fj.07-101402 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 366SF UT WOS:000260503000004 PM 18644839 ER PT J AU Klootwijk, RD Savelkoul, PJM Ciccone, C Manoli, I Caplen, NJ Krasnewich, DM Gahl, WA Huizing, M AF Klootwijk, Riko D. Savelkoul, Paul J. M. Ciccone, Carla Manoli, Irini Caplen, Natasha J. Krasnewich, Donna M. Gahl, William A. Huizing, Marjan TI Allele-specific silencing of the dominant disease allele in sialuria by RNA interference SO FASEB JOURNAL LA English DT Article DE real-time PCR; feedback inhibition; sialic acid; UDP-GlcNAc 2-epimerase/ManNAc kinase; siRNA; allosteric site ID N-ACETYLGLUCOSAMINE 2-EPIMERASE; AMYOTROPHIC-LATERAL-SCLEROSIS; IN-VIVO; PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE; REGULATORY MUTATIONS; MOUSE MODEL; GENE; DELIVERY; SUPERACTIVITY; PURIFICATION AB Dominant disease alleles are attractive therapeutic targets for allele-specific gene silencing by small interfering RNA ( siRNA). Sialuria is a dominant disorder caused by missense mutations in the allosteric site of GNE, coding for the rate-limiting enzyme of sialic acid biosynthesis, UDP-GlcNAc 2-epimerase/ManNAc kinase. The resultant loss of feedback inhibition of GNE-epimerase activity by CMP-sialic acid causes excessive production of free sialic acid. For this study we employed synthetic siRNAs specifically targeting the dominant GNE mutation c. 797G > A (p.R266Q) in sialuria fibroblasts. We demonstrated successful siRNA-mediated down-regulation of the mutant allele by allele-specific real-time PCR. Importantly, mutant allele-specific silencing resulted in a significant decrease of free sialic acid, to within the normal range. Feedback inhibition of GNE-epimerase activity by CMP-sialic acid recovered after silencing demonstrating specificity of this effect. These findings indicate that allele-specific silencing of a mutated allele is a viable therapeutic strategy for autosomal dominant diseases, including sialuria.-Klootwijk, R. D., Savelkoul, P. J. M., Ciccone, C., Manoli, I., Caplen, N. J., Krasnewich, D. M., Gahl, W. A., Huizing, M. Allele-specific silencing of the dominant disease allele in sialuria by RNA interference. FASEB J. 22, 3846-3852 (2008) C1 [Klootwijk, Riko D.; Savelkoul, Paul J. M.; Ciccone, Carla; Manoli, Irini; Krasnewich, Donna M.; Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Gahl, William A.] NIH, Off Rare Dis, Intramural Program, Bethesda, MD 20892 USA. RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Manoli, Irini/0000-0003-1543-2941; Caplen, Natasha/0000-0002-0001-9460 FU National Human Genome Research Institute; National Cancer Institute; National Institutes of Health, Bethesda, MD, USA FX This study was supported by the Intramural Research programs of the National Human Genome Research Institute and the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. NR 43 TC 10 Z9 10 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2008 VL 22 IS 11 BP 3846 EP 3852 DI 10.1096/fj.08-110890 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 366SF UT WOS:000260503000013 PM 18653764 ER PT J AU Gatsos, X Perry, AJ Anwari, K Dolezal, P Wolynec, PP Likic, VA Purcell, AW Buchanan, SK Lithgow, T AF Gatsos, Xenia Perry, Andrew J. Anwari, Khatira Dolezal, Pavel Wolynec, P. Peter Likic, Vladimir A. Purcell, Anthony W. Buchanan, Susan K. Lithgow, Trevor TI Protein secretion and outer membrane assembly in Alphaproteobacteria SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE outer membrane assembly; membrane structure; Omp85; beta-barrel proteins; Alphaproteobacteria; mitochondria ID CARBOXY-TERMINAL PHENYLALANINE; GRAM-NEGATIVE BACTERIA; BETA-BARREL PROTEINS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; MOLECULAR CHAPERONE; TREPONEMA-PALLIDUM; STRUCTURAL BASIS; EVOLUTIONARY CONSERVATION; SACCHAROMYCES-CEREVISIAE AB The assembly of beta-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of beta-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating beta-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of beta-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, beta-propeller signatures in YfgL). Given that the process of the beta-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of beta-barrel proteins in eukaryotes. C1 [Gatsos, Xenia; Perry, Andrew J.; Anwari, Khatira; Dolezal, Pavel; Purcell, Anthony W.; Lithgow, Trevor] Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, Australia. [Gatsos, Xenia; Perry, Andrew J.; Anwari, Khatira; Dolezal, Pavel; Wolynec, P. Peter; Likic, Vladimir A.; Purcell, Anthony W.; Lithgow, Trevor] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic, Australia. [Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lithgow, T (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. EM t.lithgow@unimelb.edu.au RI Perry, Andrew/E-5607-2010; OI Perry, Andrew/0000-0001-9256-6068; Purcell, Anthony/0000-0003-0532-8331 FU Intramural NIH HHS NR 139 TC 60 Z9 62 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0168-6445 EI 1574-6976 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD NOV PY 2008 VL 32 IS 6 BP 995 EP 1009 DI 10.1111/j.1574-6976.2008.00130.x PG 15 WC Microbiology SC Microbiology GA 359AQ UT WOS:000259959000006 PM 18759741 ER PT J AU Kalantaridou, SN Vanderhoof, VH Calis, KA Corrigan, EC Troendle, JF Nelson, LM AF Kalantaridou, Sophia N. Vanderhoof, Vien H. Calis, Karim A. Corrigan, Emily C. Troendle, James F. Nelson, Lawrence M. TI Sexual function in young women with spontaneous 46,XX primary ovarian insufficiency SO FERTILITY AND STERILITY LA English DT Article DE Sexual function; primary ovarian insufficiency; premature ovarian failure; premature menopause; primary hypogonadism; hypergonadotropic hypogonadism; hypergonadotropic amenorrhea; hormone replacement therapy; estrogen; testosterone ID SURGICALLY MENOPAUSAL WOMEN; TESTOSTERONE PATCH; DESIRE DISORDER; POSTMENOPAUSAL WOMEN; NATURAL MENOPAUSE; DYSFUNCTION; FAILURE; ENDOCRINE; OOPHORECTOMY; HEALTH AB Objective: To assess sexual function in women with spontaneous 46,XX primary ovarian insufficiency after at least 3 months of a standardized hormone replacement regimen. Design: Cross-sectional cohort, controlled. Setting: National Institutes of Health Clinical Research Center. Patient(s): Women with primary ovarian insufficiency (n = 143) and regularly menstruating controls (n = 70). Intervention(s): Self administered questionnaires, 100 mu g/day E-2 patch, oral medroxyprogesterone acetate 10 mg for 12 days each month for patients. Main Outcome Measure(s): Derogatis Interview for Sexual Function Self-Report (DISF-SR). Result(s): Women with primary ovarian insufficiency had significantly lower DISF-SR composite scores compared with control women. Their serum total testosterone levels were significantly correlated with DISF-SR composite score, although this accounted for only 4% of the variance in this measure. Patients with testosterone levels below normal tended to have lower DISF-SR composite scores. Of patients with primary ovarian insufficiency, 9 of 127 (7%) scored below the second percentile on the composite sexual function score, compared with 1of 49 control women (2%). Conclusion(s): As assessed by the DISF-SR, sexual function is in the normal range for most young women with 46,XX spontaneous primary ovarian insufficiency who are receiving physiologic E-2 replacement. However, as a group, these young women score significantly lower on this sexual function scale than control women. (Fertil Steril((R)) 2008;90:4805-11. (c) 2008 by American Society for Reproductive Medicine.) C1 [Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Reprod Biol & Med Branch, Intramural Res Program,NIH,CRC, Bethesda, MD 20892 USA. [Calis, Karim A.] Warren O Hatfield Clin Res Ctr, Dept Pharm, Bethesda, MD USA. [Troendle, James F.] NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Integrat Reprod Med Unit, Reprod Biol & Med Branch, Intramural Res Program,NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM lawrence_nelson@nih.gov FU Intramural Research Program; National Institute of Child Health and Human Development; National Institutes of Health FX Supported by the Intramural Research Program, National Institute of Child Health and Human Development, National Institutes of Health. Vien H. Vanderhoof and Lawrence M. Nelson are commissioned officers in the United States Public Health Service. NR 41 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2008 VL 90 IS 5 BP 1805 EP 1811 DI 10.1016/j.fertnstert.2007.08.040 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 370GZ UT WOS:000260752000036 PM 17961560 ER PT J AU Centlow, M Carninci, P Nemeth, K Mezey, E Brownstein, M Hansson, SR AF Centlow, Magnus Carninci, Piero Nemeth, Krisztian Mezey, Eva Brownstein, Michael Hansson, Stefan R. TI Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes SO FERTILITY AND STERILITY LA English DT Article DE Hematopoiesis; endothelial damage; hypoxia; inflammation ID HEME OXYGENASE EXPRESSION; MATERNAL SUSCEPTIBILITY LOCUS; LENGTH CDNA LIBRARIES; BLOOD-CELL COUNTS; TROPHOBLAST CELLS; CHORIONIC VILLI; GENE-EXPRESSION; HYPOXIA; PREGNANCIES; RISK AB Objective: To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiting of preeclampsia (PE) and high risk pregnancies. Design: Prospective study. Setting: University women's clinic and academic research laboratory. Patient(S): Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited. Intervention(s): Placenta and placenta bed biopsies were collected after delivery. Main Outcome Measure(s): Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry. Result(s): Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha 2 and gamma transcripts were significantly over-expressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains. Conclusion(s): We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation. (Fertil Steril((R)) 2008;90:1834-43. (c) 2008 by American Society for Reproductive Medicine.) C1 [Centlow, Magnus; Hansson, Stefan R.] Lund Univ, Dept Obstet & Gynecol, SE-22644 Lund, Sweden. [Carninci, Piero] RIKEN, Genome Sci Lab, Wako, Saitama, Japan. [Nemeth, Krisztian; Mezey, Eva] Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. [Brownstein, Michael] J Craig Venter Inst, Rockville, MD USA. RP Centlow, M (reprint author), Lund Univ, Dept Obstet & Gynecol, BMC C14,Klinikgatan 28, SE-22644 Lund, Sweden. EM magnus.centlow@med.lu.se RI Brownstein, Michael/B-8609-2009; Carninci, Piero/K-1568-2014 OI Carninci, Piero/0000-0001-7202-7243 FU Swedish Research Council [5775]; Knut and Alice Wallenberg Foundation; Anna Lisa & Sven Erik Lundgrens foundation for Medical Research; Crawford Foundation; Magnus Bergvalls Foundation; Swedish Society for Medical Research; Intramural Research Program; National Institute of Dental and Craniofacial Research; National Institutes of Health; Swegene DNA Microarray Resource Center in Lund FX Supported by grants from the Swedish Research Council: 5775, Anna Lisa & Sven Erik Lundgrens foundation for Medical Research, Crawford Foundation, Magnus Bergvalls Foundation, Swedish Society for Medical Research, and the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. Microarrays and protocols were obtained from the Swegene DNA Microarray Resource Center in Lund, supported by the Knut and Alice Wallenberg Foundation through the Swegene consortium. NR 50 TC 33 Z9 35 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2008 VL 90 IS 5 BP 1834 EP 1843 DI 10.1016/j.fertnstert.2007.09.030 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 370GZ UT WOS:000260752000040 PM 18166190 ER PT J AU Browne, H McCarthy-Keith, D Stegmann, B Spies, J Armstrong, A AF Browne, Hyacinth McCarthy-Keith, Desiree Stegmann, Barbara Spies, James Armstrong, Alicia TI Ovarian response in women undergoing ovarian stimulation after myomectomy SO FERTILITY AND STERILITY LA English DT Editorial Material DE Fibroids; myomectomy; ovarian reserve; assisted reproductive technology ID UTERINE ARTERY EMBOLIZATION; IN-VITRO FERTILIZATION; RESERVE; LEIOMYOMATA; HYSTERECTOMY AB Objective: To examine ovarian response in infertile women undergoing ovarian stimulation after abdominal myomectomy. Design: Case report. Setting: Academic medical research center. Patient(s): Four infertile women with known fibroids who had a failed assisted reproductive technology (ART) cycle followed by an abdominal myomectomy. Intervention(s): Infertile women with known fibroids who had a failed ART cycle, from January 2000 to December 2006, followed by an abdominal myomectomy and a subsequent ART cycle. Main Outcome Measure(s): Ovarian function before (baseline) and after myomectomy was assessed by age, day 3 and day 10 FSH levels, days of stimulation, total gonadotropins used, peak E(2) level, the number of oocytes retrieved and embryos obtained, the number of high-grade embryos, and pregnancy outcome. Result(s): The mean age was 35 and 36 years before and after myomectomy, respectively. All subjects had uterine factor infertility. Two of these women also had tubal factor infertility, and one had endometriosis and male factor infertility. There was no difference in ovarian response before and after myomectomy. Conclusion(s): As expected, abdominal myomectomy did not adversely affect ovarian response in infertile women undergoing ovarian stimulation after a failed ART cycle. Larger randomized prospective studies are needed to accurately assess whether myomectomy has a negative impact on ovarian response. (Fertil Steril (R) 2008; 90: 2004. e19-e21. (C)2008 by American Society for Reproductive Medicine.) C1 [Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Browne, Hyacinth; McCarthy-Keith, Desiree; Stegmann, Barbara; Armstrong, Alicia] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Spies, James] Georgetown Univ Hosp, Dept Radiol, Intervent Radiol Sect, Washington, DC 20007 USA. RP Browne, H (reprint author), NICHD, Program Reprod & Adult Endocrinol, NIH, CRC 1 E Rm 1-E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM brownehy@mail.nih.gov FU National Institute of Child Health and Human Development, National Institutes of Health FX Carried out under Walter Reed Army Medical Center Department of Clinical Investigations protocol WU #08-04-44018hEX(1) and supported in part by the Program in Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health. NR 14 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2008 VL 90 IS 5 AR 2004.e19 DI 10.1016/j.fertnstert.2008.04.008 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V13XQ UT WOS:000207699900010 PM 18565518 ER PT J AU Chason, RJ Levens, ED Yauger, BJ Payson, MD Cho, K Larsen, FW AF Chason, Rebecca J. Levens, Eric D. Yauger, Belinda J. Payson, Mark D. Cho, Kenneth Larsen, Frederick W. TI Balloon fluoroscopy as treatment for intrauterine adhesions: a novel approach SO FERTILITY AND STERILITY LA English DT Editorial Material DE Asherman's syndrome; synechiae; intrauterine adhesions; balloon dilation; cesarean section scar ID CESAREAN-SECTION SCAR; SONOHYSTEROGRAPHY AB Objective: To report a unique fluoroscopically guided approach to treat severe intrauterine adhesions and cervical stenosis using balloon hysteroplasty. Design: Case report. Setting: Military-based fertility center. Patient(s): A 33-year-old woman undergoing assisted reproductive technology whose uterus could not be cannulated because of the development of intrauterine synechiae and cervical stenosis after a post-IUI infection that was further complicated by a prominent lower uterine segment-filling defect in the location of a prior cesarean delivery scar. Intervention(s): Fluoroscopic cannulation and balloon uterine dilation. Main Outcome Measure(s): Resolution of synechiae by hysterosalpingogram and successful uterine cannulation. Result(s): A postprocedure hysterosalpingogram demonstrated a normalized uterine cavity with the exception of a persistent prominent lower uterine segment-filling defect from a prior cesarean delivery. A frozen ET cycle was performed successfully. Conclusion(s): Hysteroplasty, using standard interventional radiographic techniques, may provide an alternative treatment modality for patients with intrauterine adhesions and lower uterine defects from prior cesarean deliveries in select cases. While treating intrauterine adhesions improves pregnancy outcome, the effect of lower uterine segment-filling defects from cesarean deliveries on pregnancy outcome in assisted reproductive technology cycles warrants further investigation. (Fertil Steril (R) 2008; 90: 2005. e15-e17. (C)2008 by American Society for Reproductive Medicine.) C1 [Chason, Rebecca J.] NICHHD, Natl Naval Med Ctr, NIH, Bethesda, MD 20892 USA. [Levens, Eric D.; Yauger, Belinda J.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Yauger, Belinda J.; Payson, Mark D.; Cho, Kenneth; Larsen, Frederick W.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Chason, RJ (reprint author), Care of Cyoyle MP, Natl Naval Med Ctr, Bldg 1,Rm 2435,8901 Rockville Pike, Bethesda, MD 20889 USA. EM rebecca.chason@amedd.army.mil FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, Maryland FX This research was supported, in part, by the Program in Reproductive and Adult Endocrinology of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, Maryland. NR 11 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2008 VL 90 IS 5 AR 2005.e15 DI 10.1016/j.fertnstert.2008.07.1752 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA V13XQ UT WOS:000207699900016 PM 18793771 ER PT J AU Metz, DC Jensen, RT AF Metz, David C. Jensen, Robert T. TI Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors SO GASTROENTEROLOGY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ISLET-CELL TUMORS; HIPPEL-LINDAU-DISEASE; GASTRIC-ACID HYPERSECRETION; EPIDERMAL-GROWTH-FACTOR; FINE-NEEDLE-ASPIRATION; NECROLYTIC MIGRATORY ERYTHEMA; NEOPLASIA TYPE-1 MEN1; INSTITUTES-OF-HEALTH C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Metz, David C.] Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM RobertJ@bdg10.niddk.nih.gov FU Intramural NIH HHS [Z01 DK053200-16, Z01 DK053215-01] NR 308 TC 253 Z9 261 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2008 VL 135 IS 5 BP 1469 EP 1492 DI 10.1053/j.gastro.2008.05.047 PG 24 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 371YL UT WOS:000260868500016 PM 18703061 ER PT J AU Boirivant, M Amendola, A Butera, A Sanchez, M Xu, LL Marinaro, M Kitani, A Di Giacinto, C Strober, W Fuss, IJ AF Boirivant, Monica Amendola, Antonello Butera, Alessia Sanchez, Massimo Xu, Lili Marinaro, Mariarosaria Kitani, Atsushi Di Giacinto, Claudia Strober, Warren Fuss, Ivan J. TI A Transient Breach in the Epithelial Barrier Leads to Regulatory T-Cell Generation and Resistance to Experimental Colitis SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATION; MODULATION; DISEASE; ACID AB Background & Aims: Previous studies have indicated that a defective epithelial barrier leads to inflammation of the underlying lamina propria. Nevertheless, it is likely that physiologic breaks in the barrier must occur for homeostatic regulatory T cells to develop. We determined the effect of agents that disrupt epithelial tight junctions (ethanol and AT1002, a Vibrio cholerae zonula occludens toxin hexapeptide) on regulatory T-cell induction and resistance to induction of colitis by trinitrobenzene sulfonic acid (TNBS). Methods: The effects of ethanol and AT1002 on. colon immune function were evaluated by their capacity to induce direct phenotypic or functional changes in effector and regulatory cell populations and their indirect effect on the development of TNBS-induced colitis. The basis of regulatory cell development was evaluated with in vitro studies of isolated dendritic cell populations. The role of innate immunity was evaluated by in vivo gene silencing studies utilizing Toll-like receptor (TLR)-2-specific small interfering RNA (siRNA). Results: Both ethanol and AT1002 induced persistent latency-associated peptide-positive CD4(+) regulatory T cells that, as shown in adoptive transfer studies, render mice resistant to the induction of TNBS colitis. The development of these cells requires the presence of an intact microflora and the activity of CD11c(+) dendritic cells. Their induction is also influenced by innate immune factors operating through TLR-2, because attenuation of TLR-2 signaling by in vivo TLR-2 siRNA administration prevents their development. Conclusions: A mild and/or transient breach in epithelial barrier function leads to dominant regulatory T-cell responses that protect the mucosa from inflammation. C1 [Boirivant, Monica; Amendola, Antonello; Butera, Alessia; Marinaro, Mariarosaria; Di Giacinto, Claudia] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Immune Mediated Dis Sect, I-00161 Rome, Italy. [Sanchez, Massimo] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Xu, Lili; Kitani, Atsushi; Strober, Warren; Fuss, Ivan J.] NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA. RP Boirivant, M (reprint author), Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Immune Mediated Dis Sect, Viale R Elena 299, I-00161 Rome, Italy. EM monica.boirivant@iss.it RI BOIRIVANT, MONICA/B-9977-2016; AMENDOLA, ANTONELLO/B-9979-2016; Butera, Alessia /I-3399-2014 OI Butera, Alessia /0000-0002-7659-4066 FU Italian Ministry of Health FX Supported in part by ISS-NIH program 5303 and grant "ricerca Finalizzata 2005 Fasc 6ACF" from the Italian Ministry of Health. NR 18 TC 45 Z9 46 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2008 VL 135 IS 5 BP 1612 EP 1623 DI 10.1053/j.gastro.2008.07.028 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 371YL UT WOS:000260868500031 PM 18765239 ER PT J AU Geyer, CB Eddy, EM AF Geyer, Christopher B. Eddy, Edward M. TI Identification and characterization of Rhox13, a novel X-linked mouse homeobox gene SO GENE LA English DT Article DE testis; ovary; spermatogenesis; transcription; X chromosome ID HOMEODOMAIN PROTEINS; GERM-CELLS; CLUSTER; DNA; PLACENTA; TESTIS; CLASSIFICATION; FAMILY; MEMBER; MOTIF AB Homeobox genes encode transcription factors whose expression organizes programs of development. A number of homeobox genes expressed in reproductive tissues have been identified recently, including a colinear cluster on the X chromosome in mice. This has led to an increased interest in understanding the role (s) of homeobox genes in regulating development of reproductive tissues including the testis, ovary, and placenta. Here we report the identification and characterization of a novel homeobox gene of the paired-like class on the X chromosome distal to the reproductive homeobox (Rhox) cluster in mice. Transcripts are found in the testis and ovary as early as 13.5 days post coitum, (dpc). Transcription ceases in the ovary by 3 days post partum (dpp), but continues in the testis through adulthood. The Rhox13 gene encodes a 25.3 kDa protein expressed in the adult testis in germ cells at the basal aspect of the seminiferous epithelium. Published by Elsevier B.V. C1 [Geyer, Christopher B.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, 111 TW Alexander Dr,MD C4-01, Res Triangle Pk, NC 27709 USA. EM eddy1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES070076-21] NR 29 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 1 PY 2008 VL 423 IS 2 BP 194 EP 200 DI 10.1016/j.gene.2008.06.031 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 361XF UT WOS:000260160300013 PM 18675325 ER PT J AU Yang, S Cohen, CJ Peng, PD Zhao, Y Cassard, L Yu, Z Zheng, Z Jones, S Restifo, NP Rosenberg, SA Morgan, RA AF Yang, S. Cohen, C. J. Peng, P. D. Zhao, Y. Cassard, L. Yu, Z. Zheng, Z. Jones, S. Restifo, N. P. Rosenberg, S. A. Morgan, R. A. TI Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition SO GENE THERAPY LA English DT Article DE T-cell receptor; adoptive immunotherapy; tumor immunity; lentivirus; 2A peptide ID ENHANCED ANTITUMOR-ACTIVITY; RECEPTOR RETROGENIC MICE; EMBRYONIC STEM-CELLS; CD8(+) T-CELLS; IN-VIVO; HUMAN-LYMPHOCYTES; TRANSGENE EXPRESSION; RETROVIRAL VECTOR; SELECTION PROCESS; 2A PEPTIDE AB In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors in several areas, including the ability to transduce nondividing cells, resistance to gene silencing and a potentially safer integration site profile. However, unlike gamma-retroviral vectors it has been problematic to drive the expression of multiple genes efficiently and coordinately with approaches such as internal ribosome entry sites or dual promoters. Using different 2A peptides, lentiviral vectors expressing two-gene T-cell receptors directed against the melanoma differentiation antigens gp100 and MART-1 were constructed. We demonstrated that addition of amino-acid spacer sequences (GSG or SGSG) before the 2A sequence is a prerequisite for efficient synthesis of biologically active T-cell receptors and that addition of a furin cleavage site followed by a V5 peptide tag yielded optimal T-cell receptor gene expression. Furthermore, we determined that the furin cleavage site was recognized in lymphocytes and accounted for removal of residual 2A peptides at the post-translational level with an efficiency of 20-30%, which could not be increased by addition of multiple furin cleavage sites. The novel bicistronic lentiviral vector developed herein afforded robust anti-melanoma activities to engineered peripheral blood lymphocytes, including cytokine secretion, cell proliferation and lytic activity. Such optimal vectors may have immediate applications in cancer gene therapy. Gene Therapy (2008) 15, 1411-1423; doi:10.1038/gt.2008.90; published online 22 May 2008 C1 [Yang, S.; Cohen, C. J.; Peng, P. D.; Zhao, Y.; Cassard, L.; Yu, Z.; Zheng, Z.; Jones, S.; Restifo, N. P.; Rosenberg, S. A.; Morgan, R. A.] NCI, NIH, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, NIH, Ctr Canc Res, Surg Branch, 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Center for Cancer Research; National Cancer Institute; National Institutes of Health FX We thank FACS laboratory and TIL laboratory in Surgery Branch for providing technical support and maintenance of tumor cells from patients. This work is supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 56 TC 89 Z9 92 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 2008 VL 15 IS 21 BP 1411 EP 1423 DI 10.1038/gt.2008.90 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 363DZ UT WOS:000260248500001 PM 18496571 ER PT J AU Fegley, DB Holmes, A Riordan, T Faber, CA Weiss, JR Ma, S Batkai, S Pacher, P Dobolyi, A Murphy, A Sleeman, MW Usdin, TB AF Fegley, D. B. Holmes, A. Riordan, T. Faber, C. A. Weiss, J. R. Ma, S. Batkai, S. Pacher, P. Dobolyi, A. Murphy, A. Sleeman, M. W. Usdin, T. B. TI Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Anxiety; conditioned fear; mouse knockout; neuropeptide; stress ID ELEVATED PLUS-MAZE; SEROTONIN TRANSPORTER; HORMONE RECEPTOR-2; NEUROPEPTIDE-Y; DEFICIENT MICE; KNOCKOUT MICE; ANIMAL-MODEL; RESTRAINT STRESS; RAT; DEPRESSION AB Tuberoinfundibular peptide of 39 residues (TIP39) is synthesized by two groups of neurons, one in the subparafascicular area at the caudal end of the thalamus and the other in the medial paralemniscal nucleus within the lateral brainstem. The subparafascicular TIP39 neurons project to a number of brain regions involved in emotional responses, and these regions contain a matching distribution of a receptor for TIP39, the parathyroid hormone 2 receptor (PTH2-R). We have now evaluated the involvement of TIP39 in anxiety-related behaviors using mice with targeted null mutation of the TIP39 gene (Tifp39). Tifp39(-/-) mice (TIP39-KO) did not significantly differ from wild-type (WT) littermates in the open field, light/dark exploration and elevated plus-maze assays under standard test conditions. However, the TIP39-KO engaged in more active defensive burying in the shock-probe test. In addition, when tested under high illumination or after restraint, TIP39-KO displayed significantly greater anxiety-like behavior in the elevated plus-maze than WT. In a Pavlovian fear-conditioning paradigm, TIP39-KO froze more than WT during training and during tone and context recall but showed normal fear extinction. Disruption of TIP39 projections to the medial prefrontal cortex, lateral septum, bed nucleus of the stria terminalis, hypothalamus and amygdala likely account for the fear- and anxiety-related phenotype of TIP39-KO. Current data support the hypothesis that TIP39 modulates anxiety-related behaviors following environmental provocation. C1 [Fegley, D. B.; Riordan, T.; Faber, C. A.; Weiss, J. R.; Ma, S.; Usdin, T. B.] NIMH, NIH, Bethesda, MD 20892 USA. [Holmes, A.; Batkai, S.; Pacher, P.] NIAAA, NIH, Rockville, MD 20852 USA. [Dobolyi, A.] Semmelweis Univ, Hungarian Acad Sci, Neuromorphol Lab, H-1085 Budapest, Hungary. [Murphy, A.; Sleeman, M. W.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Usdin, TB (reprint author), 35 Convent Dr MSC 3728, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; FU NIH, National Institute of Mental Health FX We thank Ildiko Racz and Sarah Irwin for help with preliminary experiments, Jim Pickel and the NIMH transgenic mouse core facility for help with generation of mice, and Heather Cameron and Jacqueline Crawley for the use of behavior testing equipment. This research was supported by the Intramural Program of the NIH, National Institute of Mental Health. M. W. S. and A. M. are employees of Regeneron and own stock in Regeneron. The authors declare that there are no potential conflicts of interest. NR 61 TC 18 Z9 18 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD NOV PY 2008 VL 7 IS 8 BP 933 EP 942 DI 10.1111/j.1601-183X.2008.00432.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 376LK UT WOS:000261184900012 PM 18700839 ER PT J AU Ohali, A Avigad, S Naumov, I Goshen, Y Ash, S Yaniv, I AF Ohali, Anat Avigad, Smadar Naumov, Inna Goshen, Yacov Ash, Shifra Yaniv, Isaac TI Different telomere maintenance mechanisms in alveolar and embryonal rhabdomyosarcoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID MESSENGER-RNA EXPRESSION; SOFT-TISSUE SARCOMAS; CANCER; ASSOCIATION; LENGTH; TUMORS; LIPOSARCOMAS; OSTEOSARCOMA; PROGRESSION; CELLS AB The activation of a telomere maintenance mechanism (TMM) is crucial for the immortalization of tumor cells. Most human cancers apply telomerase-dependent TMM but some use a mechanism called alternative lengthening of telomeres (ALT). The latter was suggested to be mainly characterizing sarcomas with nonspecific complex karyotypes, whereas telomerase activation is typical of sarcomas generated by specific translocations. In this study, we investigated the TMM and its association with survival in rhabdomyosarcoma (RMS), which is characterized by two major subtypes: one that is harboring a specific translocation (alveolar) and one that has a nonspecific karyotype (embryonal). Telomerase activity (TA), using telomerase repeat amplification protocol (TRAP) assay, and telomere length (TRF), using Southern blotting, were analyzed in tumor samples from 31 patients (16 embryonal and IS alveolar). Alveolar RMS tumors exhibited no ALT phenotype and the majority presented TA. Some embryonal tumors exhibited an ALT or "ALT-like" phenotype which lacked TA, whereas others expressed telomerase-dependent TMM, and neither TA nor ALT correlated with outcome. The average TRIF length of the embryonal tumors was significantly higher than that of the alveolar tumors (10.8 vs. 7.2 kb, P = 0.003). Interestingly, some tumors of both subtypes presented no TMM. These observations suggest that alveolar RMS predominantly use telomerase-dependent TMM, whereas in embryonal tumors both telomerase and ALT may play a role. These findings have important implications for understanding the role of TMM in the development of RMS tumors, and for future designing adapted treatment strategies. (c) 2008 Wiley-Liss, Inc. C1 [Ohali, Anat; Avigad, Smadar; Goshen, Yacov; Ash, Shifra; Yaniv, Isaac] Schneider Childrens Med Ctr Israel, IL-49202 Petah Tiqwa, Israel. [Ohali, Anat; Avigad, Smadar; Naumov, Inna; Goshen, Yacov; Ash, Shifra; Yaniv, Isaac] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Ohali, Anat; Avigad, Smadar; Naumov, Inna; Yaniv, Isaac] Felsenstein Med Res Ctr, Petah Tiqwa, Israel. [Ohali, Anat] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Avigad, S (reprint author), Schneider Childrens Med Ctr Israel, 14 Kaplan St, IL-49202 Petah Tiqwa, Israel. EM savigad@post.tau.ac.il FU Tamar Kravitz Funds FX Supported by: Tamar Kravitz Funds. NR 24 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2008 VL 47 IS 11 BP 965 EP 970 DI 10.1002/gcc.20600 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 350MH UT WOS:000259356100006 PM 18663749 ER PT J AU Ullah, Z Kohn, MJ Yagi, R Vassilev, LT DePamphilis, ML AF Ullah, Zakir Kohn, Matthew J. Yagi, Rieko Vassilev, Lyubomir T. DePamphilis, Melvin L. TI Differentiation of trophoblast stem cells into giant cells is triggered by p57/Kip2 inhibition of CDK1 activity SO GENES & DEVELOPMENT LA English DT Article DE Endoreduplication; placentomegaly; trophoblast giant cell; p57; CDK1; DNA replication ID DROSOPHILA FOLLICLE CELLS; CYCLE PROGRESSION; DNA-REPLICATION; RETINOBLASTOMA PROTEIN; MAMMALIAN DEVELOPMENT; G(2)/M CHECKPOINT; CDC2 MUTANT; S-PHASE; P57(KIP2); GEMININ AB Genome endoreduplication during mammalian development is a rare event for which the mechanism is unknown. It first appears when fibroblast growth factor 4 (FGF4) deprivation induces differentiation of trophoblast stem (TS) cells into the nonproliferating trophoblast giant (TG) cells required for embryo implantation. Here we show that RO3306 inhibition of cyclin-dependent protein kinase 1 (CDK1), the enzyme required to enter mitosis, induced differentiation of TS cells into TG cells. In contrast, RO3306 induced abortive endoreduplication and apoptosis in embryonic stem cells, revealing that inactivation of CDK1 triggers endoreduplication only in cells programmed to differentiate into polyploid cells. Similarly, FGF4 deprivation resulted in CDK1 inhibition by overexpressing two CDK-specific inhibitors, p57/KIP2 and p21/CIP1. TS cell mutants revealed that p57 was required to trigger endoreduplication by inhibiting CDK1, while p21 suppressed expression of the checkpoint protein kinase CHK1, thereby preventing induction of apoptosis. Furthermore, Cdk2(-/-) TS cells revealed that CDK2 is required for endoreduplication when CDK1 is inhibited. Expression of p57 in TG cells was restricted to G-phase nuclei to allow CDK activation of S phase. Thus, endoreduplication in TS cells is triggered by p57 inhibition of CDK1 with concomitant suppression of the DNA damage response by p21. C1 [Ullah, Zakir; Kohn, Matthew J.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA. [Yagi, Rieko] Ajinomoto Inst Life Sci, Kawasaki, Kanagawa 2108681, Japan. [Vassilev, Lyubomir T.] Hoffmann La Roche Inc, Roche Res Ctr, Dept Discovery Oncol, Nutley, NJ 07110 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov NR 61 TC 87 Z9 89 U1 0 U2 6 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 NOV 1 PY 2008 VL 22 IS 21 BP 3024 EP 3036 DI 10.1101/gad.1718108 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 368DY UT WOS:000260602700012 PM 18981479 ER PT J AU Mukherjee, B Ahn, J Gruber, SB Rennert, G Moren, V Chatterjee, N AF Mukherjee, Bhramar Ahn, Jaeil Gruber, Stephen B. Rennert, Gad Moren, Victor Chatterjee, Nilanjan TI Tests for Gene-Environment Interaction From Case-Control Data: A Novel Study of Type I Error, Power and Designs SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-only designs; empirical Bayes; gene-environment interaction; genome-wide scan; Molecular Epidemiology of Colorectal Cancer ID COLORECTAL-CANCER; MAXIMUM-LIKELIHOOD; RISK; INDEPENDENCE; ASSOCIATIONS; GENOTYPE; EXPOSURE; SMOKING; DIET AB To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N-acetyl transferase type 2 and glutathione s-transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer. Genet. Epidemiol. 32:615-626, 2008. Published 2008 Wiley-Liss, Inc.(dagger) C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Mukherjee, Bhramar; Ahn, Jaeil] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Gruber, Stephen B.] Univ Michigan, Dept Internal Med Epidemiol & Human Genet, Ann Arbor, MI 48109 USA. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad] Technion Israel Inst Technol, Fac Med, CHS Natl Israeli Canc Control Ctr, Haifa, Israel. [Moren, Victor] Catalan Inst Oncol, IDIBELL, Barcelona, Spain. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. EM chattern@mail.nih.gov OI Moreno, Victor/0000-0002-2818-5487 FU NSF [DMS 07-06935]; NIH [R03 CA130045-01, R01 CA81488]; Spanish Secretaria de Estado de Universidades e Investigacion [PR2006-04743]; National Heart Lung and Blood Institute [R01 HL091172-01]; National Cancer Institute FX Contract grant sponsor: NSF; Contract grant number: DMS 07-06935; Contract grant sponsor: NIH; Contract grant numbers: R03 CA130045-01, R01 CA81488; Contract grant sponsor: Spanish Secretaria de Estado de Universidades e Investigacion; Contract grant number: PR2006-04743; Contract grant sponsor: National Heart Lung and Blood Institute; Contract grant number: R01 HL091172-01; Contract grant sponsor: National Cancer Institute. NR 18 TC 38 Z9 38 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 BP 615 EP 626 DI 10.1002/gepi.20337 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600004 PM 18473390 ER PT J AU Pfeiffer, RM Pee, D Landi, MT AF Pfeiffer, Ruth M. Pee, David Landi, Maria T. TI On Combining Family and Case-Control Studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE ascertainment; nested random effects model; marginal model; family history; stratified sampling ID MELANOMA; MC1R; RISK; REGRESSION; INFERENCE; MODELS AB Studies to detect genetic association with disease can be family-based, often using families with multiple affected members, or population based, as in population-based case-control studies. If data on both study types are available from the same population, it is useful to combine them to improve power to detect genetic associations. Two aspects of the data need to be accommodated, the sampling scheme and potential residual correlations among family members. We propose two approaches for combining data from a case-control study and a family study that collected families with multiple cases. In the first approach, we view a family as the sampling unit and specify the joint likelihood for the family members using a two-level mixed effects model to account for random familial effects and for residual genetic correlations among family members. The ascertainment of the families is accommodated by conditioning on the ascertainment event. The individuals in the case-control study are treated as families of size one, and their unconditional likelihood is combined with the conditional likelihood for the families. This approach yields subject specific maximum likelihood estimates of covariate effects. In the second approach, we view an individual as the sampling unit. The sampling scheme is accommodated using two-phase sampling techniques, marginal covariate effects are estimated, and correlations among family members are accounted for in the variance calculations. The models are compared in simulations. Data from a case-control and a family study from north-eastern Italy on melanoma and a low-risk melanoma-susceptibility gene, MC1R, are used to illustrate the approaches. Genet, Epidemiol. 32:638-646, 2008. Published 2008 Wiley-Liss, Inc.(dagger) C1 [Pfeiffer, Ruth M.; Landi, Maria T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pee, David] Informat Management Serv Inc, Rockville, MD USA. RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 8030, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 20 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 BP 638 EP 646 DI 10.1002/gepi.20338 PG 9 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600006 PM 18454494 ER PT J AU Kraft, P Wacholder, S Cornelis, M Hu, F Hayes, RB Hunter, DJ Chanock, S AF Kraft, P. Wacholder, S. Cornelis, M. Hu, F. Hayes, R. B. Hunter, D. J. Chanock, S. TI Crystal Ball, Magic 8 Ball, or Both? Empirical examples of the promise and limits of genetic risk prediction for prostate cancer and type 2 diabetes SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Kraft, P.; Hunter, D. J.] Harvard Univ, Sch Publ Hlth, Prog Mol & Gen Epi, Cambridge, MA 02138 USA. [Wacholder, S.; Hayes, R. B.] NCI, Div Can Epi & Gen, Bethesda, MD 20892 USA. [Chanock, S.] NCI, Core Geno Fac, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 12 BP 672 EP 672 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600021 ER PT J AU Daw, EW Kammerer, C Lee, JH Feitosa, M Zmuda, J Borecki, I Barral, S Hadley, E Christensen, K Maveux, R Province, M AF Daw, E. W. Kammerer, C. Lee, J. H. Feitosa, M. Zmuda, J. Borecki, I. Barral, S. Hadley, E. Christensen, K. Maveux, R. Province, M. TI Genetic contributions to Longevity SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Daw, E. W.; Feitosa, M.; Borecki, I.; Province, M.] Washington Univ, St Louis, MO USA. [Kammerer, C.; Zmuda, J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Lee, J. H.; Barral, S.; Maveux, R.] Columbia Univ, New York, NY USA. [Hadley, E.] NIA, Bethesda, MD 20892 USA. RI Feitosa, Mary/K-8044-2012 OI Feitosa, Mary/0000-0002-0933-2410 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 58 BP 685 EP 686 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600067 ER PT J AU Duggal, P Klein, A Cheng, CY Lee, K Klein, R Klein, B Bailey-Wilson, JE AF Duggal, Priya Klein, Alison Cheng, Ching-Yu Lee, Kris Klein, Ronald Klein, Barbara Bailey-Wilson, Joan E. TI SNP Linkage Scan of Glaucoma Related Traits in the Beaver Dam Eye Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Duggal, Priya; Cheng, Ching-Yu; Bailey-Wilson, Joan E.] NHGRI, NIH, Bethesda, MD 20892 USA. [Klein, Alison] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Lee, Kris; Klein, Ronald; Klein, Barbara] Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 62 BP 687 EP 687 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600071 ER PT J AU Goldin, LR Kristinsson, SY Caporaso, NE Bjorkholm, M Turesson, I Landgren, O AF Goldin, L. R. Kristinsson, S. Y. Caporaso, N. E. Bjorkholm, M. Turesson, I. Landgren, O. TI Increased risk of monoclonal gammopathy of undetermined significance (MGUS) and lymphoid tumors among first-degree relatives of MGUS cases SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Goldin, L. R.; Caporaso, N. E.; Landgren, O.] NCI, Bethesda, MD 20892 USA. [Turesson, I.] Malmo Univ Hosp, Malmo, Sweden. [Kristinsson, S. Y.; Bjorkholm, M.] Karolinska Inst, Stockholm, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 76 BP 691 EP 691 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600085 ER PT J AU Gu, E Bergen, A Chatterjee, N Sheng-Shih, J Yu, K Yeager, M Hunter, DJ Thomas, G Jacobs, K Landi, MT Chinock, S Chen, J Ziegler, R Caporaso, N Kraft, P AF Gu, E. Bergen, A. Chatterjee, N. Sheng-Shih, J. Yu, K. Yeager, M. Hunter, D. J. Thomas, G. Jacobs, K. Landi, M. T. Chinock, S. Chen, J. Ziegler, R. Caporaso, N. Kraft, P. TI Combining two genome wide association scans for seven smoking related phenotypes replicates published associations in the CHRNA3/5 region SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Gu, E.; Hunter, D. J.; Chen, J.; Kraft, P.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Chatterjee, N.; Yu, K.; Landi, M. T.; Ziegler, R.; Caporaso, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Yeager, M.; Thomas, G.; Jacobs, K.; Chinock, S.] NCI, Core Genotyping Facil, Bethesda, MD 20892 USA. [Sheng-Shih, J.] Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 83 BP 693 EP 693 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600092 ER PT J AU Hancock, DB Martin, ER Scott, W AF Hancock, D. B. Martin, E. R. Scott, Wk. TI Potential interactions among NOS genes in Parkinson disease SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Hancock, D. B.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Martin, E. R.; Scott, Wk.] Univ Miami, Inst Human Genom, Miami, FL USA. RI Hancock, Dana/D-8577-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 89 BP 695 EP 695 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600098 ER PT J AU Kim, Y Sorant, AJM Wilson, AF AF Kim, Y. Sorant, A. J. M. Wilson, A. F. TI Genetic heterogeneity and the power of population- and intra-familial based tests of association for quantitative traits SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Kim, Y.; Sorant, A. J. M.; Wilson, A. F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 105 BP 699 EP 700 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600114 ER PT J AU Liang, X Ng, D McMaster, ML Landgren, O Ciporaso, N Goldin, LR AF Liang, X. Ng, D. McMaster, M. L. Landgren, O. Ciporaso, N. Goldin, L. R. TI Common Genetic Variants in Candidate Genes and Risk of Familial Lymphoma (LP) SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Liang, X.; Ng, D.; McMaster, M. L.; Landgren, O.; Ciporaso, N.; Goldin, L. R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 118 BP 703 EP 704 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600127 ER PT J AU Mandal, DM Ledet, EM Bailey-Wilson, JE AF Mandal, D. M. Ledet, E. M. Bailey-Wilson, J. E. TI Identification of prostate cancer susceptible locus in high-risk African-American families SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Mandal, D. M.; Ledet, E. M.] LSU Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. [Bailey-Wilson, J. E.] NHGRI, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 127 BP 706 EP 706 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600136 ER PT J AU Matteini, AM Fallin, MD Kammerer, CM Schupf, N Yashin, AI Mayeux, R Barr, RG Arbeev, KG Christensen, K Hadley, EC Newman, AB Walston, JD AF Matteini, A. M. Fallin, M. D. Kammerer, C. M. Schupf, N. Yashin, A. I. Mayeux, R. Barr, R. G. Arbeev, K. G. Christensen, K. Hadley, E. C. Newman, A. B. Walston, J. D. TI Heritability of Endophenotypes of Pulmonary & Physical Function in Long Life Family Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Matteini, A. M.; Walston, J. D.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Kammerer, C. M.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Schupf, N.; Mayeux, R.; Barr, R. G.] Columbia Univ, New York, NY 10027 USA. [Yashin, A. I.; Arbeev, K. G.] Duke Univ, Durham, NC 27706 USA. [Christensen, K.] Univ So Denmark, Odense, Denmark. [Hadley, E. C.] NIA, Bethesda, MD 20892 USA. RI Christensen, Kaare/C-2360-2009 OI Christensen, Kaare/0000-0002-5429-5292 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 129 BP 706 EP 707 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600138 ER PT J AU Sung, H Herrera-Galeano, JE Sorant, AJM Mathias, RA Wilson, AF AF Sung, H. Herrera-Galeano, J. E. Sorant, A. J. M. Mathias, R. A. Wilson, A. F. TI Lack of agreement among intra-familial tests of association for quantitative traits with low heritabilities SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Sung, H.; Herrera-Galeano, J. E.; Sorant, A. J. M.; Mathias, R. A.; Wilson, A. F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Herrera-Galeano, J. E.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 160 BP 715 EP 716 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600169 ER PT J AU Tayo, BO Luke, A Zhu, X Adeyemo, A Cooper, RS AF Tayo, B. O. Luke, A. Zhu, X. Adeyemo, A. Cooper, R. S. TI Association of regions on chromosomes 6 and 7 with blood pressure in Nigerian families SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Tayo, B. O.; Luke, A.; Cooper, R. S.] Loyola Univ, Chicago Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA. [Zhu, X.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Adeyemo, A.] NIH, Intramural Ctr Genom & Hlth Dispar, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 164 BP 716 EP 717 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600173 ER PT J AU Wu, H Romieu, I Sienra-Monge, JJ Li, H del Rio-Navarro, BE London, SJ AF Wu, H. Romieu, I. Sienra-Monge, J. J. Li, H. del Rio-Navarro, B. E. London, S. J. TI Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Genetic-Epidemiology-Society CY SEP 14-16, 2008 CL St Louis, MO SP Int Genet Epidimiol Soc C1 [Romieu, I.] NIPH, Cuernavaca, Morelos, Mexico. [Sienra-Monge, J. J.; del Rio-Navarro, B. E.] HIMFG, Mexico City, DF, Mexico. [London, S. J.] NIEHS, EB, DIR, NIH,DHHS,RTP,NC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2008 VL 32 IS 7 MA 178 BP 720 EP 721 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 371ZQ UT WOS:000260871600187 ER PT J AU Brandt, SM Jaramillo-Gutierrez, G Kumar, S Barillas-Mury, C Schneider, DS AF Brandt, Stephanie M. Jaramillo-Gutierrez, Giovanna Kumar, Sanjeev Barillas-Mury, Carolina Schneider, David S. TI Use of a Drosophila Model to Identify Genes Regulating Plasmodium Growth in the Mosquito SO GENETICS LA English DT Article ID ANOPHELES-GAMBIAE; LISTERIA-MONOCYTOGENES; BACTERIAL; INFECTION; MELANOGASTER; BERGHEI AB We performed a forward genetic screen, using Drosophila as a surrogate mosquito, to identify host factors required for the growth of the avian malaria parasite, Plasmodium gallinaceum. We identified 18 presumed loss-of-function mutants that reduced the growth of the parasite in flies. Presumptive Mutation sites were identified in 14 of the mutants on the basis of the insertion site of a transposable element. None of the identified genes have been previously implicated in innate immune responses or interactions with Plasmodium. The functions of five Anopheles gambiae homologs were tested by using RNAi to knock down gene function followed by measuring the growth of the rodent parasite, Plasmodium berghei. Loss of function of four of these genes in the mosquito affected Plasmodium growth, suggesting that Drosophila can be used effectively as a Surrogate mosquito to identify relevant lost factors in the mosquito. C1 [Brandt, Stephanie M.; Schneider, David S.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Jaramillo-Gutierrez, Giovanna; Kumar, Sanjeev; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20892 USA. RP Schneider, DS (reprint author), Stanford Univ, Dept Microbiol & Immunol, D333 Fairchild Bldg,299 Campus Dr, Stanford, CA 94305 USA. EM dschneider@stanford.edu FU Ellison Medical Foundation; National Science Foundation FX This work was supported by the Ellison Medical Foundation (D.S.S.) and the National Science Foundation (S.M.B.). NR 19 TC 21 Z9 22 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2008 VL 180 IS 3 BP 1671 EP 1678 DI 10.1534/genetics.108.089748 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 374IE UT WOS:000261036200034 PM 18791251 ER PT J AU Gerken, TA Ten Hagen, KG Jamison, O AF Gerken, Thomas A. Ten Hagen, Kelly G. Jamison, Oliver TI Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase ortholog pairs SO GLYCOBIOLOGY LA English DT Article DE evolution; mucin; O-glycosylation; sequence motifs; UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase ID ACETYL-D-GALACTOSAMINE; N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY; NEIGHBORING RESIDUE GLYCOSYLATION; O-LINKED GLYCOSYLATION; UDP-GALNAC; TOXOPLASMA-GONDII; LECTIN DOMAINS; CDNA CLONING; FUNCTIONAL-CHARACTERIZATION; CAENORHABDITIS-ELEGANS AB UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltrans- ferases (ppGalNAc Ts) comprise a large family of glycosyltransferases that initiate mucin-type protein O-glycosylation, transferring alpha-GalNAc to Thr and Ser residues of polypeptide acceptors. Families of ppGalNAc Ts are found across diverse eukaryotes with orthologs identifiable from mammals to single-cell organisms. The peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remain poorly understood. Previously, we reported a series of oriented random peptide substrate libraries for quantitatively determining the peptide substrate specificities of the mammalian ppGalNAc T1 and T2 (Gerken TA, Raman J, Fritz TA, Jamison O. 2006. Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 & T2 (ppGalNAc T1 & T2) derived from oriented random peptide substrates. J Biol Chem. 281:32403-32416). With these substrates, previously unknown features of the transferases were revealed. Utilizing these and a new lengthened set of random peptides, studies have now been performed on PGANT5 and PGANT2, the Drosophila orthologs of T1 and T2. The results from these studies suggest that the major peptide substrate determinants for these transferases are contained within 2 to 3 residues flanking the site of glycosylation. It is further found that the mammalian and fly T1 orthologs display very similar peptide substrate preferences, while the T2 orthologs are nearly indistinguishable, suggesting similar peptide preferences amongst orthologous pairs have been maintained across evolution. This conclusion is further supported by sequence homology comparisons of each of the transferase orthologs, showing that the peptide substrate and UDP binding site residues are more highly conserved between species relative to their remaining catalytic and lectin domain residues. C1 [Gerken, Thomas A.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. [Gerken, Thomas A.; Jamison, Oliver] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Gerken, TA (reprint author), Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. EM txg2@cwru.edu FU National Institutes of Health [RO1-CA-78834]; National Institute of Dental and Craniofacial Research FX National Institutes of Health (Grant RO1-CA-78834 to T. A. G.); the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health (to K. G. T. H). NR 49 TC 27 Z9 27 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 BP 861 EP 870 DI 10.1093/glycob/cwn073 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400004 PM 18669915 ER PT J AU Ten Hagen, KG Zhang, Y Zhang, LP AF Ten Hagen, Kelly G. Zhang, Ying Zhang, Liping TI The Role of O-Glycosylation in Cell Adhesion During Development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Ten Hagen, Kelly G.; Zhang, Ying; Zhang, Liping] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 12 BP 942 EP 942 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400021 ER PT J AU Ishihara, M Sonon, R Chill, L Trinh, L Shiloach, J Azadi, P AF Ishihara, Mayumi Sonon, Roberto Chill, Liat Trinh, Loc Shiloach, Joseph Azadi, Parastoo TI Characterization of Glycan Structure and the Sites of Glycosylation on the Recombinant Human alpha 1-Proteinase Inhibitor, alpha-1PI By Mass Spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Ishihara, Mayumi; Sonon, Roberto; Azadi, Parastoo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Chill, Liat; Trinh, Loc; Shiloach, Joseph] NIH, Biotechnol Core Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 95 BP 963 EP 963 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400104 ER PT J AU Poling, JS Manoli, I Klootwijk, R Kurland, D Ciccone, C Patzel, K Darvish, D Zerfas, P Starost, M Dorward, H Gahl, WA Huizing, M AF Poling, Justin S. Manoli, Irini Klootwijk, Riko Kurland, David Ciccone, Carla Patzel, Katherine Darvish, Daniel Zerfas, Patricia Starost, Matthew Dorward, Heidi Gahl, William A. Huizing, Marjan TI Hyposialylation in Various Glomerulopathies and Possible Rescue by N-Acetylmannosamine SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Poling, Justin S.; Manoli, Irini; Kurland, David; Ciccone, Carla; Patzel, Katherine; Dorward, Heidi; Gahl, William A.; Huizing, Marjan] NHGRI, NIH, Bethesda, MD 20892 USA. [Klootwijk, Riko] Univ Coll, London, England. [Darvish, Daniel] HIBM Res Grp, Encino, CA USA. [Zerfas, Patricia; Starost, Matthew] NIH Vet Resources, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 97 BP 964 EP 964 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400106 ER PT J AU Hsu, KL Gildersleeve, JC Mahal, LK AF Hsu, Ku-Lung Gildersleeve, Jeffrey C. Mahal, Lara K. TI Advancing the Lectin Microarray SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Hsu, Ku-Lung; Mahal, Lara K.] Univ Texas Austin, Austin, TX 78712 USA. [Gildersleeve, Jeffrey C.] NCI, Frederick, MD 21701 USA. RI Gildersleeve, Jeffrey/N-3392-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 123 BP 970 EP 970 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400132 ER PT J AU Raman, J Guan, Y Fritz, TA Tabak, LA AF Raman, Jayalakshmi Guan, Yu Fritz, Timothy A. Tabak, Lawrence A. TI Expression Patterns and Substrate Specificities of 4 Novel Members of the UDP-GalNAc:Polypeptide a-N-Acetlygalactosaminyltransferase Family SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Raman, Jayalakshmi; Guan, Yu; Fritz, Timothy A.; Tabak, Lawrence A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 144 BP 975 EP 975 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400153 ER PT J AU Puntambekar, N Kee, Y Kramer, K AF Puntambekar, Nisha Kee, Yun Kramer, Kenneth TI Spatial and Temporal Expressions of Glypicans in Zebrafish Embryonic Development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Puntambekar, Nisha; Kee, Yun; Kramer, Kenneth] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 158 BP 979 EP 979 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400167 ER PT J AU Tian, E Hoffman, M Ten Hagen, KG AF Tian, E. Hoffman, Matthew Ten Hagen, Kelly G. TI Mucin-Type O-Glycosylation During Epithelial Tube Formation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Tian, E.; Hoffman, Matthew; Ten Hagen, Kelly G.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 157 BP 979 EP 979 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400166 ER PT J AU Oyelaran, O Joseph, M Gildersleeve, J AF Oyelaran, Oyinda Joseph, Manimala Gildersleeve, Jeff TI Profiling Antibodies with Carbohydrate Antigen Arrays SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Oyelaran, Oyinda; Joseph, Manimala; Gildersleeve, Jeff] Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 175 BP 983 EP 983 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400183 ER PT J AU Houghton, A Barchi, J Sundgren, A Morey, S Rittenhouse-Olson, K AF Houghton, Amy Barchi, Joseph Sundgren, Andreas Morey, Susan Rittenhouse-Olson, Kate TI Novel Synthetic Carbohydrate Tumor Antigen Vaccine Strategies SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Houghton, Amy; Morey, Susan; Rittenhouse-Olson, Kate] SUNY Buffalo, Buffalo, NY 14260 USA. [Barchi, Joseph; Sundgren, Andreas] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 185 BP 985 EP 986 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400194 ER PT J AU Boeggeman, EE Ramakrishnan, B Pasek, M Waybright, TJ Manzoni, MR Qasba, PK AF Boeggeman, Elizabeth E. Ramakrishnan, Boopathy Pasek, Marta Waybright, Timothy J. Manzoni, Maria R. Qasba, Pradman K. TI Applications of Galactosyltransferases in the Site-specific Conjugation of Therapeutic Monoclonal Antibodies SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Pasek, Marta; Manzoni, Maria R.; Qasba, Pradman K.] NCI, SGS, CCR NP, Frederick, MD 21701 USA. [Boeggeman, Elizabeth E.; Ramakrishnan, Boopathy; Waybright, Timothy J.] SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 236 BP 998 EP 998 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400245 ER PT J AU Pasek, M Ramakrishnan, B Boeggeman, E Manzoni, M Qasba, P AF Pasek, Marta Ramakrishnan, Boopathy Boeggeman, Elizabeth Manzoni, Maria Qasba, Pradman TI Targeted Mutations of Bovine alpha 1,3 Galactosyltransferase (a1,3 GalT) that Change it's Sugar Donor Specificity: Applications in Nanobiology SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Pasek, Marta; Manzoni, Maria; Qasba, Pradman] NCI Frederick, CCR, Struct Glycobiol Sect, Frederick, MD USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 235 BP 998 EP 998 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400244 ER PT J AU Vgontzas, A Cui, LH Merikangas, KR AF Vgontzas, Angeliki Cui, Lihong Merikangas, Kathleen R. TI Are Sleep Difficulties Associated With Migraine Attributable to Anxiety and Depression? SO HEADACHE LA English DT Article DE sleep; migraine; anxiety; depression ID QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; UNITED-STATES; YOUNG-ADULTS; HEADACHE; PREVALENCE; CHILDREN; COMORBIDITY; DISTURBANCES AB (Headache 2008;48:1451-1459) To examine whether sleep complaints reported by migraineurs can be attributed to comorbid anxiety and/or depression. A consistent association between migraine and sleep complaints has been reported in community and clinical studies. However, anxiety and depression are often comorbid with migraine. Thus, it may be possible that the increased prevalence of sleep problems in migraineurs is attributable to comorbid anxiety and depression. To our knowledge, no previous studies have demonstrated that the associations are not solely attributed to comorbid anxiety and depression. Controlled family study of anxiety disorders and substance use disorders in a community in New Haven County, CT. The sample included 221 probands (41 migraineurs) and their 261 directly interviewed first-degree relatives (39 migrainuers), including parents, siblings, and offspring over age 18. A lifetime history of migraine was obtained using the Diagnostic Interview for Headache Syndromes. A lifetime history of psychiatric disorders was obtained using the semi-structured Schedule for Affective Disorders and Schizophrenia which was modified to incorporate Diagnostic and Statistical Manual diagnostic criteria. Several sleep items on current and lifetime sleep complaints were included as a subset of the interview. There was a significant association between migraine and the number of sleep problems as well as several specific sleep symptoms among probands and their adult relatives. Adults with migraine reported having significantly more lifetime sleep problems (OR [CI] = 2.3 [1.1-4.6]), and more current sleep difficulties, specifically, inadequate sleep (2.5 [1.2-5.0]), difficulty falling asleep (3.0 [1.5-6.3]), and persistent nightmares of childhood onset (4.3 [1.8-9.9]) than those without migraine. The associations between sleep problems and migraine persisted after controlling for both lifetime and current anxiety and mood disorders. The association between sleep problems and migraine that is not solely explained by comorbid anxiety disorders or depression suggests that sleep problems should be evaluated among people with migraine. C1 [Vgontzas, Angeliki; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), 35 Convent Dr,1A201,MSC 3720, Bethesda, MD 20814 USA. FU Intramural NIH HHS [Z01 MH002804-05, Z01 MH002849-03] NR 48 TC 37 Z9 39 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-8748 J9 HEADACHE JI Headache PD NOV-DEC PY 2008 VL 48 IS 10 BP 1451 EP 1459 DI 10.1111/j.1526-4610.2008.01175.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 375OV UT WOS:000261124100006 PM 18624714 ER PT J AU Bandettini, WP Arai, AE AF Bandettini, W. P. Arai, A. E. TI Advances in clinical applications of cardiovascular magnetic resonance imaging SO HEART LA English DT Review ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; POSITRON-EMISSION-TOMOGRAPHY; WALL-MOTION ABNORMALITIES; LEFT-VENTRICULAR FUNCTION; TARGETED CONTRAST AGENT; ISCHEMIC-HEART-DISEASE; MESENCHYMAL STEM-CELLS; TIME CINE MRI; DELAYED-ENHANCEMENT AB Cardiovascular magnetic resonance (CMR) is an evolving technology with growing indications within the clinical cardiology setting. This review article summarises the current clinical applications of CMR. The focus is on the use of CMR in the diagnosis of coronary artery disease with summaries of validation literature in CMR viability, myocardial perfusion, and dobutamine CMR. Practical uses of CMR in non-coronary diseases are also discussed. C1 [Bandettini, W. P.; Arai, A. E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Bandettini, WP (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room BID416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM ingkanisorn@nih.gov FU Intramural NIH HHS [Z01 HL004607-09, Z01 HL004607-10, ZID HL006140-01, ZID HL006140-02] NR 142 TC 22 Z9 22 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD NOV PY 2008 VL 94 IS 11 BP 1485 EP 1495 DI 10.1136/hrt.2007.119016 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 361VK UT WOS:000260155100026 PM 18208827 ER PT J AU Morishima, C Morgan, TR Everhart, JE Wright, EC Apodaca, MC Gretch, DR Shiffman, ML Everson, GT Lindsay, KL Lee, WM Lok, ASF Dienstag, JL Ghany, MG Curto, TM AF Morishima, Chihiro Morgan, Timothy R. Everhart, James E. Wright, Elizabeth C. Apodaca, Minjun C. Gretch, David R. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Lee, William M. Lok, Anna S. F. Dienstag, Jules L. Ghany, Marc G. Curto, Teresa M. CA HALT C Trial Grp TI Interpretation of Positive Transcription-Mediated Amplification Test Results from Polymerase Chain Reaction-Negative Samples Obtained After Treatment of Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID INTERFERON-ALPHA THERAPY; RNA QUALITATIVE ASSAY; HCV RNA; VIRUS-RNA; VIROLOGICAL RESPONSE; PEGINTERFERON ALPHA-2A; FOLLOW-UP; RIBAVIRIN; TRIAL; TMA AB The siemens VERSANT (R) transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome. Peginterferon and ribavirin treatment was initiated in 1145 prior interferon nonresponders with advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks 12, 20, 24,48, and 72 were subsequently tested by TMA. Nine of the I I patients returned for testing (median, 30 months after the week 72 visit), and all had undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained during treatment that were tested twice by TMA, 17% overall exhibited consistently positive results, and 21% exhibited inconsistently positive results. SVR was more likely if TMA was consistently negative than if consistently or inconsistently positive. With continued treatment, patients with inconsistently positive TMA results were more likely to become TMA-negative than TMA-positive (P < 0.0001). Conclusion; In PCR-negative samples, positive TMA results may indicate the presence of low levels of HCV RNA. However, because patients with positive TMA results may achieve SVR, management decisions during therapy should not be based on a single positive TMA test result. (HEPATOLOGY 2008;48:1412-1419.) C1 [Morishima, Chihiro; Apodaca, Minjun C.; Gretch, David R.] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Lok, Anna S. F.] Univ Michigan, Div Gastroenterol, Med Ctr, Ann Arbor, MI 48109 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA USA. [Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. RI Lok, Anna /B-8292-2009; Lopes Lera, Daniele/H-6081-2016; Acorsi, Rayanne/H-6066-2016; Vieira Teixeira, Jorge Juarez/H-6495-2016; MOREIRA NETO, LUIZ JORGE/H-6588-2016; OLIVEIRA, WELLINGTON/H-6591-2016; Borges Padilha Ferreira, Fabiana/H-6597-2016; Beletini, Lucimara Fatima/H-6083-2016; Cristina Ferreira, Erika /H-6607-2016; OI MOREIRA NETO, LUIZ JORGE/0000-0002-7407-4120; Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases [N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328]; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health [M01RR-06192, M01RR-01066, M01RR-00051, M01RR-00827, M01RR-00633, M01RR-00043, M01RR-00042, M01RR-00065]; Hoffmann-La Roche, Inc; Bayer Diagnostics FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases under contract numbers N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327 and N01-DK-9-2328, with supplemental funds from the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers M01RR-06192, M01RR-01066, M01RR-00051, M01RR-00827, M01RR-00633, M01RR-00043, M01RR-00042, and M01RR-00065). Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc. through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. Financial support was also provided by Bayer Diagnostics through a Clinical Trial Agreement with the National Institutes of Health and a Research and Technology Development Agreement with the University of Washington. NR 19 TC 18 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2008 VL 48 IS 5 BP 1412 EP 1419 DI 10.1002/hep.22487 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BP UT WOS:000260596600010 PM 18816437 ER PT J AU Schonhoff, CM Thankey, K Webster, CRL Wakabayashi, Y Wolkoff, AW Anwer, MS AF Schonhoff, Christopher M. Thankey, Krishna Webster, Cynthia R. L. Wakabayashi, Yoshiyuki Wolkoff, Allan W. Anwer, M. Sawkat TI Rab4 Facilitates Cyclic Adenosine Monophosphate-Stimulated Bile Acid Uptake and Na+-Taurocholate Cotransporting Polypeptide Translocation SO HEPATOLOGY LA English DT Article ID RAT-LIVER; SIGNALING PATHWAY; NA+/TAUROCHOLATE COTRANSPORT; VESICLE TRANSPORT; GLUCOSE-TRANSPORT; INSULIN; EXPRESSION; PROTEINS; ADIPOCYTES; MEMBRANE AB Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium-taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP-induced TC uptake and Ntcp translocation. HuH-Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP-induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time-dependent, but phosphoinositide-3-kinase-independent manner. Conclusion: Taken together, these results suggest that cAMP-mediated phosphoinositide-3-kinase-independent activation of Rab4 facilitates Ntcp translocation in HuH-Ntcp cells. (HEPATOLOGY 2008;48:1665-1670.) C1 [Schonhoff, Christopher M.; Thankey, Krishna; Anwer, M. Sawkat] Tufts Cummings Sch Vet Med, Dept Biomed Sci, North Grafton, MA 01536 USA. [Webster, Cynthia R. L.] Tufts Cummings Sch Vet Med, Dept Clin Sci, North Grafton, MA 01536 USA. [Wakabayashi, Yoshiyuki] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Wolkoff, Allan W.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Anwer, MS (reprint author), Tufts Cummings Sch Vet Med, Dept Biomed Sci, 200 Westboro Rd, North Grafton, MA 01536 USA. EM SawkatAnwer@tufts.edu FU NIH [DK-33436, DK-65975, DK-07635, RR-18267, DK23026]; Intramural Program of Eunice Kennedy Shriver, NICHD, NIH FX Supported in part by NIH grants DK-33436 (to M. S.A.), DK-65975 (to C. R.L.W), DK-07635 and RR- 18267 (to K.T.), DK23026 (to A.W.W) and by the Intramural Program of Eunice Kennedy Shriver, NICHD, NIH (to Y.W) NR 33 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2008 VL 48 IS 5 BP 1665 EP 1670 DI 10.1002/hep.22495 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BP UT WOS:000260596600035 PM 18688880 ER PT J AU Laszlo, V Dezso, K Baghy, K Papp, V Kovalszky, I Safrany, G Thorgeirsson, SS Nagy, P Paku, S AF Laszlo, Viktoria Dezso, Katalin Baghy, Kornelia Papp, Veronika Kovalszky, Ilona Safrany, Geza Thorgeirsson, Snorri S. Nagy, Peter Paku, Sandor TI Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE Oval cell; Maturation; Regeneration; Retroviral transduction; Primary mitogen ID HEPATIC OVAL CELLS; STEM-CELLS; IN-VITRO; PARTIAL-HEPATECTOMY; REGENERATION; EXPRESSION; PROLIFERATION; INJURY; MODEL; HEPATOCARCINOGENESIS AB The 2-acetaminofluorene/partial hepatectomy (AAF/Phx) model is widely used to induce oval/progenitor cell proliferation in the rat liver. We have used this model to study the impact of a primary hepatocyte mitogen, triiodothyronine (T3) on the liver regenerating by the recruitment of oval/progenitor cells. Administration of T3 transiently accelerates the proliferation of the oval cells, which is followed by rapid differentiation into small hepatocytes. The oval cell origin of the small hepatocytes has been proven by tracing retrovirally transduced and BrdU marked oval cells. The differentiating oval cells become positive for hepatocyte nuclear factor-4 and start to express hepatocyte specific connexin 32, alpha 1 integrin, Prox1, cytochrom P450s, and form CD 26 positive bile canaliculi. At the same time oval cell specific OV-6 and alpha-fetoprotein expression is lost. The upregulation of hepatocyte specific mRNAs: albumin, tyrosine aminotransferase and tryptophan 2,3-dioxygenase detected by real-time PCR also proves hepatocytic maturation. The hepatocytic conversion of oval cells occurs on the seventh day after the Phx in this model while the first small hepatocytes appear 5 days later without T3 treatment. The administration of the primary hepatocyte mitogen T3 accelerates the differentiation of hepatic progenitor cells into hepatocytes in vivo, and that may have therapeutic potential. C1 [Laszlo, Viktoria; Dezso, Katalin; Baghy, Kornelia; Papp, Veronika; Kovalszky, Ilona; Nagy, Peter; Paku, Sandor] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. [Safrany, Geza] Natl Res Inst Radiobiol & Radiohyg, Budapest, Hungary. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nagy, P (reprint author), Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Ulloi Ut 26, H-1085 Budapest, Hungary. EM nagy@korb1.sote.hu NR 42 TC 18 Z9 18 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD NOV PY 2008 VL 130 IS 5 BP 1005 EP 1014 DI 10.1007/s00418-008-0482-z PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 359OR UT WOS:000259997900016 PM 18663461 ER PT J AU Read, JS Best, BM Stek, A Hu, C Capparelli, EV Holland, DT Burchett, SK Smith, ME Sheeran, EC Shearer, WT Febo, I Mirochnick, M AF Read, J. S. Best, B. M. Stek, A. M. Hu, C. Capparelli, E. V. Holland, D. T. Burchett, S. K. Smith, M. E. Sheeran, E. C. Shearer, W. T. Febo, I. Mirochnick, M. TI Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum SO HIV MEDICINE LA English DT Article DE HIV; nelfinavir; pharmacokinetics; pregnancy ID PROTEASE INHIBITORS; WOMEN; EXPOSURE AB Objectives Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum. Methods The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >= 10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 mu g h/mL). Results Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P <= 0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC(0-12) and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P < 0.01). The NFV AUC(0-12) exceeded the AUC(0-12) target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (C(min)) was above the suggested minimum trough concentration (0.8 mu g/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was < 400 HIV-1 RNA copies/mL in 81% of patients at delivery. Conculsions These results suggest that higher doses of NFV should be considered during pregnancy. C1 [Read, J. S.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. [Best, B. M.; Capparelli, E. V.; Holland, D. T.] Univ Calif San Diego, San Diego, CA 92103 USA. [Stek, A. M.] Univ So Calif, Los Angeles, CA USA. [Hu, C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Burchett, S. K.] Childrens Hosp, Boston, MA 02115 USA. [Smith, M. E.] NIAID, Bethesda, MD 20892 USA. [Sheeran, E. C.] Social & Sci Syst Inc, Silver Spring, MD USA. [Shearer, W. T.] Baylor Coll Med, Houston, TX 77030 USA. [Febo, I.] Univ Puerto Rico, San Juan, PR 00936 USA. [Mirochnick, M.] Boston Univ, Boston, MA 02215 USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11C,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. EM jennifer_read@nih.gov RI Hu, Chengcheng/A-8391-2017 FU NCRR NIH HHS [5 M01 RR01271, M01 RR000533, M01 RR001271, M01 RR00533]; NIAID NIH HHS [U01 AI068632-03, U01 AI027560, U01 AI032907, U01 AI041089, U01 AI04189, U01 AI32907, U01 AI41089, UO1 AI27560-18]; NICHD NIH HHS [N01-HD-3-3365, U01 HD031318, U01-HD-031318-11] NR 18 TC 21 Z9 21 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD NOV PY 2008 VL 9 IS 10 BP 875 EP 882 DI 10.1111/j.1468-1293.2008.00640.x PG 8 WC Infectious Diseases SC Infectious Diseases GA 366QS UT WOS:000260499100006 PM 18795962 ER PT J AU Theoret, MR Cohen, CJ Nahvi, AV Ngo, LT Suri, KB Powell, DJ Dudley, ME Morgan, RA Rosenberg, SA AF Theoret, Marc R. Cohen, Cyrille J. Nahvi, Azam V. Ngo, Lien T. Suri, Kimberly B. Powell, Daniel J., Jr. Dudley, Mark E. Morgan, Richard A. Rosenberg, Steven A. TI Relationship of p53 Overexpression on Cancers and Recognition by Anti-p53 T Cell Receptor-Transduced T Cells SO HUMAN GENE THERAPY LA English DT Article ID WILD-TYPE P53; SEQUENCE P53(264-272) PEPTIDE; PERIPHERAL-BLOOD LYMPHOCYTES; ADVANCED BREAST-CANCER; MESSENGER-RNA LEVELS; LI-FRAUMENI-SYNDROME; DENDRITIC CELLS; TUMOR-ANTIGEN; LUNG-CANCER; COLORECTAL-CANCER AB Tumor suppressor p53 is reported to be an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in inactivation and often an accumulation of the protein in the tumor cells. Only low amounts of protein are detectable in normal tissues. The differential display of antigen in normal versus tumor tissues has been reported to create an opportunity to target p53 by immunotherapy. We sought to determine the relationship between p53 expression and its recognition by cognate T cells in human tumors including common epithelial malignancies. Inasmuch as nonsense or missense p53 mutations may disrupt processing and presentation, we studied tumors with either identified wild-type or mutated p53, based on our gene-sequencing studies or published data. T cells transduced with a high-affinity, p53(264-272)-reactive T cell receptor (TCR) derived from HLA-A2.1 transgenic mice recognized a wide panel of human tumor lines. There was no significant correlation between p53 expression in tumors and recognition by the anti-p53 TCR-transduced T cells. This conclusion was based on the study of 48 cell lines and is in contrast to several prior studies that used only a limited number of selected cell lines. A panel of normal cells was evaluated for recognition, and some of these populations were capable of stimulating anti-p53 T cells, albeit at low levels. These studies raise doubts concerning the suitability of targeting p53 in the immunotherapy of cancer patients. C1 [Theoret, Marc R.; Nahvi, Azam V.; Ngo, Lien T.; Suri, Kimberly B.; Dudley, Mark E.; Morgan, Richard A.; Rosenberg, Steven A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Theoret, Marc R.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, IL-52900 Ramat Gan, Israel. [Powell, Daniel J., Jr.] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10-CRC,Room 3W3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM sar@nih.gov FU National Cancer Institute, National Institutes of Health FX Funding to support this work was provided by the Intramural Research Program, National Cancer Institute, National Institutes of Health. The authors thank Dr. Scott Garrett, Dr. Donald Sens, and Dr. Hung Khong for providing cell lines; Dr. Zhiya Yu for providing a melanoma-specific, gp100154-162-specific T cell receptor; and Dr. John Wunderlich, Dr. Bianca Heemskerk, Arnold Mixon, and Shawn Farid for help and expertise. NR 59 TC 16 Z9 17 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2008 VL 19 IS 11 BP 1219 EP 1231 DI 10.1089/hum.2008.083 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 380UW UT WOS:000261492100001 PM 19848582 ER PT J AU Muftuoglu, M Oshima, J von Kobbe, C Cheng, WH Leistritz, DF Bohr, VA AF Muftuoglu, Meltem Oshima, Junko von Kobbe, Cayetano Cheng, Wen-Hsing Leistritz, Dru F. Bohr, Vilhelm A. TI The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis SO HUMAN GENETICS LA English DT Review ID SYNDROME ADULT PROGERIA; CENTRAL-NERVOUS-SYSTEM; SYNDROME GENE; HELICASE EXPRESSION; SYNDROME PROTEIN; SYNDROME LOCUS; BREAST-CANCER; AGING PROCESS; DNA-REPAIR; WRN GENE AB Werner syndrome (WS) is an adult onset segmental progeroid syndrome caused by mutations in the WRN gene. The WRN gene encodes a 180 kDa nuclear protein that possesses helicase and exonuclease activities. The absence of WRN protein leads to abnormalities in various DNA metabolic pathways such as DNA repair, replication and telomere maintenance. Individuals with WS generally develop normally until the third decade of life, when premature aging phenotypes and a series of age-related disorders begin to manifest. In Japan, where a founder effect has been described, the frequency of Werner heterozygotes appears to be as high as 1/180 in the general population. Due to the relatively non-specific nature of the symptoms and the lack of awareness of the condition, this disease may be under-diagnosed in other parts of the world. Genetic counseling of WS patients follows the path of other autosomal recessive disorders, with special attention needed for cancer surveillance in relatives. Molecular diagnosis of WS is made by nucleotide sequencing and, in some cases, protein analysis. It is also of potential interest to measure WRN activities in WS patients. More than 50 different disease-causing mutations in the WRN gene have been identified in WS patients from all over the world. All but one of these cases has mutations that result in the premature termination of the protein. Here we describe the clinical, molecular and biochemical characteristics of WS for use by medical professionals in a health care setting. Additional information is available through the International Registry of WS. C1 [Muftuoglu, Meltem; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Oshima, Junko; Leistritz, Dru F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [von Kobbe, Cayetano] Chimera Pharma Bionostra Grp, Canc Vaccines Grp, Madrid 28760, Spain. [Cheng, Wen-Hsing] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov FU NIH, National Institute on Aging [CA78088] FX This work was partially supported by the Intramural Research Program of the NIH, National Institute on Aging, and by the NIH grant CA78088 ( to J.O). NR 44 TC 68 Z9 73 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2008 VL 124 IS 4 BP 369 EP 377 DI 10.1007/s00439-008-0562-0 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 370MU UT WOS:000260767100004 PM 18810497 ER PT J AU Nyholt, DR LaForge, KS Kallela, M Alakurtti, K Anttila, V Farkkila, M Hamalainen, E Kaprio, J Kaunisto, MA Heath, AC Montgomery, GW Gobel, H Todt, U Ferrari, MD Launer, LJ Frants, RR Terwindt, GM de Vries, B Verschuren, WMM Brand, J Freilinger, T Pfaffenrath, V Straube, A Ballinger, DG Zhan, Y Daly, MJ Cox, DR Dichgans, M van den Maagdenberg, AMJM Kubisch, C Martin, NG Wessman, M Peltonen, L Palotie, A AF Nyholt, Dale R. LaForge, K. Steven Kallela, Mikko Alakurtti, Kirsi Anttila, Verneri Farkkila, Markus Hamalainen, Eija Kaprio, Jaakko Kaunisto, Mari A. Heath, Andrew C. Montgomery, Grant W. Goebel, Hartmut Todt, Unda Ferrari, Michel D. Launer, Lenore J. Frants, Rune R. Terwindt, Gisela M. de Vries, Boukje Verschuren, W. M. Monique Brand, Jan Freilinger, Tobias Pfaffenrath, Volker Straube, Andreas Ballinger, Dennis G. Zhan, Yiping Daly, Mark J. Cox, David R. Dichgans, Martin van den Maagdenberg, Arn M. J. M. Kubisch, Christian Martin, Nicholas G. Wessman, Maija Peltonen, Leena Palotie, Aarno TI A high-density association screen of 155 ion transport genes for involvement with common migraine SO HUMAN MOLECULAR GENETICS LA English DT Article ID FAMILIAL HEMIPLEGIC MIGRAINE; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; POTASSIUM CHANNELS; POPULATION; AURA; ATP1A2; SAMPLE; POWER AB The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case -control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P 5 0.00002; global P 5 0.02) was observed in the Finnish case -control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out. C1 [Nyholt, Dale R.; Martin, Nicholas G.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia. [LaForge, K. Steven] Rockefeller Univ, Lab Biol Addict Dis, New York, NY 10065 USA. [LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Biomed Helsinki, Res Program Mol Med, FIN-00014 Helsinki, Finland. [LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Dept Clin Chem, FIN-00014 Helsinki, Finland. [LaForge, K. Steven; Alakurtti, Kirsi; Anttila, Verneri; Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Univ Helsinki, Cent Hosp, Dept Med Genet, FIN-00014 Helsinki, Finland. [Kallela, Mikko; Farkkila, Markus] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. [Hamalainen, Eija; Kaunisto, Mari A.; Wessman, Maija] Univ Helsinki, Finnish Inst Mol Med, Finnish Genome Ctr, FIN-00014 Helsinki, Finland. [Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Kaprio, Jaakko] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, SF-00300 Helsinki, Finland. [Kaunisto, Mari A.; Wessman, Maija; Palotie, Aarno] Folkhalsan Res Ctr, Helsinki 00014, Finland. [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Montgomery, Grant W.] Queensland Inst Med Res, Mol Epidemiol Lab, Brisbane, Qld 4006, Australia. [Goebel, Hartmut] Kiel Pain & Headache Ctr, D-24149 Kiel, Germany. [Todt, Unda; Kubisch, Christian] Univ Cologne, Inst Human Genet, Inst Genet, D-50923 Cologne, Germany. [Todt, Unda] Univ Cologne, Ctr Mol Med, D-50923 Cologne, Germany. [Ferrari, Michel D.; Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RC Leiden, Netherlands. [Launer, Lenore J.] NIA, IRP, NIH, Bethesda, MD 20892 USA. [Frants, Rune R.; de Vries, Boukje; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RC Leiden, Netherlands. [Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, NL-3720 BA Bilthoven, Netherlands. [Brand, Jan] Migrane & Kopfschmerz Klin Konigstein, D-61462 Konigstein, Germany. [Freilinger, Tobias; Straube, Andreas; Dichgans, Martin] Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81377 Munich, Germany. [Pfaffenrath, Volker] Neurol Gemeinschaftspraxis Leopoldstr, D-81377 Munich, Germany. [Ballinger, Dennis G.; Zhan, Yiping; Cox, David R.] Perlegen Sci Inc, Mountain View, CA 94043 USA. [Daly, Mark J.; Peltonen, Leena; Palotie, Aarno] MIT, Broad Inst, Cambridge, MA 02141 USA. [Daly, Mark J.; Peltonen, Leena; Palotie, Aarno] Harvard Univ, Cambridge, MA 02141 USA. [Peltonen, Leena] Finnish Inst Mol Med, Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland. [Peltonen, Leena; Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. RP Nyholt, DR (reprint author), Queensland Inst Med Res, Genet Epidemiol Lab, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. EM dale.nyholt@qimr.edu.au RI Kubisch, Christian/F-1893-2011; Kaprio, Jaakko/A-1820-2008; Nyholt, Dale/C-8384-2013; Montgomery, Grant/B-7148-2008; OI Kubisch, Christian/0000-0003-4220-0978; Montgomery, Grant/0000-0002-4140-8139; Anttila, Verneri/0000-0002-0073-4675; Kaunisto, Mari/0000-0002-6946-9195; Kaprio, Jaakko/0000-0002-3716-2455; Martin, Nicholas/0000-0003-4069-8020 FU Sigrid Juselius Foundation; Academy of Finland [200923, 00213]; Helsinki University Central Hospital; EuroHead [LSHM-CT-2004-504837]; GenomEUtwin [QLG2-CT-2002-01254]; Oxnard Foundation; Helsinki Biomedical Graduate School; Biomedicum Helsinki Foundation; Finnish Cultural Foundation; Finnish Neurology Foundation and National Institutes of Health [RO1 NS37675]; National Institute on Alcohol Abuse and Alcoholism (United States) [AA007535, AA013320, AA013326, AA014041, AA07728, AA10249, AA11998]; Academy of Finland Center of Excellence in Complex Disease Genetics; National Health and Medical Research Council (NHMRC) [941177, 951023, 241916, 442981]; NHMRC; Deutsche Forschungsgemeinschaft [FOR423]; Bundesministerium fur Bildung und Forschung (BMBF); Koeln Fortune Program/Faculty of Medicine; Netherlands Organization [903-52-291, 918.56.602]; Migraine Trust; Centre for Medical Systems Biology (CMSB) FX The Helsinki component of this study was supported by the Sigrid Juselius Foundation, the Academy of Finland (200923 to A. P.; 00213 to M. W.), the Helsinki University Central Hospital, the EuroHead project (LSHM-CT-2004-504837), the GenomEUtwin project (QLG2-CT-2002-01254 and to V. A.), the Oxnard Foundation, the Helsinki Biomedical Graduate School (to V. A.), the Biomedicum Helsinki Foundation, the Finnish Cultural Foundation (to V. A.), the Finnish Neurology Foundation and National Institutes of Health (RO1 NS37675 to A. P.), National Institute on Alcohol Abuse and Alcoholism (United States) grants AA007535, AA013320, AA013326, AA014041, AA07728, AA10249 and AA11998. Academy of Finland Center of Excellence in Complex Disease Genetics (to L. P., A. P. and J. K.). The Brisbane component was supported by National Health and Medical Research Council (NHMRC) (Australia) grants 941177, 951023, 241916 and 442981. D. R. N. and G. W. M were supported by NHMRC R. D. Wright and Senior Research Fellowships. The Cologne component was supported by Deutsche Forschungsgemeinschaft (DFG, FOR423), National Genome Network (NGFN) by the Bundesministerium fur Bildung und Forschung (BMBF), Koeln Fortune Program/Faculty of Medicine, University of Cologne. The Leiden component was supported by the Netherlands Organization for Scientific Research (NWO) (903-52-291 to M. D. F, R. R. F. and Vici 918.56.602 to M. D. F), the Migraine Trust (R. R. F., M. D. F.), the EuroHead project (LSHM-CT-2004-504837) and the Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI). The Munich component was supported by the Deutsche Forschungsgemeinschaft (DFG D1 722/8-1 and DI 722/8-2). NR 55 TC 49 Z9 50 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2008 VL 17 IS 21 BP 3318 EP 3331 DI 10.1093/hmg/ddn227 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 359GI UT WOS:000259974000006 PM 18676988 ER PT J AU Greenblatt, MS Brody, LC Foulkes, WD Genuardi, M Hofstra, RMW Olivier, M Plon, SE Sijmons, RH Sinilnikova, O Spurdle, AB AF Greenblatt, Marc S. Brody, Lawrence C. Foulkes, William D. Genuardi, Maurizio Hofstra, Robert M. W. Olivier, Magali Plon, Sharon E. Sijmons, Rolf H. Sinilnikova, Olga Spurdle, Amanda B. CA IARC Unclassified Genetic Variants TI Locus-Specific Databases and Recommendations to Strengthen Their Contribution to the Classification of Variants in Cancer Susceptibility Genes SO HUMAN MUTATION LA English DT Article DE locus-specific databases; LSDBs; BIC; mismatch repair; cancer; unclassified variant; variant of unknown significance; pathogenic ID UNKNOWN CLINICAL-SIGNIFICANCE; DNA-SEQUENCE VARIANTS; MUTATION DATABASES; BIALLELIC MUTATIONS; ALLELIC VARIANTS; BRCA1; P53; PREDISPOSITION; MAMMOGRAMS; PHENOTYPE AB Locus-specific databases (LSDBs) are curated collections of sequence variants in genes associated with disease. LSDBs of cancer-related genes often serve as a critical resource to researchers, diagnostic laboratories, clinicians, and others in the cancer genetics community. LSDBs are poised to play an important role in disseminating clinical classification of variants. The IARC Working Group on Unclassified Genetic Variants has proposed a new system of five classes of variants in cancer susceptibility genes. However, standards are lacking for reporting and analyzing the multiple data types that assist in classifying variants. By adhering to standards of transparency and consistency in the curation and annotation of data, LSDBs can be critical for organizing our understanding of how genetic variation relates to disease. In this article we discuss how LSDBs can accomplish these goals, using existing databases for BRCA1, BRCA2, MSH2, MLH1, TP53, and CDKN2A to illustrate the progress and remaining challenges in this field. We recommend that: 1) LSDBs should only report a conclusion related to pathogenicity if a consensus has been reached by an expert panel. 2) The system used to classify variants should be standardized. The Working Group encourages use of the five class system described in this issue by Plon and colleagues. 3) Evidence that supports a conclusion should be reported in the database, including sources and criteria used for assignment. 4) Variants should only be classified as pathogenic if more than one type of evidence has been considered. 5) All instances of all variants should be recorded. Hum Mutat 29(11), 1273-1281, 2008. Published 2008 Wiley-Liss, Inc. C1 [Greenblatt, Marc S.] Univ Vermont, Coll Med, Vermont Canc Ctr, Burlington, VT 05405 USA. [Greenblatt, Marc S.] Univ Vermont, Dept Med, Burlington, VT 05405 USA. [Brody, Lawrence C.] NHGRI, NIH, Bethesda, MD 20892 USA. [Foulkes, William D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Foulkes, William D.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Genuardi, Maurizio] Univ Florence, Dept Clin Pathophysiol, Florence, Italy. [Hofstra, Robert M. W.; Sijmons, Rolf H.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Olivier, Magali] Int Agcy Res Canc, F-69372 Lyon, France. [Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA. [Sinilnikova, Olga] Ctr Leon Berard, Hosp Civils Lyon, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Spurdle, Amanda B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Genuardi, Maurizio] Fiorgen Fdn Pharmacogenom, Sesto Fiorentino, Italy. [Sinilnikova, Olga] Univ Lyon 1, CNRS, Lab Genet Mol Signalisat & Canc, UMR5201, F-69365 Lyon, France. RP Greenblatt, MS (reprint author), Univ Vermont, Coll Med, Vermont Canc Ctr, 89 Beaumont Ave,Given E214, Burlington, VT 05405 USA. EM Marc.Greenblatt@vtmednet.org RI Spurdle, Amanda/A-4978-2011; Olivier, Magali/G-3728-2010; Sijmons, Rolf/E-5829-2012; Hoogerbrugge, Nicoline/O-1016-2013; OI Spurdle, Amanda/0000-0003-1337-7897; Olivier, Magali/0000-0002-8202-342X; Sijmons, Rolf/0000-0001-8446-2779; Hofstra, Robert/0000-0001-7498-3829; foulkes, william/0000-0001-7427-4651 FU National Institutes Of Health [CA 96536, HG 004064]; Lake Champlain Cancer Research Organization; National Human Genomic Research Institute; Fonds de la Recherche en Sante du Quebec; Canadian Breast Cancer Research Alliance; Elite Cassa di Risparmio di Firenze; Dutch Cancer Society [RUG2002-2678]; European Community; Australian National Health and Medical Research Council FX Supported by grants from the National Institutes Of Health (CA 96536 to M.S.G.; HG 004064 to S.E.P), the Lake Champlain Cancer Research Organization (to M.S.G.), the Intramural Research Program Of the National Human Genomic Research Institute (to L.C.B.), the Fonds de la Recherche en Sante du Quebec and the Canadian Breast Cancer Research Alliance (to WDF.), Elite Cassa di Risparmio di Firenze (to M.G.), the Dutch Cancer Society (RUG2002-2678 to R.M.W.H.), the European Community (to R.M.W.H.), the Australian National Health and Medical Research Council (to A.B.S.). We appreciate the helpful discussions with many colleagues, at the Human Variome Project Planning Meeting chaired by Professor Richard Cotton in May 2008. NR 40 TC 24 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2008 VL 29 IS 11 BP 1273 EP 1281 DI 10.1002/humu.20889 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 372JF UT WOS:000260897200003 PM 18951438 ER PT J AU Tsai-Morris, CH Koh, E Dufau, ML AF Tsai-Morris, Chon-Hwa Koh, Eitetsu Dufau, Maria L. TI Differences in gonadotropin-regulated testicular helicase (GRTH/DDX25) single nucleotide polymorphism between Japanese and Chinese populations SO HUMAN REPRODUCTION LA English DT Letter ID RNA HELICASE; SPERMATOGENESIS; GENE; TRANSLATION C1 [Tsai-Morris, Chon-Hwa; Dufau, Maria L.] NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. [Koh, Eitetsu] Kanazawa Univ, Sch Med, Dept Urol, Kanazawa, Ishikawa 920, Japan. RP Tsai-Morris, CH (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. EM morrisch@mail.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2008 VL 23 IS 11 BP 2611 EP 2613 DI 10.1093/humrep/den063 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 361QT UT WOS:000260142900031 PM 18487219 ER PT J AU Dessy, FJ Giannini, SL Bougelet, CA Kemp, TJ David, MPM Poncelet, SM Pinto, LA Wettendroff, MA AF Dessy, Francis J. Giannini, Sandra L. Bougelet, Catherine A. Kemp, Troy J. David, Marie-Pierre M. Poncelet, Sylviane M. Pinto, Ligia A. Wettendroff, Martine A. TI Correlation between direct ELISA, single epitope-based inhibition ELISA and pseudovirion-based neutralization assay for measuring anti-HPV-16 and anti-HPV-18 antibody response after vaccination with the AS04-adjuvanted HPV-16/18 cervical cancer vaccine SO HUMAN VACCINES LA English DT Article DE HPV-16; HPV-18; cervical cancer; vaccine; VLP; AS04 Adjuvant System; immune response; ELISA; pseudovirion; neutralization assay ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; HPV PSEUDOVIRIONS; IMMUNE-RESPONSE; DOUBLE-BLIND; HUMAN SERA; L1 AB To monitor immune status during clinical trials and after vaccine registration, several assays have been developed to measure type-specific human papillomavirus (HPV) serum antibody levels. These include neutralization assays, single epitope-based inhibition immunoassays, and direct enzyme-linked immunosorbent assays (ELISAs). Neutralization assays based on multiple epitopes and independent of vaccine material are considered the 'gold standard' for unbiased assessment of the protective potential of vaccine-induced antibodies. However, their use in large clinical trials is challenging. Here, we compare both the direct ELISA and the single epitope-based inhibition ELISA with the pseudovirion-based neutralization assay (PBNA) for HPV-16/18 antibody responses in vaccinated women enrolled in trials of Cervarix (TM), GSK's cervical cancer vaccine. The direct ELISA, which is based on multiple epitopes, was shown to have a higher degree of sensitivity and correlation with the PBNA when compared with the single epitope-based inhibition ELISA. Among double-positive results, high correlations were observed between the PBNA and the direct ELISA (0.70-0.88 for HPV-16 and 0.82-0.94 for HPV-18) and also with the single epitope-based inhibition ELISA (0.60-0.89 for HPV-16 and 0.57-0.96 for HPV-18) in women aged 15-25 years. The correlation persisted up to 6.4 years after primary vaccination. Similar levels of correlation were observed for adolescents aged 10-14 years and women aged 46-55 years. Therefore, the direct ELISA appears to be an excellent surrogate for neutralizing activity and can be used to evaluate antibody response induced by L1 virus-like particle-based cervical cancer vaccines, regardless of time elapsed after vaccination (up to 6.4 years) and the age of the vaccine recipient. C1 [Dessy, Francis J.; Giannini, Sandra L.; Bougelet, Catherine A.; David, Marie-Pierre M.; Poncelet, Sylviane M.; Wettendroff, Martine A.] GlaxoSmithKline Biol, Res & Dev, B-1330 Rixensart, Belgium. [Kemp, Troy J.; Pinto, Ligia A.] NCI, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Dessy, FJ (reprint author), GlaxoSmithKline Biol, Res & Dev, Rue Inst 89, B-1330 Rixensart, Belgium. EM francis.dessy@gskbio.com FU National Cancer Institute (NCI) HPV Vaccine Trial in Costa Rica [NCT00128661, HPV-009]; NCI; National Institutes of Health [N01-CO-12400] FX F. Dessy, S. Giannini, C. Bougelet, M.-P. David, S. Poncelet and M. Wettendorff are employees of GlaxoSmithKline Biologicals.; Testing of specimens from the National Cancer Institute (NCI) HPV Vaccine Trial in Costa Rica (NCT00128661; HPV-009) within this project has been funded in whole with Federal funds from the NCI, National Institutes of Health, under contract (N01-CO-12400). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government.; Cervarix is a trademark of the GlaxoSmithKline group of companies. GlutaMAX and Fungizone are trademarks of Invitrogen Corporation. MaxiSorp is a trademark of Nalge Nunc International. SoftMax and LMaxII are trademarks of Molecular Devices.; The authors are thankful to Ulrike Krause, Alberta Di Pasquale, Veerle Ronsse, Laurence De Moerlooze, Allan Hildesheim and Meridian HealthComms Ltd., for assistance in the preparation of this manuscript. NR 49 TC 99 Z9 102 U1 0 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD NOV-DEC PY 2008 VL 4 IS 6 BP 425 EP 434 PG 10 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 373LA UT WOS:000260971900006 PM 18948732 ER PT J AU Paoletti, LC Guttormsen, HK Christian, MS Hoberman, AM McInnes, P AF Paoletti, Lawrence C. Guttormsen, Hilde-Kari Christian, Mildred S. Hoberman, Alan M. McInnes, Pamela TI Neither antibody to a group B streptococcal conjugate vaccine nor the vaccine itself is teratogenic in rabbits SO HUMAN VACCINES LA English DT Article DE group B streptococcus; glycoconjugate vaccines; serotype III; developmental toxicity study ID POLYSACCHARIDE CONJUGATE; PREGNANT-WOMEN; IMMUNOGENICITY; INFECTION; IMMUNIZATION; EFFICACY; ANIMALS; MODEL AB Group B Streptococcus (GBS) is a leading cause of human neonatal bacterial disease, resulting in pneumonia, sepsis, meningitis and sometimes, death. Supportive preclinical studies of GBS capsular polysaccharide (CPS)-protein conjugate vaccines have led to several phase 1 and phase 2 trials in healthy, non-pregnant adults, which demonstrated that the vaccines, produced at the Channing Laboratory, were safe and immunogenic. However, evaluation of the safety and immunogenicity of a GBS conjugate vaccine administered to pregnant women demanded that it be manufactured under current good manufacturing practices (cGMP) and that it undergo developmental toxicity evaluation. In this report, we describe a GBS type III CPS-tetanus toxoid (III-TT) vaccine lot 3-1-96 manufactured and vialed under cGMP and our evaluation of the effect of this vaccine and of GBS type III CPS-specific antibody on conception and early-and late-stage fetal development in rabbits. III-TT lot 3-1-96 was compositionally similar to prototype III-TT lot 91-1, produced under non-GMP, and was potent in a mouse maternal vaccination-neonatal pup challenge model of GBS disease. Four groups of 30 female rabbits each were randomized to receive III-TT lot 3-1-96 vaccine, saline-alum, or combinations of these treatments before and after insemination. The dose of conjugated CPS on a weight basis was 1 mu g/kg, mimicking the anticipated actual human dose. Based on the weight of the rabbits, this was 20- to 100-fold greater than the expected human dose. Does were pre-assigned to deliver litters naturally or have their kits delivered by Caesarean-section at gestation day 29, to assess late fetal development. Sera from does and kits were collected, and the presence of type III CPS-specific IgG was confirmed by quantitative ELISA. Based on all assessments, GBS type III-TT lot 3-1-96, nor antibody to it did not affect embryo-fetal viability, sex ratio, growth or cause malformations (i.e., it was non-teratogenic). In addition, that III-TT lot 3-1-96 was found to be safe and immunogenic in two clinical studies involving healthy non-pregnant adults supports a clinical evaluation of this vaccine in pregnant women. C1 [Paoletti, Lawrence C.; Guttormsen, Hilde-Kari] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Christian, Mildred S.] Argus Int Inc, Horsham, PA USA. [Hoberman, Alan M.] Preclin Serv PA, Charles River Labs, Horsham, PA USA. [McInnes, Pamela] Natl Inst Dent & Craniofacial Res, Div Extramural Res, NIH, Bethesda, MD USA. RP Paoletti, LC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM lpaoletti@rics.bwh.harvard.edu FU NIAID [AI-25152, AI-060603] FX We thank John Barnett, Kristen Sherer and Joseph Lech for technical assistance as well as Valerie Sharper, Cheryl Van, Terry Clemson and Karen Parker for study coordination and report preparation at Argus. We also thank Matthew Chapdelaine for technical assistance with the ELISAs and Michael Wessels for discussion about study design. This study was funded by NIAID contract AI-25152 and grant AI-060603 (L. C. P.). NR 34 TC 7 Z9 7 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 EI 1554-8619 J9 HUM VACCINES JI Hum. Vaccines PD NOV-DEC PY 2008 VL 4 IS 6 BP 435 EP 443 PG 9 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 373LA UT WOS:000260971900007 PM 18443428 ER PT J AU Cutler, JA Sorlie, PD Wolz, M Thom, T Fields, LE Roccella, EJ AF Cutler, Jeffrey A. Sorlie, Paul D. Wolz, Michael Thom, Thomas Fields, Larry E. Roccella, Edward J. TI Trends in Hypertension Prevalence, Awareness, Treatment, and Control Rates in United States Adults Between 1988-1994 and 1999-2004 SO HYPERTENSION LA English DT Article DE hypertension; surveillance; trends; blood pressure; obesity ID NUTRITION EXAMINATION SURVEY; HIGH BLOOD-PRESSURE; NATIONAL-HEALTH; US ADULTS; PRIMARY PREVENTION; EDUCATION-PROGRAM; OBESITY; OVERWEIGHT; METAANALYSIS; POPULATION AB This study assesses trends in hypertension prevalence, blood pressure distributions and mean levels, and hypertension awareness, treatment, and control among US adults, age >= 18 years, between the third National Health and Nutrition Examination Survey (1988-1994) and the 1999-2004 National Health and Nutrition Examination Survey, a period of approximate to 10 years. The age-standardized prevalence rate increased from 24.4% to 28.9% (P < 0.001), with the largest increases among non-Hispanic women. Depending on gender and race/ethnicity, from one fifth to four fifths of the increase could be accounted for by increasing body mass index. Among hypertensive persons, there were modest increases in awareness (P = 0.04), from 68.5% to 71.8%. The rate for men increased from 61.6% to 69.3% (P = 0.001), whereas the rate for women did not change significantly. Rates remained higher for women than for men, although the difference narrowed considerably. Improvements in treatment and control rates were larger: 53.1% to 61.4% and 26.1% to 35.1%, respectively (both P < 0.001). The greatest increases occurred among non-Hispanic white men and non-Hispanic black persons, especially men. Mexican American persons showed improvement in treatment and control rates, but these rates remained the lowest among race/ethnic subgroups (47.4% and 24.3%, respectively). Among all of the race/ethnic groups, women continued to have somewhat better awareness, treatment, and control, except for control rates among non-Hispanic white persons, which became higher in men. Differences between non-Hispanic black and white persons in awareness, treatment, and control were small. These divergent trends may translate into disparate trends in cardiovascular disease morbidity and mortality. (Hypertension. 2008;52:818-827.) C1 [Cutler, Jeffrey A.; Sorlie, Paul D.; Wolz, Michael; Thom, Thomas; Roccella, Edward J.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Fields, Larry E.] Pfizer Inc, New York, NY USA. RP Sorlie, PD (reprint author), NHLBI, NIH, US Dept HHS, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM sorliep@mail.nih.gov FU National Heart, Lung, and Blood Institute [Y1-HC-8135] FX This work was funded in part by an interagency agreement with the National Center for Health Statistics by the National Heart, Lung, and Blood Institute (Y1-HC-8135). NR 45 TC 484 Z9 507 U1 1 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2008 VL 52 IS 5 BP 818 EP 827 DI 10.1161/HYPERTENSIONAHA.108.113357 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 363MT UT WOS:000260272100014 PM 18852389 ER PT J AU Leslie, DS Dascher, CC Cembrola, K Townes, MA Hava, DL Hugendubler, LC Mueller, E Fox, L Roura-Mir, C Moody, DB Vincent, MS Gumperz, JE Illarionov, PA Besra, GS Reynolds, CG Brenner, MB AF Leslie, David S. Dascher, Christopher C. Cembrola, Katherine Townes, Maria A. Hava, David L. Hugendubler, Lynne C. Mueller, Elisabetta Fox, Lisa Roura-Mir, Carme Moody, D. Branch Vincent, Michael S. Gumperz, Jenny E. Illarionov, Petr A. Besra, Gurdyal S. Reynolds, Carol G. Brenner, Michael B. TI Serum lipids regulate dendritic cell CD1 expression and function SO IMMUNOLOGY LA English DT Article DE cell surface molecules; dendritic cells; human; lipid mediators; T cells ID PROLIFERATOR-ACTIVATED RECEPTORS; PPAR-GAMMA; ANTIGEN PRESENTATION; T-CELLS; MOLECULAR-MECHANISMS; LYMPHOCYTES-T; RECOGNITION; MATURATION; RESTRICTS; PATHWAYS AB Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naive T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors. C1 [Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Leslie, David S.; Cembrola, Katherine; Townes, Maria A.; Hava, David L.; Roura-Mir, Carme; Moody, D. Branch; Vincent, Michael S.; Brenner, Michael B.] Harvard Univ, Sch Med, Boston, MA USA. [Dascher, Christopher C.] Mt Sinai Sch Med, Inst Immunol, New York, NY USA. [Hugendubler, Lynne C.; Mueller, Elisabetta] NIDDK, GDDB, Bethesda, MD USA. [Fox, Lisa; Gumperz, Jenny E.] Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Illarionov, Petr A.; Besra, Gurdyal S.] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. [Reynolds, Carol G.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Dascher, CC (reprint author), 1 Gustave Levy Pl,Box 1630, New York, NY 10029 USA. EM dascher@mssm.edu; mbrenner@rics.bwh.harvard.edu RI Roura-Mir, Carme/D-4538-2013; OI Roura-Mir, Carme/0000-0003-0514-337X; Besra, Gurdyal/0000-0002-5605-0395 FU Arthritis National Research Foundation; Pfizer, Inc.; National Institutes of Health [K08AR02171]; Medical Research Council [G9901077, G0400421]; Wellcome Trust [07221/Z/03/Z] FX This research was supported by the Arthritis National Research Foundation (D. S. L.), an ARA Award to D. S. L. sponsored by Pfizer, Inc., the National Institutes of Health (K08AR02171 to D. S. L.), the Medical Research Council (G9901077 and G0400421 to G. S. B.), and the Wellcome Trust (07221/Z/03/Z to G. S. B.). NR 40 TC 35 Z9 36 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 2008 VL 125 IS 3 BP 289 EP 301 DI 10.1111/j.1365-2567.2008.02842.x PG 13 WC Immunology SC Immunology GA 357RS UT WOS:000259864500002 PM 18445008 ER PT J AU Narum, DL Nguyen, V Zhang, YL Glen, J Shimp, RL Lambert, L Ling, IT Reiter, K Ogun, SA Long, C Holder, AA Herrera, R AF Narum, David L. Nguyen, Vu Zhang, Yanling Glen, Jacqueline Shimp, Richard L. Lambert, Lynn Ling, Irene T. Reiter, Karine Ogun, Solabomi A. Long, Carole Holder, Anthony A. Herrera, Raul TI Identification and Characterization of the Plasmodium yoelii PyP140/RON4 Protein, an Orthologue of Toxoplasma gondii RON4, Whose Cysteine-Rich Domain Does Not Protect against Lethal Parasite Challenge Infection SO INFECTION AND IMMUNITY LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; MALARIA VACCINE CANDIDATE; PASSIVE-IMMUNIZATION; MONOCLONAL-ANTIBODY; FALCIPARUM MALARIA; PICHIA-PASTORIS; MOVING JUNCTION; CLINICAL-TRIAL; CELL INVASION; EXPRESSION AB Previously, we identified a Plasmodium yoelii YM 140-kDa merozoite protein, designated PyP140, which formed a complex with apical membrane antigen 1 (AMA1). Furthermore, we produced a nonprotective monoclonal antibody (MAb), 48F8, that immunoprecipitated metabolically labeled PyP140 and localized the protein to the merozoite's apical end and, less frequently, to the merozoite surface, as observed by immunofluorescence assay (IFA). Here, using MAb 48F8, we have identified the pyp140 gene by screening a P. yoelii lambda-Zap cDNA expression library. The pyp140 cDNA covers approximately 90% of the putative open reading frame (ORF) of PY02159 from the P. yoelii NL genome sequencing project. Analysis of the complete gene identified the presence of two introns. The ORF encodes a 102,407-Da protein with an amino-terminal signal sequence, a series of three unique types of repeats, and a cysteine-rich region. The binding site of MAb 48F8 was also identified. A BLAST search with the deduced amino acid sequence shows significant similarity with the Toxoplasma gondii RON4 protein and the Plasmodium falciparum RON4 protein, and the sequence is highly conserved in other Plasmodium species. We produced the cysteine-rich domain of PyP140/RON4 by using the Pichia pastoris expression system and characterized the recombinant protein biochemically and biophysically. BALB/c mice immunized with the protein formulated in oil-in-water adjuvants produced antibodies that recognize parasitized erythrocytes by IFA and native PyP140/RON4 by immunoblotting but failed to protect against a lethal P. yoelii YM infection. Our results show that PyP140/RON4 is located within the rhoptries or micronemes. It may associate in part with AMA1, but the conserved cysteine-rich domain does not appear to elicit inhibitory antibodies, a finding that is supported by the marked sequence conservation in this protein within Plasmodium spp., suggesting that it is not under immune pressure. C1 [Narum, David L.; Nguyen, Vu; Zhang, Yanling; Glen, Jacqueline; Shimp, Richard L.; Lambert, Lynn; Reiter, Karine; Long, Carole; Herrera, Raul] NIH, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. [Ling, Irene T.; Ogun, Solabomi A.; Holder, Anthony A.] Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. RP Narum, DL (reprint author), NIH, Malaria Vaccine Dev Branch, 5640 Fishers Lane, Rockville, MD 20852 USA. EM dnarum@niaid.nih.gov RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 FU NIH; Medical Research Council (United Kingdom) FX We express our gratitude to Louis Miller for insightful discussions regarding PyP140, to Kim Lee Sim for support of this project while D.L.N. was employed by EntreMed, Inc., and to Michael Fay for assistance with the statistical analysis of parasitemias. We also thank Tin Luu (EntreMed, Inc.) for performing the phage display assays, Kelly Magee and Angela Lunger for assistance with the mouse immunization-challenge study, and Ababacar Diouf for performing the ELISAs.; This work was supported in part by the Intramural Research Program of the NIH and by the Medical Research Council (United Kingdom). NR 30 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2008 VL 76 IS 11 BP 4876 EP 4882 DI 10.1128/IAI.01717-07 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500010 PM 18710865 ER PT J AU Battisti, JM Bono, JL Rosa, PA Schrumpf, ME Schwan, TG Policastro, PF AF Battisti, James M. Bono, James L. Rosa, Patricia A. Schrumpf, Merry E. Schwan, Tom G. Policastro, Paul F. TI Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector SO INFECTION AND IMMUNITY LA English DT Article ID BORRELIA-BURGDORFERI INFECTION; WHITE-FOOTED MICE; IXODES-SCAPULARIS; PEROMYSCUS-LEUCOPUS; ANTIBODY-RESPONSE; MEMBRANE-PROTEIN; FEEDING TICKS; IXODIDAE; VACCINE; ACARI AB The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naive mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naive mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector. C1 [Battisti, James M.; Bono, James L.; Rosa, Patricia A.; Schrumpf, Merry E.; Schwan, Tom G.; Policastro, Paul F.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Policastro, PF (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM ppolicastro@niaid.nih.gov FU NIAID; NIH FX We thank Cyril Guyard and Kathy Wehrly for antibodies; Anita Mora and Gary Hettrick for assistance with illustrations; and Kena Swanson, Chris Bosio, and Phil Stewart for valuable comments on the manuscript.; We acknowledge the construction of an initial series of ospAB mutants in high-passage, noninfectious strain B31 by Aimee Geissler.; The Intramural Research Program of the NIAID, NIH, supported this research. NR 69 TC 43 Z9 45 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2008 VL 76 IS 11 BP 5228 EP 5237 DI 10.1128/IAI.00410-08 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500048 PM 18779341 ER PT J AU Hu, L Tall, BD Curtis, SK Kopecko, DJ AF Hu, Lan Tall, Ben D. Curtis, Sherill K. Kopecko, Dennis J. TI Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence to, Invasion of, Translocation across, and Exocytosis from Polarized Human Intestinal Caco-2 Cells SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; INT-407 CELLS; LINE CACO-2; SIGNAL-TRANSDUCTION; EUKARYOTIC CELLS; TIGHT JUNCTIONS; SALMONELLA; TRANSPORT; VIRULENCE; SURFACE AB Campylobacter jejuni-mediated pathogenesis involves gut adherence and translocation across intestinal cells. The current study was undertaken to examine the C. jejuni interaction with and translocation across differentiated Caco-2 cells to better understand Campylobacter's pathogenesis. The efficiency of C. jejuni 81-176 invasion of Caco-2 cells was two- to threefold less than the efficiency of invasion of INT407 cells. Adherence-invasion analyses indicated that C. jejuni 81-176 adhered to most INT407 cells but invaded only about two- thirds of the host cells over 2 h (two bacteria/cell). In contrast, only 11 to 17% of differentiated Caco-2 cells were observed to bind and internalize either C. jejuni strain 81-176 or NCTC 11168, and a small percentage of infected Caco-2 cells contained 5 to 20 internalized bacteria per cell after 2 h. Electron microscopy revealed that individual C. jejuni cells adhered to the tips of host cell microvilli via intimate flagellar contacts and by lateral bacterial binding to the sides of microvilli. Next, bacteria were observed to bind at the apical host membrane surface via presumed interactions at one pole of the bacterium and with host membrane protrusions located near intercellular junctions. The latter contacts apparently resulted in coordinated, localized plasma membrane invagination, causing simultaneous internalization of bacteria into an endosome. Passage of this Campylobacter endosome intracellularly from the apical surface to the basolateral surface occurred over time, and bacterial release apparently resulted from endosome-basolateral membrane fusion (i.e., exocytosis). Bacteria were found intercellularly below tight junctions at 60 min postinfection, but not at earlier times. This study revealed unique host cell adherence contacts, early endocytosis-specific structures, and a presumptive exocytosis component of the transcellular transcytosis route. C1 [Hu, Lan; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Tall, Ben D.; Curtis, Sherill K.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, 29 Lincoln Dr,NIH Campus,Bldg 29-420, Bethesda, MD 20892 USA. EM dennis.kopecko@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 53 TC 26 Z9 26 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2008 VL 76 IS 11 BP 5294 EP 5304 DI 10.1128/IAI.01408-07 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500055 PM 18765731 ER PT J AU Ambrose, CS Luke, C Coelingh, K AF Ambrose, Christopher S. Luke, Catherine Coelingh, Kathleen TI Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Review DE Influenza; live attenuated; vaccine ID CULTURE-CONFIRMED INFLUENZA; RANDOMIZED CONTROLLED-TRIAL; B VIRUS-VACCINES; YOUNG-CHILDREN; TEMPERATURE SENSITIVITY; B/ANN ARBOR/1/66; WORKING ADULTS; A VIRUS; CAIV-T; TRIVALENT AB A live attenuated influenza vaccine (LAIV) is currently approved in the United States for the prevention of influenza in individuals 2-49 years of age. This article summarizes the available data describing the safety and efficacy of LAIV for the prevention of influenza in both children and adults. LAIV is administered as an intranasal spray and has been shown to provide high levels of efficacy against influenza illness caused by both matched and mismatched strains in children and adults. In studies comparing LAIV and inactivated influenza vaccine in children, LAIV recipients experienced 35-53% fewer cases of culture-confirmed influenza illness caused by antigenically matched strains. Protection through a second influenza season against antigenically matched strains has also been seen in children. In adults, definitive comparative studies of LAIV and inactivated vaccine have not been conducted and no statistically significant differences in efficacy have been demonstrated. The most common adverse reactions with LAIV include runny nose/nasal congestion in all age groups, fever > 100 circle F in children, and sore throat in adults. Formulations of LAIV against pandemic influenza strains, including H5N1, H9N2, and H7N3, are currently being tested in preclinical and phase I clinical studies. C1 [Ambrose, Christopher S.; Coelingh, Kathleen] Medimmune Inc, Gaithersburg, MD 20878 USA. [Luke, Catherine] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Coelingh, K (reprint author), Medimmune Inc, 1 MedImmune Way, Gaithersburg, MD 20878 USA. EM coelinghk@medimmune.com RI Grigorieva, Elena/E-1744-2014; Rudenko, Larisa/B-5169-2015; OI Grigorieva, Elena/0000-0002-0107-9959; Rudenko, Larisa/0000-0002-0107-9959; Ambrose, Christopher/0000-0003-4175-7336 FU Intramural Research Program of the NIAID; NIH FX This research was supported in part by the Intramural Research Program of the NIAID, NIH. The authors thank Kanta Subbarao ( NIH), and Robert Walker, Seth Toback, Robert Fuentes, and Gregory Susla ( MedImmune) for helpful discussion and review of the manuscript. NR 53 TC 54 Z9 59 U1 1 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD NOV PY 2008 VL 2 IS 6 BP 193 EP 202 DI 10.1111/j.1750-2659.2008.00056.x PG 10 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 467SD UT WOS:000267761800002 PM 19453395 ER PT J AU Sweeney, DA Danner, RL Eichacker, PQ Natanson, C AF Sweeney, Daniel A. Danner, Robert L. Eichacker, Peter Q. Natanson, Charles TI Once is not enough: clinical trials in sepsis SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTENSIVE INSULIN THERAPY; GRAM-NEGATIVE BACTEREMIA; PLACEBO-CONTROLLED TRIAL; ACTIVATED PROTEIN-C; HIGH-DOSE METHYLPREDNISOLONE; HUMAN MONOCLONAL-ANTIBODY; CRITICALLY-ILL ADULTS; ESCHERICHIA-COLI J5; SEPTIC SHOCK C1 [Sweeney, Daniel A.; Danner, Robert L.; Eichacker, Peter Q.; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Sweeney, DA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145, Bethesda, MD 20892 USA. EM sweeneyda@cc.nih.gov NR 48 TC 29 Z9 31 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 2008 VL 34 IS 11 BP 1955 EP 1960 DI 10.1007/s00134-008-1274-6 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 364AN UT WOS:000260308700004 PM 18839140 ER PT J AU Lan, Q He, XZ Shen, M Tian, LW Liu, LZ Lai, H Chen, W Berndt, SI Hosgood, HD Lee, KM Zheng, TZ Blair, A Chapman, RS AF Lan, Qing He, Xingzhou Shen, Min Tian, Linwei Liu, Larry Z. Lai, Hong Chen, Wei Berndt, Sonja I. Hosgood, Howard Dean Lee, Kyoung-Mu Zheng, Tongzhang Blair, Aaron Chapman, Robert S. TI Variation in lung cancer risk by smoky coal subtype in Xuanwei, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE coal; lung cancer; indoor air pollution; Xuanwei; China ID INDOOR AIR-POLLUTION; COMBUSTION EMISSIONS; DEVELOPING-COUNTRIES; CURRENT PROGRESS; WEI; DISEASE; IMPROVEMENT; BURDEN; FUEL AB Lung cancer rates in Xuanwei County have been among the highest in China for both males and females and have been causally associated with exposure to indoor smoky (bituminous) coal emissions that contain very high levels of polycyclic aromatic hydrocarbons. There are numerous coal mines across the County. Although lung cancer risk is strongly associated with the use of smoky coal as a whole, variation in risk by smoky coal subtype has not been characterized as yet. We conducted a population-based case-control study of 498 lung cancer cases and 498 controls, individually matched to case subjects on age ( 2 years) and sex to examine risk by coal subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) for coal subtype were calculated by conditional logistic regression, adjusting for potential confounders. Overall, smoky coal use was positively and statistically significantly associated with lung cancer risk, when compared with the use of smokeless coal or wood (OR = 7.7, 95% CI = 4.5-13.3). Furthermore, there was a marked heterogeneity in risk estimates for specific subtypes of smoky coal (test for heterogeneity: p = 5.17 X 10(-10)). Estimates were highest for coal of the Laibin (OR = 24.8, 95 % CI = 12.4-49.6) and Longtan (OR = 11.6, 95 % CI = 5.0-27.2) coal types and lower for coal from other subtypes. These findings strongly suggest that in Xuanwei and elsewhere, the carcinogenic potential of coal combustion products can exhibit substantial local variation by specific coal source. Published 2008 Wiley-Liss, Inc. C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing, Peoples R China. [Tian, Linwei] Chinese Univ Hong Kong, Sch Publ Hlth, Stanley Ho Ctr Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. [Liu, Larry Z.] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA. [Lai, Hong] Johns Hopkins Univ, Wilmer Eye Inst, Dept Radiol & Ophthalmol, Baltimore, MD 21218 USA. [Chen, Wei] Forest Labs Inc, Harborside Financial Ctr, Jersey City, NJ USA. [Zheng, Tongzhang] Yale Univ, Sch Med, Div Environm Sci, New Haven, CT USA. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Tian, Linwei/A-9736-2009 OI Tian, Linwei/0000-0002-4739-1534 FU Chinese Academy of Preventive Medicine, Beijing, China; Yunnan Province Antiepidemic Station, Kunming, China; U.S. Environmental Protection Agency; National Institutes of Health (Intramural Research Program) FX Chinese Academy of Preventive Medicine, Beijing, China, Yunnan Province Antiepidemic Station, Kunming, China, U.S. Environmental Protection Agency, National Institutes of Health (Intramural Research Program). NR 28 TC 33 Z9 42 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2008 VL 123 IS 9 BP 2164 EP 2169 DI 10.1002/ijc.23748 PG 6 WC Oncology SC Oncology GA 357HE UT WOS:000259836100024 PM 18712724 ER PT J AU Chong, VZ Webster, MJ Rothmond, DA Weickert, CS AF Chong, Victor Z. Webster, Maree J. Rothmond, Debora A. Weickert, Cynthia Shannon TI Specific developmental reductions in subventricular zone ErbB1 and ErbB4 mRNA in the human brain SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Subventricular zone; ErbB1; ErbB2; ErbB3; ErbB4; Postnatal; Development; Human; In situ hybridization; mRNA; Immunohistochemistry ID RECEPTOR TYROSINE KINASE; CENTRAL-NERVOUS-SYSTEM; ADULT MAMMALIAN FOREBRAIN; MOUSE-BRAIN; SUBEPENDYMAL LAYER; PREFRONTAL CORTEX; GENE-EXPRESSION; OLFACTORY-BULB; STEM-CELLS; RAT-BRAIN AB The primate postnatal subventricular zone (SVZ) ties under the ventrolateral borders of the lateral ventricles as a discrete region of cells with gliogenic and neurogenic capacity regulated by ErbB receptors. However, the specific role of each ErbB subtype in SVZ cell development remains unclear, particularly in the human brain. The postnatal spatial and temporal expression profile of ErbB subtypes in the human brain may provide valuable insight into their distinct functions in the SVZ following birth. Hence, we examined the expression profile of ErbB1, ErbB2, ErbB3 and ErbB4 mRNA in the SVZ of human postmortem brains from neonates, infants, toddlers, school age subjects, adolescents, young adults and adults using in situ hybridization. SVZ transcript levels of ErbB1 and ErbB4 were highest in neonates and diminished with age. SVZ ErbB4 mRNA quantities significantly decreased by >85% to almost undetectable levels after the first year of life, while SVZ ErbB1 transcript levels displayed more gradual reductions, stabilizing to similar to 30-40% of neonate levels after the age of 5 years. In the neonate and infant SVZ, ErbB4 mRNA was localized to cell clusters resembling migratory neuroblast aggregates whereas ErbB1 mRNA was expressed in cells along but not within these clusters. ErbB2 mRNA appeared to be constantly expressed in the human SVZ at all postnatal ages as opposed to ErbB3 transcripts, which were not detected in the human SVZ at any age following birth. These findings suggest that ErbB1 and ErbB4 may play more salient roles than ErbB2 and ErbB3 in mediating early postnatal neurodevelopmental events. In addition, ErbB1- and ErbB4-immunoreactive cells and fibers were extensive throughout the human infant SVZ, but did not appear to overlap with PSA-NCAM-immunopositive clusters. The restriction of robust SVZ ErbB4 expression to neonate and infant age groups may indicate that SVZ-derived ErbB4-dependent postnatal neuronal development is most extensive within a narrow time frame early after birth. (C) 2008 ISDN. Published by Elsevier Ltd. All rights reserved. C1 [Rothmond, Debora A.; Weickert, Cynthia Shannon] Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Sch Psychiat, Randwick, NSW 2031, Australia. [Chong, Victor Z.; Rothmond, Debora A.; Weickert, Cynthia Shannon] NIMH, MiNDS Unit, CBDB, Natl Inst Hlth, Bethesda, MD 20892 USA. [Webster, Maree J.] USUHS, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD USA. RP Weickert, CS (reprint author), Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Sch Psychiat, Corner Barker & Easy St, Randwick, NSW 2031, Australia. EM c.weickert@powmri.edu.au RI Shannon Weickert, Cynthia/G-3171-2011 FU NSERC Postdoctoral Fellowship; Stanley Medical Research Institute FX Victor Z. Chong is a recipient of the NSERC Postdoctoral Fellowship. This work was also supported by the Stanley Medical Research Institute.; We are grateful for the help of Dr. H. Ronald Zielke and Robert Vigorito of the University of Maryland Brain and Tissue Bank for Developmental Disorders. NR 59 TC 9 Z9 9 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD NOV PY 2008 VL 26 IS 7 BP 791 EP 803 DI 10.1016/j.ijdevneu.2008.06.004 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 373EH UT WOS:000260953300017 PM 18662768 ER PT J AU Bhattacharjee, AK Chang, L Chen, M White, L Bell, JM Bazinet, RP Rapoport, SI AF Bhattacharjee, Abesh K. Chang, Lisa Chen, Mei White, Laura Bell, Jane M. Bazinet, Richard P. Rapoport, Stanley I. TI Chronic d-amphetamine depresses an imaging marker of arachidonic acid metabolism in rat brain SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Arachidonic acid; d-amphetamine; dopamine; quinpirole; SKF-38393 ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; INDUCED DOPAMINE RELEASE; UNANESTHETIZED RATS; SIGNAL-TRANSDUCTION; PHOSPHOLIPASE A(2); TRANSCRIPTION FACTOR; NONHUMAN-PRIMATES; SENSITIZED RATS; RECEPTOR AB Acute d-amphetamine (d-Amph) administration to rats leads to the release of arachiclonic acid (AA, 20:4n-6) as a second messenger following indirect agonism at dopamine D-2-like receptors in the brain. We hypothesized that chronically administered d-Amph in rats also would alter brain AA metabolism and signalling. To test this, adult male rats were injected i.p. daily for 2 wk with saline or 2.5 mg/kg d-Amph. After a 1-d washout, the unanaesthetized rats were injected acutely with i.v. saline, 1 mg/kg quinpirole (a D-2-like receptor agonist) or 5.0 mg/kg SKF-38393 (a D-1-like receptor agonist), followed by i.v. [1-C-14]AA. The AA incorporation coefficient k* (brain radioactivity/integrated plasma radioactivity), a marker of AA signalling and metabolism, was quantified using autoractiography in each of 62 brain regions. Compared with chronic saline, chronic d-Amph widely decreased baseline values of k* in brain regions having D2-like receptors. On the other hand, chronic amphetamine did not alter the k* responses to quinpirole seen in chronic saline-treated rats. SKF-38393 had minimal effects on V in both chronic saline-treated and amphetamine-treated rats, consistent with D-1-like receptors not being coupled to AA signalling. The ability of chronic d-Amph after 1-d washout to down-regulate baseline values of k* probably reflects neuroplastic changes in brain AA signalling, and may correspond to depressive behaviours noted following withdrawal from chronic amphetamine in humans and in rats. C1 [Bhattacharjee, Abesh K.; Chang, Lisa; Chen, Mei; White, Laura; Bell, Jane M.; Bazinet, Richard P.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bhattacharjee, AK (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM abeshb@mail.nih.gov FU Intramural Program of the National Institute on Aging FX ``This work was entirely supported by the Intramural Program of the National Institute on Aging. NR 74 TC 5 Z9 5 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD NOV PY 2008 VL 11 IS 7 BP 957 EP 969 DI 10.1017/S1461145708008833 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 364BL UT WOS:000260311100007 PM 18570702 ER PT J AU Rajagopal, R Dattilo, LK Kaartinen, V Deng, CX Umans, L Zwijsen, A Roberts, AB Bottinger, EP Beebe, DC AF Rajagopal, Ramya Dattilo, Lisa K. Kaartinen, Vesa Deng, Chu-Xia Umans, Lieve Zwijsen, An Roberts, Anita B. Bottinger, Erwin P. Beebe, David C. TI Functions of the Type 1 BMP Receptor Acvr1 (Alk2) in Lens Development: Cell Proliferation, Terminal Differentiation, and Survival SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSFORMATION; NEURAL CREST CELLS; MOUSE EMBRYO; CONDITIONAL KNOCKOUT; P53-DEPENDENT APOPTOSIS; TRANSCRIPTION FACTOR; C-MAF; GROWTH; MICE; GENERATION AB PURPOSE. Bone morphogenetic protein (BMP) signaling is essential for the induction and subsequent development of the lens. The purpose of this study was to analyze the function(s) of the type 1 BMP receptor, Acvr1, in lens development. METHODS. Acvr1 was deleted from the surface ectoderm of mouse embryos on embryonic day 9 using the Cre-loxP method. Cell proliferation, cell cycle exit, and apoptosis were measured in tissue sections by immunohistochemistry, immunofluorescence, and TUNEL staining. RESULTS. Lenses formed in the absence of Acvr1. However, Acvr1(CKO) (conditional knockout) lenses were small. Acvr1 signaling promoted proliferation at early stages of lens formation but inhibited proliferation at later stages. Inhibition of cell proliferation by Acvr1 was necessary for the proper regionalization of the lens epithelium and promoted the withdrawal of lens fiber cells from the cell cycle. In spite of the failure of all Acvr1CKO fiber cells to withdraw from the cell cycle, they expressed proteins characteristic of differentiated fiber cells. Although the stimulation of proliferation was Smad independent, the ability of Acvr1 to promote cell cycle exit later in development depended on classical R-Smad-Smad4 signaling. Loss of Acvr1 led to an increase in apoptosis of lens epithelial and fiber cells. Increased cell death, together with the initial decrease in proliferation, appeared to account for the smaller sizes of the Acvr1CKO lenses. CONCLUSIONS. This study revealed a novel switch in the functions of Acvr1 in regulating lens cell proliferation. Previously unknown functions mediated by this receptor included regionalization of the lens epithelium and cell cycle exit during fiber cell differentiation. (Invest Ophthalmol Vis Sci. 2008;49: 4953-4960) DOI: 10.1167/iovs.08-2217 C1 [Rajagopal, Ramya; Dattilo, Lisa K.; Beebe, David C.] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Beebe, David C.] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Kaartinen, Vesa] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dev Biol Program,Dept Pathol, Los Angeles, CA 90033 USA. [Kaartinen, Vesa] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dev Biol Program,Dept Surg, Los Angeles, CA 90033 USA. [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. [Umans, Lieve; Zwijsen, An] VIB, Dept Mol & Dev Genet, Lab Mol Biol Celgen, Louvain, Belgium. [Umans, Lieve; Zwijsen, An] Katholieke Univ Leuven, Ctr Human Genet, Lab Mol Biol Celgen, Louvain, Belgium. [Roberts, Anita B.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Bottinger, Erwin P.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Rajagopal, R (reprint author), Washington Univ, Dept Ophthalmol & Visual Sci, Box 8096,660 S Euclid St, St Louis, MO 63110 USA. EM rajagopal@vision.wustl.edu RI deng, chuxia/N-6713-2016; OI Kaartinen, Vesa/0000-0002-9432-510X FU National Institutes of Health [EY02687, EY04853, 5R01HL074862, 5R01DE013085] FX Supported by an unrestricted grant from Research to Prevent Blindness and by National Institutes of Health Core Grant EY02687 (Department of Ophthalmology and Visual Sciences) and Grants EY04853 (DCB), 5R01HL074862 (VK), and 5R01DE013085 (VK). NR 45 TC 25 Z9 25 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2008 VL 49 IS 11 BP 4953 EP 4960 DI 10.1167/iovs.08-2217 PG 8 WC Ophthalmology SC Ophthalmology GA 366RX UT WOS:000260502200037 PM 18566469 ER PT J AU Gangnon, RE Davis, MD Hubbard, LD Aiello, LM Chew, EY Ferris, FL Fisher, MR AF Gangnon, Ronald E. Davis, Matthew D. Hubbard, Larry D. Aiello, Lloyd M. Chew, Emily Y. Ferris, Frederick L., III Fisher, Marian R. CA Early Treatment Diabetic Retinopa TI A Severity Scale for Diabetic Macular Edema Developed from ETDRS Data SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY AB PURPOSE. To develop a severity scale for diabetic macular edema (DME) and to assess relationships between severity and duration of DME and visual acuity (VA). METHODS. From the Early Treatment Diabetic Retinopathy Study (ETDRS), mean baseline VA scores were tabulated for 7422 eyes cross-classified by (1) location of retinal thickening (RT) and its area within 1 disc diameter of the macular center, and (2) degree of RT at the center. Adjacent (row, column, and off-diagonal) cells with the greatest similarity in baseline VA (mean and SD) based on a Gaussian (normal) likelihood were merged. An initial eight-step scale was chosen using the Schwarz criterion (Bayesian information criterion; BIC) and was revised based on clinical judgment to nine steps. Relationships between baseline VA and other photographic and fluorescein angiographic characteristics were examined singly and in combination with the scale. RESULTS. Modeling baseline VA as a function of the nine-step scale yielded an R-2 of 38.0%, compared with 38.4% using the full cross-classification of these variables. Addition of each of the other baseline characteristics changed the adjusted R2 for the combination very little. Between scale levels 1A and 5B mean (SD) VA decreased from 86.8 (5.8) letters to 59.8 (13.6) letters. In a model of change in VA as a function of time spent at each DME severity level, VA loss increased progressively from 1 letter per year at level 2 to 17 letters per year at level 5B. CONCLUSIONS. The scale facilitates documentation of the relationship of severity and duration of DME with VA. (Invest Ophthalmol Vis Sci. 2008;49:5041-5047) DOI:10.1167/iovs.08-2231 C1 [Davis, Matthew D.; Hubbard, Larry D.] Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Madison, WI 53711 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53711 USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Stat, Madison, WI 53711 USA. [Fisher, Marian R.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53711 USA. [Aiello, Lloyd M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Chew, Emily Y.; Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA. RP Hubbard, LD (reprint author), Univ Wisconsin, FPRC, Dept Ophthalmol & Visual Sci, Pk W 1, Madison, WI 53711 USA. EM hubbard@rc.ophth.wisc.edu FU National Eye Institute [R03 EY1029-01] FX Supported by Grant R03 EY1029-01 from the National Eye Institute. NR 13 TC 19 Z9 20 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2008 VL 49 IS 11 BP 5041 EP 5047 DI 10.1167/iovs.08-2231 PG 7 WC Ophthalmology SC Ophthalmology GA 366RX UT WOS:000260502200047 PM 18539929 ER PT J AU Bingham, RJ AF Bingham, Raymond J. TI Annotated Bibliography of NINR Findings on Women's Health Across the Lifespan, 2008 Update SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article C1 NINR, Off Sci Policy & Publ Lias, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bingham, RJ (reprint author), NINR, Off Sci Policy & Publ Lias, Natl Inst Hlth, 31 Ctr Dr,MSC-2178 Bldg 31,Room 5B-10, Bethesda, MD 20892 USA. EM info@ninr.nih.gov FU Intramural NIH HHS [Z99 NR999999] 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 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD NOV-DEC PY 2008 VL 37 IS 6 BP 702 EP 704 DI 10.1111/j.1552-6909.2008.00294.x PG 3 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 370CK UT WOS:000260740100011 PM 19012719 ER PT J AU Fitzgibbon, JE Sagripanti, JL AF Fitzgibbon, J. E. Sagripanti, J. -L. TI Analysis of the survival of Venezuelan equine encephalomyelitis virus and possible viral simulants in liquid suspensions SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE alphavirus; biodefense; disinfection; environmental water; Sindbis; simulant; Venezuelan equine encephalitis; water ID PLASMA-DERIVED PRODUCTS; FELINE CALICIVIRUS; ESCHERICHIA-COLI; SOLAR-RADIATION; SINDBIS-VIRUS; PLAQUE-ASSAY; INACTIVATION; MS2; COLIPHAGE; TEMPERATURE AB Aims: To compare the inactivation rate of Venezuelan equine encephalomyelitis (VEE) virus in liquids to that of Sindbis virus (SV, another alphavirus) and to a bacteriophage (MS2) generally used as a viral simulant in the development of countermeasures in biodefense. Methods and Results: Viruses were inoculated into liquids and viral titres were determined at various times postinoculation. The viruses were stable in distilled-deionized (dd) water at 4 degrees C during the 21 days of the study. The inactivation rates of VEE and SV in dd water at 21 and 30 degrees C were very similar (between 0.12 and 0.14 log(10) per day), while MS2 was three-fold slower. In tap water (chlorine content between 4 and 5 ppm) at 21 degrees C, VEE and SV were inactivated at twice the rate measured in dd water. Conclusions: The inactivation rates of VEE and SV were similar to each other and faster than MS2 in all liquids tested. Significance and Impact of the Study: VEE is likely to remain viable for many days after release into water, snow, or even chlorinated tap water. SV can be used to estimate the persistence of VEE in liquids, but using MS2 as a simulant would overestimate of the stability of VEE. C1 [Sagripanti, J. -L.] USA, Edgewood Chem Biol Ctr, Res Engn & Dev Command, Aberdeen Proving Ground, MD 21010 USA. [Fitzgibbon, J. E.] NIH, Div Aids, Therapeut Res Program, Drug Dev & Clin Sci Branch, Bethesda, MD 20892 USA. RP Sagripanti, JL (reprint author), USA, Edgewood Chem Biol Ctr, Res Engn & Dev Command, AMSRD ECB RT 5183 Blackhawk Rd,Edgewood Area, Aberdeen Proving Ground, MD 21010 USA. EM joseluis.sagripanti@us.army.mil FU US Department of Defense Chemical and Biological Defense; Defense Threat Reduction Agency; In-House Laboratory Independent Research (ILIR); Research and Technology Directorate, Edgewood Chemical Biological Center, Research Development and Engineering Command, US Army FX We gratefully acknowledge Dr Mike Parker of USAMRIID for supplying the VEE TC-83 virus. This work was supported by the US Department of Defense Chemical and Biological Defense program administered by the Defense Threat Reduction Agency and by In-House Laboratory Independent Research (ILIR) funds from the Research and Technology Directorate, Edgewood Chemical Biological Center, Research Development and Engineering Command, US Army. NR 24 TC 4 Z9 4 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD NOV PY 2008 VL 105 IS 5 BP 1477 EP 1483 DI 10.1111/j.1365-2672.2008.03919.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 361FP UT WOS:000260113200026 PM 19146486 ER PT J AU Walsh, S Liu, DM Metter, EJ Ferrucci, L Roth, SM AF Walsh, Sean Liu, Dongmei Metter, E. Jeffrey Ferrucci, Luigi Roth, Stephen M. TI ACTN3 genotype is associated with muscle phenotypes in women across the adult age span SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE genetics; muscle strength; sex differences; skeletal muscle ID FAT-FREE MASS; ALPHA-ACTININ-3 DEFICIENCY; ATHLETIC PERFORMANCE; R577X POLYMORPHISM; GENERAL-POPULATION; BODY-COMPOSITION; ALPHA-ACTININ; HEALTHY-MEN; STRENGTH; EVOLUTION AB Walsh S, Liu D, Metter EJ, Ferrucci L, Roth SM. ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol 105: 1486-1491, 2008. First published August 28, 2008; doi:10.1152/japplphysiol.90856.2008.-The R577X polymorphism in the alpha-actinin-3 encoding gene (ACTN3) has been associated with elite athletic performance, and recently with differences in isometric and dynamic muscle strength and power in the general population. In this study we sought to determine the association of ACTN3 R577X genotype with muscle strength and mass phenotypes in men and women across the adult age span. Eight hundred forty-eight (n = 848) adult volunteers (454 men and 394 women) aged 22-90 yr were genotyped for ACTN3 R577X. Knee extensor (KE) shortening and lengthening peak torque values were determined using isokinetic dynamometry and fat-free mass (FFM) by dual-energy X-ray absorptiometry. Women deficient in alpha-actinin-3 (X/X; n = 53) displayed lower KE shortening peak torque (30 degrees/s: 89.5 +/- 3.5 vs. 99.3 +/- 1.4 N.m, P = 0.011; 180 degrees/s: 60.3 +/- 2.6 vs. 67.0 +/- 1.0 N.m, P = 0.019) and KE lengthening peak torque (30 degrees/s: 122.8 +/- 5.7 vs. 137.0 +/- 2.2 N.m, P = 0.022; 180 degrees/s: 121.8 +/- 5.8 vs. 138.5 +/- 2.2 N.m, P = 0.008) compared with R/X + R/R women (n = 341). Women X/X homozygotes also displayed lower levels of both total body FFM (38.9 +/- 0.5 vs. 40.1 +/- 0.2 kg, P = 0.040) and lower limb FFM (11.9 +/- 0.2 vs. 12.5 +/- 0.1 kg, P = 0.044) compared with R/X + R/R women. No genotype-related differences were observed in men. In conclusion, our results indicate that the absence of alpha-actinin-3 protein (i.e., ACTN3 X/X genotype) influences KE peak torque and FFM in women but not men. C1 [Walsh, Sean; Liu, Dongmei; Roth, Stephen M.] Univ Maryland, Dept Kinesiol, Sch Publ Hlth, College Pk, MD 20742 USA. Cent Connecticut State Univ, New Britain, CT 06050 USA. [Metter, E. Jeffrey; Ferrucci, Luigi] Harbor Hosp, Clin Res Branch, NIA, Baltimore, MD USA. RP Roth, SM (reprint author), Univ Maryland, Dept Kinesiol, Sch Publ Hlth, 2134 SPH Bldg, College Pk, MD 20742 USA. EM sroth1@umd.edu RI Liu, Dongmei/C-1525-2012; OI Roth, Stephen/0000-0002-7841-3695 FU National Institutes of Health [AG-021500, AG-022791] FX The BLSA research was conducted as a component of the Intramural Research Program of the National Institute on Aging. This work was further sponsored by National Institutes of Health Grants AG-021500 and AG-022791. NR 34 TC 67 Z9 68 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2008 VL 105 IS 5 BP 1486 EP 1491 DI 10.1152/japplphysiol.90856.2008 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 368GO UT WOS:000260609800014 PM 18756004 ER PT J AU Schirmbeck, F Georgi, A Strohmaier, J Schmael, C Boesshenz, KV Muhleisen, TW Herms, S Hoffmann, P Rami, RA Schumacher, J Maier, W Propping, P Nothen, MM Cichon, S Rietschel, M Schulze, TG AF Schirmbeck, Frederike Georgi, Alexander Strohmaier, Jana Schmael, Christine Boesshenz, Katja V. Muehleisen, Thomas W. Herms, Stefan Hoffmann, Per Jamra, Rami Abou Schumacher, Johannes Maier, Wolfgang Propping, Peter Noethen, Markus M. Cichon, Sven Rietschel, Marcella Schulze, Thomas G. TI Brief Report: No Association Between Premorbid Adjustment in Adult-Onset Schizophrenia and Genetic Variation in Dysbindin SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Premorbid functioning; Susceptibility genes; Haplotypes; Phenotype dissection; Complex genetics; Endophenotype ID BIPOLAR DISORDER; FAMILIAL RISK; 6P22.3 GENE; DTNBP1; PHENOTYPE; LINKAGE; INTELLIGENCE; PSYCHIATRY; PSYCHOSIS; RARE AB Whereas Dysbindin is considered a schizophrenia vulnerability gene, there is no consistency of findings. Phenotype refinement approaches may help to increase the genetic homogeneity and thus reconcile conflicting results. Premorbid adjustment (PMA) has been suggested to aid the phenotypic dissection. Gornick et al. (J Autism Dev Disord 35:831-838, 2005) reported an association between Dysbindin and PMA in US-Caucasian individuals with childhood-onset psychosis. In a sample of 222 adult-onset schizophrenia inpatients from Germany, we could not detect an association between PMA and 36 SNPs in Dysbindin. Our results suggest that genetic variation in Dysbindin may not contribute to the schizophrenia phenotype with an onset beyond childhood. Further studies including even larger samples and more SNPs may be warranted to clarify the relationship between Dysbindin and PMA. C1 [Schulze, Thomas G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Schirmbeck, Frederike; Georgi, Alexander; Strohmaier, Jana; Schmael, Christine; Boesshenz, Katja V.; Rietschel, Marcella; Schulze, Thomas G.] Univ Heidelberg, Dept Genet Epidemiol, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. [Muehleisen, Thomas W.; Herms, Stefan; Hoffmann, Per; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom Life & Brain Ctr, D-5300 Bonn, Germany. [Jamra, Rami Abou; Schumacher, Johannes; Propping, Peter; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Maier, Wolfgang] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, 35 Convent Dr,Bldg 35,Rm 1A202,MSC 3719, Bethesda, MD 20892 USA. EM schulzet@mail.nih.gov RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schirmbeck, Frederike/G-8187-2016; Schumacher, Johannes/F-4970-2015; Herms, Stefan/J-1949-2014; OI Cichon, Sven/0000-0002-9475-086X; Nothen, Markus/0000-0002-8770-2464; Cichon, Sven/0000-0002-9475-086X; Hoffmann, Per/0000-0002-6573-983X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Georgi, Alexander/0000-0002-1499-8524; Herms, Stefan/0000-0002-2786-8200; Schirmbeck, Frederike/0000-0003-1700-0958 NR 34 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2008 VL 38 IS 10 BP 1977 EP 1981 DI 10.1007/s10803-008-0582-6 PG 5 WC Psychology, Developmental SC Psychology GA 373FJ UT WOS:000260956100017 PM 18473158 ER PT J AU Gawel, D Hamilton, MD Schaaper, RM AF Gawel, Damian Hamilton, Michael D. Schaaper, Roel M. TI A Novel Mutator of Escherichia coli Carrying a Defect in the dgt Gene, Encoding a dGTP Triphosphohydrolase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEOXYGUANOSINE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; DNA MISMATCH-REPAIR; ADAPTIVE MUTATION; REPLICATION FIDELITY; INDUCED MUTAGENESIS; BASE SUBSTITUTIONS; NUDIX HYDROLASES; POLYMERASE-IV; 1.2 PROTEIN; MUTT AB A novel mutator locus in Escherichia coli was identified from a collection of random transposon insertion mutants. Several mutators in this collection were found to have an insertion in the dgt gene, encoding a previously characterized dGTP triphosphohydrolase. The mutator activity of the dgt mutants displays an unusual specificity. Among the six possible base pair substitutions in a lacZ reversion system, the G center dot C -> C center dot G transversion and A center dot T -> G center dot C transition are strongly enhanced (10- to 50-fold), while a modest effect (two- to threefold) is also observed for the G center dot C -> A center dot T transition. Interestingly, a two- to threefold reduction in mutant frequency (antimutator effect) is observed for the G center dot C -> T center dot A transversion. In the absence of DNA mismatch repair (mutL) some of these effects are reduced or abolished, while other effects remain unchanged. Analysis of these effects, combined with the DNA sequence contexts in which the reversions take place, suggests that alterations of the dGTP pools as well as alterations in the level of some modified dNTP derivatives could affect the fidelity of in vivo DNA replication and, hence, account for the overall mutator effects. C1 [Gawel, Damian; Hamilton, Michael D.; Schaaper, Roel M.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Schaaper, RM (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov FU NIH; National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We thank S. Covo and Z. Pursell of the NIEHS for their helpful review of the manuscript for this paper and Sean Moore for his help in constructing the strains containing the chromosomal lacZ alleles. NR 54 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2008 VL 190 IS 21 BP 6931 EP 6939 DI 10.1128/JB.00935-08 PG 9 WC Microbiology SC Microbiology GA 361ZF UT WOS:000260166900001 PM 18776019 ER PT J AU Thein, M Bunikis, I Denker, K Larsson, C Cutler, S Drancourt, M Schwan, TG Mentele, R Lottspeich, F Bergstrom, S Benz, R AF Thein, Marcus Bunikis, Ignas Denker, Katrin Larsson, Christer Cutler, Sally Drancourt, Michel Schwan, Tom G. Mentele, Reinhard Lottspeich, Friedrich Bergstroem, Sven Benz, Roland TI Oms38 Is the First Identified Pore-Forming Protein in the Outer Membrane of Relapsing Fever Spirochetes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LIPID BILAYER-MEMBRANES; LYME-DISEASE SPIROCHETE; FRACTURE ELECTRON-MICROSCOPY; BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; ANTIGENIC VARIATION; BINDING-SITE; MITOCHONDRIAL PORIN; TREPONEMA-PALLIDUM; HERMSII AB Relapsing fever is a worldwide, endemic disease caused by several spirochetal species belonging to the genus Borrelia. During the recurring fever peaks, borreliae proliferate remarkably quickly compared to the slow dissemination of Lyme disease Borrelia and therefore require efficient nutrient uptake from the blood of their hosts. This study describes the identification and characterization of the first relapsing fever porin, which is present in the outer membranes of B. duttonii, B. hermsii, B. recurrentis, and B. turicatae. The pore-forming protein was purified by hydroxyapatite chromatography and designated Oms38, for outer membrane-spanning protein of 38 kDa. Biophysical characterization of Oms38 was done by using the black lipid bilayer method, demonstrating that Oms38 forms small, water-filled channels of 80 pS in 1 M KCl that did not exhibit voltage-dependent closure. The Oms38 channel is slightly selective for anions and shows a ratio of permeability for cations over anions of 0.41 in KCl. Analysis of the deduced amino acid sequences demonstrated that Oms38 contains an N-terminal signal sequence which is processed under in vivo conditions. Oms38 is highly conserved within the four studied relapsing fever species, sharing an overall amino acid identity of 58% and with a strong indication for the presence of amphipathic beta-sheets. C1 [Thein, Marcus; Benz, Roland] Univ Wurzburg, Dept Biotechnol, Bioctr, D-97074 Wurzburg, Germany. [Bunikis, Ignas; Larsson, Christer; Bergstroem, Sven] Umea Univ, Dept Mol Biol, Umea, Sweden. [Denker, Katrin] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, Wurzburg, Germany. [Cutler, Sally] Univ E London, Sch Hlth & Biosci, London E15 4LZ, England. [Drancourt, Michel] Univ Aix Marseille 2, Unite Rickettsies, CNRS UMR 6020, IFR 48, Marseille, France. [Schwan, Tom G.] NIAID, Rocky Mt Lab, Natl Inst Hlth, Hamilton, MT 59840 USA. [Mentele, Reinhard; Lottspeich, Friedrich] Max Planck Inst Biochem, D-82152 Martinsried, Germany. RP Benz, R (reprint author), Univ Wurzburg, Dept Biotechnol, Bioctr, D-97074 Wurzburg, Germany. EM roland.benz@mail.uni-wuerzburg.de OI Larsson, Christer/0000-0002-5714-924X; Benz, Roland/0000-0002-9510-9265 FU Fonds der Chemischen Industrie; Swedish Medical Research Council FX We thank Christian Andersen for critical discussion of the results and Stephen Porcella and Sandra Steward for the help with sequencing.; This work was supported by grants from the joint project between Stint (Sweden) and DAAD (Germany) to S. B. and R. B., from the Fonds der Chemischen Industrie (to R. B.), and from the Swedish Medical Research Council (to S. B.). NR 75 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2008 VL 190 IS 21 BP 7035 EP 7042 DI 10.1128/JB.00818-08 PG 8 WC Microbiology SC Microbiology GA 361ZF UT WOS:000260166900011 PM 18757545 ER PT J AU Ogura, K Shiga, T Yokochi, M Yuzawa, S Burke, TR Inagaki, F AF Ogura, Kenji Shiga, Takanori Yokochi, Masashi Yuzawa, Satoru Burke, Terrence R., Jr. Inagaki, Fuyuhiko TI Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Perdeuterated Grb2 SH2; Solution structure; Inhibitor; Structure-based drug design ID RECEPTOR TYROSINE KINASES; STRUCTURE-BASED DESIGN; HUMAN BREAST-CANCER; NUCLEOTIDE EXCHANGE; CRYSTAL-STRUCTURES; RAS PATHWAY; PROTEIN; PEPTIDE; ACTIVATION; BINDING AB The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity. C1 [Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Inagaki, Fuyuhiko] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kita Ku, Sapporo, Hokkaido 0600812, Japan. [Burke, Terrence R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Inagaki, F (reprint author), Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kita Ku, N12 W6, Sapporo, Hokkaido 0600812, Japan. EM finagaki@pharm.hokudai.ac.jp RI Burke, Terrence/N-2601-2014 FU Ministry of Education, Science and Culture of Japan; International Research Program of the NIH, Center for Cancer Research, National Cancer Institute FX This work was supported by Grant-in-Aid for Scientific Research and the National Projects on Protein Structure and Functional Analysis from the Ministry of Education, Science and Culture of Japan. This research was also supported in part by the International Research Program of the NIH, Center for Cancer Research, National Cancer Institute. NR 39 TC 15 Z9 15 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 2008 VL 42 IS 3 BP 197 EP 207 DI 10.1007/s10858-008-9272-0 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 363QM UT WOS:000260281800005 PM 18830565 ER PT J AU Nesti, LJ Jackson, WM Shanti, RM Koehler, SM Aragon, AB Bailey, JR Sracic, MK Freedman, BA Giuliani, JR Tuan, RS AF Nesti, Leon J. Jackson, Wesley M. Shanti, Rabie M. Koehler, Steven M. Aragon, Amber B. Bailey, James R. Sracic, Michael K. Freedman, Brett A. Giuliani, Jeffrey R. Tuan, Rocky S. TI Differentiation Potential of Multipotent Progenitor Cells Derived from War-Traumatized Muscle Tissue SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MESENCHYMAL STEM-CELLS; BONE-MARROW; STROMAL CELLS; CARTILAGE; IDENTIFICATION; REGENERATION; FRACTURES; INJURY; MICE AB Background: Recent military conflicts have resulted in numerous extremity injuries requiring complex orthopaedic reconstructive procedures, which begin with a thorough debridement of all contaminated and necrotic tissue in the zone of injury. The site of injury is also the site of healing, and we propose that debrided muscle tissue contains cells with robust reparative and regenerative potential. Methods: Debrided muscle from soldiers who had sustained traumatic open extremity injuries was collected during surgical debridement procedures at Walter Reed Army Medical Center. With modifications to a previously described stem-cell-isolation protocol, mesenchymal progenitor cells were harvested from traumatized muscle, enriched, expanded in culture, and exposed to induction media for osteogenesis, adipogenesis, and chondrogenesis. Results: The isolated mesenchymal progenitor cells stained positive for cell-surface markers (CD73, CD90, CD105), which are characteristic of adult human mesenchymal stem cells. Histological identification of lineage-specific markers demonstrated the potential of these cells to differentiate into multiple mesenchymal lineages. Reverse transcription-polymerase chain reaction analysis confirmed multilineage mesenchymal differentiation at the gene-expression level. Conclusions: To our knowledge, the present report provides the first description of mesenchymal progenitor cell isolation from traumatized human muscle. These cells may play an integral role in tissue repair and regeneration and merit additional investigation as they could be useful in future cell-based tissue-engineering strategies. Clinical Significance: Mesenchymal progenitor cells isolated from war-traumatized tissues have the potential for applications in cell-based tissue engineering. Elucidating the cellular mechanisms regulating their differentiation activities may lead to the development of novel treatments for musculoskeletal trauma and pathological healing responses, such as heterotopic ossification. C1 [Jackson, Wesley M.; Shanti, Rabie M.; Koehler, Steven M.; Aragon, Amber B.; Giuliani, Jeffrey R.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Bailey, James R.; Sracic, Michael K.] Uniformed Serv Univ Hlth Sci, Washington, DC USA. [Freedman, Brett A.] Walter Reed Army Med Ctr, Integrated Dept Orthopaed & Rehabil, Washington, DC 20307 USA. RP Nesti, LJ (reprint author), 6900 Georgia Ave NW,Bldg 2,Room 5B28, Washington, DC 20307 USA. EM leonnesti@gmail.com FU Military Amputee Research Program [P05-A011]; NIH; NIAMS [Z01 AR41131] FX In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Military Amputee Research Program at Walter Reed Army Medical Center (P05-A011) and by the Intramural Research Program at the NIH, NIAMS (Z01 AR41131). Neither they nor a member of their immediate families received payments or other benefits ora commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families. are affiliated or associated. NR 28 TC 81 Z9 85 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2008 VL 90A IS 11 BP 2390 EP 2398 DI 10.2106/JBJS.H.00049 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 372NA UT WOS:000260907100009 PM 18978407 ER PT J AU Kuznetsov, SA Cherman, N Riminucci, M Collins, MT Robey, PG Bianco, P AF Kuznetsov, Sergei A. Cherman, Natasha Riminucci, Mara Collins, Michael T. Robey, Pamela Gehron Bianco, Paolo TI Age-Dependent Demise of GNAS-Mutated Skeletal Stem Cells and "Normalization" of Fibrous Dysplasia of Bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibrous dysplasia; Gs alpha; mutation; skeletal stem cells; bone marrow stromal cells ID MCCUNE-ALBRIGHT SYNDROME; ACTIVATING G(S)ALPHA MUTATION; MARROW STROMAL FIBROBLASTS; STIMULATORY G-PROTEIN; IN-VIVO; GENE; ABNORMALITIES; PIGMENTATION; OSTEOGENESIS; DYSFUNCTION AB We Studied the role of somatic mosaicism in fibrous dysplasia of bone (FD) within the context of skeletal ("mesenchymal") stern cells by assessing the frequency of mutated colony forming unit-fibroblasts (CFU-Fs) from FD lesions. and in some cases, from unaffected sites, in a series of patients. There was a tight inverse correlation between the percentage mutant CFU-F versus age, suggesting demise of mutant stem cells caused by exuberant apoptosis noted in samples from young patients. In older patients. either partially or completely normal bone/marrow histology was observed. On in vivo transplantation. FD ossicles were generated only by cell strains in which mutant CFU-Fs were identified. strains that lacked mutant CFU-F (but were mutation positive) failed to regenerate an FD ossicle. These data indicate that GNAS Mutations are only Pathogenic when in clonogenic skeletal stern cells. From these data, we have evolved the novel concept of "normalization" of FD. As a lesion ages, mutant stern cells fail to self-renew, and their progeny are consumed by apoptosis. whereas residual normal stern cells survive, self-renew. and enable formation of a normal Structure. This suggests that activating GNAS Mutations disrupt a pathway that is required for skeletal stern cell self-renewal. C1 [Kuznetsov, Sergei A.; Cherman, Natasha; Collins, Michael T.; Robey, Pamela Gehron] NIDCR, CSDB, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Riminucci, Mara] Univ Laquila, Dept Expt Med, Laquila, Italy. [Bianco, Paolo] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. [Riminucci, Mara; Bianco, Paolo] Biomed Sci Pk, Rome, Italy. RP Robey, PG (reprint author), NIDCR, CSDB, NIH, US Dept HHS, 30 Convent Dr,MSC 4320,Bldg 30,Room 228, Bethesda, MD 20892 USA. EM probey@dir.nidcr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [GGP0463]; MIUR; AIRL; DIR; NIDCR; NII; DHHS FX This work Was Supported by Telethon Grant GGP0463 (to PB), MIUR (PB, MR), AIRL (PB), and the DIR, NIDCR of the IRP, NII, DHHS (to SAK, NC, MTC, and PGR). NR 26 TC 44 Z9 44 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2008 VL 23 IS 11 BP 1731 EP 1740 DI 10.1359/JBMR.080609 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 362KF UT WOS:000260195900004 PM 18597624 ER PT J AU Chen, A Leikina, E Melikov, K Podbilewicz, B Kozlov, MM Chernomordik, LV AF Chen, Andrew Leikina, Eugenia Melikov, Kamran Podbilewicz, Benjamin Kozlov, Michael M. Chernomordik, Leonid V. TI Fusion-pore expansion during syncytium formation is restricted by an actin network SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cell fusion; Syncytium formation; Fusion-pore expansion; Actin cytoskeleton; Membrane-bending proteins; Baculovirus gp64 ID INDUCED POLYKARYOCYTE FORMATION; VIRUS MEMBRANE-FUSION; CELL-CELL FUSION; MYOBLAST FUSION; CAENORHABDITIS-ELEGANS; BACULOVIRUS GP64; INFLUENZA HEMAGGLUTININ; C-ELEGANS; PROTEIN; MORPHOGENESIS AB Cell-cell fusion in animal development and in pathophysiology involves expansion of nascent fusion pores formed by protein fusogens to yield an open lumen of cell-size diameter. Here we explored the enlargement of micron-scale pores in syncytium formation, which was initiated by a well-characterized fusogen baculovirus gp64. Radial expansion of a single or, more often, of multiple fusion pores proceeds without loss of membrane material in the tight contact zone. Pore growth requires cell metabolism and is accompanied by a local disassembly of the actin cortex under the pores. Effects of actin-modifying agents indicate that the actin cortex slows down pore expansion. We propose that the growth of the strongly bent fusion-pore rim is restricted by a dynamic resistance of the actin network and driven by membrane-bending proteins that are involved in the generation of highly curved intracellular membrane compartments. C1 [Chen, Andrew; Leikina, Eugenia; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Podbilewicz, Benjamin] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. [Kozlov, Michael M.] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Chernomordik, LV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov RI Melikov, Kamran/A-6604-2009; Podbilewicz, Benjamin/N-4825-2014; OI Podbilewicz, Benjamin/0000-0002-0411-4182 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health FX We are indebted to Gary Blissard for the generous gift of Sf9Op1D cells and Myoungsoon S. Hong for her kind help with electron-microscopy experiments. We thank Alexander Bershadsky, Jean-Philippe Richard and Joshua Zimmerberg for very helpful discussions. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (L.V.C.). NR 75 TC 28 Z9 28 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2008 VL 121 IS 21 BP 3619 EP 3628 DI 10.1242/jcs.032169 PG 10 WC Cell Biology SC Cell Biology GA 363KR UT WOS:000260266700015 PM 18946025 ER PT J AU Jozwiak, K Moaddel, R Ravichandran, S Plazinska, A Kozak, J Patel, S Yamaguchi, R Wainer, IW AF Jozwiak, Krzysztof Moaddel, Ruin Ravichandran, Sarangan Plazinska, Anita Kozak, Joanna Patel, Sharvil Yamaguchi, Rika Wainer, Irving W. TI Exploring enantiospecific ligand-protein interactions using cellular membrane affinity chromatography: Chiral recognition as a dynamic process SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Nicotinic acetylcholine receptors; Organic cation transporters; Pharmacophore modeling; Non-linear chromatography; Molecular modeling ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CATION TRANSPORTER HOCT1; STATIONARY-PHASE; NONCOMPETITIVE INHIBITORS; NONLINEAR CHROMATOGRAPHY; MOLECULAR DOCKING; AMINO-ACIDS; SEPARATION; MODEL; ALPHA-3-BETA-4 AB The chiral recognition mechanisms responsible for the enantioselective binding on the alpha(3)beta(4) nicotinic acetylcholine receptor (alpha(3)beta(4) nAChR) and human organic cation transporter 1 (hOCT1) have been reviewed. The results indicate that chiral recognition on the CON nAChR is a process involving initial tethering of dextromethorphan and levomethorphan at hydrophobic pockets within the central lumen followed by hydrogen bonding interactions favoring dextromethorphan. The second step is the defining enantioselective step. Studies with the hOCT1 indentified four binding sites within the transporter that participated in chiral recognition. Each of the enantiomers of the compounds used in the study interacted with three of these sites, while (R)-verapamil interacted with all four. Chiral recognition arose from the conformational adjustments required to produce optimum interactions. With respect to the prevailing interaction-based models, the data suggest that chiral recognition is a dynamic process and that the static point-based models should be amended to reflect this. (c) 2008 Elsevier B.V. All rights reserved. C1 [Moaddel, Ruin; Patel, Sharvil; Yamaguchi, Rika; Wainer, Irving W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Jozwiak, Krzysztof; Plazinska, Anita; Kozak, Joanna] Med Univ Lublin, Lab Drug Receptor Interact, PL-20081 Lublin, Poland. [Ravichandran, Sarangan] NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Patel, Sharvil] Cadilia Healthcare Ltd, Ahmadabad 380015, Gujarat, India. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov OI Plazinska, Anita/0000-0002-3698-2574 FU National Institute on Aging Intramural Research Program; Foundation for Polish Science [FOCUS 4/2006] FX This work was supported by funding from the National Institute on Aging Intramural Research Program (IWW) and from the Foundation for Polish Science (FOCUS 4/2006 programme) (K.J.). NR 47 TC 9 Z9 9 U1 0 U2 9 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 NOV 1 PY 2008 VL 875 IS 1 BP 200 EP 207 DI 10.1016/j.jchromb.2008.07.048 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 373BK UT WOS:000260945800027 PM 18723411 ER PT J AU Batista, DL Courcoutsakis, N Riar, J Keil, MF Stratakis, CA AF Batista, Dalia L. Courcoutsakis, Nikos Riar, Jehan Keil, Margaret F. Stratakis, Constantine A. TI Severe Obesity Confounds the Interpretation of Low-Dose Dexamethasone Test Combined with the Administration of Ovine Corticotrophin-Releasing Hormone in Childhood Cushing Syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SALIVARY CORTISOL MEASUREMENT; URINARY FREE CORTISOL; BODY-MASS INDEX; SUPPRESSION TEST; STIMULATION TEST; DIFFERENTIAL-DIAGNOSIS; METABOLIC SYNDROME; CHILDREN; ADOLESCENTS; STATES AB Context: Suppression of cortisol secretion with a low-dose dexamethasone (Dex) followed by the administration of ovine CRH (Dex-oCRH) is used in the evaluation of adults with a pseudo-Cushing syndrome state (PCSS) vs. Cushing syndrome (CS). Objective: The aim of the study was to determine the value of Dex-oCRH testing in the investigation of childhood CS. Design: We conducted a retrospective analysis of data from children evaluated for CS vs. PCSS from 1998-2006; body mass index Z (BMIZ) and height-for-age Z (HAZ) scores were estimated. Setting: A clinical research center was the setting for the study. Main Outcome Measures: The main outcomes were confirmation of the diagnosis of CS by histology and response to Dex-oCRH. Results: Thirty-two children (ages 3-17 yr) were studied: 11 had CS and 21 had PCSS; of the latter, 11 had a BMIZ score greater than 2. Children with CS had a mean HAZ score of -1.3 +/- 0.51 vs. 0.31 +/- 0.38 in nonobese and 0.71 +/- 0.39 in obese children (P < 0.001). The previously established criterion of a cortisol of 1.4 mu g/dl (38 nmol/liter) after Dex-oCRH identified all 10 normal children who were not very obese and those with CS; 5 of 11 normal children with more severe obesity had cortisol values greater than 1.4 mu g/dl (38 nmol/liter) after Dex-oCRH, lowering the test specificity to 55%. Without consideration for obesity, an increase of the cutoff cortisol value after Dex-oCRH to 3.2 mu g/dl (88 nmol/liter) will have 91% sensitivity and 95% specificity; the corresponding values for a cutoff of 2.2 mu g/dl (61 nmol/liter) were 100 and 90.5%, respectively. Conclusion: Our study showed that height gain is a simple way of distinguishing children with PCCS from those with CS; the interpretation of Dex-oCRH in children is confounded by severe obesity, which limits the utility of this test. (J Clin Endocrinol Metab 93: 4323-4330, 2008) C1 [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Batista, Dalia L.; Riar, Jehan; Stratakis, Constantine A.] NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA. [Courcoutsakis, Nikos] Univ Hosp Alexandroupolis, Dept Radiol, Alexandroupolis 68100, Greece. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC E Labs,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU National Institutes of Health; National Institute of Child Health and Human Development [Z01-HD-000642-04] FX This work was supported by the National Institutes of Health, National Institute of Child Health and Human Development intramural project Z01-HD-000642-04 (Principal Investigator, C. A. Stratakis). NR 33 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2008 VL 93 IS 11 BP 4323 EP 4330 DI 10.1210/jc.2008-0985 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368ZI UT WOS:000260661900023 PM 18728165 ER PT J AU Nwachuku, CE Bastien, A Cutler, JA Grob, GM Margolis, KL Roccella, EJ Pressel, S Davis, BR Caso, M Sheps, S Weber, M AF Nwachuku, Chuke E. Bastien, Arnaud Cutler, Jeffrey A. Grob, Glenda M. Margolis, Karen L. Roccella, Edward J. Pressel, Sara Davis, Barry R. Caso, Michael Sheps, Sheldon Weber, Michael TI Management of High Blood Pressure in Clinical Practice: Perceptible Qualitative Differences in Approaches Utilized by Clinicians SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; UNITED-STATES; ACTIVE TREATMENT; PLACEBO; PREVENTION; PREVALENCE; COMMITTEE; AWARENESS AB The authors recruited a group of physicians among the investigators participating in the Anti-bypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with a greater (more successful) or lesser (less successful) proportion of trial patients meeting blood pressure (BP) control goals. The authors utilized qualitative focus group methods to identify similarities and differences in practice behaviors. Successful and less successful physicians bad similarities in knowledge and practice behaviors regarding awareness of treatment guidelines, approaches to diagnosis, use of pharmacologic management, and the opinion that systolic BP guidelines should consider a patient's age. However, there were discernible differences between the two physician groups in their views on doctor-patient relationships: physicians from the less successful group were more paternalistic with their patients, while physicians from the more successful group were more likely to use a patient-centered clinical approach to BP awareness and management. J Clin Hypertens (Greenwich). 2008;10:822-829. (C) 2008 Le Jacq C1 [Pressel, Sara; Davis, Barry R.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Bastien, Arnaud] Bristol Myers Squibb Co, Princeton, NJ USA. [Bastien, Arnaud] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Grob, Glenda M.] Adelphi Res Design, Doylestown, PA USA. [Margolis, Karen L.] Hlth Partners Res Fdn, Minneapolis, MN USA. [Roccella, Edward J.] NHLBI, Ctr Applicat Res Discoveries, Bethesda, MD 20892 USA. [Caso, Michael] Nexus Commun Inc, N Wales, PA USA. [Sheps, Sheldon] Mayo Med Sch & Clin, Rochester, MN USA. [Weber, Michael] SUNY Downstate Coll Med, Brooklyn, NY USA. RP Pressel, S (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA. EM sara.l.pressel@uth.tmc.edu FU Boehringer Ingelheim; National Heart, Lung, and Blood Institute [N01-HC-3S130]; Pfizer Inc FX The authors are fully responsible for the methodology, inclusion and interpretation of data, and opinions and conclusions expressed in this article, which are independent of and do not necessarily reflect the study funders. The authors bad access to the data, reviewed each manuscript draft, and approved the final manuscript. We would like to thank Joe Riley (Editorial Director, Nexus Communications, Inc.), Carol Greco (Managing Editor, Nexus Communications, Inc.), and Wendy Henson (Editorial Associate, Nexus Communications, Inc.) for their editorial support during preparation of the revised manuscript. This study was funded by Boehringer Ingelheim and the National Heart, Lung, and Blood Institute. ALLHAT was supported by contract N01-HC-3S130 from the National Heart, Lung, and Blood Institute and by Pfizer Inc. The authors of this paper disclose their affiliations below, and these relate to personal or institutional-affiliated receipt of income in the areas of research grants, consultant fees, or other compensation: KLM, King; BRD, BioMarin, GlaxoSmithKline, Proctor & Gamble, and Takeda Pharmaceuticals; MC, GlaxoSmithKline and Sanofi Aventis; SS, Kos Pharmaceuticals; and MW, Novartis, Bristol-Myers Squibb, Pfizer, Merck, Sanofi Aventis, DaiichiSankyo, Boehringer Ingelheim, ClaxoSmithKline, Forest Laboratories, Gilead, and Takeda Pharmaceuticals. AB was associate professor of medicine at Robert Wood Johnson School of Medicine's Camden, NJ, campus at Cooper University Hospital, and GMG was account manager at Migliara-Kaplan, Princeton, NJ, at the time of the study. The other authors report no competing interests. NR 28 TC 6 Z9 6 U1 2 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD NOV PY 2008 VL 10 IS 11 BP 822 EP 829 DI 10.1111/j.1751-7176.2008.00035.x PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AJ UT WOS:000261223800003 PM 19128270 ER PT J AU Milner, J Paul, WE AF Milner, Joshua Paul, William E. TI Limited T-Cell Receptor Diversity Predisposes to Th2 Immunopathology: Involvement of Tregs and Conventional CD4 T Cells SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE TCR; receptor repertoire; eosinophil; immunopathology; TH2 ID MUTAGENESIS AB Introduction A variety of immunodeficiencies characterized by limitations in the T-cell repertoire are also associated with Th2-like immunopathology. Methods We established a model of this phenomenon by transferring limited numbers of mature CD4+ T-cells into lymphopenic mice. Result This transfer resulted in eosinophilic pneumonia with alternatively activated macrophages, eosinophilic gastritis. and other organ infiltration, associated with elevated IgE levels and Th2 cytokine production by the transferred cells. Transfer of large numbers of T-cells did not result in any pathology. The disease Could be suppressed by CD25+ Foxp3+ regulatory T cells, but only when the T-cell receptor repertoire of the Tregs was diverse. Conclusion Collectively, the data suggest that limited T-cell receptor repertoires derived from normal CD4+ T cells can cause severe Th2 immunopathology, and that failure of control by Tregs due to limitation of their repertoire is partially responsible for this phenotype. C1 [Milner, Joshua; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike,NIH Bldg 10-11N311, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU NIH [1 Z01 AI00926-06-LI]; NIAID FX This research was Supported by Project 1 Z01 AI00926-06-LI of the Intramural Research Program of the NIH, NIAID. NR 10 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2008 VL 28 IS 6 BP 631 EP 634 DI 10.1007/s10875-008-9245-9 PG 4 WC Immunology SC Immunology GA 399XW UT WOS:000262833600004 PM 18792766 ER PT J AU Shevach, EM Davidson, TS Huter, EN DiPaolo, RA Andersson, J AF Shevach, Ethan M. Davidson, Todd S. Huter, Eva N. DiPaolo, Richard A. Andersson, John TI Role of TGF-beta in the Induction of Foxp3 Expression and T Regulatory Cell Function SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE TGF-beta; gastritis; infectious tolerance; immune suppression; latency-associated peptide ID GROWTH-FACTOR-BETA; SUPPRESSOR FUNCTION; TGF-BETA-1; RECEPTOR; MICE; AUTOIMMUNITY; INFLAMMATION AB Introduction A number of studies have suggested that transforming growth factor beta (TGF-beta) plays a critical role In immune suppression mediated by Foxp3(+) regulatory T cells. TGF-beta in concert with interleukin 2 is a potent induction factor for the differentiation of Foxp3(+) Treg from naive precursors. Polyclonal TGF-beta-induced Treg (iTreg) are capable of preventing the autoimmune syndrome that develops in scurfy mice that lack Foxp3(+) Treg. Antigen-specific iTreg can be used to both prevent and treat autoimmune gastritis that is induced by transfer of naive or primed autoantigen-specific T cells. TGF-beta complexed with latency-associated peptide is expressed on the surface of activated thymus-derived Treg. Coculture of activated Treg with naive responder T cells results in the de novo generation of fully functional Foxp3(+) T cells in a contact-dependent and TGF-beta-dependent manner. Conclusions and Speculations Generation of functional Foxp3(+) T cells via this pathway may represent a mechanism by which Treg maintain tolerance and expand their repertoire. C1 [Shevach, Ethan M.; Davidson, Todd S.; Huter, Eva N.; DiPaolo, Richard A.; Andersson, John] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Blg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov RI Andersson, John/A-4436-2009; OI Andersson, John/0000-0003-2799-6349 NR 22 TC 63 Z9 67 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2008 VL 28 IS 6 BP 640 EP 646 DI 10.1007/s10875-008-9240-1 PG 7 WC Immunology SC Immunology GA 399XW UT WOS:000262833600006 PM 18810612 ER PT J AU Wohlfert, E Belkaid, Y AF Wohlfert, Elizabeth Belkaid, Yasmine TI Role of Endogenous and Induced Regulatory T Cells During Infections SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Regulatory T cells; peripheral homeostasis; controlled immune response ID TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR FOXP3; DENDRITIC CELLS; RETINOIC-ACID; IMMUNE-RESPONSES; IFN-GAMMA; LAMINA-PROPRIA; TGF-BETA; TUBERCULOSIS PATIENTS; INTERFERON-GAMMA AB Background Various populations of regulatory cells, including Foxp3+ T(Reg), have been shown to play a central role in the maintenance of peripheral homeostasis and establishment of controlled immune responses. Objective In this review, we discuss current hypotheses and points of polemic associated with the origin, mode of action. and antigen specificity of both endogenous and induced regulatory T cells during infections. C1 [Wohlfert, Elizabeth; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We would like to thank David B. Chow for the confocal image. We apologize to those authors whose work we were unable to cite because of space limitations, NR 93 TC 32 Z9 32 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2008 VL 28 IS 6 BP 707 EP 715 DI 10.1007/s10875-008-9248-6 PG 9 WC Immunology SC Immunology GA 399XW UT WOS:000262833600013 PM 18810611 ER PT J AU Kasai, M Harrington, SM Francesconi, A Petraitis, V Petraitiene, R Beveridge, MG Knudsen, T Milanovich, J Cotton, MP Hughes, J Schaufele, RL Sein, T Bacher, J Murray, PR Kontoyiannis, DP Walsh, TJ AF Kasai, Miki Harrington, Susan M. Francesconi, Andrea Petraitis, Vidmantas Petraitiene, Ruta Beveridge, Mara G. Knudsen, Tena Milanovich, Jeffery Cotton, Margaret P. Hughes, Johanna Schaufele, Robert L. Sein, Tin Bacher, John Murray, Patrick R. Kontoyiannis, Dimitrios P. Walsh, Thomas J. TI Detection of a Molecular Biomarker for Zygomycetes by Quantitative PCR Assays of Plasma, Bronchoalveolar Lavage, and Lung Tissue in a Rabbit Model of Experimental Pulmonary Zygomycosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; ORGAN TRANSPLANT RECIPIENTS; ASPERGILLUS-FUMIGATUS; PANFUNGAL PCR; MAGNA PURE; GENETIC IDENTIFICATION; FUNGAL-INFECTIONS; FILAMENTOUS FUNGI; CANDIDA-ALBICANS AB We developed two real-time quantitative PCR (qPCR) assays, targeting the 28S rRNA gene, for the diagnosis of zygomycosis caused by the most common, clinically significant Zygomycetes. The amplicons of the first qPCR assay (qPCR-1) from Rhizopus, Mucor, and Rhizomucor species were distinguished through melt curve analysis. The second qPCR assay (qPCR-2) detected Cunninghamella species using a different primer/probe set. For both assays, the analytic sensitivity for the detection of hyphal elements from germinating sporangiospores in bronchoalveolar lavage (BAL) fluid and lung tissue homogenates from rabbits was 1 to 10 sporangiospores/ml. Four unique and clinically applicable models of invasive pulmonary zygomycosis served as surrogates of human infections, facilitating the validation of these assays for potential diagnostic utility. For qPCR-1, 5 of 98 infarcted lung specimens were positive by qPCR and negative by quantitative culture (qCx). None were qCx positive only. Among 23 BAL fluid samples, all were positive by qPCR, while 22 were positive by qCx. qPCR-1 detected Rhizopus and Mucor DNA in 20 (39%) of 51 serial plasma samples as early as day 1 postinoculation. Similar properties were observed for qPCR-2, which showed greater sensitivity than qCx for BAL fluid (100% versus 67%; P = 0.04; n = 15). The assay detected Cunninghamella DNA in 18 (58%) of 31 serial plasma samples as early as day 1 postinoculation. These qPCR assays are sensitive and specific for the detection of Rhizopus, Mucor, Rhizomucor, and Cunninghamella species and can be used for the study and detection of infections caused by these life-threatening pathogens. C1 [Kasai, Miki; Francesconi, Andrea; Petraitis, Vidmantas; Petraitiene, Ruta; Beveridge, Mara G.; Knudsen, Tena; Milanovich, Jeffery; Cotton, Margaret P.; Hughes, Johanna; Schaufele, Robert L.; Sein, Tin; Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA. [Harrington, Susan M.; Murray, Patrick R.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. [Petraitis, Vidmantas; Petraitiene, Ruta] SAIC Frederick Inc, LASP, Frederick, MD USA. [Bacher, John] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Walsh, TJ (reprint author), Natl Canc Inst, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10-CRC,Room 1-5740, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 52 TC 51 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2008 VL 46 IS 11 BP 3690 EP 3702 DI 10.1128/JCM.00917-08 PG 13 WC Microbiology SC Microbiology GA 367DH UT WOS:000260532200022 PM 18845827 ER PT J AU Herzlich, AA Yeh, S Shen, D Ding, X Uzel, G Holland, SM Chan, C AF Herzlich, A. A. Yeh, S. Shen, D. Ding, X. Uzel, G. Holland, S. M. Chan, C. TI Identification of Pseudomonas aeruginosa DNA in a chorioretinal lesion associated with chronic granulomatous disease SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 [Herzlich, A. A.; Yeh, S.; Shen, D.; Ding, X.; Chan, C.] NIAID, Immunol Lab, NEI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Uzel, G.; Holland, S. M.] NIAID, Lab Clin Infect Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Chan, C (reprint author), NEI, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS NR 5 TC 4 Z9 4 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD NOV PY 2008 VL 61 IS 11 BP 1229 EP 1230 DI 10.1136/jcp.2008.059147 PG 4 WC Pathology SC Pathology GA 365RI UT WOS:000260425100014 PM 18755713 ER PT J AU Bissmarck, F Nakahara, H Doya, K Hikosaka, O AF Bissmarck, Fredrik Nakahara, Hiroyuki Doya, Kenji Hikosaka, Okihide TI Combining Modalities with Different Latencies for Optimal Motor Control SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID OPTIMAL FEEDBACK-CONTROL; BASAL GANGLIA; VISUAL FEEDBACK; SENSORIMOTOR CONTROL; FUNCTIONAL-ANATOMY; PRISM ADAPTATION; POPULATION CODES; MANUAL TRACKING; TASK; ARCHITECTURE AB Feedback signals may be of different modality, latency, and accuracy. To learn and control motor tasks, the feedback available may be redundant, and it would not be necessary to rely on every accessible feedback loop. Which feedback loops should then be utilized? In this article, we propose that the latency is a critical factor to determine which signals will be influential at different learning stages. We use a computational framework to study the role of feedback modules with different latencies in optimal motor control. Instead of explicit gating between modules, the reinforcement learning algorithm learns to rely on the more useful module. We tested our paradigm for two different implementations, which confirmed our hypothesis. In the first, we examined how feedback latency affects the competitiveness of two identical modules. In the second, we examined an example of visuomotor sequence learning, where a plastic, faster somatosensory module interacts with a preacquired, slower visual module. We found that the overall performance depended on the latency of the faster module alone, whereas the relative latency determines the independence of the faster from the slower. In the second implementation, the somatosensory module with shorter latency overtook the slower visual module, and realized better overall performance. The visual module played different roles in early and late learning. First, it worked as a guide for the exploration of the somatosensory module. Then, when learning had converged, it contributed to robustness against system noise and external perturbations. Overall, these results demonstrate that our framework successfully learns to utilize the most useful available feedback for optimal control. C1 [Bissmarck, Fredrik; Doya, Kenji] ATR Int, Kyoto, Japan. [Bissmarck, Fredrik] NICT, Kyoto, Japan. [Nakahara, Hiroyuki] RIKEN, Brain Sci Inst, Saitama, Japan. [Doya, Kenji] Okinawa Inst Sci & Technol, Okinawa, Japan. [Hikosaka, Okihide] NIH, Bethesda, MD 20892 USA. [Bissmarck, Fredrik] NAIST, Nara, Japan. RP Bissmarck, F (reprint author), ATR, Computat Neurosci Labs, 2-2-2 Hikaridai Keihanna Sci City, Kyoto 6190288, Japan. EM fredrik.bissmarck@gmail.com RI Doya, Kenji/B-5841-2015; Nakahara, Hiroyuki/N-5411-2015 OI Doya, Kenji/0000-0002-2446-6820; Nakahara, Hiroyuki/0000-0001-6891-1175 FU Core Research for Evolutional Science and Technology (CREST); Japan Science and Technology Agency FX F. B. thanks Mitsuo Kawato, Erhan Oztop, and Jun Morimoto for comments on an earlier draft. This research was funded by Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency. NR 37 TC 4 Z9 4 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 2008 VL 20 IS 11 BP 1966 EP 1979 DI 10.1162/jocn.2008.20133 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 360GM UT WOS:000260046000004 PM 18416676 ER PT J AU Dolle, RE Le Bourdonnec, B Goodman, AJ Morales, GA Thomas, CJ Zhang, W AF Dolle, Roland E. Le Bourdonnec, Bertrand Goodman, Allan J. Morales, Guillermo A. Thomas, Craig J. Zhang, Wei TI Comprehensive Survey of Chemical Libraries for Drug Discovery and Chemical Biology: 2007 SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Review ID SOLID-PHASE SYNTHESIS; ONE-POT SYNTHESIS; DIVERSITY-ORIENTED SYNTHESIS; ONE-STEP SYNTHESIS; APOPTOSIS-INDUCING PROPERTIES; MICROWAVE-ASSISTED SYNTHESIS; CALCIUM-CHANNEL BLOCKERS; FLUOROUS BIPHASE SYSTEM; SOLVENT-FREE CONDITIONS; PROMOTED 3-COMPONENT SYNTHESIS C1 [Dolle, Roland E.; Le Bourdonnec, Bertrand; Goodman, Allan J.] Adolor Corp, Exton, PA 19341 USA. [Morales, Guillermo A.] Semafore Pharmaceut Inc, Indianapolis, IN 46268 USA. [Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Rockville, MD 20850 USA. [Zhang, Wei] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA. RP Dolle, RE (reprint author), Adolor Corp, 700 Penn Dr, Exton, PA 19341 USA. EM rdolle@adolor.com NR 530 TC 74 Z9 74 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD NOV-DEC PY 2008 VL 10 IS 6 BP 753 EP 802 DI 10.1021/cc800119z PG 50 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 371SK UT WOS:000260851400001 PM 18991466 ER PT J AU Cho, CH Neuenswander, B Lushington, GH Larock, RC AF Cho, Chul-Hee Neuenswander, Benjamin Lushington, Gerald H. Larock, Richard C. TI Parallel Synthesis of a Multi-Substituted Benzo[b]furan Library SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID PALLADIUM-CATALYZED CYCLIZATION; HETEROAROMATIC RING-SYSTEMS; CROSS-COUPLING REACTIONS; O-ALKYNYLPHENOLS; ELECTROPHILIC CYCLIZATION; CARBONYLATIVE ANNULATION; DEVELOPMENT SETTINGS; ESTIMATE SOLUBILITY; SELECTIVE LIGANDS; DRUG DISCOVERY AB The solution-phase parallel synthesis of a 121-member library of multi-substituted benzo[b]furans is described. 2.3,5-Trisubstituted benzo[b]furans have been prepared by the palladium-catalyzed substitution of 3-iodobenzofurans by Suzuki-Miyaura, carbonylative Suzuki, Sonogashira, Heck, and carboalkoxylation chemistry. The 3-iodobenzofurans are readily prepared in good to excellent yields by the palladium/copper-catalyzed cross-coupling of various o-iodoanisoles and terminal alkynes, followed by electrophilic cyclization with ICI. C1 [Cho, Chul-Hee; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Neuenswander, Benjamin; Lushington, Gerald H.] Univ Kansas, NIH, Ctr Excellence Chem Methodol, Lawrence, KS 66047 USA. [Neuenswander, Benjamin; Lushington, Gerald H.] Univ Kansas, NIH, Lib Dev, Lawrence, KS 66047 USA. RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM larock@iastate.edu FU National Institute of General Medical Sciences [GM070620, GM079593]; National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence [GM069663]; Johnson Matthey, Inc; Kawaken Fine Chemicals Co., Ltd FX We thank the National Institute of General Medical Sciences (GM070620 and GM079593) and the National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence (GM069663) for support of this research, Johnson Matthey, Inc., and Kawaken Fine Chemicals Co., Ltd., for donations of palladium catalysts, and Frontier Scientific and Synthonix for donations of boronic acids. NR 55 TC 53 Z9 54 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD NOV-DEC PY 2008 VL 10 IS 6 BP 941 EP 947 DI 10.1021/cc800120y PG 7 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 371SK UT WOS:000260851400021 PM 18937516 ER PT J AU McCrae, RR Terracciano, A Realo, A Allik, J AF McCrae, Robert R. Terracciano, Antonio Realo, Anu Allik, Jueri TI Interpreting GLOBE Societal Practices Scales SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE personality traits; national character; cultural identity; stereotypes; GLOBE scales ID NATIONAL CHARACTER; CULTURES; VALUES; MODEL AB Some of the Global Leadership and Organizational Behavior Effectiveness (GLOBE) Societal Practices scales ask for descriptions of typical personality traits that might be interpreted as judgments of national character. Ratings of national character reflect cultural identities and social dynamics, but previous research suggests that they are unrelated to the mean personality traits of the culture's members. Analyses at the culture level comparing GLOBE scales with aggregate assessed personality traits (n = 34) and with measures of perceived national character (n = 33) showed that these GLOBE scales are better construed as unfounded stereotypes than as actual depictions of the society members' personality traits. C1 [McCrae, Robert R.] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Terracciano, Antonio] NIA, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Allik, Jueri] Univ Tartu, Fac Social Sci, Tartu, Estonia. RP McCrae, RR (reprint author), NIA, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04B329, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; Allik, Juri/D-5609-2009; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; NR 19 TC 17 Z9 17 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD NOV PY 2008 VL 39 IS 6 BP 805 EP 810 DI 10.1177/0022022108323806 PG 6 WC Psychology, Social SC Psychology GA 358ZM UT WOS:000259956000010 ER PT J AU Masse, M Falanga, V Zhou, LH AF Masse, Maureen Falanga, Vincent Zhou, Linda Hua TI Use of topical povidone-iodine resulting in an iododerma-like eruption SO JOURNAL OF DERMATOLOGY LA English DT Article DE iododerma; povidone-iodine; leg pustules; leg abscesses; iodine ID VEGETATING IODODERMA AB Iododerma is a rare skin eruption that is usually induced by the systemic use of iodide-containing radiographic contrast medium or treatment with oral potassium iodide therapy. Iododerma has also rarely been reported to occur following topical application of iodine. We herein report the case of a 42-year-old male who developed multiple pinpoint pustules on both lower extremities. Three days after the eruption began, the patient started applying topical 10% povidone-iodine solution to the lesions. During this treatment, the lesions enlarged into multiple 2-9-cm pus-filled bullae, limited to the treated areas. Lesional bacterial culture swab and Gram stain were negative. Blood cultures were also negative and the patient's white blood cell count was normal. A punch biopsy specimen revealed pseudoepitheliomatous hyperplasia and dermal-epidermal separation with epidermal necrosis and underlying abscess formation. A superficial and deep perivascular, interstitial and perifollicular infiltrate containing numerous neutrophils, with abscess formation and eosinophils was also seen. This histology was consistent with iododerma and the patient's lesions involuted following cessation of topical iodine use, leaving only post-inflammatory hyperpigmentation. In summary, our patient likely had a folliculitis that was then treated with topical povidone-iodine that led to iododerma. Although it remains possible that the reaction was an unusual contact hypersensitivity response, the ulceration, pseudoepitheliomatous hyperplasia and abscess formation do support an iododerma-like eruption. C1 [Zhou, Linda Hua] Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Providence, RI 02908 USA. Roger Williams Med Ctr, NIH, Ctr Biomed Res Excellence, Providence, RI 02908 USA. RP Zhou, LH (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Elmhurst Bldg,50 Maude St, Providence, RI 02908 USA. EM lindahuazhou@yahoo.com FU NIH [P20RR018757] FX This work was supported in part by NIH grant P20RR018757 (Center of Biomedical Research Excellence). NR 13 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD NOV PY 2008 VL 35 IS 11 BP 744 EP 747 DI 10.1111/j.1346-8138.2008.00554.x PG 4 WC Dermatology SC Dermatology GA 377LB UT WOS:000261251600009 PM 19120771 ER PT J AU Mohania, D Nagpal, R Kumar, M Bhardwaj, A Yadav, M Jain, S Marotta, F Singh, V Parkash, O Yadav, H AF Mohania, Dheeraj Nagpal, Ravinder Kumar, Manoj Bhardwaj, Aarti Yadav, Mukesh Jain, Shalini Marotta, Francesco Singh, Vinod Parkash, Om Yadav, Hariom TI Molecular approaches for identification and characterization of lactic acid bacteria SO JOURNAL OF DIGESTIVE DISEASES LA English DT Review DE lactic acid bacteria; lactobacilli; molecular identification; polymerase chain reaction; probiotics ID GRADIENT GEL-ELECTROPHORESIS; AMPLIFIED POLYMORPHIC DNA; 16S RIBOSOMAL-RNA; POTENTIALLY PROBIOTIC LACTOBACILLUS; POLYMERASE CHAIN-REACTION; INTERGENIC SPACER REGION; HUMAN COLONIC BIOTA; REAL-TIME PCR; GENETIC DIVERSITY; CASEI STRAINS AB The last few years have produced a revolution in the development of very sensitive, rapid, automated, molecular detection methods for a variety of various species of lactic acid bacteria (LAB) associated with food and dairy products. Nowadays many such strains of LAB are considered probiotics. The genome-based methods are useful in identifying bacteria as a complementary or alternative tool to phenotypical methods. Over the years, identification methodologies using primers that target different sequences, such as the 16S ribosomal RNA (rRNA)-encoding gene, the 16S-23S rRNA intergenic spacer region, the 23S rRNA-encoding, recA and ldhD genes; randomly amplified polymorphic DNA, restriction fragment length polymorphism, denaturing gradient gel electrophoresis, temperature gradient gel electrophoresis, amplification rDNA restriction analysis, restriction enzyme analysis, rRNA, pulse field gel electrophoresis and amplification fragment length polymorphism have played a significant role in probiotic bacteriology. Hence, the aim of this review is to provide an overview of some rapid and reliable polymerase chain reaction-based molecular methods used for identifying and differentiating closely related species and strains of LAB associated with food and industry. C1 [Yadav, Hariom] NIDDK, NIH, Bethesda, MD 20892 USA. [Nagpal, Ravinder; Kumar, Manoj] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India. [Bhardwaj, Aarti] Meerut Inst Engn & Technol, Meerut, Uttar Pradesh, India. [Yadav, Mukesh] Jiwaji Univ, Sch Studies Chem, Gwalior 474011, Madhya Pradesh, India. [Jain, Shalini] Univ Illinois, Urbana, IL 61801 USA. [Marotta, Francesco] GAIA Fdn, Nutraceut Nutragenom Unit, Milan, Italy. [Singh, Vinod] Barkatullah Univ, Dept Microbiol, Bhopal 462026, Madhya Pradesh, India. [Parkash, Om] Natl JALMA Inst Leprosy & Other Mycobacterial Dis, Agra, Uttar Pradesh, India. RP Yadav, H (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM yadavh@mail.nih.gov OI Yadav, Hariom/0000-0003-4504-1597 NR 78 TC 44 Z9 45 U1 2 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1751-2972 J9 J DIGEST DIS JI J. Dig. Dis. PD NOV PY 2008 VL 9 IS 4 BP 190 EP 198 DI 10.1111/j.1751-2980.2008.00345.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 364PZ UT WOS:000260348900002 PM 18959589 ER PT J AU Szaszak, M Chen, HD Chen, HC Baukal, A Hunyady, L Catt, KJ AF Szaszak, Marta Chen, Hung-Dar Chen, Hao-Chia Baukal, Albert Hunyady, Laszlo Catt, Kevin J. TI Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ANTIGEN-PROCESSING COMPARTMENTS; II TYPE-1 RECEPTOR; ENDOPLASMIC-RETICULUM; AT(1) RECEPTOR; CELL-SURFACE; COUPLED RECEPTORS; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; SORTING MOTIFS; KINASE-C AB Little is known about the protein-protein interactions that regulate the trafficking of the angiotensin II type I receptor (AGTR1) through the biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the AGTR1 has been identified by site-directed mutagenesis studies as an essential site for normal AGTR1 folding and surface expression. Based oil yeast two-hybrid screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as a bait, we identified the invariant chain (CD74) as a novel interacting protein. This association was confirmed by co-immunoprecipitation and co-localization Studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was localized to a site previously identified as important For the exit of the AGTR1 front the endoplasmic reticulum (ER), and conserved in many G protein-coupled receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells consistently reduced the AGTR1 density at the cell surface. Furthermore, the interaction of CD74 with the carboxyl-terminal tail of the AGTR1 caused its retention in the ER and promoted its proteasomal degradation. These observations indicate that CD74 and the AGTK1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression. C1 [Szaszak, Marta; Chen, Hung-Dar; Chen, Hao-Chia; Baukal, Albert; Catt, Kevin J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocirnol & Genet, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, Bethesda, MD 20892 USA. [Hunyady, Laszlo] Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary. RP Catt, KJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocirnol & Genet, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, Bethesda, MD 20892 USA. EM cattk@mail.nih.gov RI Szaszak, Marta/G-7957-2011 FU Intramural NIH HHS NR 51 TC 10 Z9 11 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2008 VL 199 IS 2 BP 165 EP 176 DI 10.1677/JOE-08-0190 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 370NJ UT WOS:000260768600003 PM 18719072 ER PT J AU Chigurupati, S Son, TG Hyun, DH Lathia, JD Mughal, MR Savell, J Li, SC Nagaraju, GPC Chan, SL Arumugam, TV Mattson, MP AF Chigurupati, Srinivasulu Son, Tae Gen Hyun, Dong-Hoon Lathia, Justin D. Mughal, Mohamed R. Savell, Jason Li, Shuan C. Nagaraju, G. P. C. Chan, Sic L. Arumugam, Thiruma V. Mattson, Mark P. TI Lifelong running reduces oxidative stress and degenerative changes in the testes of mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PHYSICAL-ACTIVITY; SERTOLI-CELLS; TESTOSTERONE LEVELS; LIPID-PEROXIDATION; FUNCTIONAL-CHANGES; LEYDIG-CELLS; AGING MALE; EXERCISE; MEN; CARDIOPROTECTION AB Regular exercise can counteract the adverse effects of aging oil the musculoskeletal and cardiovascular systems. In males, the normal aging process is associated with reductions in testosterone production and impaired spermatogenesis, but the underlying mechanisms and their potential modification by exercise are unknown. Here, we report that lifelong regular exercise (running) protects the testes against the adverse effects of advancing age, and that this effect of running is associated with decreased amounts of oxidative damage to proteins, lipids, and DNA in spermatogenic and Leydig cells. Six-month-old male mice were divided into a sedentary group and a group that ran an average of 1.75 km/day, until the mice reached the age of 20 months. Seminiferous tubules of runners exhibited a full complement of cells at different stages of the spermatogenic process and a clear central lumen with large numbers of spermatozoa, in contrast to sedentary truce that exhibited disorganized spermatogenic cells and lacked spermatocytes in a central lumen. Levels of protein carbonyls, nitrotyrosine, lipid peroxidation products, and oxidatively modified DNA were significantly greater in spermatogenic and Leydig cells of sedentary mice compared with runners. These findings, suggest that lifelong regular exercise suppresses aging of testes by a mechanism that involves reduced oxidative damage to spermatogenic and Leydig cells. C1 [Mattson, Mark P.] NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Savell, Jason; Li, Shuan C.] Orlando Reg Hlth Care, Dept Pathol, Orlando, FL 32806 USA. [Chigurupati, Srinivasulu; Nagaraju, G. P. C.; Chan, Sic L.] Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32816 USA. [Arumugam, Thiruma V.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. [Hyun, Dong-Hoon] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. RP Mattson, MP (reprint author), NIA, Biomed Res Ctr, Neurosci Lab, Intramural Res Program, 5th Floor,251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Ganji, Purna chandra N/D-4193-2011 OI Ganji, Purna chandra N/0000-0002-4989-5234 FU Intramural Research Program of the National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 48 TC 27 Z9 30 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2008 VL 199 IS 2 BP 333 EP 341 DI 10.1677/JOE-08-0306 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 370NJ UT WOS:000260768600018 PM 18701639 ER PT J AU Rodes, CE Pellizzari, ED Dellarco, MJ Erickson, MD Vallero, DA Reissman, DB Lioy, PJ Lippmann, M Burke, TA Goldstein, BD AF Rodes, Charles E. Pellizzari, Edo D. Dellarco, Michael J. Erickson, Mitchell D. Vallero, Daniel A. Reissman, Dori B. Lioy, Paul J. Lippmann, Morton Burke, Thomas A. Goldstein, Bernard D. TI ISEA2007 panel: Integration of better exposure characterizations into disaster preparedness for responders and the public SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Review DE disaster; exposure assessment; personal exposure; risk AB An expert panel was convened in October 2007 at the International Society for Exposure Analysis Annual Meeting in Durham, NC, entitled "The Path Forward in Disaster Preparedness Since WTC-Exposure Characterization and Mitigation: Substantial Unfinished Business!" The panel prospectively discussed the critical exposure issues being overlooked during disaster responses and highlighted the needs for an optimal blending of exposure characterizations and hazard controls within disaster settings. The cases were made that effective and timely exposure characterizations must be applied during responses to any disaster, whether terrorist, manmade, or natural in origin. The consistent application of exposure sciences across acute and chronic disaster timelines will assure that the most effective strategies are applied to collect the needed information to guide risk characterization and management approaches. Exposure sciences must be effectively applied across all phases of a disaster (defined as rescue, reentry, recovery, and rehabitation-the four Rs) to appropriately characterize risks and guide risk-mitigation approaches. Failure to adequately characterize and control hazardous exposures increases the likelihood of excess morbidity and mortality. Advancing the infrastructure and the technologies to collect the right exposure information before, during, and immediately after disasters would advance our ability to de. ne risks and protect responders and the public better. The panel provided conclusions, recommendations, and next steps toward effective and timely integration of better exposure science into disaster preparedness, including the need for a subsequent workshop to facilitate this integration. All panel presentations and a summary were uploaded to the ISES1 website (http://www.iseaweb.org/Disaster_Preparedness/index.php). C1 [Rodes, Charles E.] RTI Int, CAT ATEEP, Res Triangle Pk, NC 27709 USA. [Dellarco, Michael J.] NICHHD, Bethesda, MD 20892 USA. [Erickson, Mitchell D.] Sci & Technol Directorate, Dept Homeland Secur, Washington, DC USA. [Vallero, Daniel A.] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. [Reissman, Dori B.] NIOSH, CDC, Washington, DC USA. [Lioy, Paul J.] RWJMS, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA. [Lioy, Paul J.] Rutgers Univ UMDNJ, Piscataway, NJ USA. [Lippmann, Morton] NYU Med Ctr, Tuxedo Pk, NY USA. [Burke, Thomas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Goldstein, Bernard D.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Rodes, CE (reprint author), RTI Int, CAT ATEEP, 3040 Cornwallis Rd,Bldg 11 Room 409, Res Triangle Pk, NC 27709 USA. EM charlesr@rti.org RI Lioy, Paul/F-6148-2011 FU NIEHS NIH HHS [P30 ES005022] NR 13 TC 5 Z9 5 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD NOV PY 2008 VL 18 IS 6 BP 541 EP 550 DI 10.1038/jes.2008.42 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 364CJ UT WOS:000260313500006 PM 18685563 ER PT J AU Meissner, HI Tiro, JA Haggstrom, D Lu-Yao, G Breen, N AF Meissner, Helen I. Tiro, Jasmin A. Haggstrom, David Lu-Yao, Grace Breen, Nancy TI Does Patient Health and Hysterectomy Status Influence Cervical Cancer Screening in Older Women? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cervical screening; hysterectomy; older age; health status; comorbidity ID CHARLSON COMORBIDITY INDEX; REGIONAL-VARIATIONS; INTERVIEW SURVEYS; BEHAVIORAL-MODEL; UNITED-STATES; US WOMEN; CARE; MAMMOGRAPHY; VALIDATION; BREAST AB BACKGROUND: Decisions to screen older patients for cancer are complicated by the fact that aging populations are heterogeneous with respect to life expectancy. OBJECTIVE: To examine national trends in the association between cervical cancer screening and age, health and hysterectomy status. DESIGN AND PARTICIPANTS: Cross-sectional data from the 1993, 1998, 2000, and 2005 National Health Interview Surveys (NHIS) were used to examine trends in screening for women age 35-64 and 65+ years of age. We investigated whether health is associated with Pap testing among older women using the 2005 NHIS (N=3,073). We excluded women with a history of cervical cancer or who had their last Pap because of a problem. MEASUREMENTS: The dependent variable was having a Pap test within the past 3 years. Independent variables included three measures of respondent health (the Charlson comorbidity index (CCI), general health status and having a chronic disability), hysterectomy status and sociodemographic factors. MAIN RESULTS: NHIS data showed a consistent pattern of lower Pap use among older women (65+) compared to younger women regardless of hysterectomy status. Screening also was lower among older women who reported being in fair/poor health, having a chronic disability, or a higher CCI score (4+). Multivariate models showed that over 50% of older women reporting poor health status or a chronic disability and 47% with a hysterectomy still had a recent Pap. CONCLUSIONS: Though age, health and hysterectomy status appear to influence Pap test use, current national data suggest that there still may be overutilization and inappropriate screening of older women. C1 [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Tiro, Jasmin A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Haggstrom, David] Indiana Univ, Regenstrief Inst Inc, Ctr Hlth Serv & Outcomes Res,Roudenbush Vet Affai, VA Hlth Serv Res & Dev Ctr Excellence Implementin, Indianapolis, IN 46204 USA. [Haggstrom, David] Indiana Univ, Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA. [Lu-Yao, Grace] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Breen, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Meissner, HI (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31 Room B1C19, Bethesda, MD 20892 USA. EM meissneh@od.nih.gov OI Tiro, Jasmin/0000-0001-8300-0441 NR 48 TC 12 Z9 12 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2008 VL 23 IS 11 BP 1822 EP 1828 DI 10.1007/s11606-008-0775-x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VI UT WOS:000261423900015 PM 18784967 ER PT J AU Yan, ZH Li, S Liang, ZD Tomic, M Stojilkovic, SS AF Yan, Zonghe Li, Shuo Liang, Zhaodong Tomic, Melanija Stojilkovic, Stanko S. TI The P2X(7) Receptor Channel Pore Dilates under Physiological Ion Conditions SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID FUNCTIONAL EVIDENCE; AGONIST BINDING; XENOPUS OOCYTES; CELLS; PURINOCEPTOR; PERMEABILITY; PANNEXIN-1; EXPRESSION; DYNAMICS; CURRENTS AB Activation of the purinergic P2X(7) receptor leads to the rapid opening of an integral ion channel that is permeable to small cations. This is followed by a gradual increase in permeability to fluorescent dyes by integrating the actions of the pannexin-1 channel. Here, we show that during the prolonged agonist application a rapid current that peaked within 200 ms was accompanied with a slower current that required tens of seconds to reach its peak. The secondary rise in current was observed under different ionic conditions and temporally coincided with the development of conductivity to larger organic cations. The biphasic response was also observed in cells with blocked pannexin channels and in cells not expressing these channels endogenously. The biphasic current was preserved in N-terminal T15A, T15S, and T15V mutants that have low or no permeability to organic cations, reflecting enhanced permeability to inorganic cations. In contrast, the T15E, T15K, and T15W mutants, and the Delta 18 mutant with deleted P2X(7) receptor-specific 18-amino acid C-terminal segment, were instantaneously permeable to organic cations and generated high amplitude monophasic currents. These results indicate that the P2X(7) receptor channel dilates under physiological ion conditions, leading to generation of biphasic current, and that this process is controlled by residues near the intracellular side of the channel pore. C1 [Yan, Zonghe; Li, Shuo; Liang, Zhaodong; Tomic, Melanija; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Tomic, Melanija/C-3371-2016 FU Intramural Research Program of the National National Institutes of HealthInstitute of Child Health and Human Development, FX We are thankful to Tomas Obsil for helpful discussion.; This work is supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. NR 32 TC 83 Z9 85 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 2008 VL 132 IS 5 BP 563 EP 573 DI 10.1085/jgp.200810059 PG 11 WC Physiology SC Physiology GA 454HK UT WOS:000266672800008 PM 18852304 ER PT J AU Bourhy, H Reynes, JM Dunham, EJ Dacheux, L Larrous, F Huong, VTO Xu, GL Yan, JX Miranda, MEG Holmes, EC AF Bourhy, Herve Reynes, Jean-Marc Dunham, Eleca J. Dacheux, Laurent Larrous, Florence Huong, Vu Thi Oue Xu, Gelin Yan, Jiaxin Miranda, Mary Elizabeth G. Holmes, Edward C. TI The origin and phylogeography of dog rabies virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID MOLECULAR EPIDEMIOLOGY; NUCLEOPROTEIN GENE; EVOLUTIONARY DYNAMICS; INFECTIOUS-DISEASES; LYSSAVIRUS GENUS; SRI-LANKA; HISTORY; AFRICA; HOST; EAST AB Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV. C1 [Bourhy, Herve; Dacheux, Laurent; Larrous, Florence] Inst Pasteur, WHO, Collaborating Ctr Reference & Res Rabies, UPRE Lyssavirus Dynam & Host Adaptat, F-75724 Paris 15, France. [Reynes, Jean-Marc] Inst Pasteur Cambodia, Phnom Penh, Cambodia. [Dunham, Eleca J.; Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Huong, Vu Thi Oue] Inst Pasteur Ho Chi Minh City, Ho Chi Minh City, Vietnam. [Miranda, Mary Elizabeth G.] Res Inst Trop Med, Vet Res Dept, Manila, Philippines. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Bourhy, H (reprint author), Inst Pasteur, WHO, Collaborating Ctr Reference & Res Rabies, UPRE Lyssavirus Dynam & Host Adaptat, F-75724 Paris 15, France. EM hbourhy@pasteur.fr RI Bourhy, Herve/F-5272-2010; Reynes, Jean-Marc/M-6108-2014; OI Holmes, Edward/0000-0001-9596-3552 FU 'Programme de Recherches Avancees de Cooperations Franco-Chinoises' [PRA B01-06]; European Union [FP6/VIZIER]; NIH [GM080533-01] FX This work was supported by the 'Programme de Recherches Avancees de Cooperations Franco-Chinoises' (PRA B01-06): 'Epidemiologie moleculaire de la rage en Chine et standardisation des techniques de detection du virus rabique', by the European Union through the FP6/VIZIER program, and by NIH grant GM080533-01. We are also grateful to the genomic platform of Institut Pasteur, Paris, France and particularly to M. Tichit and C. Bouchier for their help with sequencing. We also thank Andres Paez Fernandez for providing RABV isolates from Colombia and Alan Calaor from the Research Institute for Tropical Medicine, Metro Manila, Philippines, for his help. NR 52 TC 96 Z9 106 U1 3 U2 26 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2008 VL 89 BP 2673 EP 2681 DI 10.1099/vir.0.2008/003913-0 PN 11 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 372ES UT WOS:000260885500003 PM 18931062 ER PT J AU Han, JY Shaw, BR Hawkins, RP Pingree, S Mctavish, F Gustafson, DH AF Han, Jeong Yeob Shaw, Bret R. Hawkins, Robert P. Pingree, Suzanne Mctavish, Fiona Gustafson, David H. TI Expressing Positive Emotions within Online Support Groups by Women with Breast Cancer SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE breast cancer; emotional expression; online support groups; positive emotions ID NEGATIVE EMOTIONS AB Based upon Fredrickson's Broaden-and-Build Theory of Positive Emotions, this study examined the role of expressing positive emotions in online support groups for women with breast cancer. Underserved women with breast cancer in rural Wisconsin and Detroit, Michigan were recruited from 2001 to 2003, and they were given access to online support groups. Both pretest and four-month posttest surveys were conducted with a sample of 231 women. Messages from 96 active participants were analyzed using a computerized text analysis program. Psychological benefits that occurred following the expression of positive emotions were greater among those who expressed more negative emotions. C1 [Han, Jeong Yeob] Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Telecommun, Athens, GA 30602 USA. [Shaw, Bret R.; Hawkins, Robert P.; Pingree, Suzanne] Univ Wisconsin, Natl Canc Inst, Ctr Excellence Canc Commun Res, Madison, WI 53706 USA. [Mctavish, Fiona] Univ Wisconsin, Ctr Hlth Enhancement Syst Studies, Madison, WI 53706 USA. [Gustafson, David H.] Univ Wisconsin, Natl Canc Inst, Ctr Excellence Canc Commun, Madison, WI 53706 USA. RP Han, JY (reprint author), Univ Georgia, Grady Coll Journalism & Mass Commun, Dept Telecommun, Athens, GA 30602 USA. EM jeonghan@uga.edu FU NCI NIH HHS [P50 CA095817] NR 19 TC 35 Z9 37 U1 1 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD NOV PY 2008 VL 13 IS 8 BP 1002 EP 1007 DI 10.1177/1359105308097963 PG 6 WC Psychology, Clinical SC Psychology GA 370CD UT WOS:000260739400005 PM 18987072 ER PT J AU Chung, JY Braunschweig, T Williams, R Guerrero, N Hoffmann, KM Kwon, M Song, YK Libutti, SK Hewitt, SM AF Chung, Joon-Yong Braunschweig, Till Williams, Reginald Guerrero, Natalie Hoffmann, Karl M. Kwon, Mijung Song, Young K. Libutti, Steven K. Hewitt, Stephen M. TI Factors in Tissue Handling and Obtained From Formalin-fixed, Processing That Impact RNA Paraffin-embedded Tissue SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE paraffin embedded; gene expression; RNA integrity; real-time; RT-PCR; tissue fixation and processing ID POLYMERASE CHAIN-REACTION; EXPRESSION ANALYSIS; GENE-EXPRESSION; DNA; OPTIMIZATION; AMPLIFICATION; PURIFICATION; EXPERIENCE; FIXATION; QUALITY AB Formalin-fixed, paraffin-embedded (FFPE) tissue is the most common specimen available for molecular assays on tissue after diagnostic histopathological examination. RNA from FFPE tissue suffers from strand breakage and cross-linking. Despite excellent extraction methods, RNA quality from FFPE material remains variable. To address the RNA quality factors within FFPE tissues, we studied RNA quality, isolating individual elements of the tissue fixation and processing including length of fixation in formalin and the type of buffer incorporated in the fixative. We examined the impact of the length of the tissue processing cycle as well. The optimal fixation period of 12-24 hr in phosphate-buffered formalin resulted in better-quality RNA. Longer tissue processing times were associated with higher quality RNA. We determined that the middle region of gene suffers less damage by these processes as shown by real-time quantitative RT-PCR. These data provide key information for the development of methods of analysis of gene expression in archival FFPE tissues and contribute to the establishment of objective standards for the processing and handling of tissue in surgical pathology. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 56:1033-1042, 2008) C1 [Chung, Joon-Yong; Braunschweig, Till; Williams, Reginald; Guerrero, Natalie; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20892 USA. [Kwon, Mijung; Libutti, Steven K.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Song, Young K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Song, Young K.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Hoffmann, Karl M.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Hewitt, SM (reprint author), TARP Lab, Adv Technol Ctr, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Chung, Joon-Yong/0000-0001-5041-5982 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 22 TC 54 Z9 56 U1 0 U2 9 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD NOV PY 2008 VL 56 IS 11 BP 1033 EP 1042 DI 10.1369/jhc.2008.951863 PG 10 WC Cell Biology SC Cell Biology GA 361UI UT WOS:000260152200008 PM 18711211 ER PT J AU Noguchi, M Yi, HF Rosenblatt, HM Filipovich, AH Adelstein, S Modl, WS McBride, OW Leonard, WJ AF Noguchi, Masayuki Yi, Huefang Rosenblatt, Howard M. Filipovich, Alexandra H. Adelstein, Stephen Modl, William S. McBride, O. Wesley Leonard, Warren J. TI Interleukin-2 Receptor gamma Chain Mutation Results in X-Linked Severe Combined Immunodeficiency in Humans SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR BETA-CHAIN; GENETIC-LINKAGE MAP; IL-2 RECEPTOR; B-CELLS; MOLECULAR-CLONING; ALPHA-CHAIN; CHROMOSOME INACTIVATION; IMMATURE THYMOCYTES; SIGNAL TRANSDUCER; HUMAN GENOME AB The Interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) Is a component of high and Intermediate affinity IL-2 receptors that Is required to achieve full ligand binding affinity and Internalization. We have localized the IL-2R gamma gone to human chromosome Xq13. Genetic linkage analysis Indicates that the IL-2R gamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. Moreover, we demonstrate that each of three unrelated patients with XSCID has a different mutation In his IL-2R gamma gone resulting In a different premature stop codon and predicted C-terminal truncation. These data establish that XSCID Is associated with mutations of the IL-2R gamma gene product. Since XSCID Is characterized by absent or markedly reduced numbers of T cells, our findings Imply that IL-2R gamma plays a vital role In thymic maturation of T cells. These results also have Important Implications for prenatal and postnatal diagnosis, carrier female detection, and gene therapy for XSCID. C1 [Noguchi, Masayuki; Adelstein, Stephen; Leonard, Warren J.] NHLBI, Sect Pulm & Mol Immunol, Off Director Intramural Res Program, Bethesda, MD 20892 USA. [Yi, Huefang; McBride, O. Wesley] NCI, Biochem Lab, Div Canc Biol & Diag, Bethesda, MD 20892 USA. [Rosenblatt, Howard M.] Baylor Coll Med, Dept Pediat, Div Allergy & Immunol, Houston, TX 77030 USA. [Filipovich, Alexandra H.] Univ Minnesota, Univ Hosp & Clin, Dept Pediat, Div Immunol, Minneapolis, MN 55455 USA. [Modl, William S.] NCI, Biol Carcinogenesis & Dev Program, Program Resources Inc Dyncorp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Noguchi, M (reprint author), NHLBI, Sect Pulm & Mol Immunol, Off Director Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA. FU NIH GCRC [M01 RR00188]; David Research Fund FX We thank G. Tosato (FDA) for establishing cell lines from patients 1 and 2, J. Ott for LINKAGE v, 5.1, H. Cann for CEPH database v. 5 and database management system v. 5.2, J. P. Siegel (FDA), A. Weissman (NCL), and K.-I. Jeang (NIAID) for critical comments, and the XSCID patients whose cells were studied. H. M. R. was supported by NIH GCRC grant M01 RR00188 and the David Research Fund. We thank W. T. Shearer for support and work through the David Center and R. Shapiro, H. Jyonouchi, and B. Loechelt (V. of Minnesota) and C. Roifman (Toronto) for their work with patients 1 and 2. NR 64 TC 9 Z9 9 U1 3 U2 20 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2008 VL 181 IS 9 BP 5817 EP 5827 PG 11 WC Immunology SC Immunology GA 368YI UT WOS:000260659000004 PM 18941169 ER PT J AU Sahu, N Venegas, AM Jankovic, D Mitzner, W Gomez-Rodriguez, J Cannons, JL Sommers, C Love, P Sher, A Schwartzberg, PL August, A AF Sahu, Nisebita Venegas, Ana M. Jankovic, Dragana Mitzner, Wayne Gomez-Rodriguez, Julio Cannons, Jennifer L. Sommers, Connie Love, Paul Sher, Alan Schwartzberg, Pamela L. August, Avery TI Selective Expression Rather than Specific Function of Txk and Itk Regulate Th1 and Th2 Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; TYROSINE KINASE ITK; TEC FAMILY KINASES; ALLERGIC-ASTHMA; MICE LACKING; AIRWAY HYPERRESPONSIVENESS; CYTOKINE PRODUCTION; ACTIVE ITK; DEFICIENT; ABSENCE AB Itk and Txk/Rlk are Tee family kinases expressed in T cells. Itk is expressed in both Th1 and Th2 cells. By contrast, Txk is preferentially expressed in Th1 cells. Although Itk is required for Th2 responses in vivo and Txk is suggested to regulate IFN-gamma expression and Th1 responses, it remains unclear whether these kinases have distinct roles in Th cell differentiation/function. We demonstrate here that Txk-null CD4(+) T cells are capable of producing both Th1 and Th2 cytokines similar to those produced by wild-type CD4(+) T cells. To further examine whether Itk and Txk play distinct roles in Th cell differentiation and function, we examined Itk-null mice carrying a transgene that expresses Txk at levels similar to the expression of Itk in Th2 cells. Using two Th2 model systems, allergic asthma and schistosome egg-induced lung granulomas, we found that the Txk transgene rescued Th2 cytokine production and all Th2 symptoms without notable enhancement of IFN-gamma expression. These results suggest that Txk is not a specific regulator of Th1 responses. Importantly, they suggest that Itk and Txk exert their effects on Th cell differentiation/function at the level of expression. The Journal of Immunology, 2008, 181: 6125-6131. C1 [Sahu, Nisebita; August, Avery] Penn State Univ, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA. [Sahu, Nisebita; August, Avery] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Sahu, Nisebita] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Jankovic, Dragana; Sher, Alan] NIAID, Bethesda, MD 20892 USA. [Sommers, Connie; Love, Paul] NICHHD, NIH, Bethesda, MD 20892 USA. [Mitzner, Wayne] Johns Hopkins Univ, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Venegas, Ana M.; Gomez-Rodriguez, Julio; Cannons, Jennifer L.] NHGRI, Bethesda, MD 20892 USA. RP August, A (reprint author), Penn State Univ, Ctr Mol Immunol & Infect Dis, 115 Henning Bldg, University Pk, PA 16802 USA. EM pams@imail.nih.gov; avery@psu.cdu FU Intramural NIH HHS [Z01 HG000123-10]; NIAID NIH HHS [R01 AI051626, AI051626, AI065566, R01 AI051626-04, R01 AI051626-05, R01 AI065566, R01 AI065566-02A2, R01 AI065566-03, R56 AI065566] NR 33 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2008 VL 181 IS 9 BP 6125 EP 6131 PG 7 WC Immunology SC Immunology GA 368YI UT WOS:000260659000037 PM 18941202 ER PT J AU Yang, S Rosenberg, SA Morgan, RA AF Yang, Shicheng Rosenberg, Steven A. Morgan, Richard A. TI Clinical-scale Lentiviral Vector Transduction of PBL for TCR Gene Therapy and Potential for Expression in Less-differentiated Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE lentivirus; T-cell receptor; adoptive immunotherapy; gene therapy ID EMBRYONIC STEM-CELLS; CD8(+) T-CELLS; CENTRAL-MEMORY; IN-VIVO; LYMPHOCYTES; TUMOR; ANTIGEN; RECOGNITION; IMPAIRS; MODEL AB In human gene therapy applications, lentiviral vectors may have advantages over gamma-retroviral vectors because of their ability to transduce nondividing cells, their resistance to gene silencing, and a lack of integration site preference. In this study, we used VSV-G pseudotype third generation lentiviral vectors harboring specific antitumor T-cell receptor (TCR) to establish clinical-scale lentiviral transduction of peripheral blood lymphocyte (PBL). Spinoculation (1000g, 32 degrees C for 2h) in the presence of protamine sulfate represents the most efficient and economical approach to transduce a large number of PBLs compared with RetroNectin-based methods. Up to 20 million cells per well of a 6-well plate were efficiently transduced and underwent an average 50-fold expansion in 2 weeks. TCR transduced PBL-mediated specific antitumor activities including interferon-7 release and cell lysis. Compared with gammaretroviral vectors, the TCR transgene could be preferentially expressed on a less-differentiated cell population. C1 [Yang, Shicheng; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-33] NR 39 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 830 EP 839 DI 10.1097/CJI.0b013e31818817c5 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800005 PM 18833004 ER PT J AU Restifo, NP AF Restifo, Nicholas P. TI Three Ways to Enhance the Destructive Power of Tumor-specific T Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc ID ADOPTIVE IMMUNOTHERAPY; AUTOIMMUNITY; ANTIGEN C1 [Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 925 EP 925 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800027 ER PT J AU Shafer-Weaver, KA Watkins, SK Malyguine, A Hurwitz, AA AF Shafer-Weaver, Kimberly A. Watkins, Stephanie K. Malyguine, Anatoli Hurwitz, Arthur A. TI Provision of CD4+T Cell Help Prevents Tolerization of Tumorspecific CTLs and Enhances Tumor Immunity in a Murine Model of Prostate Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Shafer-Weaver, Kimberly A.; Malyguine, Anatoli] SAIC Frederick Inc, Clin Serv Program, Lab Cell Mediated Immun, Frederick, MD USA. [Shafer-Weaver, Kimberly A.; Watkins, Stephanie K.; Hurwitz, Arthur A.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 925 EP 925 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800028 ER PT J AU Pos, Z Selleri, S Spivey, TL Liu, H Worschech, A Sabatino, M Monaco, A Falus, A Wang, E Marincola, FM AF Pos, Zoltan Selleri, Silvia Spivey, Tara L. Liu, Hui Worschech, Andrea Sabatino, Marianna Monaco, Alessandro Falus, Andras Wang, Ena Marincola, Francesco M. TI The Genetic Background of IFN-alpha Responsiveness: A Genome-wide Study SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Pos, Zoltan; Spivey, Tara L.; Liu, Hui; Worschech, Andrea; Sabatino, Marianna; Monaco, Alessandro; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. [Selleri, Silvia] San Raffaele Telethon Inst, Milan, Italy. [Falus, Andras] Semmelweis Univ, HAS, Immunogenom Res Grp, H-1085 Budapest, Hungary. RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 930 EP 931 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800045 ER PT J AU Weiss, JM Bouchlaka, M Subleski, J Back, T Wilkins, D Alderson, K Welniak, L Redelman, D Murphy, WJ Wiltrout, RH AF Weiss, Jonathan M. Bouchlaka, Myriam Subleski, Jeff Back, Tim Wilkins, Danice Alderson, Kory Welniak, Lisbeth Redelman, Doug Murphy, William J. Wiltrout, Robert H. TI Impairment of Secondary Antitumor Responses After IL-2/Anti-CD40 Immunotherapy: A Putative Role for Natural Killer Cells and Perforin SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Weiss, Jonathan M.; Subleski, Jeff; Back, Tim; Wiltrout, Robert H.] NCI Frederick, Canc & Inflammat Program, Frederick, MD USA. [Bouchlaka, Myriam; Wilkins, Danice; Alderson, Kory; Welniak, Lisbeth; Redelman, Doug; Murphy, William J.] Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 934 EP 934 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800055 ER PT J AU Wilkins, DE Alderson, KL Weiss, JM Bouchlaka, M Redelman, D Welniak, LA Murphy, WJ AF Wilkins, Danice E. Alderson, Kory L. Weiss, Jonathan M. Bouchlaka, Myriam Redelman, Doug Welniak, Lisbeth A. Murphy, William J. TI Immunotherapy With Anti-CD40 and IL-2 Results in Antigen Independent CD8+T Cell Activation In Vivo SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Wilkins, Danice E.; Alderson, Kory L.; Bouchlaka, Myriam; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Sch Med, Reno, NV 89557 USA. [Weiss, Jonathan M.] NCI, Canc Inflammat Program, Frederick, MD 21701 USA. [Redelman, Doug] Univ Nevada, Sch Med, Dept Physiol, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 934 EP 934 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800056 ER PT J AU Fiammenghi, L Ancarani, V Petrini, M Riccobon, A Granato, AM Pancisi, E Ridolfi, L Ridolfi, R Knutson, JR Rosales, T Neyroz, P AF Fiammenghi, Laura Ancarani, Valentina Petrini, Massimiliano Riccobon, Angela Granato, Anna Maria Pancisi, Elena Ridolfi, Laura Ridolfi, Ruggero Knutson, Jay R. Rosales, Tilman Neyroz, Paolo TI Tumor Lysate Capture and Processing by Dendritic Cells: A Kinetic and an Immunofluorescence Study by Flow Cytometry and Confocal Microscopy Imaging SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Ancarani, Valentina; Neyroz, Paolo] Univ Bologna, Dept Biochem, I-40126 Bologna, Italy. [Knutson, Jay R.; Rosales, Tilman] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 935 EP 935 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800059 ER PT J AU Han, TH Jin, P Ren, JQ Slezak, S Marincola, FM Stroncek, DF AF Han, Tae Hee Jin, Ping Ren, Jiaqiang Slezak, Stefanie Marincola, Francesco M. Stroncek, David F. TI The Evaluation of Monocyte Derived Mature Dendritic Cells With Gene and Microrna Expression Microarrays SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Han, Tae Hee; Jin, Ping; Ren, Jiaqiang; Slezak, Stefanie; Marincola, Francesco M.; Stroncek, David F.] NIH, DTM, Bethesda, MD 20892 USA. [Han, Tae Hee] Inje Univ, Sanggye Paik Hosp, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 935 EP 936 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800060 ER PT J AU Steel, JC Ramlogan, CA Yu, P Waldmann, TA Morris, JC AF Steel, Jason C. Ramlogan, Charmaine A. Yu, Ping Waldmann, Thomas A. Morris, John C. TI Interleukin-15 and Its Receptor Enhance Antitumor Activity Following a Genetically Modified Dendritic Cell Vaccine SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Steel, Jason C.; Ramlogan, Charmaine A.; Yu, Ping; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Bethesda, MD 20892 USA. RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 949 EP 949 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800104 ER PT J AU Monaco, A Marincola, FM Sabatino, M Pos, Z Tornesello, ML Stroncek, DF Wang, E Gallo, RC Lewis, GK Buonaguro, FM Buonaguro, L AF Monaco, Alessandro Marincola, F. M. Sabatino, M. Pos, Zoltan Tornesello, Maria Lina Stroncek, David F. Wang, Ena Gallo, Robert C. Lewis, George K. Buonaguro, Franco M. Buonaguro, Luigi TI Gauging Innate Immunity in HIV Infection SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Monaco, Alessandro; Marincola, F. M.; Sabatino, M.; Pos, Zoltan; Stroncek, David F.; Wang, Ena] NIH, DTM, Bethesda, MD 20892 USA. [Monaco, Alessandro] IRCCS Giovanni Paolo II, CEO Lab, Bari, Italy. [Tornesello, Maria Lina; Buonaguro, Franco M.; Buonaguro, Luigi] Ist Naz Tumori, Lab Mol Biol Viral Oncogen, Naples, Italy. [Gallo, Robert C.; Lewis, George K.; Buonaguro, Luigi] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RI Tornesello, Maria Lina/A-1564-2009; Monaco, Alessandro/O-5338-2015 OI Tornesello, Maria Lina/0000-0002-3523-3264; Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 953 EP 953 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800118 ER PT J AU Worschech, A Chen, NH Yu, Y Zhang, Q Sabatino, M Monaco, A Pos, Z Lui, H Buller, MR Wang, E Szalay, AA Marincola, FM AF Worschech, Andrea Chen, Nanhai Yu, Yong Zhang, Qian Sabatino, Marianna Monaco, Alessandro Pos, Zoltan Lui, Hui Buller, Mark R. Wang, Ena Szalay, Aladar A. Marincola, Francesco M. TI Predicting the Immunologic Constant of Rejection SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Worschech, Andrea; Chen, Nanhai; Yu, Yong; Zhang, Qian; Szalay, Aladar A.] Genelux Corp, San Diego, CA USA. [Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Virchow Ctr Expt Biomed, Wurzburg, Germany. [Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Wurzburg, Germany. [Worschech, Andrea; Sabatino, Marianna; Monaco, Alessandro; Pos, Zoltan; Lui, Hui; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Buller, Mark R.] St Louis Univ, Sch Med, Dept Mol Biol & Immunol, St Louis, MO USA. RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Monaco, Alessandro/0000-0002-9941-7003 NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 954 EP 955 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800122 ER PT J AU Sabatino, M Kim-Schulze, S Kim, DW Panelli, MC Stroncek, D Wang, E Marincola, FM Kaufman, HL AF Sabatino, Marianna Kim-Schulze, Seunghee Kim, Dae Won Panelli, Monica C. Stroncek, David Wang, Ena Marincola, Francesco M. Kaufman, Howard L. TI Serum Vascular Endothelial Growth Factor (VEGF) and Fibronectin as a Potential Predictor of Responsiveness to High-dose Interleukin (IL)-2 Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Sabatino, Marianna; Stroncek, David; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Bethesda, MD USA. [Kim-Schulze, Seunghee; Kim, Dae Won; Kaufman, Howard L.] Columbia Univ, Dept Surg, New York, NY USA. [Panelli, Monica C.] Univ Pittsburgh, Pittsburgh Canc Inst, Dept Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 960 EP 960 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800140 ER PT J AU Watkins, SK Shafer-Weaver, KA Hurwitz, AA AF Watkins, Stephanie K. Shafer-Weaver, Kimberly A. Hurwitz, Arthur A. TI Increasing Immunostimulatory Ability of Tolerogenic APCs Enhances Anti-tumor Immunity SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Watkins, Stephanie K.; Hurwitz, Arthur A.] NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. [Shafer-Weaver, Kimberly A.] SAIC Frederick, Clin Serv Program, Lab Cell Mediated Immun, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 968 EP 968 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800167 ER PT J AU Baskar, S Yang, JH Rader, C AF Baskar, Sivasubramanian Yang, Jiahui Rader, Christoph TI Targeting Human B Cell Chronic Lymphocytic Leukemia With a Monoclonal Antibody Specific for the Receptor Tyrosine Kinase ROR1 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Baskar, Sivasubramanian; Yang, Jiahui; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 969 EP 969 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800170 ER PT J AU Crompton, PD Traore, B Kayentao, K Doumbo, S Ongoiba, A Diakite, SAS Krause, MA Doumtabe, D Kone, Y Weiss, G Huang, CY Doumbia, S Guindo, A Fairhurst, RM Miller, LH Pierce, SK Doumbo, OK AF Crompton, Peter D. Traore, Boubacar Kayentao, Kassoum Doumbo, Safiatou Ongoiba, Aissata Diakite, Seidina A. S. Krause, Michael A. Doumtabe, Didier Kone, Younoussou Weiss, Greta Huang, Chiung-Yu Doumbia, Seydou Guindo, Aldiouma Fairhurst, Rick M. Miller, Louis H. Pierce, Susan K. Doumbo, Ogobara K. TI Sickle cell trait is associated with a delayed onset of malaria: Implications for time-to-event analysis in clinical studies of malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg ID PLASMODIUM-FALCIPARUM MALARIA; EXTENDED FOLLOW-UP; UGANDAN CHILDREN; PARASITE DENSITY; PROTECTION; MECHANISM; HEMOGLOBIN; ANTIGENS; MALI; ERYTHROCYTES AB Background. The World Health Organization (WHO) recently recommended that the time to first malaria episode serve as the primary end point in phase III malaria vaccine trials-the first of which will be held in Africa. Although common red blood cell (RBC) polymorphisms such as sickle hemoglobin (HbS) are known to protect against malaria in Africa, their impact on this end point has not been investigated. Methods. A longitudinal study of 225 individuals aged 2-25 years was conducted in Mali. The association between common RBC polymorphisms and the time to first malaria episode was evaluated. Results. Among children aged 2-10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median time to first malaria episode (P = .017). Cox regression analysis showed that greater age (hazard ratio [HR], 0.87 [95% CI, 0.80-0.94]; P = .001), HbAS (HR, 0.48 [95% CI, 0.26-0.91]; P = .024), and asymptomatic parasitemia at enrollment (HR, 0.35 [95% CI, 0.14-0.85]; P = .021) were associated with decreased malaria risk. Conclusion. Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical trials and observational studies that use this end point to include Hb typing in the design of studies conducted in areas where HbAS is prevalent. C1 [Crompton, Peter D.; Weiss, Greta] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. [Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Krause, Michael A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. [Traore, Boubacar; Kayentao, Kassoum; Doumbo, Safiatou; Ongoiba, Aissata; Diakite, Seidina A. S.; Doumtabe, Didier; Kone, Younoussou; Doumbia, Seydou; Guindo, Aldiouma; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Fac Med Pharm & Odonto Stomatol, Bamako, Mali. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2 Bldg,Rm 213,12441 Parklawn Dr, Rockville, MD 20852 USA. EM pcrompton@niaid.nih.gov RI Crompton, Peter/N-1130-2016 FU Intramural NIH HHS [Z01 AI000949-04] NR 41 TC 54 Z9 55 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2008 VL 198 IS 9 BP 1265 EP 1275 DI 10.1086/592224 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 360AU UT WOS:000260030200004 PM 18752444 ER PT J AU Pandey, JP Namboodiri, AM Luo, YQ Wu, YP Elston, RC Thomas, DL Rosen, HR Goedert, JJ AF Pandey, Janardan P. Namboodiri, Aryan M. Luo, Yuqun Wu, Yuping Elston, Robert C. Thomas, David L. Rosen, Hugo R. Goedert, James J. TI Genetic markers of IgG influence the outcome of infection with hepatitis C virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CORE PROTEIN; IMMUNOGLOBULIN ALLOTYPES; GAMMA; CLEARANCE; GENOTYPES; GM AB We examined the role that immunoglobulin GM and KM allotypes-genetic markers of gamma and kappa chains, respectively-play in the outcome of hepatitis C virus (HCV) infection in white Americans. A total of 119 persons who had cleared HCV and 111 with persistent HCV infection were genotyped for the presence of several GM and KM determinants. Persistent HCV infection was more than three times as likely (odds ratio, 3.50; P = .01) in subjects who were carriers of the GM3 allele than in those who were noncarriers. These results show that particular GM alleles may be important determinants of the outcome of HCV infection. C1 [Pandey, Janardan P.; Namboodiri, Aryan M.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Luo, Yuqun; Elston, Robert C.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Wu, Yuping] Cleveland State Univ, Dept Math, Cleveland, OH 44115 USA. [Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Goedert, James J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD USA. [Rosen, Hugo R.] Univ Colorado, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. RP Pandey, JP (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM pandeyj@musc.edu FU National Institutes of Health [DK070877, DA13224, HG003054] FX Financial support: National Institutes of Health (grants DK070877 to J.P.P., DA13224 to D.L.T., and HG003054 to Y.L.). NR 15 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2008 VL 198 IS 9 BP 1334 EP 1336 DI 10.1086/592282 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 360AU UT WOS:000260030200012 PM 18855559 ER PT J AU Fang, L Lonsdorf, AS Hwang, ST AF Fang, Lei Lonsdorf, Anke S. Hwang, Sam T. TI Immunotherapy for Advanced Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; CD8(+) T-CELLS; ACTIVE SPECIFIC IMMUNOTHERAPY; TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT INTERLEUKIN-2; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; HIGH-RISK MELANOMA; STAGE-IV MELANOMA; PHASE-III TRIAL AB Immunotherapy for melanoma has undergone significant change since the first attempts to treat patients with high dose IL-2. Herein, strategies to boost patient antitumor immunity through vaccination, treatment with agents that augment host immunity, and adoptive cell transfer will be discussed. The first two strategies have yielded only limited clinical success, but adoptive cell transfer therapy, particularly following a lymphodepleting, preconditioning regimen has resulted in objective response rates approaching 50%. For a number of reasons, lymphodepletion appears to be critical for maintenance of circulating antitumor T cells following adoptive cell transfer. Balancing antitumor efficacy, autoimmunity, and reconstitution of a functioning immune system remain challenging and potentially life-threatening issues. C1 [Fang, Lei; Lonsdorf, Anke S.; Hwang, Sam T.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908 NIH,Bldg 10,Rm 12N238, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov FU German Research Foundation (DFG); NIH FX We thank Drs Mark C. Udey (Dermatology Branch, NCI) and Steven A. Rosenberg (Surgery Branch, NCI) for helpful comments and suggestions. ASL is a recipient of a German Research Foundation (DFG)-NIH Career Transition Award. This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 99 TC 52 Z9 54 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2008 VL 128 IS 11 BP 2596 EP 2605 DI 10.1038/jid.2008.101 PG 10 WC Dermatology SC Dermatology GA 364XL UT WOS:000260368800006 PM 18927541 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI HMGB1, a novel biomarker of inflammatory demyelinating disease: an interview with Dr. Robert A. Harris SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID PROTEIN C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, NIH, Lab Allerg Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV 1 PY 2008 VL 84 IS 5 BP 1256 EP 1258 DI 10.1189/jlb.1307844 PG 3 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 359VN UT WOS:000260016300004 PM 18780873 ER PT J AU Millum, J AF Millum, J. TI Are pharmaceutical patents protected by human rights? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID MEDICINES; HEALTH AB The International Bill of Rights enshrines a right to health, which includes a right to access essential medicines. This right frequently appears to conflict with the intellectual property regime that governs pharmaceutical patents. However, there is also a human right that protects creative works, including scientific productions. Does this right support intellectual property protections, even when they may negatively affect health? This article examines the recent attempt by the Committee on Economic, Social and Cultural Rights to resolve this issue and argues that it fails. This is problematic because it means defenders of the present patent regime can continue using human rights documents to support their position. I offer a new framework for resolving the problem by examining the values that underlie human rights. C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Dept Bioeth, Bldg 10,1C118,10 Ctr Dr, Bethesda, MD 20892 USA. EM millumj@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 19 TC 2 Z9 2 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD NOV PY 2008 VL 34 IS 11 AR e25 DI 10.1136/jme.2007.022483 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 367EZ UT WOS:000260536600018 PM 18974405 ER PT J AU Liem, DA Zhao, P Angelis, E Chan, SS Zhang, J Wang, G Berthet, C Kaldis, P Ping, P MacLellan, WR AF Liem, David A. Zhao, Peng Angelis, Ekaterini Chan, Shing S. Zhang, Jun Wang, Guangwu Berthet, Cyril Kaldis, Philipp Ping, Peipei MacLellan, W. Robb TI Cyclin-dependent kinase 2 signaling regulates myocardial ischemia/reperfusion injury SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Myocardial ischemia; Cardioprotection; Apoptosis; Cyclin-dependent kinase 2; Retinoblastoma gene ID HYPOXIA-INDUCED APOPTOSIS; DEATH IN-VITRO; CELL-DEATH; RETINOBLASTOMA PROTEIN; NERVOUS-SYSTEM; ISCHEMIA-REPERFUSION; DEFICIENT MICE; CDK2 ACTIVITY; RB; ACTIVATION AB Ischemia/reperfusion (I/R) injury to the heart is accompanied by the upregulation and posttranslational modification of a number of proteins normally involved in regulating cell cycle progression. Two proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. Myocardial ischemia activates Cdk2, resulting in the phosphorylation and inactivation of Rb. Blocking Cdk2 activity reduces apoptosis in cultured cardiac myocytes. Genetic or pharmacological inhibition of Cdk2 activity in vivo during I/R injury led to a 36% reduction in infarct size (IFS), when compared to control mice, associated with a reduction in apoptotic myocytes. To confirm that Rb was the critical target in Cdk2-mediated I/R injury, we determined the consequences of I/R injury in cardiac-specific Rb-deficient mice (CRbL/L). IFS was increased 140% in CRbL/L mice compared to CRb+/+ controls. TUNEL positive nuclei and caspase-3 activity were augmented by 92% and 36%, respectively, following injury in the CRbL/L mice demonstrating that loss of Rb in the heart significantly exacerbates I/R injury. These data suggest that Cdk2 signaling pathways are critical regulators of cardiac I/R injury in vivo and support a cardioprotective role for Rb. (C) 2008 Elsevier Inc. All rights reserved. C1 [Liem, David A.; Zhao, Peng; Angelis, Ekaterini; Chan, Shing S.; Ping, Peipei; MacLellan, W. Robb] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab, Los Angeles, CA 90095 USA. [Liem, David A.; Zhang, Jun; Wang, Guangwu; Ping, Peipei; MacLellan, W. Robb] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Berthet, Cyril; Kaldis, Philipp] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Liem, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Lab, 675 CE Young Dr,MRL 3-645, Los Angeles, CA 90095 USA. EM rmaclellan@mednet.ucla.edu RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; Ping, Peipei/0000-0003-3583-3881 FU NHLBI NIH HHS [P01 HL080111, P01 HL080111-040004, R01 HL065431, R01 HL070748, R01 HL070748-04, R01 HL65431, R01 HL70748] NR 56 TC 9 Z9 9 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2008 VL 45 IS 5 BP 610 EP 616 DI 10.1016/j.yjmcc.2008.07.003 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 373PD UT WOS:000260983300003 PM 18692063 ER PT J AU Igbokwe, A Lacbawani, F Pineda, D Muenke, M AF Igbokwe, A. Lacbawani, F. Pineda, D. Muenke, M. TI Molecular Characterization and Postmortem Review of Holoprosencephaly (HPE) Cases SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 14th Annual Meeting of the Association-for-Molecular-Pathology CY OCT 29-NOV 02, 2008 CL Grapevine, TX SP Assoc Mol Pathol C1 [Igbokwe, A.; Lacbawani, F.] Suny Downstate, Brooklyn, NY USA. [Lacbawani, F.] NHGRI, MGB, NIH, Brooklyn, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2008 VL 10 IS 6 BP 574 EP 574 PG 1 WC Pathology SC Pathology GA 367DV UT WOS:000260533600052 ER PT J AU Wragg, A Mellad, JA Beltran, LE Konoplyannikov, M San, H Boozer, S Deans, RJ Mathur, A Lederman, RJ Kovacic, JC Boehm, M AF Wragg, Andrew Mellad, Jason A. Beltran, Leilani E. Konoplyannikov, Mikhail San, Hong Boozer, Sherry Deans, Robert J. Mathur, Anthony Lederman, Robert J. Kovacic, Jason C. Boehm, Manfred TI VEGFR1/CXCR4-positive progenitor cells modulate local inflammation and augment tissue perfusion by a SDF-1-dependent mechanism SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Vascular biology; Cell therapy; Stem cell; Inflammation ID MESENCHYMAL STEM-CELLS; MARROW-DERIVED CELLS; ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL GROWTH-FACTOR; BONE-MARROW; MONONUCLEAR-CELLS; ISCHEMIC LIMBS; STROMAL CELLS; RAT MODEL; FACTOR-I AB Recruitment and retention of circulating progenitor cells at the site of injured or ischemic tissues facilitates adult neo-vascularization. We hypothesized that cell therapy could modulate local neo-vascularization through the vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1) axis and by paracrine effects on local endothelial cells. We isolated from rat bone marrow a subset of multipotent adult progenitor cell-derived progenitor cells (MDPC). In vitro, MDPCs secreted multiple cytokines related to inflammation and angiogenesis, including monocyte chemotactic protein-1, SDF-1, basic fibroblast growth factor, and VEGF, and expressed the chemokine receptors CXCR4 and VEGFR1. To investigate in vivo properties, we transplanted MDPCs into the ischemic hind limbs of rats. Elevated levels of the chemokine SDF-1 and colocalization of CD11b(+) cells marked the initial phase of tissue remodeling after cell transplantation. Prolonged engraftment was observed in the adventitial-medial border region of arterioles of ischemic muscles. However, engrafted cells did not differentiate into endothelial or smooth muscle cells. Limb perfusion normalized 4 weeks after cell injection. Inhibition of SDF-1 reduced the engraftment of transplanted cells and decreased endothelial cell proliferation. These findings suggest a two-stage model whereby transplanted MDPCs modulate wound repair through recruitment of inflammatory cells to ischemic tissue. This is an important potential mechanism for cell transplantation, in addition to the direct modulation of local vascular cells through paracrine mechanisms. C1 [Wragg, Andrew; Mellad, Jason A.; Beltran, Leilani E.; Konoplyannikov, Mikhail; San, Hong; Lederman, Robert J.; Kovacic, Jason C.; Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20817 USA. [Boozer, Sherry; Deans, Robert J.] Athersys, Cleveland, OH 44115 USA. [Wragg, Andrew; Mathur, Anthony] William Harvey Res Inst, London EC1M 6BQ, England. RP Boehm, M (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC,Room 5-3132, Bethesda, MD 20817 USA. EM boehmm@nhlbi.nih.gov OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z99 HL999999, Z01 HL005066-04] NR 37 TC 26 Z9 26 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD NOV PY 2008 VL 86 IS 11 BP 1221 EP 1232 DI 10.1007/s00109-008-0390-7 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 362TL UT WOS:000260219900003 PM 18690419 ER PT J AU Park, J Kim, TY Jung, Y Song, SH Kim, SH Oh, DY Im, SA Bang, YJ AF Park, Jinah Kim, Tae-You Jung, Yeonjoo Song, Sang-Hyun Kim, Sung-Hak Oh, Do-Youn Im, Seock-Ah Bang, Yung-Jue TI DNA methyltransferase 3B mutant in ICF syndrome interacts non-covalently with SUMO-1 SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE DNMT3B; ICF syndrome; SUMOylation; S270P mutation ID NF-KAPPA-B; IMMUNODEFICIENCY SYNDROME; SACCHAROMYCES-CEREVISIAE; DNMT3B MUTATIONS; PWWP DOMAIN; METHYLATION; GENE; TRANSCRIPTION; SUMOYLATION; PROTEINS AB Mutations of the DNA methyltransferase 3B (DNMT3B) gene have been detected in patients with immunodeficiency, centromere instability, and facial anomalies (ICF) syndrome. Most of these mutations are clustered in its catalytic domain and thus lead to defective DNA methylation. Nevertheless, the S270P mutation in the N-terminal PWWP (Pro-Trp-Trp-Pro) domain of the DNMT3B gene has prompted questions as to how this mutation contributes to the development of ICF syndrome. In this study, we found that wild-type DNMT3B is SUMOylated through covalent modification, whereas the S270P mutant interacts with SUMO-1 via non-covalent interaction. The S270P mutation results in diffuse nucleus localization. Moreover, the S270P mutant fails to interact with PIAS1, a small ubiquitin-related modifier (SUMO) E3 ligase, and causes the constitutive activation of nuclear factor-kappa B, which induces the expression of interleukin 8. Collectively, our data demonstrate that the S270P mutation affects DNMT3B functions via specific, non-covalent interaction with SUMO-1. C1 [Kim, Tae-You; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea. [Park, Jinah; Kim, Tae-You; Jung, Yeonjoo; Kim, Sung-Hak; Oh, Do-Youn; Im, Seock-Ah; Bang, Yung-Jue] Canc Res Inst, Natl Res Lab Canc Epigenet, Seoul, South Korea. [Song, Sang-Hyun] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bang, YJ (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28 Yongon Dong, Seoul 110744, South Korea. EM bangyj@plaza.snu.ac.kr RI Kim, Tae-You/J-2750-2012; Im, Seock-Ah/J-5620-2012; Bang, Yung Jue/J-2759-2012 FU Korea Science and Engineering Foundation (KOSEF); Ministry of Science and Technology [M10400000336-06J0000-33610, BK21] FX We thank Dr. Jong-Soo Lee (Ajou University, Korea) for discussions and providing the SUMO-1 constructs. We also thank all members of Bang's laboratory. This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the National Research Lab. Program funded by the Ministry of Science and Technology (No. M10400000336-06J0000-33610) and the BK21 Project for Medicine, Dentistry and Pharmacy. NR 32 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD NOV PY 2008 VL 86 IS 11 BP 1269 EP 1277 DI 10.1007/s00109-008-0392-5 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 362TL UT WOS:000260219900007 PM 18762900 ER PT J AU Wu, MX Yu, KF AF Wu, Mi-Xia Yu, Kai-Fun TI Remarks on between estimator in the intraclass correlation model with missing data SO JOURNAL OF MULTIVARIATE ANALYSIS LA English DT Article DE Between estimator; Intraclass correlation model; Contrast; Missing data; Exact test; Confidence interval ID SIMULTANEOUS CONFIDENCE-INTERVALS; MULTIVARIATE NORMAL-DISTRIBUTION; NORMAL-MEAN VECTOR; INCOMPLETE DATA AB In this paper, we consider the between estimator under the intraclass correlation model with missing data. We give a necessary and sufficient condition for existing exact simultaneous confidence intervals for all contrasts in the means under the between transformed model, which indicates the F-test statistic and simultaneous confidence intervals, constructed by Seo et al. [T. Seo, J. Kikuchi, K. Koizumi, On simultaneous confidence intervals for all contracts in the means of the intraclass correlation model with missing data, J. Multivariate Anal. 97 (2006) 1976-1983] based on the between estimator, is invalid. Furthermore, using the distribution of the between estimator, we present the exact test statistics and confidence intervals for partial contrasts. Published by Elsevier Inc. C1 [Wu, Mi-Xia; Yu, Kai-Fun] NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Rockville, MD 20852 USA. [Wu, Mi-Xia] Beijing Univ Technol, Coll Appl Sci, Beijing 100022, Peoples R China. RP Wu, MX (reprint author), NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd,Rm 7B05A, Rockville, MD 20852 USA. EM wumixia@mail.nih.gov FU National Institute of Child Health and Human Development, National Institutes of Health; Academic Human Resources Development in Institutions of Higher Learning; National Natural Science Foundation of China (NSFC) [10771010] FX The work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. Wu's research was also partially supported by Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality PHR(IHLB) and National Natural Science Foundation of China (NSFC) (10771010). We are grateful to the two referees for their detailed suggestions which considerably improved the quality of the paper. NR 10 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0047-259X J9 J MULTIVARIATE ANAL JI J. Multivar. Anal. PD NOV PY 2008 VL 99 IS 10 BP 2444 EP 2452 DI 10.1016/j.jmva.2008.02.030 PG 9 WC Statistics & Probability SC Mathematics GA 369MD UT WOS:000260697700017 ER PT J AU Summy-Long, JY Hu, S Long, A Phillips, TM AF Summy-Long, J. Y. Hu, S. Long, A. Phillips, T. M. TI Interleukin-1 beta Release in the Supraoptic Nucleus Area During Osmotic Stimulation Requires Neural Function SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE magnocellular system; microdialysis; oxytocin; vasopressin; microglia ID RAT HYPOTHALAMUS; MAGNOCELLULAR NEURONS; MONOCLONAL-ANTIBODIES; VASOPRESSIN RELEASE; RECEPTOR ANTAGONIST; SPINAL-CORD; IN-VITRO; CHANNELS; BRAIN; CALCIUM AB Interleukin (IL)-1 beta is present throughout the magnocellular neuroendocrine system and co-depletes with oxytocin and vasopressin from the neural lobe during salt-loading. To examine whether IL-1 beta is released from the dendrites/soma of magnocellular neurones during osmotic stimulation, microdialysis adjacent to the supraoptic nucleus (SON) in conscious rats was combined with immunocapillary electrophoresis and laser-induced fluorescence detection to quantify cytokine in 5-min dialysates collected before (0-180 min; basal), and after (180-240 min), hypertonic saline injected s.c. (1.5 M NaCl). Osmotic release of IL-1 beta was compared after inhibiting local voltage-gated channels for Na+ (tetrodotoxin) and Ca2+ (cadmium and nickel) or by reducing intracellular Ca2+ stores (thapsigargin). Immunohistochemistry combined with microdialysis was used to localise cytokine sources (IL-1 beta(+)) and microglia (OX-42(+)). Under conditions of microdialysis, the basal release of IL-1 beta(+) in the SON area was measurable and stable (pg/ml; mean +/- SEM) from 0-60 min (2.2 +/- 0.06), 60-120 min (2.32 +/- 0.05) and 120-180 min (2.33 +/- 0.06), likely originating locally from activated microglia (OX42(+); IL-1 beta(+); ameboid, hypertrophied) and magnocellular neurones expressing IL-1 beta. In response to osmotic stimulation, IL-1 beta increased progressively in dialysates of the SON area by a mechanism dependent on intracellular Ca2+ stores sensitive to thapsigargin and, similar to dendritic secretion of oxytocin and vasopressin, required local voltage-gated Na+ and Ca2+ channels for activation by osmoregulatory pathways from the forebrain. During osmotic stimulation, neurally dependent release of IL-1 beta in the SON area likely upregulates osmosensitive cation currents on magnocellular neurones (observed in vitro by others), to facilitate dendritic release of neurohypophysial hormones. C1 [Summy-Long, J. Y.; Hu, S.; Long, A.] Penn State Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. [Phillips, T. M.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. RP Summy-Long, JY (reprint author), Penn State Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. EM jsl2@psu.edu FU NIMH [R01-MH65271] FX This research was supported by the NIMH (R01-MH65271 to J.S-L). The authors appreciate technical support from Mindy Lull, Xiaofen Chen, Ann Pruss, David Widitz and X. Wang. A portion of this research was published previously as an abstract: Long, A., T. M. Phillips, X. Wang, X. Chen, A. Pruss, K. Seaton and J. Y. Summy-Long. Basal and osmotic-stimulated release of interleukin-1 beta from the supraoptic nucleus: dependence on Na+ and Ca++ channels. Programme No. 422.14. 2004 Abstract Viewer/Itinerary Planner; Washington, DC: Society for Neuroscience. NR 60 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-8194 EI 1365-2826 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD NOV PY 2008 VL 20 IS 11 BP 1224 EP 1232 DI 10.1111/j.1365-2826.2008.01783.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 359VQ UT WOS:000260016600002 PM 18752652 ER PT J AU Miura, K Sugita, Y Matsuura, K Inaba, N Kawano, K Miles, FA AF Miura, K. Sugita, Y. Matsuura, K. Inaba, N. Kawano, K. Miles, F. A. TI The Initial Disparity Vergence Elicited With Single and Dual Grating Stimuli in Monkeys: Evidence for Disparity Energy Sensing and Nonlinear Interactions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OCULAR-FOLLOWING RESPONSES; PURSUIT EYE-MOVEMENTS; RADIAL OPTIC FLOW; OPPOSITE-CONTRAST STIMULI; VISUAL-CORTEX NEURONS; TAKE-ALL MECHANISM; BINOCULAR DISPARITY; MACAQUE MONKEY; DEPTH-PERCEPTION; STRIATE CORTEX AB Miura K, Sugita Y, Matsuura K, Inaba N, Kawano K, Miles FA. The initial disparity vergence elicited with single and dual grating stimuli in monkeys: evidence for disparity energy sensing and non-linear interactions. J Neurophysiol 100: 2907-2918, 2008. First published September 3, 2008; doi: 10.1152/jn.90535.2008. We recorded the initial vertical vergence eye movements elicited in monkeys at short latency (similar to 70 ms) when the two eyes see one-dimensional (1D) horizontal grating patterns that are identical except for a phase difference (disparity) of one-quarter wavelength. With gratings composed of single sine waves, responses were always compensatory, showing Gaussian dependence on log spatial frequency (on average: peak = 0.75 cycles/deg; SD = 0.74; r(2) = 0.980) and monotonic dependence on log contrast with a gradual saturation well described by the Naka-Rushton equation (on average: n = 0.89; C-50 = 4.1%; r(2) = 0.978). With gratings composed of two sine waves whose spatial frequencies were in the ratio 3: 5 and whose disparities were of opposite sign (the 3f5f stimulus), responses were determined by the disparities and contrasts of the two sine-wave components rather than the disparity of the features, consistent with early spatial filtering of the monocular inputs before their binocular combination and mediation by detectors sensitive to disparity energy. In addition, responses to the 3f5f stimulus showed a nonlinear dependence on the relative contrasts of the two sine waves. Thus on average, when the contrast of one sine wave was 2.3 times greater than that of the other, the one with the lower contrast was largely ineffective as though suppressed, and responses were determined almost entirely by the sine wave of higher contrast: Winner-Take-All. These findings are very similar to those published previously on the vertical vergence responses of humans, indicating that the monkey provides a good animal model for studying these disparity vergence responses. C1 [Miura, K.; Sugita, Y.; Matsuura, K.; Inaba, N.; Kawano, K.] Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Kyoto 6068501, Japan. [Sugita, Y.; Kawano, K.] Kyoto Univ, Nanomed Merger Educ Unit, Kyoto 6068501, Japan. [Miles, F. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miura, K (reprint author), Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Konoe Cho, Kyoto 6068501, Japan. EM kmiura@brain.med.kyoto-u.ac.jp OI Inaba, Naoko/0000-0002-0073-275X FU Japan Society for the Promotion of Science [16GS0312]; Japan-U.S. Brain Research Cooperative Program; Intramural Program of the National Eye Institute at the National Institutes of Health FX This work was supported by Grant-in-Aid for Scientific Research 16GS0312 from the Japan Society for the Promotion of Science, the Japan-U.S. Brain Research Cooperative Program, and the Intramural Program of the National Eye Institute at the National Institutes of Health. NR 82 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2008 VL 100 IS 5 BP 2907 EP 2918 DI 10.1152/jn.90535.2008 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 370XE UT WOS:000260795600041 PM 18768642 ER PT J AU Joiner, WM Smith, MA AF Joiner, Wilsaan M. Smith, Maurice A. TI Long-Term Retention Explained by a Model of Short-Term Learning in the Adaptive Control of Reaching SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADIC EYE-MOVEMENTS; GROSS MOTOR SKILL; MEMORY; ADAPTATION; DYNAMICS; CONSOLIDATION; CORTEX; MONKEY; PET AB Joiner WM, Smith MA. Long-term retention explained by a model of short-term learning in the adaptive control of reaching. J Neurophysiol 100: 2948-2955, 2008. First published September 10, 2008; doi: 10.1152/jn.90706.2008. Extensive theoretical, psychophysical, and neurobiological work has focused on the mechanisms by which short-term learning develops into long-term memory. Better understanding of these mechanisms may lead to the ability to improve the efficiency of training procedures. A key phenomenon in the formation of long-term memory is the effect of over learning on retention discovered by Ebbinghaus in 1885: when the initial training period in a task is prolonged even beyond what is necessary for good immediate recall, long-term retention improves. Although this over learning effect has received considerable attention as a phenomenon in psychology research, the mechanisms governing this process are not well understood, and the ability to predict the benefit conveyed by varying degrees of over learning does not yet exist. Here we studied the relationship between the duration of an initial training period and the amount of retention 24 h later for the adaptation of human reaching arm movements to a novel force environment. We show that in this motor adaptation task, the amount of long-term retention is predicted not by the overall performance level achieved during the training period but rather by the level of a specific component process in a multi-rate model of short-term memory formation. These findings indicate that while multiple learning processes determine the ability to learn a motor adaptation, only one provides a gateway to long-term memory formation. Understanding the dynamics of this key learning process may allow for the rational design of training and rehabilitation paradigms that maximize the long-term benefit of each session. C1 [Smith, Maurice A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Joiner, Wilsaan M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St,325 Pierce Hall, Cambridge, MA 02138 USA. EM mas@seas.harvard.edu FU Alfred P. Sloan Foundation; McKnight Endowment FX This work was supported by Sloan Research Fellowship from the Alfred P. Sloan Foundation and a Scholar Award from the McKnight Endowment for Neuroscience to M. A. Smith. NR 41 TC 65 Z9 65 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2008 VL 100 IS 5 BP 2948 EP 2955 DI 10.1152/jn.90706.2008 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 370XE UT WOS:000260795600045 PM 18784273 ER PT J AU Kontos, MC Haney, A Ornato, JP Jesse, RL Tatum, JL AF Kontos, Michael C. Haney, Anthony Ornato, Joseph P. Jesse, Robert L. Tatum, James L. TI Value of simultaneous functional assessment in association with acute rest perfusion imaging for predicting short- and long-term outcomes in emergency department patients with chest pain SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; emergency department; chest pain ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR EJECTION FRACTION; ST-SEGMENT ELEVATION; RISK STRATIFICATION; UNSTABLE ANGINA; HEART-FAILURE; THROMBOLYTIC THERAPY; PROGNOSTIC VALUE; NORMAL LIMITS; WALL MOTION AB Background. Rest tomographic myocardial perfusion imaging (MPI) has significant utility for clinical decision making in emergency department chest pain patients. The role of functional data, commonly acquired with perfusion, has not been systematically evaluated. Methods and Results. Low- to moderate-risk patients undergoing rest MPI for risk stratification were included. The patients' MPI findings were classified as normal (normal perfusion or function), abnormal (perfusion defect with abnormal regional function), or discordant (perfusion defect with normal regional function). Ejection fraction was determined from the gated MPI studies. Events based on perfusion classifications and ejection fraction were evaluated. A total of 2,826 consecutive patients (abnormal MPI results in 40%, normal in 32%, and discordant in 27%) were studied. Outcomes were similar for those with normal MPI results versus those with discordant MPI results (myocardial infarction [MI] based on troponin I [TnI], 3.5% vs 4.0%; MI based on creatine kinase-MB, 1.5% vs 1.7%; revascularization, 5.2% vs 5.5%; and MI/revascularization based on TnI, 7.9% vs 8.1%) (P = not significant for all). Both groups had significantly fewer events (P <.001 for all) when compared with patients with abnormal MPI studies (MI based on TnI, 15%; MI based on creatine kinase-MB, 10%; revascularization, 17%; MI based on TnI or revascularization, 24%). The mortality rate was not different among the 3 groups. Multivariate analysis showed that mild/moderate and severe systolic dysfunction were independent predictors of 30-day and 1-year mortality rates (P.001). Conclusions. The concurrent evaluation of perfusion and function (regional and global) with MPI provides significant risk/outcome predictive power. (J Nucl Cardiol 2008;15:774-82.) C1 [Kontos, Michael C.; Haney, Anthony; Jesse, Robert L.] Virginia Commonwealth Univ, Dept Internal Med, Div Cardiol, Richmond, VA USA. [Kontos, Michael C.; Ornato, Joseph P.] Virginia Commonwealth Univ, Dept Emergency Med, Richmond, VA USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Dept Radiol, Richmond, VA USA. [Tatum, James L.] NCI, NIH, Bethesda, MD 20892 USA. RP Kontos, MC (reprint author), Room 285 Gateway Bldg,2nd Floor,POB 980051,1200 E, Richmond, VA 23298 USA. EM mkontos@mcvh-vcu.edu NR 34 TC 11 Z9 11 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD NOV-DEC PY 2008 VL 15 IS 6 BP 774 EP 782 DI 10.1016/j.nuclcard.2008.06.004 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 368TG UT WOS:000260644800007 PM 18984452 ER PT J AU Radican, L Blair, A Stewart, P Wartenberg, D AF Radican, Larry Blair, Aaron Stewart, Patricia Wartenberg, Daniel TI Mortality of Aircraft Maintenance Workers Exposed to Trichloroethylene and Other Hydrocarbons and Chemicals: Extended Follow-Up SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID RETROSPECTIVE COHORT MORTALITY; OBSTRUCTIVE PULMONARY-DISEASE; CANCER INCIDENCE; RESPIRATORY SYMPTOMS; AEROSPACE WORKERS; ORGANIC-SOLVENTS; EPIDEMIOLOGY; FACILITY; SMOKING; RISK AB Objective: To extend follow-up of 14,455 workers from 1990 to 2000, and evaluate mortality risk from exposure to trichloroethylene (TCE) and other chemicals. Methods: Multivariable Cox models were used to estimate relative risk (RR) for exposed versus unexposed workers based on previously developed exposure surrogates. Results: Among TCE-exposed workers, there was no statistically significant increased risk of all-cause mortality (RR = 1.04) or death from all cancers (RR = 1.03). Exposure-response gradients for TCE, were relatively flat and did not materially change since 1990. Statistically significant excesses were found for several chemical exposure subgroups and causes and were generally consistent with the previous follow-up. Conclusions: Patterns of mortality have not changed substantially since 1990. Although positive associations with several cancers were observed, and are consistent with the published literature, interpretation is limited due to the small numbers of events for specific exposures. (J Occup Environ Med. 2008;50:1306-1319) C1 [Radican, Larry] Merck & Co Inc, Global Outcomes Res Dept, Whitehouse Stn, NJ 08889 USA. [Blair, Aaron; Stewart, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wartenberg, Daniel] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, Div Environm Epidemiol, Newark, NJ 07103 USA. RP Radican, L (reprint author), Merck & Co Inc, Global Outcomes Res Dept, 1 Merck Dr, Whitehouse Stn, NJ 08889 USA. EM larry_radican@merck.com FU Intramural Research Program of the National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (National Cancer Institute. Division of Cancer Epidemiology and Genetics) and by an unrestricted educational grant from Merck and Co. NR 34 TC 19 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 2008 VL 50 IS 11 BP 1306 EP 1319 DI 10.1097/JOM.0b013e3181845f7f PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 372DC UT WOS:000260880800012 PM 19001957 ER PT J AU Milner, J Jensen, GL AF Milner, John Jensen, Gordon L. TI The Best Is Yet to Come: The Future of Nutrition and Inflammation Research SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT Intersociety Research Workshop on Nutrition and Inflammation CY FEB 08-09, 2008 CL Chicago, IL SP Amer Dietet Assoc, Amer Soc Nutr, Amer Soc Parenteral & Enteral Nutr, Obes Soc C1 [Jensen, Gordon L.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Milner, John] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Jensen, GL (reprint author), Penn State Univ, Dept Nutr Sci, 126 Henderson S, University Pk, PA 16802 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 2008 VL 32 IS 6 BP 667 EP 668 DI 10.1177/0148607108325250 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 365YU UT WOS:000260446800015 PM 18974250 ER PT J AU De Ravin, SS Shum, E Zarember, KA Rezvani, G Rosenfeld, RG Stratakis, CA Malech, HL AF De Ravin, Suk See Shum, Elaine Zarember, Kol A. Rezvani, Geoffrey Rosenfeld, Ron G. Stratakis, Constantine A. Malech, Harry L. TI Short Stature in Partially Corrected X-linked Severe Combined Imniunodeficiency - Suboptimal Response to Growth Hormone SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE X-linked severe combined immunodeficiency; growth hormone; IGF-I; gamma c; short stature ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; IMMUNE RECONSTITUTION; GENE-THERAPY; GAMMA-CHAIN; GH; PHENOTYPE; PATIENT AB Background: X-linked severe combined immunodeficiency (XSCID) results from defects in the common cytokine receptor gamma chain (gamma c) required for signaling by receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21(1). Following haploidentical bone marrow transplant without myelo-conditioning for XSCID, most patients achieve partial reconstitution 2 often limited to T lymphocytes. Many partially corrected patients manifest extreme short stature (< 5(th) percentile). Previous reports have implicated gamma c in growth hormone (GH) receptor signaling, thus severe growth failure in XSCID may be related to the underlying ye defect. Aim: To evaluate the GH/insulin-like growth factor-I (IGF-I) axis in three children with XSCID and partial immune reconstitution with profound growth failure. Methods: The IGF-I generation test was performed by administering recombinant GH subcutaneously for 5 days, and measuring serum levels for IGF-I before GH injection, and on days 5 and 8. Results: Study of the somatotropic axis revealed profoundly diminished IGF-I production following rGH challenge in all three patients. Conclusion: The data indicate that the GH/IGF-I axis in these partially corrected XSCID patients with severe short stature is profoundly impaired, and supports previous studies suggesting that the underlying gamma c defect may contribute to the severe growth failure in XSCID. This supports a role for defective gamma c in the extreme short stature of XSCID, and raises the possibility of recombinant IGF-I treatment to bypass this defect. C1 [De Ravin, Suk See] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Rezvani, Geoffrey; Stratakis, Constantine A.] NICHD, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. [Rosenfeld, Ron G.] NICHD, Lucile Packard Fdn Childrens Hlth, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, Bldg 10-CRC,Room 5-3816,10 Ctr Dr, Bethesda, MD 20892 USA. EM sderavin@niaid.nih.gov FU NIH [Z01-HD-00064204]; National Institute of Allergy and Infectious Diseases; NICHD FX This project was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, and, in part, by NICHD, NIH intramural project Z01-HD-00064204 to Dr. C.A. Stratakis. We have no other financial relationships to disclose. NR 23 TC 2 Z9 2 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 2008 VL 21 IS 11 BP 1057 EP 1063 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 388KN UT WOS:000262018800006 PM 19189700 ER PT J AU Hamilton, FA AF Hamilton, Frank A. TI NIH Funding Opportunities for Functional Bowel Disorders in the Pediatric Age Group SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Symposium on New Insights into Children Functional Abdominal Pain and Irritable Bowel Syndrome CY OCT 24, 2007 CL Salt Lake City, UT SP NASPGHAN ID GASTROINTESTINAL DISORDERS; ABDOMINAL-PAIN; CHILDREN C1 NIDDK, Digest Dis Program, NIH, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Hamilton, FA (reprint author), NIDDK, Digest Dis Program, NIH, Div Digest Dis & Nutr, 6707 Democracy Blvd,Room 669, Bethesda, MD 20892 USA. EM fh14c@nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2008 VL 47 IS 5 BP 709 EP 711 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 366YL UT WOS:000260519400040 PM 18955887 ER PT J AU Varma, S Jenkins, T Wendler, D AF Varma, Sumeeta Jenkins, Tammara Wendler, David TI How do Children and Parents Make Decisions About Pediatric Clinical Research? SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE assent; research; permission ID ASSENT; PARTICIPATION; PROTECTION; UNDERSTAND; PERMISSION; TRIALS AB Little is known about how children and parents make decisions regarding pediatric research. To provide data, we surveyed children aged 7 to 14 years who were enrolled in clinical research or receiving clinical care for cancer or asthma at one of 7 sites. and a parent or guardian. The present manuscript reports data on the respondents' attitudes and experiences regarding the child's involvement in making clinical care and research decisions. Of 117 parent-child pairs invited to participate. 81 completed the survey (response rate = 69.2%). Pediatric respondents reported that their decisions regarding research enrollment were influenced primarily by I desire to benefit themselves. and to help others. In the research group, 90.5% of pediatric respondents believed they should be involved in making research enrollment decisions. whereas only 61.5% of the adult respondents believed children Should be involved in making these decisions. These findings highlight the potential for disagreement within families regarding children's involvement in making decisions about research enrollment. Investigators should be aware of and find ways to address these disagreements when soliciting assent from children. C1 [Varma, Sumeeta; Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Jenkins, Tammara] NICHHD, Pediat Crit Care & Rehabil Res Program, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 21 TC 15 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 2008 VL 30 IS 11 BP 823 EP 828 DI 10.1097/MPH.0b013e318180bc0d PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 369XK UT WOS:000260727000007 PM 18989159 ER PT J AU Wallis, D Russell, HF Muenke, M AF Wallis, Deeann Russell, Heather F. Muenke, Maximilian TI Review: Genetics of Attention Deficit/Hyperactivity Disorder SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Review DE ADHD; association studies; DAT1; DRD4; genetics; linkage analysis ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; CATECHOL-O-METHYLTRANSFERASE; ADOLESCENT FEMALE TWINS; LATENT CLASS ANALYSIS; CONDUCT DISORDER; RECEPTOR GENE; ADHD SYMPTOMS; PREFERENTIAL TRANSMISSION; ENVIRONMENT INTERACTIONS AB Objective The intent of this review is to provide an overview for the practicing psychologist/psychiatrist regarding the complexities of and the most recent advances made in the study of the genetic basis of attention-deficit/hyperactivity disorder (ADHD). Methods We review a variety of concepts including: (a) complexities involved in studying the genetics of ADHD, (b) evidence for a primarily genetic component of ADHD, (c) evidence suggesting that there are only a few genes with major effects contributing to ADHD, (d) identification of the best candidate genes, (e) linkage analysis for the identification of novel candidate genes, and (f) data on geneenvironment interactions. Results It is now generally accepted that ADHD has a biological and even primarily genetic basis. However, despite the identification of several candidate genes, none of them seems to have a substantial effect and the exact etiology underlying ADHD has remained elusive. Genome-wide linkage analysis can help in the identification of novel candidate genes. While several independent groups have initiated these studies, we await further details and specific genes from fine-mapping studies. Most recently, researchers have been trying to identify gene by environment interactions to help understand ADHD. Replication of positive findings will be essential in teasing out these combinatorial influences. Conclusions Ideally, one day specific genes with major effects and specific risk factors with which they interact will be identified and we will be able to implement personalized medicine. Knowledge of such genes will allow us to identify specific diagnostic biological markers. In addition, defining the target genes is the first step in developing novel drug therapies to treat the ADHD symptoms that lead to impairment. Furthermore, such markers could also identify at risk individuals at a younger age in order to implement treatments sooner to decrease the severity of ADHD symptoms or even to prevent future ADHD symptomatology. C1 [Wallis, Deeann] Texas Inst Genom Med, Houston, TX 77030 USA. [Wallis, Deeann; Muenke, Maximilian] NIH, Med Genet Branch, NHGRI, Bethesda, MD 20892 USA. [Russell, Heather F.] Shriners Hosp Children Philadelphia, Philadelphia, PA USA. RP Wallis, D (reprint author), Texas Inst Genom Med, 2121W Holcombe Blvd, Houston, TX 77030 USA. EM dwallis@tigm.org NR 112 TC 48 Z9 48 U1 9 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD NOV-DEC PY 2008 VL 33 IS 10 BP 1085 EP 1099 DI 10.1093/jpepsy/jsn049 PG 15 WC Psychology, Developmental SC Psychology GA 367NB UT WOS:000260557600003 PM 18522996 ER PT J AU Haerynck, F Holland, SM Rosenzweig, SD Casanova, JL Schelstraete, P De Baets, F AF Haerynck, Filomeen Holland, Steve M. Rosenzweig, Sergio D. Casanova, Jean-Laurent Schelstraete, Petra De Baets, Frans TI Disseminated Mycobacterium avium Infection in a Patient with a Novel Mutation in the Interleukin-12 Receptor-beta 1 Chain SO JOURNAL OF PEDIATRICS LA English DT Article ID MENDELIAN SUSCEPTIBILITY; DEFICIENCY AB A girl with relapsing cervical lymphadenopathy due to Mycobacterium avium subsequently developed abdominal endenopathy and intestinal inflammation. 1 known (c.1623_1624delGCinsTT) and 1 novel mutation (c.65_68delCTGC of exons2) of the Interleukin-12 Receptor-beta 1 (IL-12R beta 1) gene was detected. Unlike reports of a more favorable outcome in these patients, our patient died of severe intestinal involvement. (J Pediatr 2008;153:721-2) C1 [Haerynck, Filomeen; Schelstraete, Petra; De Baets, Frans] Ghent Univ Hosp, Dept Pediat Pulmonol & Immunol, B-9000 Ghent, Belgium. [Holland, Steve M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Rosenzweig, Sergio D.] Hosp Nacl Pediat, Serv Immunol, Buenos Aires, DF, Argentina. [Casanova, Jean-Laurent] Univ Paris 05, Lab Human Genet Infect Dis, INSERM, U550, Paris, France. Univ Paris 05, Hop Necker Enfants Malad, Unite Clin Immunol & Hematol Pediat, Paris, France. RP Haerynck, F (reprint author), Ghent Univ Hosp, Dept Pediat Pulmonol & Immunol, Pintelaan 185, B-9000 Ghent, Belgium. EM filomeen.haerynck@Ugent.be NR 9 TC 12 Z9 12 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD NOV PY 2008 VL 153 IS 5 BP 721 EP 722 DI 10.1016/j.jpeds.2008.05.050 PG 2 WC Pediatrics SC Pediatrics GA 372EC UT WOS:000260883600035 PM 18940359 ER PT J AU Mazaki-Tovi, S Romero, R Kusanovic, JP Erez, O Gotsch, F Mittal, P Than, NG Nhan-Chang, CL Hamill, N Vaisbuch, E Chaiworapongsa, T Edwin, SS Nien, JK Gomez, R Espinoza, J Kendal-Wright, C Hassan, SS Bryant-Greenwood, G AF Mazaki-Tovi, Shali Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Mittal, Pooja Than, Nandor Gabor Nhan-Chang, Chia-Lang Hamill, Neil Vaisbuch, Edi Chaiworapongsa, Tinnakorn Edwin, Samuel S. Nien, Jyh Kae Gomez, Ricardo Espinoza, Jimmy Kendal-Wright, Claire Hassan, Sonia S. Bryant-Greenwood, Gillian TI Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Microbial invasion of the amniotic cavity (MIAC); pre-B cell colony-enhancing factor (PBEF); preterm labor; preterm prelabor rupture of membranes (preterm PROM); visfatin ID TUMOR-NECROSIS-FACTOR; DIFFERENTIALLY EXPRESSED GENES; GESTATIONAL DIABETES-MELLITUS; HUMAN FETAL MEMBRANES; NF-KAPPA-B; VASCULAR ENDOTHELIAL-CELLS; MESSENGER-RNA EXPRESSION; SMOOTH-MUSCLE-CELLS; PREMATURE RUPTURE; INTRAAMNIOTIC INFECTION AB Objective: Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). Methods: In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. Results: 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. Conclusions: 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that visfatin participates in the host response against infection. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Mittal, Pooja; Than, Nandor Gabor; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Edwin, Samuel S.; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Bethesda, MD USA. [Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Erez, Offer; Mittal, Pooja; Nhan-Chang, Chia-Lang; Hamill, Neil; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Nien, Jyh Kae; Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Kendal-Wright, Claire; Bryant-Greenwood, Gillian] Univ Hawaii, John A Burns Sch Med, Dept Obstet Gynecol & Womens Hlth, Honolulu, HI 96822 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS,Hutzel Womens Hospital, Box 4,3990 John R, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 136 TC 55 Z9 55 U1 0 U2 5 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD NOV PY 2008 VL 36 IS 6 BP 485 EP 496 DI 10.1515/JPM.2008.084 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 381CK UT WOS:000261512500003 PM 18598235 ER PT J AU Park, CW Lee, SM Park, JS Jun, JK Romero, R Yoon, BH AF Park, Chan-Wook Lee, Seung Mi Park, Joong Shin Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI The antenatal identification of funisitis with a rapid MMP-8 bedside test SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE bedside test; chorioamnionitis; funisitis; MMP-8; preterm gestation ID FLUID MATRIX METALLOPROTEINASE-8; INFLAMMATORY RESPONSE SYNDROME; PRETERM PREMATURE RUPTURE; INTRAAMNIOTIC INFLAMMATION; POLYMORPHONUCLEAR LEUKOCYTES; CLINICAL-SIGNIFICANCE; INTACT MEMBRANES; COLLAGENASE; INFECTION; LABOR AB Aims: The purpose of this study was to determine if a bedside test, the MMP-8 PTD Check (TM), can be of value in the antenatal identification of funisitis. This test can be performed in 15 min without any laboratory equipment. Methods: The relationship between the presence or absence of funisitis and the results of an MMP-8 PTD Check (TM) was examined in 139 patients who delivered preterm singleton neonates (gestational age <35 weeks) within 72 h of amniocentesis. Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas. AF was analyzed for white blood cell (WBC) count, interleukin-6 (IL-6) and an MMP-8 PTD Check (TM). The IL-6 concentration was also determined in umbilical cord plasma collected at birth. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly. Results: 1) Funisitis was present in 27% (38/139) of cases; 2) A positive MMP-8 PTD Check (TM) had a sensitivity of 97% (37/38), a specificity of 63% (64/101), a positive predictive value of 50% (37/74) and a negative predictive value of 99% (64/65) in the identification of funisitis; 3) Among cases without funisitis, patients with a positive MMP-8 PTD Check (TM) had a significantly higher median AF IL-6 concentration, AF WBC count, and umbilical cord plasma IL-6 concentration at birth than those with a negative MMP-8 PTD Check (TM) (P<0.05 for each). Conclusions: The MMP-8 PTD Check (TM) is a rapid, simple and sensitive bedside test which allows assessment of the risk of funisitis. C1 [Park, Chan-Wook; Lee, Seung Mi; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM Yoonbh@snu.ac.kr RI Jun, Jong Kwan/D-5776-2012; Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012; OI Jun, Jong Kwan/0000-0002-0242-1736; Park, Joong Shin/0000-0002-5246-0477 FU Intramural NIH HHS [Z01 HD002400-16] NR 24 TC 31 Z9 31 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD NOV PY 2008 VL 36 IS 6 BP 497 EP 502 DI 10.1515/JPM.2008.079 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 381CK UT WOS:000261512500004 PM 19127606 ER PT J AU Cheung, C Gonzalez, FJ AF Cheung, Connie Gonzalez, Frank J. TI Humanized Mouse Lines and Their Application for Prediction of Human Drug Metabolism and Toxicological Risk Assessment SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; PREGNANE-X-RECEPTOR; HEPATIC CYTOCHROME-P450 3A4; TRANSGENIC MICE; PPAR-ALPHA; SPECIES-DIFFERENCES; GENE-EXPRESSION; HUMAN LIVER; PEROXISOME PROLIFERATORS; HETEROCYCLIC AMINES AB Cytochrome P450s (P450s) are important enzymes involved in the metabolism of xenobiotics, particularly clinically used drugs, and are also responsible for metabolic activation of chemical carcinogens and toxins. Many xenobiotics can activate nuclear receptors that in turn induce the expression of genes encoding xenobiotic metabolizing enzymes and drug transporters. Marked species differences in the expression and regulation of cytochromes P450 and xenobiotic nuclear receptors exist. Thus, obtaining reliable rodent models to accurately reflect human drug and carcinogen metabolism is severely limited. Humanized transgenic mice were developed in an effort to create more reliable in vivo systems to study and predict human responses to xenobiotics. Human P450s or human xenobiotic-activated nuclear receptors were introduced directly or replaced the corresponding mouse gene, thus creating "humanized" transgenic mice. Mice expressing human CYP1A1/CYP1A2, CYP2E1, CYP2D6, CYP3A4, CY3A7, pregnane X receptor, and peroxisome proliferator-activated receptor alpha were generated and characterized. These humanized mouse models offer a broad utility in the evaluation and prediction of toxicological risk that may aid in the development of safer drugs. C1 [Cheung, Connie; Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), Natl Canc Inst, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov FU Intramural NIH HHS [Z01 BC005562-20] NR 70 TC 73 Z9 74 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2008 VL 327 IS 2 BP 288 EP 299 DI 10.1124/jpet.108.141242 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 361YZ UT WOS:000260166000001 PM 18682571 ER PT J AU Scherma, M Panlilio, LV Fadda, P Fattore, L Gamaleddin, I Le Foll, B Justinova, Z Mikics, E Haller, J Medalie, J Stroik, J Barnes, C Yasar, S Tanda, G Piomelli, D Fratta, W Goldberg, SR AF Scherma, Maria Panlilio, Leigh V. Fadda, Paola Fattore, Liana Gamaleddin, Islam Le Foll, Bernard Justinova, Zuzana Mikics, Eva Haller, Jozsef Medalie, Julie Stroik, Jessica Barnes, Chanel Yasar, Sevil Tanda, Gianluigi Piomelli, Daniele Fratta, Walter Goldberg, Steven R. TI Inhibition of Anandamide Hydrolysis by Cyclohexyl Carbamic Acid 3 '-Carbamoyl-3-yl Ester (URB597) Reverses Abuse-Related Behavioral and Neurochemical Effects of Nicotine in Rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-for-Neuroscience CY NOV 03-07, 2007 CL San Diego, CA SP Soc Neurosci ID ENDOGENOUS CANNABINOID ANANDAMIDE; VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCES; ANTIDEPRESSANT-LIKE ACTIVITY; ACETYLCHOLINE-RECEPTORS; NUCLEUS-ACCUMBENS; OLEOYLETHANOLAMIDE; ENDOCANNABINOIDS; ANTAGONIST; ACTIVATION AB Emerging evidence suggests that the rewarding, abuse-related effects of nicotine are modulated by the endocannabinoid system of the brain. For example, pharmacological blockade or genetic deletion of cannabinoid CB1 receptors can reduce or eliminate many abuse-related behavioral and neurochemical effects of nicotine. Furthermore, doses of Delta(9)-tetrahydrocannabinol and nicotine that are ineffective when given alone can induce conditioned place preference when given together. These previous studies have used systemically administered CB1 receptor agonists and antagonists and gene deletion techniques, which affect cannabinoid CB1 receptors throughout the brain. A more functionally selective way to alter endocannabinoid activity is to inhibit fatty acid amide hydrolase (FAAH), thereby magnifying and prolonging the effects of the endocannabinoid anandamide only when and where it is synthesized and released on demand. Here, we combined behavioral and neurochemical approaches to evaluate whether the FAAH inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) could alter the abuse-related effects of nicotine in rats. We found that URB597, at a dose (0.3 mg/kg) that had no behavioral effects by itself, prevented development of nicotine-induced conditioned place preference (CPP) and acquisition of nicotine self-administration. URB597 also reduced nicotine-induced reinstatement in both CPP and self-administration models of relapse. Furthermore, in vivo microdialysis showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. These findings suggest that FAAH inhibition can counteract the addictive properties of nicotine and that FAAH may serve as a new target for development of medications for treatment of tobacco dependence. C1 [Scherma, Maria; Fadda, Paola; Fratta, Walter] Univ Cagliari, Bb Brodie Dept Neurosci, I-09124 Cagliari, Italy. [Fattore, Liana] Inst Neurosci, CNR, Cagliari, Italy. [Gamaleddin, Islam; Le Foll, Bernard] Univ Toronto, Translat Addict Res Lab, Toronto, ON, Canada. [Le Foll, Bernard] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Mikics, Eva; Haller, Jozsef] Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. [Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Biomed Res Ctr 05A711, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Tanda, Gianluigi] Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Biomed Res Ctr 05A711, Intramural Res Program,NIH,Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sgoldber@mail.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Le Foll, Bernard/K-2952-2014; OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484; Le Foll, Bernard/0000-0002-6406-4973; FADDA, PAOLA/0000-0002-0642-6710; Haller, Jozsef/0000-0002-1953-3726 FU Intramural NIH HHS [Z01 DA000003-22, Z99 DA999999]; NIDA NIH HHS [N01 DA059909] NR 45 TC 74 Z9 75 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2008 VL 327 IS 2 BP 482 EP 490 DI 10.1124/jpet.108.142224 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 361YZ UT WOS:000260166000021 PM 18725543 ER PT J AU Jia, L Noker, PE Piazza, GA Leuschner, C Hansel, W Gorman, GS Coward, LU Tomaszewski, J AF Jia, Lee Noker, Patricia E. Piazza, Gary A. Leuschner, Carola Hansel, William Gorman, Gregory S. Coward, Lori U. Tomaszewski, Joseph TI Pharmacokinetics and pharmacodynamics of Phor21-beta CG(ala), a lytic peptide conjugate SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID LUTEINIZING-HORMONE RECEPTORS; PROSTATE-CANCER CELLS; CG-BETA CONJUGATE; IN-VITRO; TARGETED DESTRUCTION; DRUG-METABOLISM; LUCIFERASE GENE; BREAST; VIVO; XENOGRAFTS AB Phor21-beta CG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the beta-chain of chorionic gonadotropin (beta CG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-beta CG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.luc). Plasma stability, protease hydrolysis and pharmacokinetics of Phor21-beta CG(ala) were measured by using liquid chromatography mass spectrometry (LC/MS/MS). Phor21-beta CG(ala) selectively inhibited proliferation in-vitro and in-vivo metastases of PC-3 cells. Phor21-beta CG(ala) was relatively stable in mouse, rat, dog and human plasma. Its degradation was partially due to protease hydrolysis and thermodynamic catalysis. Intravenous administration of Phor21-beta CG(ala) showed its blood C-max and AUC(0 ->infinity) around the in-vitro effective levels. In the tested rodents, Phor21-beta CG(ala) displayed a moderate volume of distribution at steady state (Vd(ss)) and slow clearance (Cl) in the rodents. In conclusion, Phor21-beta CG(ala) displayed promising in-vitro and in-vivo anti-cancer activity with favourable pharmacokinetics, and may offer a novel approach to metastatic cancer chemotherapy. C1 [Jia, Lee] NCI, NIH, Rockville, MD 20852 USA. [Noker, Patricia E.; Piazza, Gary A.; Gorman, Gregory S.; Coward, Lori U.] So Res Inst, Birmingham, AL 35255 USA. [Leuschner, Carola; Hansel, William] Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Jia, L (reprint author), NCI, NIH, 6130 Execut Blvd,Rm 8042, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU Gordon and Mary Cain Foundation; Department of Defense [DAMD-17-03-1-0150]; National Cancer Institute. [N01-CM-07110] FX Funding: The studies were supported by Gordon and Mary Cain Foundation, Grant #DAMD-17-03-1-0150 from the Department of Defense, and Contract No. N01-CM-07110 from the National Cancer Institute. NR 26 TC 7 Z9 7 U1 0 U2 3 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD NOV PY 2008 VL 60 IS 11 BP 1441 EP 1448 DI 10.1211/jpp.60.11.0004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 372SG UT WOS:000260921500004 PM 18957164 ER PT J AU Crespo, CJ Garcia-Palmieri, MR Smit, E Lee, IM McGee, D Muti, P Valle, NRF Ramirez-Marrero, FA Freudenheim, JL Sorlie, P AF Crespo, Carlos J. Garcia-Palmieri, Mario R. Smit, Ellen Lee, I-Min McGee, Daniel Muti, Paola Valle, Nayda R. Figueroa Ramirez-Marrero, Farah A. Freudenheim, Jo L. Sorlie, Paul TI Physical Activity and Prostate Cancer Mortality in Puerto Rican Men SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE cancer; epidemiology; physical activity; mortality; chronic disease AB Studies on the association between physical activity and fatal prostate cancer have produced inconclusive results. The Puerto Rico Heart Health Program was a cohort study of a randomly selected sample of 9824 men age 35 to 79 years at baseline who were followed for mortality until 2002. Multiple examinations collected information on lifestyle, diet, body composition, exercise, urban-rural residence, and smoking habits. Physical activity status was measured using the Framingham Physical Activity Index, an assessment of occupational, leisure-time, and other physical activities measured as usual activity over the course of a 24-hour day. Physical activity was stratified into quartiles. Multivariate logistic regression analysis was used to assess the association of physical activity with prostate cancer mortality. Other covariates included age, education, urban-rural residence, smoking, and body mass index. Compared with the lowest level of physical activity (Q1), the risk of prostate cancer mortality was OR = 0.99 (95% CI = 0.64-1.55) for Q2, OR = 1.34 (95% CI = 0.88-2.05) for Q3, and OR = 1.19 (95% CI = 0.75-1.90) for Q4. Further analyses by age group, overweight status, or vigorous physical activity also did not show a significant association between physical activity and prostate cancer mortality. Physical activity did not predict prostate cancer mortality in this group of Puerto Rican men. C1 [Crespo, Carlos J.; Smit, Ellen] Portland State Univ, Sch Community Hlth, Portland, OR 97207 USA. [Garcia-Palmieri, Mario R.; Valle, Nayda R. Figueroa; Ramirez-Marrero, Farah A.] Univ Puerto Rico, San Juan, PR 00936 USA. [Lee, I-Min; Muti, Paola] Harvard Univ, Sch Med, Boston, MA 02446 USA. [McGee, Daniel] Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA. [Muti, Paola] Italian Natl Canc Inst, Rome, Italy. [Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Sorlie, Paul] NHLBI, Bethesda, MD 20892 USA. RP Crespo, CJ (reprint author), Portland State Univ, Sch Community Hlth, Portland, OR 97207 USA. FU NCI NIH HHS [1P20CA96256-01A1, 1R03 CA103475-01] NR 64 TC 2 Z9 3 U1 0 U2 3 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD NOV PY 2008 VL 5 IS 6 BP 918 EP 929 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V18PB UT WOS:000208015600012 PM 19164825 ER PT J AU Oermann, MH Nordstrom, CK Ineson, V Wilmes, NA AF Oermann, Marilyn H. Nordstrom, Cheryl K. Ineson, Vicki Wilmes, Nancy A. TI WEB CITATIONS IN THE NURSING LITERATURE: HOW ACCURATE ARE THEY? SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE Web citation; References; Nursing literature; Citation analysis ID EPISTEMIC ORIGINS; COMMUNICATION; INTERNET; JOURNALS AB One problem with using Web citations is whether those documents will be available over time. We examined 573 Web citations in articles published in nursing journals and checked their availability (either by direct link or by searching the main site). There was a mean of 3.1 Web citations per article. Most Web citations were to documents that related to clinical practice, for example, clinical guidelines and explanations of clinical conditions and treatments. Of the 573 Web citations, 414 (72.3%) were still available; of those, 229 (55.3%) were able to be accessed by direct link and the other 185 (44.7%) by searching the main Web site. However, 159 (27.7%) of the references were not available, not even by searching the Internet using key terms from the citation. Considering that more than a fourth of the Web citations in this study were no longer available, authors need to be cautious about using the Web as a primary source of information for their publications. C1 [Oermann, Marilyn H.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27515 USA. [Nordstrom, Cheryl K.] Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA. [Ineson, Vicki] Wayne State Univ, Serv Support Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI USA. [Wilmes, Nancy A.] Wayne State Univ, Univ Lib, Sci & Engn Lib, Detroit, MI USA. RP Oermann, MH (reprint author), Univ N Carolina, Sch Nursing, Chapel Hill, NC 27515 USA. EM moermann@email.unc.edu NR 19 TC 5 Z9 5 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD NOV-DEC PY 2008 VL 24 IS 6 BP 347 EP 351 DI 10.1016/j.profnurs.2007.12.004 PG 5 WC Nursing SC Nursing GA 381JQ UT WOS:000261532600004 PM 19022207 ER PT J AU Rodriguez, H AF Rodriguez, Henry TI International Summit on Proteomics Data Release and Sharing Policy SO JOURNAL OF PROTEOME RESEARCH LA English DT Editorial Material C1 NCI, Clin Proteom Technol Canc, NIH, Bethesda, MD 20892 USA. RP Rodriguez, H (reprint author), NCI, Clin Proteom Technol Canc, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV PY 2008 VL 7 IS 11 BP 4609 EP 4609 DI 10.1021/pr800779q PG 1 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 370VU UT WOS:000260792000001 PM 18837532 ER PT J AU Albe, E Chang, JH Azar, NF Ivanov, AR Azar, DT AF Albe, Elena Chang, Jin-Hong Azar, Nathalie F. Ivanov, Alexander R. Azar, Dimitri T. TI Proteomic Analysis of the Hyaloid Vascular System Regression during Ocular Development SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE hyaloid vascular system; vasa hyaloidea propria; tunica vasculosa lentis; proteomic analysis; kininogen; angiogenic factors; antiangiogenic factors; vessel regression ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; CELL-GROWTH; APOPTOSIS; NEOVASCULARIZATION; MACROPHAGES; INHIBITION; KININOGEN; MICE; EYE AB We describe a proteomic approach to investigate the differential protein expression patterns and identify the physiologically relevant angiogenic and antiangiogenic factors involved in the hyaloid vascular system regression. Differentially expressed proteins were identified using two-dimensional gel electrophoresis followed by nanoflow chromatography coupled with tandem mass spectrometry. These proteins are expected to provide insight as to their function in the early maintenance and eventual regression of the hyaloid vascular system. C1 [Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Albe, Elena; Chang, Jin-Hong; Azar, Nathalie F.; Azar, Dimitri T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Ivanov, Alexander R.] Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Environm Hlth Proteom Facil, Boston, MA 02115 USA. RP Azar, DT (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM dazar@uic.edu FU S. Elizabeth O'Brien Trust; NIH [EY10101, P30-001792, EY14048]; Research to Prevent Blindness (New York, NY) FX The authors wish to thank Drs. Faisal Tobaigy and Ramon Ghanem for immunoconfocal microscopy. Supported by S. Elizabeth O'Brien Trust (D.TA.), NIH EY10101 (D.TA.), P30-001792 (D.TA.), EY14048 (J.H.C.), and an unrestricted departmental support from Research to Prevent Blindness (New York, NY). NR 46 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV PY 2008 VL 7 IS 11 BP 4904 EP 4913 DI 10.1021/pr800551m PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 370VU UT WOS:000260792000030 PM 18841878 ER PT J AU Mamasakhlisov, Y Naji, A Podgornik, R AF Mamasakhlisov, Yevgeni S. Naji, Ali Podgornik, Rudolf TI Partially Annealed Disorder and Collapse of Like-Charged Macroions SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article DE Classical charged systems; Like-charge attraction; Charge disorder; Partial annealing ID DENSITY-FUNCTIONAL THEORY; ELECTRICAL DOUBLE-LAYER; POISSON-BOLTZMANN; COUPLED DYNAMICS; FAST SPINS; AMPHOTERIC SURFACES; SLOW INTERACTIONS; NEURAL-NETWORKS; COULOMB FLUID; SOFT MATTER AB Charged systems with partially annealed charge disorder are investigated using field-theoretic and replica methods. Charge disorder is assumed to be confined to macroion surfaces surrounded by a cloud of mobile neutralizing counterions in an aqueous solvent. A general formalism is developed by assuming that the disorder is partially annealed (with purely annealed and purely quenched disorder included as special cases), i.e., we assume in general that the disorder undergoes a slow dynamics relative to fast-relaxing counterions making it possible thus to study the stationary-state properties of the system using methods similar to those available in equilibrium statistical mechanics. By focusing on the specific case of two planar surfaces of equal mean surface charge and disorder variance, it is shown that partial annealing of the quenched disorder leads to renormalization of the mean surface charge density and thus a reduction of the inter-plate repulsion on the mean-field or weak-coupling level. In the strong-coupling limit, charge disorder induces a long-range attraction resulting in a continuous disorder-driven collapse transition for the two surfaces as the disorder variance exceeds a threshold value. Disorder annealing further enhances the attraction and, in the limit of low screening, leads to a global attractive instability in the system. C1 [Naji, Ali] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. [Mamasakhlisov, Yevgeni S.] Yerevan State Univ, Dept Mol Phys, Yerevan 375025, Armenia. [Naji, Ali] Univ Calif Santa Barbara, Mat Res Lab, Santa Barbara, CA 93106 USA. [Naji, Ali; Podgornik, Rudolf] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA. [Podgornik, Rudolf] Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 1000, Slovenia. [Podgornik, Rudolf] Jozef Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. [Podgornik, Rudolf] Natl Inst Hlth, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. RP Naji, A (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. EM anaji@chem.ucsb.edu RI Naji, Ali/F-6352-2010; Podgornik, Rudolf/C-6209-2008 OI Naji, Ali/0000-0003-3436-1499; Podgornik, Rudolf/0000-0002-3855-4637 NR 69 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD NOV PY 2008 VL 133 IS 4 BP 659 EP 681 DI 10.1007/s10955-008-9635-7 PG 23 WC Physics, Mathematical SC Physics GA 373GF UT WOS:000260958300004 ER PT J AU Dawson, DA Stinson, FS Chou, SP Grant, BF AF Dawson, Deborah A. Stinson, Frederick S. Chou, S. Patricia Grant, Bridget F. TI Three-Year Changes in Adult Risk Drinking Behavior in Relation to the Course of Alcohol-Use Disorders SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; DSM-IV ALCOHOL; HEAVY DRINKING; YOUNG ADULTHOOD; BINGE DRINKING; UNITED-STATES; DRUG-USE; LONGITUDINAL PROJECT; EMERGING ADULTHOOD; ANXIETY DISORDERS AB Objective: This study examines the associations between the course of alcohol-use disorder (AUD) and changes in average daily volume of ethanol intake, frequency of risk drinking, and maximum quantity of drinks consumed per day over a 3-year follow-up interval in a sample of U.S. adults. Method: Data were taken from a longitudinal of a nationally representative sample of U.S. adults, who were 18 years of age and older (mean age = 46.4) when initially interviewed in 2001-2002 and successfully reinterviewed approximately 3 years later (n = 22,245 baseline drinkers). The time reference period for the drinking measures was the 12 months preceding the interviews Changes in consumption reflect differences between Wave I and Wave 2 measures for individuals with nonmissing values at both Waves (n = 22,003 for volume of intake, 22,132 for frequency of risk drinking and 2 1,942 for maximum quantity of drinks). Results: There were positive changes in all consumption measures associated with developing an AUD and negative changes associated with remission of ail AUD, even among individuals who continued to drink. Increases and decreases associated with onset and offset of dependence exceeded those associated with onset/offset of abuse only. and the decreases associated with full remission from dependence exceeded those associated with partial remission. There were few changes in consumption among individuals whose AUD status did not change. Interactions of AUD transitions with other factors indicate that development of an AUD is associated with a greater increase in consumption among men, possibly reflecting their greater total body water and lower blood alcohol concentration in response to a given dose of ethanol, and among individuals with high baseline levels of consumption. Conclusions: Changes in consumption associated with onset and offset of AUD are substantial enough to have important implications for the risk of associated physical and psychological harm. (J. Stud. Alcohol Drugs 69: 866-877, 2008) C1 [Dawson, Deborah A.; Stinson, Frederick S.; Chou, S. Patricia; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3071,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov FU National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism; U.S. Department of Health and Human Services; National Institute on Drug Abuse FX This research was supported, in part, by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, The study on which this article is based. the National Epidemiologic Survey on Alcohol and Related Conditions, is sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, with supplemental support from the National Institute on Drug Abuse. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies. or the U.S. government. NR 66 TC 26 Z9 27 U1 2 U2 5 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD NOV PY 2008 VL 69 IS 6 BP 866 EP 877 PG 12 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 373BS UT WOS:000260946600010 PM 18925345 ER PT J AU Leibenluft, E AF Leibenluft, Ellen TI Skating to Where the Puck Will Be: The Importance of Neuroimaging Literacy in Child Psychiatry SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID YOUNG-CHILDREN; MATURATION; DISORDER; AUTISM C1 NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,Dept Hlth & Human Serv, Bldg 15K,Room 203,15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 21 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2008 VL 47 IS 11 BP 1213 EP 1216 DI 10.1097/CHI.0b013e318185dab8 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 365YC UT WOS:000260444800001 PM 18931607 ER PT J AU Pine, DS Guyer, AE Leibenluft, E AF Pine, Daniel S. Guyer, Amanda E. Leibenluft, Ellen TI Functional Magnetic Resonance Imaging and Pediatric Anxiety SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID PREFRONTAL CORTEX ACTIVATION; ATTENTIONAL BIAS; ANGRY FACES; DISORDER; THREAT; ADOLESCENTS; PLASTICITY; VIGILANCE; AMYGDALA; CHILDREN C1 [Pine, Daniel S.; Guyer, Amanda E.; Leibenluft, Ellen] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bldg 15K,Room 203,15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM pined@mail.nih.gov FU Intramural NIH HHS [Z01 MH002782-06] NR 14 TC 17 Z9 17 U1 7 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2008 VL 47 IS 11 BP 1217 EP 1221 DI 10.1097/CHI.0b013e318185dad0 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 365YC UT WOS:000260444800002 PM 18931608 ER PT J AU Mahindra, P DiGiovanna, JJ Tamura, D Brahim, JS Hornyak, TJ Stern, JB Lee, CCR Khan, SG Brooks, BP Smith, JA Driscoll, BP Montemarano, AD Sugarman, K Kraemer, KH AF Mahindra, Priya DiGiovanna, John J. Tamura, Deborah Brahim, Jaime S. Hornyak, Thomas J. Stern, Jere B. Lee, Chyi-Chia Richard Khan, Sikandar G. Brooks, Brian P. Smith, Janine A. Driscoll, Brian P. Montemarano, Andrew D. Sugarman, Kate Kraemer, Kenneth H. TI Skin cancers, blindness, and anterior tongue mass in African brothers SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DNA-REPAIR DISORDERS; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; XPC GENE; TRICHOTHIODYSTROPHY; MANIFESTATIONS; MUTATION; PROTECTS; DAMAGE; CELL C1 [Mahindra, Priya; DiGiovanna, John J.; Tamura, Deborah; Khan, Sikandar G.; Kraemer, Kenneth H.] NCI, Basic Res Lab, DNA Repair Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Mahindra, Priya] NIH, Clin Res Training Program, Bethesda, MD 20892 USA. [DiGiovanna, John J.] Brown Univ, Warren Alpert Sch Med, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02912 USA. [Hornyak, Thomas J.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Stern, Jere B.; Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Driscoll, Brian P.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Montemarano, Andrew D.] Skin Canc Surg Ctr, Bethesda, MD USA. [Sugarman, Kate] Community Hope Hlth Serv, Washington, DC USA. RP Kraemer, KH (reprint author), NCI, Basic Res Lab, DNA Repair Sect, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA. FU Center for Cancer Research; National Cancer Institute; National Institute of Dental and Craniofacial Research; National Eye Institute; National Institute of Deafness; National Institutes of Health (NIH); Pfizer Inc FX Supported by the Intramural Research Programs of the Center for Cancer Research, National Cancer Institute, of the National Institute of Dental and Craniofacial Research, of the National Eye Institute, and of the National Institute of Deafness and other Communication Disorders of the National Institutes of Health (NIH). Support for author Mahindra was made possible through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). NR 25 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2008 VL 59 IS 5 BP 881 EP 886 DI 10.1016/j.jaad.2008.06.030 PG 6 WC Dermatology SC Dermatology GA 365CT UT WOS:000260384200018 PM 19119101 ER PT J AU Dang, V Bao, S Ault, A Murray, C McFarlane-Mills, J Chiedi, C Dillon, M Todd, JP DeTolla, L Rao, S AF Dang, Vi Bao, Saran Ault, Alida Murray, Catherine McFarlane-Mills, Joy Chiedi, Carmelo Dillon, Marlon Todd, John-Paul DeTolla, Louis Rao, Srinivas TI Efficacy and Safety of Five Injectable Anesthetic Regimens for Chronic Blood Collection from the Anterior Vena Cava of Guinea Pigs SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID LABORATORY-ANIMALS; KETAMINE; XYLAZINE AB Despite several published methods of inducing surgical anesthesia in guinea pigs, viable methods of anesthesia for blood collection from the vena cava are inadequate. We compared 5 anesthesia regimens and their efficacy in inducing anesthesia for blood sampling in guinea pigs: ketamine-xylazine (30 and 2.5 mg/kg) administered subcutaneously, intramuscularly, or intraperitoneally; pentobarbital (37 mg/kg) administered intraperitoneally; and medetomidine (0.5 mg/kg) administered intramuscularly. Parameters measured included time to onset of anesthesia, time to recovery from anesthesia, and complete blood count (CBC) and serum chemistry values. CBC values did not differ among the 5 regimens, but serum glucose, BUN, phosphorous, and creatine phosphokinase levels varied among groups. Based on our data, intraperitoneal ketamine-xylazine appears to emerge as a preferable injectable anesthetic regimen in guinea pigs for blood collection from the anterior vena cava. C1 [Dang, Vi; Bao, Saran; Ault, Alida; Murray, Catherine; McFarlane-Mills, Joy; Chiedi, Carmelo; Dillon, Marlon; Todd, John-Paul; Rao, Srinivas] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [DeTolla, Louis] Univ Maryland, Sch Med, Program Comparat Med, Baltimore, MD 21201 USA. [DeTolla, Louis] Univ Maryland, Sch Med, Dept Pathol Epidemiol & Prevent Med & Med, Div Infect Dis, Baltimore, MD 21201 USA. RP Rao, S (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM srao1@mail.nih.gov NR 27 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2008 VL 47 IS 6 BP 56 EP 60 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 380AR UT WOS:000261438400012 PM 19049255 ER PT J AU Ayres, EJ Hoggle, LB AF Ayres, Elaine J. Hoggle, Lindsey B. TI ADA Nutrition Informatics Member Survey: Results and Future Steps SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material C1 [Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Ayres, EJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM eayres@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 6 TC 8 Z9 9 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2008 VL 108 IS 11 BP 1822 EP + DI 10.1016/j.jada.2008.09.016 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 368LK UT WOS:000260622400003 PM 18954567 ER PT J AU Guenther, PM Reedy, J Krebs-Smith, SM Reeve, BB AF Guenther, Patricia M. Reedy, Jill Krebs-Smith, Susan M. Reeve, Bryce B. TI Evaluation of the Healthy Eating Index-2005 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIET QUALITY INDEX; NUTRIENT INTAKE; PATTERNS; NONSMOKERS; ADHERENCE; GUIDANCE; SMOKING; SMOKERS; WOMEN; RISK AB Background The Healthy Eating Index (HEI), a measure of diet quality as specified by federal dietary guidance, was revised to conform to the Dietary Guidelines for Americans 2005. The HEI has several components, the scores of which are totaled. Objective The validity and reliability of the HEI-2005 were evaluated. Design Validity was assessed by answering four questions: Does the HEI-2005 1) give maximum scores to menus developed by experts; 2) distinguish between groups wit known differences in diet quality-smokers and nonsmokers; 3) measure diet quality independently of energy intake, a proxy for diet quantity; and 4) have more than one underlying dimension? The relevant type of reliability, internal consistency, was also assessed. Subjects Twenty-four-hour recalls from 8,650 participants, aged 2 years and older, in the National Health and Nutrition Examination Survey, 2001-2002 were analyzed to answer questions 2 to 4. Results were weighted to consider sample design and nonresponse. Statistical analyses T tests determined differences in scores between smokers and nonsmokers. Pearson correlation coefficients determined the relationship between energy intake and scores. Principal components analysis determined the number of factors that comprise the HEI-2005. Cronbach's coefficient a tested internal consistency. Results HEI-2005 scores are at or very near the maximum levels for all sets of exemplary menus with one exception; the Harvard menus scored low on the milk component because these menus intentionally include only small amounts of milk products. Nine of 12 component scores were lower for smokers than nonsmokers. The correlations of component scores were virtually independent of energy intake (< 1.221). Multiple factors underlie the HEI-2005. Coefficient a was .43. The a value for all tests was .01, Conclusions The HEI-2005 is a valid measure of diet quality. Potential uses include population monitoring, evaluation of interventions, and research. The individual component scores provide essential information in addition to that provided by the total score. C1 [Guenther, Patricia M.] Ctr Nutr Policy & Promot, USDA, Alexandria, VA 22302 USA. [Reedy, Jill; Krebs-Smith, Susan M.] Natl Canc Inst, Div Canc Control & Populat Sci, Risk Factor Monitoring & Methods Branch, Appl Res Program, Bethesda, MD USA. [Reeve, Bryce B.] Natl Canc Inst, Div Canc Control & Populat Sci, Outcomes Res Branch, Appl Res Program, Bethesda, MD USA. RP Guenther, PM (reprint author), Ctr Nutr Policy & Promot, USDA, 3101 Pk Ctr Dr,Suite 1034, Alexandria, VA 22302 USA. EM Patricia.Guenther@cnpp.usda.gov NR 32 TC 125 Z9 128 U1 0 U2 20 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2008 VL 108 IS 11 BP 1854 EP 1864 DI 10.1016/j.jada.2008.08.011 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 368LK UT WOS:000260622400011 PM 18954575 ER PT J AU Guenther, PM Reedy, J Krebs-Smith, SM AF Guenther, Patricia M. Reedy, Jill Krebs-Smith, Susan M. TI Development of the Healthy Eating Index-2005 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB The Healthy Eating Index (HEI) is a measure of diet quality as specified by Federal dietary guidance, and publication of the Dietary Guidelines for Americans 2005 necessitated its revision. An interagency working group based the HEI-2005 on the food patterns found in My-Pyramid. Diets that meet the least restrictive of the food-group recommendations, expressed on a per 1,000 calorie basis, receive maximum scores for the nine adequacy components of the index: total fruit (5 points), whole fruit (5 points), total vegetables (5 points), dark green and orange vegetables and legumes (5 points), total grains (5 points), whole grains (5 points), milk (10 points), meat and beans (10 points), and oils (10 points). Lesser amounts are prorated linearly. Population probability densities were examined when setting the standards for minimum and maximum scores for the three moderation components: saturated fat (10 points), sodium (10 points), and calories from solid fats, alcoholic beverages (ie, beer, wine, and distilled spirits), and added sugars (20 points). Calories from solid fats, alcoholic beverages, and added sugars is a proxy for the discretionary calorie allowance. The 2005 Dietary Guideline for saturated fat and the Adequate Intake and Tolerable Upper Intake Level for sodium, expressed per 1,000 calories, were used when setting the standards for those components. Intakes between the maximum and minimum standards are prorated. The HEI-2005 is a measure of diet quality as described by the key diet-related recommendations of the 2005 Dietary Guidelines. It has a variety of potential uses, including monitoring the diet quality of the US population and subpopulations, evaluation of interventions, and research. C1 [Guenther, Patricia M.] Ctr Nutr Policy & Promot, USDA, Alexandria, VA 22302 USA. [Reedy, Jill; Krebs-Smith, Susan M.] Natl Canc Inst, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control, Bethesda, MD USA. RP Guenther, PM (reprint author), Ctr Nutr Policy & Promot, USDA, 3101 Pk Ctr Dr,Suite 1034, Alexandria, VA 22302 USA. EM Patricia.Guenther@cnpp.usda.gov NR 20 TC 261 Z9 269 U1 3 U2 31 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2008 VL 108 IS 11 BP 1896 EP 1901 DI 10.1016/j.jada.2008.08.016 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 368LK UT WOS:000260622400016 PM 18954580 ER PT J AU Houston, DK Schwartz, AV Cauley, JA Tylavsky, FA Simonsick, EM Harris, TB de Rekeneire, N Schwartz, GG Kritchevsky, SB AF Houston, Denise K. Schwartz, Ann V. Cauley, Jane A. Tylavsky, Frances A. Simonsick, Eleanor M. Harris, Tamara B. de Rekeneire, Nathalie Schwartz, Gary G. Kritchevsky, Stephen B. CA Health Aging & Body Composition TI Serum Parathyroid Hormone Levels Predict Falls in Older Adults with Diabetes Mellitus SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE PTH; falls; physical performance ID VITAMIN-D STATUS; COMMUNITY-DWELLING WOMEN; MUSCLE STRENGTH; NURSING-HOME; CYSTATIN-C; SECONDARY HYPERPARATHYROIDISM; AFRICAN-AMERICAN; BLACK-WOMEN; RISK; INJURIES AB To examine the association between serum parathyroid hormone (PTH) levels and incident falls in older adults with diabetes mellitus. Longitudinal analysis of incident falls over 1 year in a substudy of participants with diabetes mellitus in the Health, Aging and Body Composition Study. Pittsburgh, Pennsylvania, and Memphis, Tennessee. Well-functioning, community-dwelling black and white adults aged 70 to 79 with diabetes mellitus (N=472). Measured baseline serum PTH. Self-report of falls over the subsequent 12 months. Baseline physical performance and self-reported demographic, behavioral, and health status measures including kidney function, chronic conditions, and medication use. One-third (30.3%) of participants reported falling over 1 year of follow-up. Mean baseline serum PTH was 53.5 +/- 30.0 pg/mL in nonfallers and 62.6 +/- 46.2 pg/mL in fallers (P=.01). For every 1 standard deviation (36 pg/mL) increment in baseline serum PTH, there was approximately a 30% greater likelihood of reporting a fall in the subsequent year, after adjusting for age, sex, race, field center, alcohol consumption, body mass index, physical activity, and winter or spring season (adjusted odds ratio (aOR)=1.30, 95% confidence interval (CI)=1.06-1.59). Further adjustment for kidney function, chronic conditions, medication and supplement use, and physical performance attenuated the association slightly (aOR=1.26, 95% CI=1.01-1.58). A trend remained after additional adjustment for reported falls in the previous year. Higher serum PTH was associated with incident falls in older, well-functioning men and women with diabetes mellitus. Further investigation aimed at understanding the underlying mechanism for the association between serum PTH and falls is needed. C1 [Houston, Denise K.; Schwartz, Gary G.; Kritchevsky, Stephen B.] Wake Forest Univ, Med Ctr, Sch Med, Dept Internal Med,Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostatist, San Francisco, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Tennessee Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Harris, Tamara B.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Natl Inst Aging, Clin Res Branch, Baltimore, MD USA. [de Rekeneire, Nathalie] Div Diabet Translat, Centers Dis Control & Prevent, Atlanta, GA USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Schwartz, Gary G.] Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27157 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [de Rekeneire, Nathalie] Ctr Dis Control & Prevent, Div Diabet, Atlanta, GA USA. RP Houston, DK (reprint author), Wake Forest Univ, Med Ctr, Sch Med, Dept Internal Med,Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dhouston@wfubmc.edu RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Kritchevsky, Stephen/0000-0003-3336-6781 FU Merck Company; Eli Lilly Company; Pfizer Pharmaceuticals; Novartis Pharmaceuticals FX Jane A. Cauley has received research support from Merck & Company, Eli Lilly & Company, Pfizer Pharmaceuticals, and Novartis Pharmaceuticals. She has also received consulting fees from Eli Lilly & Company and Novartis Pharmaceuticals. NR 41 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2008 VL 56 IS 11 BP 2027 EP 2032 DI 10.1111/j.1532-5415.2008.01966.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 374SS UT WOS:000261064600006 PM 19016936 ER PT J AU Semba, RD Patel, KV Sun, K Guralnik, JM Ershler, WB Longo, DL Ferrucci, L AF Semba, Richard D. Patel, Kushang V. Sun, Kai Guralnik, Jack M. Ershler, William B. Longo, Dan L. Ferrucci, Luigi TI ASSOCIATION BETWEEN SERUM CARBOXYMETHYL-LYSINE, A DOMINANT ADVANCED GLYCATION END PRODUCT, AND ANEMIA IN ADULTS: THE BALTIMORE LONGITUDINAL STUDY OF AGING SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID N-EPSILON-(CARBOXYMETHYL)LYSINE; ERYTHROCYTES; PROTEINS; BLOOD; AGES C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA. [Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Biometry & Dermog, NIH, Bethesda, MD 20892 USA. [Ershler, William B.; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA. FU NIA NIH HHS [R01 AG027012, R01 AG027012-03, R01 AG029148, R01 AG029148-02] NR 10 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2008 VL 56 IS 11 BP 2145 EP 2147 DI 10.1111/j.1532-5415.2008.01968.x PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 374SS UT WOS:000261064600027 PM 19016950 ER PT J AU Kanapuru, B Posani, K Muller, D Ershler, WB AF Kanapuru, Bindu Posani, Karuna Muller, Denis Ershler, William B. TI DECREASED CANCER PREVALENCE IN THE NURSING HOME SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID FRAILTY; INTERLEUKIN-6; DISEASES C1 [Kanapuru, Bindu; Posani, Karuna; Muller, Denis; Ershler, William B.] NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kanapuru, B (reprint author), NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2008 VL 56 IS 11 DI 10.1111/j.1532-5415.2008.01864.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 374SS UT WOS:000261064600040 ER PT J AU Feero, WG Bigley, MB Brinner, KM AF Feero, W. Gregory Bigley, Mary Beth Brinner, Kristin M. CA Amer Hlth Information Community TI New Standards and Enhanced Utility for Family Health History Information in the Electronic Health Record: An Update from the American Health Information Community's Family Health History Multi-Stakeholder Workgroup SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PRIMARY-CARE AB Family health history is a complex, Multifaceted tool for assessing disease risk that can offer insight into the interplay between inherited and social factors relevant to patient care. Family health history tools in electronic health records can enable the user to collect, represent, and interpret structured data that properly supports clinical decisions. If these data can be made interoperable, important health information can be shared with minimal duplication of effort among entities involved in the Continuum of patient care. This paper reviews the efforts by the American Health Information Community's Family Health History Multi-Stakeholder Workgroup to create a core data set for family health history information and to determine requirements to promote incorporation of such information in electronic health records. The Workgroup is a component of the U.S. Department of Health and Human Services' Personalized Health Care Initiative. C1 [Feero, W. Gregory] NHGRI, Genom Healthcare Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bigley, Mary Beth] US Dept HHS, Off US Srug Gen, Washington, DC 20201 USA. [Brinner, Kristin M.] US Dept HHS, Personalized Hlth Care Initiat, Amer Assoc Adv Sci, Washington, DC 20201 USA. RP Feero, WG (reprint author), NHGRI, Genom Healthcare Branch, NIH, Dept Hlth & Human Serv, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM feerow@mail.nih.gov NR 16 TC 57 Z9 57 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 723 EP 728 DI 10.1197/jamia.M2793 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 372MK UT WOS:000260905500003 PM 18755994 ER PT J AU Del Fiol, G Haug, PJ Cimino, JJ Narus, SP Norlin, C Mitchell, JA AF Del Fiol, Guilherme Haug, Peter J. Cimino, James J. Narus, Scott P. Norlin, Chuck Mitchell, Joyce A. TI Effectiveness of Topic-specific Infobuttons: A randomized Controlled Trial SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATION-RETRIEVAL TECHNOLOGY; CLINICAL QUESTIONS; ONLINE EVIDENCE; MIXED METHODS; PHYSICIANS; IMPACT; NEEDS; CARE; KNOWLEDGE; SYSTEMS AB Objective: Infobuttons are decision support tools that provide links within electronic medical record systems to relevant content in online information resources. The aim of infobuttons is to help clinicians promptly meet their information needs. The objective of this Study was to determine whether infobutton links that direct to specific content topics ("topic links") are more effective than links that point to general overview content ("nonspecific links"). Design: Randomized controlled trial with a control and an intervention group. Clinicians in the control group had access to nonspecific links, while those in the intervention group had access to topic links. Measurements: Infobutton session duration, number of infobutton sessions, session success rate, and the self-reported impact that the infobutton session produced on decision making. Results: The analysis was performed On 90 Subjects and 3,729 infobutton sessions. Subjects in the intervention group spent 17.4% less time seeking for information (35.5 seconds vs. 43 seconds, p = 0.008) than those in the control group. Subjects in the intervention group used infobuttons 20.5% (22 sessions vs. 17.5 sessions, p = 0.21) more often than in the control group, but the difference was not significant. The information seeking success rate was equally high in both groups (89.4%, control vs. 87.2% intervention, p = 0.99). Subjects reported a high positive clinical impact (i.e., decision enhancement or knowledge update) in 62% of the sessions. Limitations: The exclusion Of users with a low frequency of infobutton use and the focus on medication-related information needs may limit the generalization of the results, The session outcomes measurement was based on clinicians' setf-assessment and therefore prone to bias. Conclusion: The results support the hypothesis that topic links are more efficient than nonspecific links regarding the time seeking for information. It is unclear whether the statistical difference demonstrated will result in a clinically significant impact. However, the overall results confirm previous evidence that infobuttons are effective at helping clinicians to answer questions at the point of care and demonstrate a modest incremental change in the efficiency of information delivery for routine users of this tool. C1 [Del Fiol, Guilherme; Haug, Peter J.; Narus, Scott P.; Mitchell, Joyce A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Del Fiol, Guilherme; Haug, Peter J.] Intermt Healthcare, Salt Lake City, UT USA. [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. [Norlin, Chuck] Univ Utah, Dept Pediat, Salt Lake City, UT USA. RP Del Fiol, G (reprint author), Intermt Healthcare, 4646 Lake Pk Blvd, Salt Lake City, UT USA. EM guilheme.delfiol@utah.edu OI Del Fiol, Guilherme/0000-0001-9954-6799; Cimino, James/0000-0003-4101-1622 FU NLM NIH HHS [1T15LM007124-10, R01 LM007593, R01-LM07593, T15 LM007124] NR 35 TC 31 Z9 31 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 752 EP 759 DI 10.1197/jamia.M2725 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 372MK UT WOS:000260905500007 PM 18755999 ER PT J AU Jackson, SN Ugarov, M Post, JD Egan, T Langlais, D Schultz, JA Woods, AS AF Jackson, Shelley N. Ugarov, Michael Post, Jeremy D. Egan, Thomas Langlais, Denis Schultz, J. Albert Woods, Amina S. TI A Study of Phospholipids by Ion Mobility TOFMS SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID FLIGHT MASS-SPECTROMETRY; BRAIN-TISSUE; MALDI; LIPIDOMICS; DEFICIENCY; SYSTEMS; MS AB Combining matrix-assisted laser desorption/ionization (MALDI) mass spectrometry with ion mobility (IM) results in the fast sorting of biomolecules in complex mixtures along trend lines. In this two-dimensional (2D) analysis of biological families, lipids, peptides, and nucleotides are separated from each other by differences in their ion mobility drift times in a timescale of hundreds of microseconds. Molecular ions of similar chemical type fall along trend lines when plotted in 2D plots of ion mobility drift time as a function of m/z. In this study, MALDI-IM MS is used to analyze species from all of the major phospholipid classes. Complex samples, including tissue extracts and sections, were probed to demonstrate the effects that radyl chain length, degree of unsaturation, and class/head group have upon an ion's cross section in the gas phase. We illustrate how these changes can be used to identify individual lipid species in complex Mixtures, as well as the effects of cationization on ion cross section and ionization efficiency. (J Am Soc Mass Spectrom 2008, 19, 1655-1662) (C) 2008 American Society for Mass Spectrometry C1 [Jackson, Shelley N.; Post, Jeremy D.; Woods, Amina S.] NIDA, IRP, NIH, Baltimore, MD 21224 USA. [Ugarov, Michael; Egan, Thomas; Langlais, Denis; Schultz, J. Albert] Ionwerks Inc, Houston, TX USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [N44DA-3-7727]; PHS HHS [HHSN271200677593C, HHSN271200677563C] NR 31 TC 52 Z9 52 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 2008 VL 19 IS 11 BP 1655 EP 1662 DI 10.1016/j.jasms.2008.07.005 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 378TD UT WOS:000261345900009 PM 18703352 ER PT J AU Cohen, SD Kimmel, PL Neff, R Agodoa, L Abbottt, KC AF Cohen, Scott D. Kimmel, Paul L. Neff, Robert Agodoa, Lawrence Abbottt, Kevin C. TI Association of Incident Gout and Mortality in Dialysis Patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol ID SERUM URIC-ACID; STAGE RENAL-DISEASE; CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; MIDDLE-AGED MEN; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR MORTALITY; RISK-FACTOR; FOLLOW-UP; METABOLIC SYNDROME AB Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study. C1 [Neff, Robert; Abbottt, Kevin C.] Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. [Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis, Washington, DC 20052 USA. [Agodoa, Lawrence] NIDDK, NIH, Bethesda, MD USA. [Neff, Robert; Abbottt, Kevin C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Abbottt, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 57 TC 39 Z9 42 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2008 VL 19 IS 11 BP 2204 EP 2210 DI 10.1681/ASN.2007111256 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 367YI UT WOS:000260588100021 PM 18508965 ER PT J AU Arlen, PM Bander, NH Hall, SJ AF Arlen, Philip M. Bander, Neil H. Hall, Simon J. TI Treatment of Biochemical Recurrence of Prostate Cancer With Granulocyte-Macrophage Colony-Stimulating Factor Secreting, Allogeneic, Cellular Immunotherapy COMMENTS SO JOURNAL OF UROLOGY LA English DT Editorial Material ID VACCINE C1 [Arlen, Philip M.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Bander, Neil H.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA. [Hall, Simon J.] Mt Sinai Sch Med, Dept Urol, New York, NY USA. RP Arlen, PM (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 5 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 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2008 VL 180 IS 5 BP 2017 EP 2018 DI 10.1016/j.juro.2008.07.127 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 361BH UT WOS:000260102000042 ER PT J AU McDermott, MM Ades, PA Dyer, A Guralnik, JM Kibbe, M Criqui, MH AF McDermott, Mary M. Ades, Philip A. Dyer, Alan Guralnik, Jack M. Kibbe, Melina Criqui, Michael H. TI Corridor-based functional performance measures correlate better with physical activity during daily life than treadmill measures in persons with peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID LOWER-EXTREMITY FUNCTION; CHRONIC HEART-FAILURE; 6-MINUTE WALK; INTERMITTENT CLAUDICATION; SUBSEQUENT DISABILITY; LEG SYMPTOMS; ASSOCIATION; DECLINE; UTILITY; INDEX AB Objective: To compare associations of physical activity during daily life with treadmill walking performance and corridor-based functional performance measures in persons with lower extremity peripheral arterial disease (PAD). Study Design: Cross-sectional. Subjects: One hundred fifty-six men and women with PAD who completed baseline measurements and were randomized into the study to improve leg circulation (SILC) exercise clinical trial. Main Outcome Measures. Participants completed a Gardner-Skinner treadmill protocol. Corridor-based functional performance measures were the 6-minute walk, walking velocity over four meters at usual and fastest pace, and the short physical performance battery (SPPB) (0-12 scale, 12 = best). Physical activity during daily life was measured continuously over 7 days with a Caltrac (Muscle Dynamics Fitness Network, Inc, Torrence, Calif) accelerometer. Results. Adjusting for age, gender, and race, higher levels of physical activity during daily life were associated with greater distance achieved in the 6-minute walk (P trend = .001), faster fast-paced four-meter walking velocity (P trend < .001 faster usual-paced four-meter walking speed (P trend = .027) and a higher SPPB (P trend = .005). The association of physical activity level with maximum treadmill walking distance did not reach statistical significance (P trend = .083). There were no associations of physical activity with treadmill distance to onset of leg symptoms (P trend = .795). Conclusion: Functional performance measures arc more strongly associated with physical activity levels during daily life than treadmill walking measures. (J Vasc Surg 2008;48:1231-7.) C1 [McDermott, Mary M.; Dyer, Alan; Kibbe, Melina] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Dyer, Alan; Kibbe, Melina] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Ades, Philip A.] Vermont Sch Med, Dept Med, Burlington, VT USA. [Guralnik, Jack M.] NIA, Demog & Biochem & Clin Res Branch, Lab Epidemiol, Bethesda, MD 20892 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Prevent Med, San Diego, CA 92103 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart Lung and Blood Institute [R01-HL073551]; National Center for Research Resources [RR-00048]; National Institutes of Health (NIH); Intramural Research Program; National Institutes on Aging; ClinicalTrials.gov Identifier [NCT00106327] FX Supported by R01-HL073551 from the National Heart Lung and Blood Institute and by grant #RR-00048 from the National Center for Research Resources, National Institutes of Health (NIH). Supported in part by the Intramural Research Program, National Institutes on Aging, NIH May 16, 2008. ClinicalTrials.gov Identifier: NCT00106327. NR 24 TC 51 Z9 51 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2008 VL 48 IS 5 BP 1231 EP 1237 DI 10.1016/j.jvs.2008.06.050 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 369WT UT WOS:000260725300023 PM 18829215 ER PT J AU Aitichou, M Saleh, S Kyusung, P Huggins, J O'Guinn, M Jahrling, P Ibrahim, S AF Aitichou, Mohamed Saleh, Sharron Kyusung, Park Huggins, John O'Guinn, Monica Jahrling, Peter Ibrahim, Sofi TI Dual-probe real-time PCR assay for detection of variola or other orthopoxviruses with dried reagents SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Orthopox virus; Smallpox; Variola; Monkeypox; Cowpox; Vaccinia; Taqman; PCR; Real-time PCR; Multiplex PCR; Dried PCR reagents ID SMALLPOX-VIRUS; ROCHE LIGHTCYCLER; MONKEYPOX; IDENTIFICATION; DNA; COWPOX AB A real-time, multiplexed polymerase chain reaction (PCR) assay based on dried PCR reagents was developed. Only variola virus could be specifically detected by a FAM (6-carboxyfluorescein)-labeled probe while camelpox, cowpox, monkeypox and vaccinia viruses could be detected by a TET (6-carboxytetramethylrhodamine)-labeled probe in a single PCR reaction. Approximately 25 copies of cloned variola virus DNA and 50 copies of genomic orthopoxviruses DNA could be detected with high reproducibility. The assay exhibited a dynamic range of seven orders of magnitude with a correlation coefficient value greater than 0.97. The sensitivity and specificity of the assay, as determined from 100 samples that contained nucleic acids from a multitude of bacterial and viral species were 96% and 98%, respectively. The limit of detection, sensitivity and specificity of the assay were comparable to standard real-time PCR assays with wet reagents. Employing a multiplexed format in this assay allows simultaneous discrimination of the variola virus from other closely related orthopoxviruses. Furthermore, the implementation of dried reagents in real-time PCR assays is an important step towards simplifying such assays and allowing their use in areas where cold storage is not easily accessible. (C) 2008 Elsevier B.V. All rights reserved. C1 [Aitichou, Mohamed; Saleh, Sharron; Huggins, John; O'Guinn, Monica; Ibrahim, Sofi] USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA. [Jahrling, Peter] NIAID, NIH, Bethesda, MD 20892 USA. [Kyusung, Park] Invitrogen Corp, Carlsbad, CA USA. RP Aitichou, M (reprint author), USA, Med Res Inst Infect Dis, Div Virol, 1425 Porter St,Ft Frederick, Frederick, MD 21702 USA. EM mohamed.aitichou@amedd.army.mil FU Defense Threat Reduction Agency [02-4-41-091] FX This work was supported by research program funds managed by the Defense Threat Reduction Agency grant #02-4-41-091. We thank Katheryn Kenyon for reviewing the manuscript. The mention of materials or products in this article does not constitute endorsement by the Department of Defense or the United States government. NR 28 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2008 VL 153 IS 2 BP 190 EP 195 DI 10.1016/j.jviromet.2008.07.018 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 367PV UT WOS:000260565200017 PM 18725245 ER PT J AU Gillim-Ross, L Santos, C Chen, ZY Aspelund, A Yang, CF Ye, D Jin, H Kemble, G Subbarao, K AF Gillim-Ross, Laura Santos, Celia Chen, Zhongying Aspelund, Amy Yang, Chin-Fen Ye, Dan Jin, Hong Kemble, George Subbarao, Kanta TI Avian Influenza H6 Viruses Productively Infect and Cause Illness in Mice and Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID A H5N1 VIRUSES; HONG-KONG; MOUSE MODEL; INTERSPECIES TRANSMISSION; SOUTHERN CHINA; POULTRY; HUMANS; PATHOGENESIS; CHICKENS; GENE AB Influenza pandemic preparedness has focused on influenza virus H5 and H7 subtypes. However, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. An H6 influenza virus was identified as a potential progenitor of the H5N1 viruses that emerged in Hong Kong in 1997. This virus continues to circulate in the bird population in Asia, and other H6 viruses are prevalent in birds in North America and Asia. The high rate of reassortment observed in influenza viruses and the prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic risk. Very little is known about the replicative capacity, immunogenicity, and correlates of protective immunity for low-pathogenicity H6 influenza viruses in mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza viruses and their abilities to replicate and induce a cross-reactive immune response in two animal models: mice and ferrets. The different H6 viruses replicated to different levels in the respiratory tracts of mice and ferrets, causing varied degrees of morbidity and mortality in these two models. H6 virus infection induced similar patterns of neutralizing antibody responses in mice and ferrets; however, species-specific differences in the cross-reactivity of the antibody responses were observed. Overall, cross-reactivity of neutralizing antibodies in H6 virus-infected mice did not correlate well with protection against heterologous wild-type H6 viruses. However, we have identified an H6 virus that induces protective immunity against viruses in the North American and Eurasian lineages. C1 [Gillim-Ross, Laura; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Chen, Zhongying; Aspelund, Amy; Yang, Chin-Fen; Ye, Dan; Jin, Hong; Kemble, George] MedImmune, Mountain View, CA 94043 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU NIAID, NIH; Laboratory of Infectious Diseases, NIAID; MedImmune, Inc FX This research was supported by the Intramural Research Program of the NIAID, NIH. This research was performed under a Cooperative Research and Development Agreement (CRADA no. AI-0155) between the Laboratory of Infectious Diseases, NIAID, and MedImmune, Inc.; We thank Jadon Jackson, the staff of SoBran Inc., and the Comparative Medicine Branch, NIAID, for excellent technical support for animal work. We also thank Robert G. Webster for providing the virus isolates used in this study. NR 48 TC 53 Z9 61 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2008 VL 82 IS 21 BP 10854 EP 10863 DI 10.1128/JVI.01206-08 PG 10 WC Virology SC Virology GA 361EF UT WOS:000260109600051 PM 18715930 ER PT J AU Demberg, T Boyer, JD Malkevich, N Patterson, LJ Venzon, D Summers, EL Kalisz, I Kalyanaraman, VS Lee, EM Weiner, DB Robert-Guroff, M AF Demberg, Thorsten Boyer, Jean D. Malkevich, Nina Patterson, L. Jean Venzon, David Summers, Ebonita L. Kalisz, Irene Kalyanaraman, V. S. Lee, Eun Mi Weiner, David B. Robert-Guroff, Marjorie TI Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251 Mucosal Challenge SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; HOST-RANGE MUTANT; REGIMEN INDUCES BROAD; MEMORY T-CELLS; RHESUS MACAQUES; DISEASE PROGRESSION; SHIV89.6P CHALLENGE; NEUTRALIZING ANTIBODIES; PROTECTIVE EFFICACY; VIRAL REPLICATION AB Previously, combination DNA/nonreplicating adenovirus (Ad)-or poxvirus-vectored vaccines have strongly protected against SHIV89.6P, DNAs expressing cytokines have modulated immunity elicited by DNA vaccines, and replication-competent Ad-recombinant priming and protein boosting has strongly protected against simian immunodeficiency virus (SIV) challenge. Here we evaluated a vaccine strategy composed of these promising components. Seven rhesus macaques per group were primed twice with multigenic SIV plasmid DNA with or without interleukin-12 (IL-12) DNA or IL-15 DNA. After a multigenic replicating Ad-SIV immunization, all groups received two booster immunizations with SIV gp140 and SIV Nef protein. Four control macaques received control DNA plasmids, empty Ad vector, and adjuvant. All vaccine components were immunogenic, but the cytokine DNAs had little effect. Macaques that received IL-15-DNA exhibited higher peak anti-Nef titers, a more rapid anti-Nef anamnestic response postchallenge, and expanded CD8(CM) T cells 2 weeks postchallenge compared to the DNA-only group. Other immune responses were indistinguishable between groups. Overall, no protection against intrarectal challenge with SIVmac251 was observed, although immunized non-Mamu-A*01 macaques as a group exhibited a statistically significant 1-log decline in acute viremia compared to non-Mamu-A*01 controls. Possible factors contributing to the poor outcome include administration of cytokine DNAs to sites different from the Ad recombinants (intramuscular and intratracheal, respectively), too few DNA priming immunizations, a suboptimal DNA delivery method, failure to ensure delivery of SIV and cytokine plasmids to the same cell, and instability and short half-life of the IL-15 component. Future experiments should address these issues to determine if this combination approach is able to control a virulent SIV challenge. C1 [Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Boyer, Jean D.; Weiner, David B.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Kalisz, Irene; Kalyanaraman, V. S.; Lee, Eun Mi] Adv BioSci Labs Inc, Kensington, MD 20895 USA. RP Robert-Guroff, M (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov RI Weiner, David/H-8579-2014 FU National Institutes of Health National Cancer Institute FX We thank Ronald C. Desrosiers, New England National Primate Research Center, and Nancy Miller, Division of AIDS, NIAID, for the SIVmac251 challenge virus, Barbara Felber and George Pavlakis for the DNA plasmids originally provided to the Weiner laboratory, and Ersell Richardson and Kris Aldrich for their technical assistance. We also acknowledge the contributions of Sanjeev Kumar, who sadly passed away during the course of this study. Complete sets of SIVmac239 Gag and SIVmac239 Env peptides were provided by the AIDS Research and Reference Reagent Program, NIAID, NIH.; This work was supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute. NR 66 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2008 VL 82 IS 21 BP 10911 EP 10921 DI 10.1128/JVI.01129-08 PG 11 WC Virology SC Virology GA 361EF UT WOS:000260109600057 PM 18753198 ER PT J AU Willcox, BJ Willcox, DC Ferrucci, L AF Willcox, Bradley J. Willcox, D. Craig Ferrucci, Luigi TI Secrets of Healthy Aging and Longevity From Exceptional Survivors Around the Globe: Lessons From Octogenarians to Supercentenarians SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID OKINAWAN CENTENARIANS; GENETIC-DETERMINANTS; FUNCTIONAL STATUS; OLD-AGE; POPULATIONS; LIFE; PREVALENCE; DISABILITY; PHENOTYPES; MORBIDITY C1 [Willcox, Bradley J.; Willcox, D. Craig] Pacific Hlth Res Inst, Honolulu, HI 96813 USA. [Willcox, Bradley J.] Queens Med Ctr, Dept Res Planning & Dev, Honolulu, HI USA. [Willcox, Bradley J.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. [Willcox, Bradley J.; Willcox, D. Craig] Okinawa Res Ctr Longev Sci, Okinawa, Japan. [Willcox, D. Craig] Okinawa Int Univ, Dept Human Welf, Okinawa, Japan. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Willcox, BJ (reprint author), Pacific Hlth Res Inst, 846 S Hotel St,Suite 201, Honolulu, HI 96813 USA. EM bjwillcox@phrihawaii.org FU Intramural NIH HHS [Z01 AG000015-49]; NIA NIH HHS [R01 AG027060, R01AG027060-01] NR 61 TC 22 Z9 22 U1 2 U2 7 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2008 VL 63 IS 11 BP 1181 EP 1185 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 379KR UT WOS:000261395600006 PM 19038832 ER PT J AU Delmonico, MJ Zmuda, JM Taylor, BC Cauley, JA Harris, TB Martini, TM Schwartz, A Li, R Roth, SM Hurley, BF Bauer, DC Ferrell, RE Newman, AB AF Delmonico, Matthew J. Zmuda, Joseph M. Taylor, Brent C. Cauley, Jane A. Harris, Tamara B. Martini, Todd M. Schwartz, Ann Li, Rongling Roth, Stephen M. Hurley, Ben F. Bauer, Douglas C. Ferrell, Robert E. Newman, Anne B. CA Health ABC & MrOs Res Grp TI Association of the ACTN3 Genotype and Physical Functioning With Age in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Genetics; Elderly; Sarcopenia; Skeletal muscle ID LOWER-EXTREMITY FUNCTION; BODY-COMPOSITION; MUSCLE MASS; ALPHA-ACTININ-3 DEFICIENCY; OSTEOPOROTIC FRACTURES; ATHLETIC PERFORMANCE; STRENGTH; WOMEN; MEN; DISABILITY AB Objective. The purpose of this study was to examine the association of the alpha-actinin-3 (ACTN3) R577X polymorphism on muscle function and physical performance in older adults. Methods. We measured knee extensor torque, midthigh muscle cross-sectional area, muscle quality, short physical performance battery score, and 400-meter walk time at baseline and after 5 years in white older adults aged 70-79 years in the Health, Aging and Body Composition Study cohort (n = 1367). Incident persistent lower extremity limitation (PLL) over 5 years was additionally assessed. We also examined white men in the Osteoporotic Fractures in Men Study, a longitudinal, observational cohort (n = 1152) of men 65 years old or older as a validation cohort for certain phenotypes. Results. There were no significant differences between genotype groups in men or women for adjusted baseline phenotypes. Male X-homozygotes had a significantly greater adjusted 5-year increase in their 400-meter walk time compared to R-homozygotes and heterozygotes (p = .03). In women, X-homozygotes had a similar to 35% greater risk of incident PILL compared to R-homozygotes (hazard ratio = 0.65, 95% confidence interval = 0.44-0.94). There were no other significant associations between any of the phenotypes and ACTN3 genotype with aging in either cohort. Conclusions. The ACTN3 polymorphism may influence declines in certain measures of physical performance with aging in older white adults, based on longitudinal assessments. However, the influence of the ACTN3 R577X polymorphism does not appear to have a strong effect on skeletal muscle-related phenotypes based on the strength and consistency of the associations and lack of replication with regard to specific phenotypes. C1 [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Delmonico, Matthew J.; Zmuda, Joseph M.; Cauley, Jane A.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Zmuda, Joseph M.; Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15260 USA. [Taylor, Brent C.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Martini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Schwartz, Ann] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Li, Rongling] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Roth, Stephen M.; Hurley, Ben F.] Univ Maryland, Sch Publ Hlth, Dept Kinesiol, College Pk, MD 20742 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Delmonico, MJ (reprint author), Univ Rhode Isl, Dept Kinesiol, 210 Flag Rd,Room 120, Kingston, RI 02881 USA. EM delmonico@uri.edu RI Taylor, Brent/A-8069-2009; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Taylor, Brent/0000-0002-2140-8377; Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Roth, Stephen/0000-0002-7841-3695 FU National Institutes of Health (NIH), NIA [1-AG-6-2101, 1-AG-6-2103, 1-AG-6-2106, U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140, R01-AR051124, R01-AG021024, AG-022791]; National Center for Research Resources (NCRR) [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; Department of Epidemiology, University of Pittsburgh FX The Health ABC study was supported by research contracts #1-AG-6-2101, #1-AG-6-2103, and #1-AG-6-2106 from the National Institute on Aging (NIA). This study was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), NIA. The MrOS Study is supported by NIH funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the NIA, the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Additional Support was also provided by NIAMS grants R01-AR051124, R01-AG021024, AG-022791, the NIA Aging Training Grant, and a grant from the Department of Epidemiology, University of Pittsburgh. NR 33 TC 39 Z9 40 U1 0 U2 6 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2008 VL 63 IS 11 BP 1227 EP 1234 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 379KR UT WOS:000261395600012 PM 19038838 ER PT J AU Alley, DE Ferrucci, L Barbagallo, M Studenski, SA Harris, TB AF Alley, Dawn E. Ferrucci, Luigi Barbagallo, Mario Studenski, Stephanie A. Harris, Tarnara B. TI A Research Agenda: The Changing Relationship Between Body Weight and Health in Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER OBESE ADULTS; MASS INDEX; LONGITUDINAL CHANGES; KNEE OSTEOARTHRITIS; PHYSICAL-DISABILITY; MUSCLE STRENGTH; SKELETAL-MUSCLE; ELDERLY-MEN; MORTALITY; WOMEN C1 [Ferrucci, Luigi] Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,NIA ASTRA Unit, Baltimore, MD 21225 USA. [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Barbagallo, Mario] Univ Palermo, I-90133 Palermo, Italy. [Studenski, Stephanie A.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15260 USA. [Studenski, Stephanie A.] Pittsburgh Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Pittsburgh, PA USA. [Harris, Tarnara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,NIA ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov OI BARBAGALLO, MARIO/0000-0002-1349-6530 FU Intramural NIH HHS [Z01 AG000015-49] NR 40 TC 15 Z9 15 U1 1 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2008 VL 63 IS 11 BP 1257 EP 1259 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 379KR UT WOS:000261395600016 PM 19038842 ER PT J AU Mottl, AK Vupputuri, S Cole, SA Almasy, L Goring, HHH Diego, VP Laston, S Franceschini, N Shara, NM Lee, ET Best, LG Fabsitz, RR MacCluer, JW Umans, JG North, KE AF Mottl, Amy K. Vupputuri, Suma Cole, Shelley A. Almasy, Laura Goering, Harald H. H. Diego, Vincent P. Laston, Sandra Franceschini, Nora Shara, Nawar M. Lee, Elisa T. Best, Lyle G. Fabsitz, Richard R. MacCluer, Jean W. Umans, Jason G. North, Kari E. TI Linkage analysis of glomerular filtration rate in American Indians SO KIDNEY INTERNATIONAL LA English DT Article DE glomerular filtration rate; genetic epidemiology; linkage analysis ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; GENES-CONTROLLING VARIATION; URINARY ALBUMIN EXCRETION; STRONG HEART FAMILY; DIABETIC-NEPHROPATHY; CARDIOVASCULAR-DISEASE; AFRICAN-AMERICANS; BLOOD-PRESSURE; COLLABORATIVE APPROACH AB American Indians have a disproportionately high rate of kidney disease likely due to a combination of environmental and genetic factors. We performed a genome wide scan of estimated glomerular filtration rate in 3665 participants of the Strong Heart Family Study to localize genes influencing kidney disease risk factors. The participants were men and women from 13 American Indian tribes recruited from 3 centers located in Arizona, the Dakotas and Oklahoma. Multipoint variance component linkage analysis was performed for each center and on the entire cohort after controlling for center effects. Modeling strategies that incorporated age, gender and interaction terms ( model 1) and another that also controlled for diabetes mellitus, systolic and diastolic blood pressure, body mass index, low density and high density lipoproteins, triglycerides and smoking status ( model 2) were used. Significant evidence for linkage in the Arizona group was found on chromosome 12p12.2 at 39cM ( nearest marker D12S310) using model 1. Additional loci with very suggestive evidence for linkage were detected at 1p36.31 for all groups using both models and at 2q33.3 and 9q34.2 for the Dakotas group each using model 1. No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. This evidence for linkage of a quantitative trait locus influencing estimated glomerular filtration rate to a region of chromosome 12p in a large cohort of American Indians will be worth studying in more detail in the future. C1 [Mottl, Amy K.; Vupputuri, Suma] Univ N Carolina, Kidney Ctr, Sch Med, Chapel Hill, NC 27599 USA. [Vupputuri, Suma; Franceschini, Nora; North, Kari E.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Cole, Shelley A.; Almasy, Laura; Goering, Harald H. H.; Diego, Vincent P.; Laston, Sandra; MacCluer, Jean W.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Shara, Nawar M.; Umans, Jason G.] NHLBI, MedStar Res Inst, Bethesda, MD 20892 USA. [Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Fabsitz, Richard R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Umans, Jason G.] Georgetown Univ, Gen Clin Res Ctr, Dept Med, Div Obstet & Gynecol, Washington, DC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. RP Mottl, AK (reprint author), Univ N Carolina, Kidney Ctr, Sch Med, CB 7155,6008 Burnett Womack Bldg, Chapel Hill, NC 27599 USA. EM amy_mottl@med.unc.edu OI Mottl, Amy/0000-0002-4258-1726; Diego, Vincent/0000-0002-0007-2085 FU National Heart, Lung and Blood Institute [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521]; National Institutes of Health [MH059490] FX We thank the Strong Heart Family Study participants. Without their participation, this project would not have been possible. In addition, the cooperation of the Indian Health Service hospitals and clinics, and the directors of the SHS clinics, and the many collaborators and staff of the Strong Heart Study have made this project possible. This research was funded by a cooperative agreement that includes grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521 from the National Heart, Lung and Blood Institute. Development of SOLAR and the methods implemented in it are supported by US Public Health Service grant MH059490 from the National Institutes of Health. The views expressed in this paper are those of the authors and do not necessarily reflect those of the Indian Health Service. NR 58 TC 17 Z9 17 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2008 VL 74 IS 9 BP 1185 EP 1191 DI 10.1038/ki.2008.410 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 360MJ UT WOS:000260061300013 PM 18854848 ER PT J AU Jacob, VA Harbaugh, CM Dietz, JR Fenton, RA Kim, SM Castrop, H Schnermann, J Knepper, MA Chou, CL Anderson, SA AF Jacob, Vinitha A. Harbaugh, Calista M. Dietz, John R. Fenton, Robert A. Kim, Soo M. Castrop, Hayo Schnermann, Jurgen Knepper, Mark A. Chou, Chung-Lin Anderson, Stasia A. TI Magnetic resonance imaging of urea transporter knockout mice shows renal pelvic abnormalities SO KIDNEY INTERNATIONAL LA English DT Article DE hydronephrosis; renal pelvic reflux; blood pressure ID SALT-SENSITIVE HYPERTENSION; POLYCYSTIC KIDNEY-DISEASE; CONCENTRATING ABILITY; LACKING AQUAPORIN-1; HYDRONEPHROSIS; URINE; MODEL; RATS; MRI AB Many transgenic and knockout mice with increased urine flow have structural abnormalities of the renal pelvis and inner medulla. Here, we used high resolution contrast enhanced T1-weighted magnetic resonance imaging of mice whose urea transporters UT-A1 and UT-A3 were deleted (UT-A1/3(-/-) mice) as a model for the in vivo study of such abnormalities. Three distinct variations in the appearance of the renal pelvis were found. These included normal kidneys with no accumulation of contrast agent in the renal pelvis; infrequent frank right-sided unilateral hydronephrosis with marked atrophy of the renal medulla; and a renal pelvic reflux pattern characterized by the presence of contrast agent in the renal pelvis surrounding the renal inner medulla but no substantial atrophy of the medulla. This last pattern was found in most of the advanced age UT-A1/3(-/-) mice and in aquaporin-1 knockout mice. The UT-A1/3(-/-) mice also had increased mean arterial blood pressures. Feeding the mice a low protein diet did not prevent development of their renal pelvic abnormalities. Our studies show that real time imaging of renal pelvic structure in genetically manipulated mice provides a tool for the non-destructive, temporal evaluation of kidney structure. C1 [Jacob, Vinitha A.; Harbaugh, Calista M.; Knepper, Mark A.; Chou, Chung-Lin] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Dietz, John R.] Univ S Florida, Dept Physiol & Biophys, Tampa, FL USA. [Fenton, Robert A.] Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Aarhus, Denmark. [Kim, Soo M.; Castrop, Hayo; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD 20892 USA. [Anderson, Stasia A.] NHLBI, Anim MRI Imaging Core, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM knepperm@nhlbi.nih.gov FU NHLBI [Z01-HL00185]; NIDDK [Z01-DK043408] FX We thank Aneeka Chaudhry for her excellent technical assistance with MRI imaging. The work described in this paper was supported by the Intramural budgets of NHLBI (Z01-HL00185) and NIDDK (Z01-DK043408). NR 23 TC 14 Z9 14 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2008 VL 74 IS 9 BP 1202 EP 1208 DI 10.1038/ki.2008.392 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 360MJ UT WOS:000260061300016 PM 18854850 ER PT J AU Motoyoshi, Y Matsusaka, T Saito, A Pastan, I Willnow, TE Mizutani, S Ichikawa, I AF Motoyoshi, Yaeko Matsusaka, Taiji Saito, Akihiko Pastan, Ira Willnow, Thomas E. Mizutani, Shuki Ichikawa, Iekuni TI Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY OCT 31-NOV 05, 2007 CL San Francisco, CA SP Amer Soc Nephrol DE chronic kidney disease; endocytosis; focal segmental glomerulosclerosis; nephrotic syndrome ID SEGMENTAL GLOMERULOSCLEROSIS; RENAL AQUAPORINS; TRANSGENIC MICE; KAPPA-B; EXPRESSION; ALBUMIN; GENE; APOPTOSIS; OVERLOAD; DISEASE AB Megalin, a member of the LDL receptor family, is expressed on the apical membrane of proximal tubules and serves as an endocytic scavenger of filtered proteins and hence might contribute to the tubule injury as a consequence of glomerular disease. To study its role, we crossed megalin knockout mosaic mice (lacking megalin expression in 60% of proximal tubule cells) with NEP25 mice (a transgenic line expressing human CD25 in the podocyte). Treatment of this transgenic mouse with the immunotoxin causes nephrotic syndrome, focal segmental glomerulosclerosis and tubule-interstitial injury. Following this treatment, the double transgenic mice had massive non-selective proteinuria and mild glomerular and tubular injury. Comparison of megalin-containing to megalin-deficient proximal tubule cells within each kidney showed that albumin, immunoglobulin light chain, IgA and IgG were preferentially accumulated in proximal tubule cells expressing megalin. Tubule injury markers such as heme-oxygenase-1, monocyte chemoattractant protein-1 and cellular apoptosis were also preferentially found in these megalin-expressing cells. These results show that megalin plays a pivotal role in the reabsorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury. C1 [Motoyoshi, Yaeko; Ichikawa, Iekuni] Tokai Univ, Sch Med, Dept Bioeth, Isehara, Kanagawa 2591193, Japan. [Motoyoshi, Yaeko; Mizutani, Shuki] Tokyo Med & Dent Univ, Grad Sch Med, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo, Japan. [Matsusaka, Taiji; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37212 USA. [Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan. [Saito, Akihiko] Niigata Univ, Grad Sch Med & Dent Sci, Dept Appl Mol Med, Niigata, Japan. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Willnow, Thomas E.] Max Delbruck Ctr Mol Med, Berlin, Germany. RP Ichikawa, I (reprint author), Tokai Univ, Sch Med, Dept Bioeth, 143 Shimo Kasuya, Isehara, Kanagawa 2591193, Japan. EM ichikawaMD@aol.com FU Intramural NIH HHS [Z01 BC008753-25] NR 32 TC 54 Z9 55 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2008 VL 74 IS 10 BP 1262 EP 1269 DI 10.1038/ki.2008.405 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 367DI UT WOS:000260532300008 PM 18769366 ER PT J AU O'Meara, WP Bejon, P Mwangi, TW Okiro, EA Peshu, N Snow, RW Newton, CRJC Marsh, K AF O'Meara, Wendy P. Bejon, Phillip Mwangi, Tabitha W. Okiro, Emelda A. Peshu, Norbert Snow, Robert W. Newton, Charles R. J. C. Marsh, Kevin TI Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya SO LANCET LA English DT Article ID PLASMODIUM-FALCIPARUM TRANSMISSION; INSECTICIDE-TREATED BEDNETS; AFRICAN CHILDREN; REDUCING TRANSMISSION; PROGNOSTIC INDICATORS; CLINICAL PRESENTATION; CHILDHOOD MALARIA; SEVERE DISEASE; DRUG POLICY; COAST AB Background As efforts to control malaria are expanded across the world, understanding the role of transmission intensity in determining the burden of clinical malaria is crucial to the prediction and measurement of the effectiveness of interventions to reduce transmission. Furthermore, studies comparing several endemic sites led to speculation that as transmission decreases morbidity and mortality caused by severe malaria might increase. We aimed to assess the epidemiological characteristics of malaria in Kilifi, Kenya, during a period of decreasing transmission intensity. Methods We analyse 18 years (1990-2007) of surveillance data from a paediatric ward in a malaria-endemic region of Kenya. The hospital has a catchment area of 250000 people. Clinical data and blood-film results for more than 61000 admissions are reported. Findings Hospital admissions for malaria decreased from 18-43 per 1000 children in 2003 to 3.42 in 2007. Over 18 years of surveillance, the incidence of cerebral malaria initially increased; however, malaria mortality decreased overall because of a decrease in incidence of severe malarial anaemia since 1997 (4.75 to 0.37 per 1000 children) and improved survival among children admitted with non-severe malaria. Parasite prevalence, the mean age of children admitted with malaria, and the proportion of children with cerebral malaria began to change 10 years before hospitalisation for malaria started to fall. Interpretation Sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies. Changes in transmission might not lead to immediate reductions incidence of clinical disease. However, longitudinal data do not indicate that reductions in transmission intensity lead to transient increases in morbidity and mortality. Funding Wellcome Trust, Kenya Medical Research Institute. C1 [O'Meara, Wendy P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Okiro, Emelda A.; Snow, Robert W.] Kenya Govt Med Res Ctr, Wellcome Trust Collaborat Program, Nairobi, Kenya. [Bejon, Phillip; Snow, Robert W.; Marsh, Kevin] Univ Oxford, John Radcliffe Hosp, Ctr Trop Med, Nuffield Dept Clin Med, Oxford OX3 9DU, England. [Newton, Charles R. J. C.] UCL, Inst Child Hlth, London, England. [O'Meara, Wendy P.; Bejon, Phillip; Mwangi, Tabitha W.; Peshu, Norbert; Newton, Charles R. J. C.; Marsh, Kevin] Kenya Govt Med Res Ctr, Ctr Geog Med Res, Wellcome Trust Collaborat Program, Kilifi, Kenya. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov OI Newton, Charles/0000-0002-6999-5507 FU Fogarty International Center; Wellcome Trust FX This work is published with the permission of the Director of Kenya Medical Research Institute. We wish to thank all the clinical, field, and laboratory staff at the Kenya Medical Research Institute-Wellcome Must Programme who made this study possible. WPO is funded by the Fogarty International Center. CRJCN is funded by the Wellcome Trust. RWS is a Wellcome Trust Principal Research Fellow (#079080). NR 38 TC 263 Z9 264 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 1 PY 2008 VL 372 IS 9649 BP 1555 EP 1562 DI 10.1016/S0140-6736(08)61655-4 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 367ZG UT WOS:000260590500027 PM 18984188 ER PT J AU Morens, DM Folkers, GK Fauci, AS AF Morens, David M. Folkers, Gregory K. Fauci, Anthony S. TI Emerging infections: a perpetual challenge SO LANCET INFECTIOUS DISEASES LA English DT Review ID PANDEMIC INFLUENZA; BIOLOGICAL WARFARE; EPIDEMIC ANTHRAX; DISEASES; ORIGIN; PERSPECTIVE; EMERGENCE; MORTALITY; OUTBREAK; PLAGUES AB Emerging and re-emerging infectious diseases, and their determinants, have recently attracted substantial scientific and popular attention. HIV/AIDS, severe acute respiratory syndrome, H5N1 avian influenza, and many other emerging diseases have either proved fatal or caused international alarm. Common and interactive co-determinants of disease emergence, including population growth, travel, and environmental disruption, have been increasingly documented and studied. Are emerging infections a new phenomenon related to modern life, or do more basic determinants, transcending time, place, and human progress, govern disease generation? By examining a number of historically notable epidemics, we suggest that emerging diseases, similar in their novelty, impact, and elicitation of control responses, have occurred throughout recorded history. Fundamental determinants, typically acting in concert, seem to underlie their emergence, and infections such as these are likely to continue to remain challenges to human survival. C1 [Morens, David M.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Room 7A10,31 Ctr Dr, Bethesda, MD 20892 USA. EM dm270q@nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 87 TC 66 Z9 71 U1 1 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD NOV PY 2008 VL 8 IS 11 BP 710 EP 719 DI 10.1016/S1473-3099(08)70256-1 PG 10 WC Infectious Diseases SC Infectious Diseases GA 365EK UT WOS:000260388500020 PM 18992407 ER PT J AU Simon-Sanchez, J Singleton, A AF Simon-Sanchez, Javier Singleton, Andrew TI Genome-wide association studies in neurological disorders SO LANCET NEUROLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; PERIODIC LIMB MOVEMENTS; GENETIC RISK-FACTOR; PARKINSON-DISEASE; SUSCEPTIBILITY GENE; MULTIPLE-SCLEROSIS; ISCHEMIC-STROKE; REVEALS; VARIANTS; RELEASE AB Background During the past decade, the genetic causes of monogenic forms of disease have been successfully defined; this work has helped the progression of basic scientific investigation into many disorders, and has helped to characterise several molecular biological processes. An important goal of genetic research is to extend this work and define genetic risk factor loci for complex disorders. The aim is for these data not only to offer further basic understanding of the disease process, but also to provide the opportunity to obtain genetic risk assessments that could be generalised to the public. Recent developments The development of resources such as the Human Genome Project and the international Human Haplotype Map Project, coupled with technological advances in ultra-high-throughput genotyping, have provided the basis for genome-wide association studies (GWAS). This approach has been successful for several complex disorders in a short time. Although GWAS are still a new method, these studies have been used for a small number of neurological disorders and, despite varied results for these conditions, GWAS can usefully show the power and limitations of this approach. Where next? GWAS have the potential to show and emphasise common genetic variability associated with disease. However, a challenge of this approach is that large sample series and considerable resources are required. One important consideration will be the interpretation of the results of GWAS in a clinically meaningful way and to discern the implications for all therapy areas, including neurological disorders; this challenge will require specialised skills and resources from both the medical and the scientific communities. C1 [Simon-Sanchez, Javier; Singleton, Andrew] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Simon-Sanchez, Javier] CSIC, Inst Biomed, Dept Genom & Prote, Unidad Genet Mol, Valencia, Spain. [Singleton, Andrew] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Singleton, A (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU National Institute on Aging; National Institutes of Health; Department of Health and Human Services; Intramural project [Z01 AG000949-02] FX This work was supported by the Intramural Research Program of the National Institute on Aging, the National Institutes of Health, and the Department of Health and Human Services, and relates to concepts developed under Intramural project Z01 AG000949-02. NR 28 TC 23 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2008 VL 7 IS 11 BP 1067 EP 1072 DI 10.1016/S1474-4422(08)70241-2 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 370EP UT WOS:000260745800018 PM 18940696 ER PT J AU Klier, M Anastasov, N Hermann, A Meindl, T Angermeier, D Raffeld, M Fend, F Quintanilla-Martinez, L AF Klier, M. Anastasov, N. Hermann, A. Meindl, T. Angermeier, D. Raffeld, M. Fend, F. Quintanilla-Martinez, L. TI Specific lentiviral shRNA-mediated knockdown of cyclin D1 in mantle cell lymphoma has minimal effects on cell survival and reveals a regulatory circuit with cyclin D2 SO LEUKEMIA LA English DT Article DE cyclin D1; cyclin D1 knockdown; MCL; lentiviral infection ID MESSENGER-RNA LEVELS; MOLECULAR PATHOGENESIS; MULTIPLE-MYELOMA; EXPRESSION; APOPTOSIS; GENES; OVEREXPRESSION; PROLIFERATION; INDUCTION; PERSPECTIVES AB Cyclin D1 overexpression is the hallmark of mantle cell lymphoma (MCL). However, the importance of cyclin D1 in the maintenance and progression of the disease remains to be defined. The aim of this study was to elucidate the role of cyclin D1 overexpression using an efficient cyclin D1-shRNA and a lentiviral system in well-characterized MCL cell lines. Surprisingly, the knockdown of cyclin D1 led to a moderate retardation in growth, without induction of apoptosis. The cyclin D1-shRNA-transduced MCL cells showed a 15% shift from S phase to G(1) phase of the cell cycle, a weak induction of p27(Kip1), decreased Rb (Ser807/811) phosphorylation, and a consistent upregulation of cyclin D2 mRNA and protein expression. However, double knockdown of cyclins D1 and D2 did not intensify the effects observed with cyclin D1 knockdown alone. These data suggest that the moderate effects of cyclin D1 downregulation on survival and proliferation are likely the result of compensatory cyclin-independent mechanisms governing proliferation or alternatively, secondary genetic events that make cyclin D1 dispensable. These findings have important implications for MCL therapy, as strategies targeting only cyclin D1 function might be hampered by compensatory regulatory mechanisms, resulting in a low probability of treatment response. C1 [Klier, M.; Anastasov, N.; Angermeier, D.; Quintanilla-Martinez, L.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Pathol, D-85764 Neuherberg, Germany. [Hermann, A.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Stem Cell Res, D-85764 Neuherberg, Germany. [Meindl, T.] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Toxicol, D-85764 Neuherberg, Germany. [Raffeld, M.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Fend, F.] Univ Tubingen, Inst Pathol, Tubingen, Germany. RP Quintanilla-Martinez, L (reprint author), German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Pathol, Bldg 35,Room 2055,Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM quintanilla-fend@helmholtz-muenchen.de RI Anastasov, Natasa/M-9848-2014 OI Anastasov, Natasa/0000-0002-4088-1119 FU Mantle cell lymphoma Consortium; Lymphoma Research foundation FX We are grateful to Dr Dolors Colomer (University of Barcelona) for donating some of the MCL cell lines used in this study. We thank Dr Ludger Hengst (University of Innsbruck) for donating pSuper vector and Ulrike Reich for her excellent technical assistance. This study was supported in part by-grant from the Mantle cell lymphoma Consortium, Lymphoma Research foundation (to LQ-M). LQ-M, FF and MR designed the research; MK, NA, TM, AH and DA performed the research; and LQ-M, MK, FF and MR drafted the paper. NR 36 TC 49 Z9 49 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2008 VL 22 IS 11 BP 2097 EP 2105 DI 10.1038/leu.2008.213 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 371LM UT WOS:000260832800014 PM 18685613 ER PT J AU Lu, HB Yang, SL Zuo, YT Demny, S Stein, EA Yang, YH AF Lu, Hanbing Yang, Shaolin Zuo, Yantao Demny, Steven Stein, Elliot A. Yang, Yihong TI Real-time animal functional magnetic resonance imaging and its application to neurophamacological studies SO MAGNETIC RESONANCE IMAGING LA English DT Article DE Real-time MRI; Manganese-enhanced MRI; Functional MRI; phMR; Cocaine ID HUMAN BRAIN; RAT-BRAIN; MRI; FMRI; COCAINE; ACTIVATION; RESPONSES; BOLD; MEMRI; PHYSIOLOGY AB In pharmacological magnetic resonance imaging (phMRI) with anesthetized animals, there is usually only a single time window to observe the dynamic signal change to an acute drug administration since subsequent drug injections are likely to result in altered response properties (e.g., tolerance). Unlike the block-design experiments in which fMRI signal can be elicited with multiple repetitions of a task, these single-event experiments require stable baseline in order to reliably identify drug-induced signal changes. Such factors as subject motion, scanner instability and/or alterations in physiological conditions of the anesthetized animal could confound the baseline signal. The unique feature of such functional MRI (fMRI) studies necessitates a technique that is able to monitor MRI signal in a real-time fashion and to interactively control certain experimental procedures. In the present Study, an approach for real-time MRI on a Bruker scanner is presented. The custom software runs on the console computer in parallel with the scanner imaging software, and no additional hardware is required. The utility of this technique is demonstrated in manganese-enhanced MRI (MEMRI) with acute cocaine challenge, in which temporary disruption of the blood-brain barrier (BBB) is a critical step for MEMRI experiments. With the aid of real-time MRI, we were able to assess the outcome of BBB disruption following bolus injection of hyperosmolar mannitol in a near real-time fashion prior to drug administration, improving experimental success rate. It is also shown that this technique can be applied to monitor baseline physiological conditions in conventional fMRI experiments using blood oxygenation level-dependent (BOLD) contrast, further demonstrating the versatility of this technique. (c) Published by Elsevier Inc. C1 [Lu, Hanbing; Yang, Shaolin; Zuo, Yantao; Demny, Steven; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lu, HB (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM luha@intra.nida.nih.gov FU Intramural Research Program of the National Institute on Drug Abuse,; National Institutes of Health FX The authors thank T.J. Ross at the National Institute on Drug Abuse and M. Mattingly of Bruker Biospin MRI, Inc., for valuable discussions. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 34 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD NOV PY 2008 VL 26 IS 9 BP 1266 EP 1272 DI 10.1016/j.mri.2008.02.020 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 375AS UT WOS:000261085500010 PM 18448300 ER PT J AU Fried, LP Varadhan, R Bohr, VA AF Fried, Linda P. Varadhan, Ravi Bohr, Vilhelm A. TI Opinion section on frailty Preface SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material C1 [Bohr, Vilhelm A.] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. [Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Varadhan, Ravi] Johns Hopkins Univ, Baltimore, MD USA. RP Bohr, VA (reprint author), NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU Intramural NIH HHS [Z01 AG000726-15]; NIA NIH HHS [R37 AG019905] NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV PY 2008 VL 129 IS 11 BP 665 EP 665 DI 10.1016/j.mad.2008.10.001 PG 1 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 397KJ UT WOS:000262661300007 PM 18951913 ER PT J AU Ferrucci, L Giallauria, F Schlessinger, D AF Ferrucci, Luigi Giallauria, Francesco Schlessinger, David TI Mapping the road to resilience: Novel math for the study of frailty SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material DE frailty; aging; resilience; biological homeostasis; biology of aging ID SPECTROSCOPY; DISORDERS AB Frailty stands at the nexus of geriatrics and gerontology, and requires both basic biology and clinical knowledge for its analysis. Understanding frailty difficulties much more than simply adding another outcome measure in epidemiological studies. The major challenge is the identification of multiple feed-forward and feed-back signaling pathways involved in the maintenance of biological homeostasis in complex organisms that may fail with aging. The cause of frailty and loss of resilience is probably a progressive loss of redundancy in these response patterns and connections. Advances toward the development of a theoretical model that can potentially embrace the complexity of frailty should be highly encouraged, especially models designed to explain the biology of aging which can promote a better integration and communication between scientists who study this problem from different perspectives. Published by Elsevier Ireland Ltd. C1 [Ferrucci, Luigi; Giallauria, Francesco; Schlessinger, David] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, NIH, Longitudinal Studies Sect,Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Giallauria, Francesco/B-5681-2013 OI Giallauria, Francesco/0000-0003-4119-9397 FU NIA NIH HHS [Z01 AG000971-01] NR 10 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV PY 2008 VL 129 IS 11 BP 677 EP 679 DI 10.1016/j.mad.2008.09.007 PG 3 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 397KJ UT WOS:000262661300012 PM 18929593 ER PT J AU Romagnoli, R Baraldi, PG Sarkar, T Cara, CL Lopez, OC Carrion, MD Preti, D Tolomeo, M Balzarini, J Hamel, E AF Romagnoli, Romeo Baraldi, Pier Giovanni Sarkar, Taradas Cara, Carlota Lopez Lopez, Olga Cruz Carrion, Maria Dora Preti, Delia Tolomeo, Manlio Balzarini, Jan Hamel, Ernest TI Synthesis and Biological Evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofurans as a New Class of Antitubulin Agents SO MEDICINAL CHEMISTRY LA English DT Article DE Microtubule; benzofuran; antiproliferative activity ID POTENT ANTITUMOR AGENTS; ETHYL-ESTER DERIVATIVES; ANTIMITOTIC AGENTS; TUBULIN; CANCER; POLYMERIZATION; DISCOVERY; GROWTH AB Microtubules are among the most successful targets for development of compounds useful for anticancer therapy. Continuing our project to develop new small molecule antitumor agents, two new series of derivatives based on the 2-aroyl-4-phenylbenzofuran molecular skeleton were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. SAR were elucidated with various substitutions on the benzoyl moiety at the 2-position of the benzofuran ring. The most promising compound in this series, the (5-hydroxy-4-phenylbenzofuran-2yl)( 4-methoxyphenyl) methanone derivative (3d), has significant growth inhibitory activity in the submicromolar range against the Molt4, CEM and HeLa cancer cell lines and interacts with tubulin by binding to the colchicine site. Exposure to 3d led to the arrest of K562 cells in the G2-M phase of the cell cycle and to the induction of apoptosis. C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Cara, Carlota Lopez; Lopez, Olga Cruz; Carrion, Maria Dora; Preti, Delia] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. [Sarkar, Taradas; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Tolomeo, Manlio] Univ Palermo, Div Ematol, Palermo, Italy. [Tolomeo, Manlio] Univ Palermo, Policlin P Giaccone, Dipartimento Oncol, AIDS Serv, Palermo, Italy. [Balzarini, Jan] Rega Inst, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium. RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. EM rmr@unife.it RI LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Carrion, M. Dora/G-8638-2015; preti, delia/G-9916-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017 OI LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; Carrion, M. Dora/0000-0002-6794-3949; preti, delia/0000-0002-1075-3781; FU Ramon Areces Foundation FX OC- L thanks the Ramon Areces Foundation for financial support. NR 17 TC 6 Z9 8 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 J9 MED CHEM JI Med. Chem. PD NOV PY 2008 VL 4 IS 6 BP 558 EP 564 DI 10.2174/157340608786242007 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 387BK UT WOS:000261926500008 PM 18991740 ER PT J AU van der Hilst, JCH Bodar, EJ Barron, KS Frenkel, J Drenth, JPH van der Meer, JWM Simon, A AF van der Hilst, Jeroen C. H. Bodar, Evelien J. Barron, Karyl S. Frenkel, Joost Drenth, Joost P. H. van der Meer, Jos W. M. Simon, Anna CA Int HIDS Study Grp TI Long-Term Follow-Up, Clinical Features, and Quality of Life in a Series of 103 Patients With Hyperimmunoglobulinemia D Syndrome SO MEDICINE LA English DT Article ID PERIODIC FEVER SYNDROME; FAMILIAL MEDITERRANEAN FEVER; HYPER-IGD SYNDROME; MEVALONATE KINASE-DEFICIENCY; INTERLEUKIN-1-BETA SECRETION; DIAGNOSTIC-VALUE; SYNDROME HIDS; HEALTH-STATUS; MUTATIONS; SPECTRUM AB The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). one of the autoinflammatory syndromes, is caused by Mutations in the gene coding for mevalonate kinase (MVK). We conducted the current study to assess the genetic, laboratory, and clinical features as well as the complications and course of disease in patients with genetically confirmed HIDS. fit addition. we studied the quality of lite Mid Course of life in a selection of patients. Follow-up data were obtained by a questionnaire sent to all physicians of patients in the international HIDS Database. In addition. we assessed the course of life and quality of life in Dutch patients aged >16 years using validated quality of life instruments. Data were obtained from 103 patients from 18 different countries. The median age of first attack was 6 months (rang-c. 0-120 mo). with a median period of 9.9 years from onset of disease to diagnosis. The most frequent symptoms that accompanied attacks of fever were lymphadenopathy, abdominal pain, arthralgia, diarrhea. vomiting, skin lesions, and aphthous ulcers. Amyloidosis was a severe but infrequent complication (2.9%). The median serum IgD level was 400 U/mL. IgD levels were normal in 22%, of patients. The 4 most prevalent Mutations (V3771, 1268T, H20P/N, P167L) accounted for 71.5% of mutations found. The frequency Of attacks decreased with the patient's increasing age, although 50% of patients over the age of 20 years still had 6 or more attacks per year. Many drugs have been tried in HIDS. Some patients responded to high-close prednisone (24.4% response). Anakinra and etanercept can also be effective (33.3% response). Quality of life was determined in a Subgroup of patients (n = 28). Social functioning, general health perception, and vitality were significantly lower in patients with HIDS than in controls, as were autonomy and social development. In addition, HIDS had all adverse impact oil educational achievements and employment status. In conclusion, HIDS is ail early-onset disease that is accompanied by in array of inflammatory symptoms. Although the frequently of attacks decreases during the patient's life, many patients continue to have frequent attacks. HIDS impairs several aspects of quality of life. C1 [van der Hilst, Jeroen C. H.; Bodar, Evelien J.; van der Meer, Jos W. M.; Simon, Anna] Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. [Drenth, Joost P. H.] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands. [Frenkel, Joost] Univ Med Ctr, Div Pediat, Dept Gen Pediat, Utrecht, Netherlands. [Frenkel, Joost] Univ Med Ctr, Div Pediat, Dept Pediat Immunol, Utrecht, Netherlands. [Barron, Karyl S.] NIAID, NIH, Bethesda, MD 20892 USA. RP van der Hilst, JCH (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med 463, St Radboud,Geert Grrotepl 8,POB 9101, NL-6500 HB Nijmegen, Netherlands. EM j.vanderhilst@aig.umcn.nl RI Simon, Anna/D-3757-2009; Gardner-Medwin, Janet/J-2512-2012; Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI Simon, Anna/0000-0002-6141-7921; van der Meer, Jos/0000-0001-5120-3690 FU Intramural Research Divisions of the National Institute of Allergy and Infectious Diseases; National Institute of Arthritis and Musculosketal and Skin Diseases; National Institutes of Health, Bethesda, Maryland FX This work was partially supported by the Intramural Research Divisions of the National Institute of Allergy and Infectious Diseases and the National Institute of Arthritis and Musculosketal and Skin Diseases, National Institutes of Health, Bethesda, Maryland. NR 40 TC 127 Z9 128 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2008 VL 87 IS 6 BP 301 EP 310 DI 10.1097/MD.0b013e318190cfb7 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 373NG UT WOS:000260978100001 PM 19011501 ER PT J AU Cooper, R Mishra, G Clennell, S Guralnik, J Kuh, D AF Cooper, Rachel Mishra, Gita Clennell, Suzie Guralnik, Jack Kuh, Diana TI Menopausal status and physical performance in midlife: findings from a British birth cohort study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Hysterectomy; Grip strength; Chair rises; Standing balance; Physical performance ID HORMONE REPLACEMENT THERAPY; MUSCLE STRENGTH; GRIP STRENGTH; DEVELOPMENTAL ORIGINS; POSTMENOPAUSAL WOMEN; NATIONAL-SURVEY; ELDERLY-WOMEN; RISK-FACTORS; LIFE-COURSE; AGE AB Objective: To test the associations of menopausal status, timing of menopause, and hysterectomy with physical performance at age 53 years. Design: Using data on women participating in the Medical Research Council National Survey of Health and Development who have been followed up since birth in March 1946 (N = 1,386), associations of interest were examined. Menopausal status, grip strength, chair rises, and standing balance time were assessed at age 53, and covariates were measured across life. Results: Women who were postmenopausal and not using hormone therapy at age 53 had lower mean grip strength than women who were still pre- or perimenopausal at this age. However, this trend of decreasing grip strength across the three natural menopausal categories (from pre- to postmenopausal) was explained by current body size. Those women who had undergone hysterectomy before age 40 had significantly weaker grip strength than women who had undergone hysterectomy at later ages; in fully adjusted analyses, those women who had a hysterectomy before age 40 had a mean grip strength 5.21 kg (95% CI: 2.18-8.25) lower than women who had a hysterectomy between ages 50 and 53. There were no significant associations between menopausal status or age at hysterectomy and chair rise or standing balance time and also no significant associations between timing of menopause and any of the performance measures. Conclusions: Women who have hysterectomies at young ages represent a group who may require more support than other women to achieve and maintain good physical performance, especially muscle strength, in midlife. C1 [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Cooper, Rachel; Mishra, Gita; Clennell, Suzie; Kuh, Diana] UCL, MRC Unit Lifelong Hlth & Ageing, Dept Epidemiol & Publ Hlth, London, England. RP Cooper, R (reprint author), Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, MRC Natl Survery Hlth & Dev, 1-19 Torrington Pl, London WC1E 6BT, England. EM r.cooper@nshd.mrc.ac.uk RI Mishra, Gita/F-8052-2011; OI Mishra, Gita/0000-0001-9610-5904; Cooper, Rachel/0000-0003-3370-5720 FU Medical Research Council, United Kingdom; Intramural Research Program; National Institute oil Aging; National Institutes of Health FX This Study was supported by the Medical Research Council, United Kingdom and in part by the Intramural Research Program, National Institute oil Aging, National Institutes of Health. NR 33 TC 19 Z9 22 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2008 VL 15 IS 6 BP 1079 EP 1085 DI 10.1097/gme.0b013e31816f63a3 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 371VA UT WOS:000260858500013 PM 18520694 ER PT J AU Varnai, P Balla, T AF Varnai, Peter Balla, Tamas TI Live cell imaging of phosphoinositides with expressed inositide binding protein domains SO METHODS LA English DT Article DE Calcium signaling; Pleckstrin homology domain; Phosphoinositide; Green fluorescent protein; Confocal microscopy ID PLECKSTRIN-HOMOLOGY-DOMAIN; RESONANCE ENERGY-TRANSFER; BRUTONS TYROSINE KINASE; SINGLE LIVING CELLS; PLASMA-MEMBRANE; PH DOMAIN; PHOSPHATIDYLINOSITOL 3,5-BISPHOSPHATE; STIMULATED TRANSLOCATION; PHOSPHOLIPASE-C; LIPID PRODUCTS AB Inositol lipids and calcium signaling has been inseparable twins during the 1980s when the molecular details of phospholipase C-mediated generation of inositol 1,4,5-trisphosphate (InsP(3)) and its Ca2+ mobilizing action were discovered. Since then, both the Ca2+ and inositol lipid signaling fields have hugely expanded and the tools allowing dissection of the finest details of their molecular organization also followed closely. Although phosphoinositides regulate many cell functions unrelated to Ca2+ signaling there are still many open questions even in the Ca2+ field that would benefit from single cell monitoring of PtdIns(4,5)P-2. or InSP3 changes during agonist stimulation. This chapter is designed to provide practical guidance as well as some theoretical background on measurements of phosphoinositides in live cells using protein domain-GFP chimeras that could be also useful for people working on calcium signaling. (C) 2008 Elsevier Inc. All rights reserved. C1 [Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, H-1088 Budapest, Hungary. [Balla, Tamas] NICHD, Program Dev Neurosc, Sect Mol Signal Transduct, Bethesda, MD 20892 USA. RP Varnai, P (reprint author), Semmelweis Univ, Fac Med, Dept Physiol, Puskin Utca 9, H-1088 Budapest, Hungary. EM varnai@puskin.sote.hu OI Balla, Tamas/0000-0002-9077-3335 FU Intramural Research Program of the National Institute of Child Health and Human Development of the National Institutes of Health; Hungarian Scientific Research fund [OTKA NF-68563]; Medical Research Council [ETT 440/2006] FX The authors wish to thank Dr. Kees Jalink (The Netherlands Cancer Institute) for his collaboration, critical comments and fruitful discussions over the years. This research was supported in part by the Intramural Research Program of the National Institute of Child Health and Human Development of the National Institutes of Health. P.V. is a Bolyai Fellow of the Hungarian Academy of Science and was also supported by the Hungarian Scientific Research fund (OTKA NF-68563) and the Medical Research Council (ETT 440/2006). NR 74 TC 32 Z9 32 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 2008 VL 46 IS 3 BP 167 EP 176 DI 10.1016/j.ymeth.2008.09.019 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 381NW UT WOS:000261544200005 PM 18930153 ER PT J AU Bird, GS DeHaven, WI Smyth, JT Putney, JW AF Bird, Gary S. DeHaven, Wayne I. Smyth, Jeremy T. Putney, James W., Jr. TI Methods for studying store-operated calcium entry SO METHODS LA English DT Article DE Calcium signaling; Inositol trisphosphate; Store-operated calcium entry; Icrac; Fluorescence; Electrophysiology ID CAPACITATIVE CA2+ ENTRY; PAROTID ACINAR-CELLS; 2-AMINOETHOXYDIPHENYL BORATE 2-APB; VASCULAR ENDOTHELIAL-CELLS; EMBRYONIC KIDNEY-CELLS; CURRENT I-CRAC; PLASMA-MEMBRANE; INOSITOL TRISPHOSPHATE; 2ND MESSENGER; T-LYMPHOCYTES AB Activation of surface membrane receptors coupled to phospholipase C results in the generation of cytoplasmic Ca(2+), signals comprised of both intracellular Ca(2+) release, and enhanced entry of Ca(2+) across the plasma membrane. A primary mechanism for this Ca(2+) entry process is attributed to store-operated Ca(2+) entry, a process that is activated by depletion of Ca(2+) ions from an intracellular store by inositol 1,4,5-trisphosphate. Our understanding of the mechanisms underlying both Ca(2+) release and store-operated Ca(2+) entry have evolved from experimental approaches that include the use of fluorescent Ca(2+) indicators and electrophysiological techniques. Pharmacological manipulation of this Ca(2+) signaling process has been somewhat limited; but recent identification of key molecular players, STIM and Orai family proteins, has provided new approaches. Here we describe practical methods involving fluorescent Ca(2+) indicators and electrophysiological approaches for dissecting the observed intracellular Ca(2+) signal to reveal characteristics of store-operated Ca(2+) entry. highlighting the advantages, and limitations, of these approaches. Published by Elsevier Inc. C1 [Bird, Gary S.; DeHaven, Wayne I.; Smyth, Jeremy T.; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Bird, GS (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM bird@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 87 TC 99 Z9 100 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 2008 VL 46 IS 3 BP 204 EP 212 DI 10.1016/j.ymeth.2008.09.009 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 381NW UT WOS:000261544200009 PM 18929662 ER PT J AU Ionin, B Hammamieh, R Shupp, JW Das, R Pontzer, CH Jett, M AF Ionin, Boris Hammamieh, Rasha Shupp, Jeffrey W. Das, Rina Pontzer, Carol H. Jett, Marti TI Staphylococcal enterotoxin B causes differential expression of Rnd3 and RhoA in renal proximal tubule epithelial cells while inducing actin stress fiber assembly and apoptosis SO MICROBIAL PATHOGENESIS LA English DT Article DE Renal proximal tubule epithelium; SEB; Toxic shock syndrome; RhoE; Rnd3; RhoA ID IN-VIVO; PROTEIN; SHOCK; RECEPTOR; TOXINS AB Staphylococcal enterotoxin B (SEB) is a toxic shock-inducing agent produced by Staphylococcus aureus. The hallmark of SEB-induced lethal shock is acute vasodilation leading to severe hypotension. Animal studies reveal that approximate to 70% of intravenously administered toxin localizes to renal proximal tubule epithelial cells (RPTEC). This evidence, together with the well-documented role of the kidney in regulation of vascular tone, suggests that molecular events induced in RPTEC by SEB may contribute to the blood pressure dysregulation seen in enterotoxic shock. In an attempt to elucidate these molecular mechanisms, differential display was performed on SEB-treated and untreated RPTEC, and 32 differentially expressed transcripts (DETs) were identified. One of the down-regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein function. Consistent with Rnd3 down-regulation, message for RhoA was shown to increase upon SEB exposure, and actin stress fiber formation was dramatically increased. Further, SEB-exposed cells showed both increased enzymatic activity of caspase-3 and an increase in the percentage of apoptotic cells. Taken together, these results support the hypothesis that RPTEC undergo apoptosis upon exposure to SEB. Furthermore, these data implicate the involvement of the Rho family proteins in the molecular signaling pathway induced by SEB in RPTEC. (C) 2008 Published by Elsevier Ltd. C1 [Ionin, Boris; Hammamieh, Rasha; Shupp, Jeffrey W.; Das, Rina; Jett, Marti] Walter Reed Army Inst Res, Div Pathol, Dept Mol Pathol, Silver Spring, MD 20910 USA. [Pontzer, Carol H.] NIH, NCCAM, Bethesda, MD 20892 USA. RP Jett, M (reprint author), Walter Reed Army Inst Res, Div Pathol, Dept Mol Pathol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM martijett@us.army.mil NR 29 TC 9 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD NOV-DEC PY 2008 VL 45 IS 5-6 BP 303 EP 309 DI 10.1016/j.micpath.2008.07.002 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA 397SG UT WOS:000262681800001 PM 18721871 ER PT J AU Jamison, WP Hackstadt, T AF Jamison, Wendy P. Hackstadt, Ted TI Induction of type III secretion by cell-free Chlamydia trachomatis elementary bodies SO MICROBIAL PATHOGENESIS LA English DT Article DE Chlamydia trachomatis; Type III secretion; Actin; Endocytosis ID SMALL-MOLECULE INHIBITOR; OUTER-MEMBRANE PROTEIN; EPITHELIAL-CELLS; HOST-CELLS; PSEUDOMONAS-AERUGINOSA; TRANSLOCATED PROTEIN; BACTERIAL EFFECTORS; ACTIN CYTOSKELETON; IPA INVASINS; ENTRY AB Chlamydiae secrete type III effector proteins at two distinct stages of their developmental cycle. Elementary bodies (EBs) secrete at least one pre-formed effector protein, Tarp, across the host plasma membrane from an extracellular location. Once internalized, a set of newly transcribed proteins are secreted to modify the inclusion membrane. In an effort to better understand the triggers for chlamydial type III secretion and develop means to identify new effectors, we investigated various inducers of T3SS in other Gram-negative bacterial systems to determine if they were able to activate chlamydial type III secretion from EBs using Tarp secretion as an indicator of activation. Chlamydial EBs are induced to secrete Tarp by exposure to FBS, BSA, or sphingolipid and cholesterol-rich liposomes (SCRLs). The induction by FBS and BSA, but not SCRL, is enhanced in the presence of the calcium-chelator, EGTA. This secretion was temperature dependent and inhibited by paraformaldehyde fixation of the EBs. Published by Elsevier Ltd. C1 [Jamison, Wendy P.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Janet Sager for excellent technical assistance, the RML Microscopy Unit for confirmation of liposome morphology, Drs. T. Jewett, B. Kleba, and E. Moore for critical reading of the manuscript, and members of the Hackstadt lab for helpful comments and suggestions. This work was supported by the Intramural Research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 46 TC 23 Z9 23 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD NOV-DEC PY 2008 VL 45 IS 5-6 BP 435 EP 440 DI 10.1016/j.micpath.2008.10.002 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA 397SG UT WOS:000262681800018 PM 18984037 ER PT J AU Seo, DW Kim, SH Eom, SH Yoon, HJ Cho, YR Kim, PH Kim, YK Han, JW Diaz, T Wei, BY Stetler-Stevenson, WG AF Seo, Dong-Wan Kim, Soo Hyeon Eom, Seok-Hyun Yoon, Hyun Jae Cho, Young-Rak Kim, Pyeung-Hyeun Kim, Yong Kee Han, Jeung-Whan Diaz, Tere Wei, Bei-yang Stetler-Stevenson, William G. TI TIMP-2 disrupts FGF-2-induced downstream signaling pathways SO MICROVASCULAR RESEARCH LA English DT Article DE TIMP-2; Angiogenesis; Integrin alpha 3 beta 1; Shp-1; FGF-2 ID TISSUE INHIBITOR; METALLOPROTEINASE INHIBITORS; MATRIX METALLOPROTEINASES; ANGIOGENESIS; MECHANISM; PROTEIN; CANCER; INTEGRINS; TARGET; CELLS AB We have previously reported that tissue inhibitor of metalloproteinases-2 (TIMP-2), an endogenous inhibitor of matrix metalloproteinase, modulates angiogenic responses through the MMP inhibition-independent activity. In this study, we investigate the molecular mechanisms of TIMP-2-mediated growth inhibition in response to fibroblast growth factor-2 (FGF-2). Pre-treatment with a protein tyrosine phosphatase inhibitor orthovanadate or expression of a dominant negative Shp-1 mutant fails to induce TIMP-2 inactivation of FGF-2 signaling pathways in human microvascular endothelial cells. We also show that TIMP-2 inhibition of FGF-2-induced p42/44(MAPK) activation and cell proliferation is associated with TIMP-2 binding to integrin alpha 3 beta 1 on endothelial cell surfaces, as demonstrated by use of anti-integrin alpha 3 or beta 1 blocking antibodies, or disruption of integrin alpha 3 expression by siRNA. Collectively, our results indicate that TIMP-2 inhibits FGF-2 signaling pathways through association with integrin alpha 3 beta 1 and Shp-1-dependent inhibition of p42/44(MAPK) signaling, which in turn, results in suppression of FGF-2-stimulated endothelial cell mitogenesis. (C) 2008 Elsevier Inc. All rights reserved C1 [Seo, Dong-Wan; Kim, Soo Hyeon; Eom, Seok-Hyun; Yoon, Hyun Jae; Cho, Young-Rak; Kim, Pyeung-Hyeun] Kangwon Natl Univ, Sch Biosci & Biotechnol, Dept Mol Biosci, Inst Biosci & Biotechnol, Chunchon 200701, South Korea. [Diaz, Tere; Wei, Bei-yang; Stetler-Stevenson, William G.] Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Cell & Canc Biol Branch, Gaithersburg, MD 20877 USA. [Kim, Yong Kee] Kwandong Univ, Coll Med, Dept Pharmacol, Kangnung 210701, South Korea. [Han, Jeung-Whan] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. RP Seo, DW (reprint author), Kangwon Natl Univ, Sch Biosci & Biotechnol, Dept Mol Biosci, Inst Biosci & Biotechnol, Nat Sci Bldg 4-113, Chunchon 200701, South Korea. EM dwseomb@kangwon.ac.kr; sstevenw@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; cho, young-rak/0000-0002-1077-796X; Seo, Dong-Wan/0000-0003-4971-834X FU NCI; Center for Cancer Research [Z01SC 009179]; Korean Government (MOEHRD) [KRF-2006-311-C00547]; Korea Food & Drug Administration [07102Biotechnology398]; Korea Science and Engineering Foundation; Kangwon National University FX This work was supported by intramural research funds from the NCI, Center for Cancer Research Project Z01SC 009179, the Korea Research Foundation Grant from the Korean Government (MOEHRD) (KRF-2006-311-C00547), the Research Grant from the Korea Food & Drug Administration (07102Biotechnology398), the Vascular System Research Center Grant from the Korea Science and Engineering Foundation, and 2006 Research Grant from Kangwon National University. NR 31 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2008 VL 76 IS 3 BP 145 EP 151 DI 10.1016/j.mvr.2008.07.003 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368FT UT WOS:000260607700002 PM 18721821 ER PT J AU Hurt, EM Saykally, JN Anose, BM Kalli, KR Sanders, MM AF Hurt, Elaine M. Saykally, Jessica N. Anose, Bynthia M. Kalli, Kimberly R. Sanders, Michel M. TI Expression of the ZEB1 (delta EF1) transcription factor in human: additional insights SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ZEB1; delta EF1; Estrogen; Gynecologic carcinomas; TCF8 ID BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN EXPRESSION; QUANTITATIVE RT-PCR; ZINC-FINGER; GENE-REGULATION; ENDOMETRIAL CARCINOMA; LUNG-CANCER; TGF-BETA; REPRESSOR AB The zinc finger E-box binding transcription factor ZEB1 (delta EF1/Nil-2-a/AREB6/zfhx1a/TCF8/zfhep/BZP) is emerging as an important regulator of the epithelial to mesenchymal transitions (EMT) required for development and cancer metastasis. ZEB1 promotes EMT by repressing genes contributing to the epithelial phenotype while activating those associated with the mesenchymal phenotype. TCF8 (zfhx1a), the gene encoding ZEB1, is induced by several potentially oncogenic ligands including TGF-beta, estrogen, and progesterone. TGF-beta appears to activate EMT, at least in part, by inducing ZEB1. However, our understanding of how ZEB1 contributes to signaling pathways elicited by estrogen and progesterone is quite limited, as is our understanding of its functional roles in normal adult tissues. To begin to address these questions, a human tissue mRNA array analysis was done. In adults, the highest ZEB1 mRNA expression is in bladder and uterus, whereas in the fetus highest expression is in lung, thymus, and heart. To further investigate the regulation of TCF8 by estrogen, ZEB1 mRNA was measured in ten estrogen-responsive cell lines, but it is only induced in the OV266 ovarian carcinoma line. Although high expression of ZEB1 mRNA is estrogen-dependent in normal human ovarian and endometrial biopsies, high expression is estrogen-independent in late stage ovarian and endometrial carcinomas, raising the possibility that deregulated expression promotes cancer progression. In contrast, TCF8 is at least partially deleted in 4 of 5 well-differentiated, grade I endometrial carcinomas, which may contribute to their non-aggressive phenotype. These data support the contention that high ZEB1 encourages gynecologic carcinoma progression. C1 [Saykally, Jessica N.; Sanders, Michel M.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Hurt, Elaine M.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Anose, Bynthia M.] Bethel Univ, Dept Chem, St Paul, MN 55112 USA. [Kalli, Kimberly R.] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA. RP Sanders, MM (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 6-155 Jackson Hall,321 Church St SE, Minneapolis, MN 55455 USA. EM sande001@umn.edu FU NIH [R01 DK40082, DK061913] FX This research was supported by NIH grants R01 DK40082 and DK061913 to MMS. The technical assistance of Michelle Hon is gratefully acknowledged. NR 54 TC 35 Z9 37 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2008 VL 318 IS 1-2 BP 89 EP 99 DI 10.1007/s11010-008-9860-z PG 11 WC Cell Biology SC Cell Biology GA 363UO UT WOS:000260292600011 PM 18622689 ER PT J AU Monge, C Beraud, N Kuznetsov, AV Rostovtseva, T Sackett, D Schlattner, U Vendelin, M Saks, VA AF Monge, Claire Beraud, Nathalie Kuznetsov, Andrey V. Rostovtseva, Tatiana Sackett, Dan Schlattner, Uwe Vendelin, Marko Saks, Valdur A. TI Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Brain; Creatine kinase; Functional coupling; Mitochondria; Synaptosomes; Tubulin ID ENZYME-CATALYZED REACTIONS; RAT-HEART MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; KINETIC-PROPERTIES; ENERGY-METABOLISM; OUTER-MEMBRANE; INTACT SYNAPTOSOMES; ELECTRON-TRANSPORT; MUSCLE-CELLS; GIANT AXONS AB The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 +/- 11 mu M) in comparison with isolated brain mitochondria (9 +/- 1 mu M). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 +/- 52 mu M after their incubation with 1 mu M of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 +/- 1 mu M in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (Ka) from 0.13 +/- 0.02 to 0.018 +/- 0.007 mM and that from binary complex MtCK. MgATP (Kia) from 1.1 +/- 0.29 mM to 0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine-creatine kinase systemin energy transfer in brain cells, including synaptosomes. C1 [Monge, Claire; Beraud, Nathalie; Schlattner, Uwe; Saks, Valdur A.] Univ Grenoble 1, Lab Fundamental & Appl Bioenerget, Grenoble, France. [Kuznetsov, Andrey V.] D Swarovski Res Lab, Dept Transplant Surg, Innsbruck, Austria. [Rostovtseva, Tatiana] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Sackett, Dan] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Vendelin, Marko] Tallinn Univ Technol, Inst Cybernet Tallin, Lab Syst Biol, EE-200108 Tallinn, Estonia. [Saks, Valdur A.] NICPB, Lab Bioenerget, Tallinn, Estonia. RP Saks, VA (reprint author), 2280 Rue Piscine,BP53X, F-38041 Grenoble 9, France. EM Valdur.Saks@ujf-grenoble.fr RI Schlattner, Uwe/D-1267-2009; Monge, Claire/E-2933-2012 OI Schlattner, Uwe/0000-0003-1159-5911; FU INSERM, France; Agence National de la Recherche [BLAN07-2_188128]; Estonian Science Foundation [6142, 7117] FX This work was supported by INSERM, France; Agence National de la Recherche (project no BLAN07-2_188128), France, to C. M. and V. S.; grants of Estonian Science Foundation (No 6142 and 7117 to V. S.). NR 82 TC 45 Z9 46 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2008 VL 318 IS 1-2 BP 147 EP 165 DI 10.1007/s11010-008-9865-7 PG 19 WC Cell Biology SC Cell Biology GA 363UO UT WOS:000260292600016 PM 18629616 ER PT J AU Nguyen, P Bar-Sela, G Sun, LC Bisht, KS Cui, HM Kohn, E Feinberg, AP Gius, D AF Nguyen, Phuongmai Bar-Sela, Gil Sun, Lunching Bisht, Kheem S. Cui, Hengmi Kohn, Elise Feinberg, Andrew P. Gius, David TI BAT3 and SET1A Form a Complex with CTCFL/BORIS To Modulate H3K4 Histone Dimethylation and Gene Expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; THIOREDOXIN REDUCTASE; BINDING PROTEIN; CTCF-BINDING; METHYLATION; H19; CANCER; CHROMATIN; IGF2; PROMOTER AB Chromatin status is characterized in part by covalent posttranslational modifications of histones that regulate chromatin dynamics and direct gene expression. BORIS (brother of the regulator of imprinted sites) is an insulator DNA-binding protein that is thought to play a role in chromatin organization and gene expression. BORIS is a cancer-germ line gene; these are genes normally present in male germ cells (testis) that are also expressed in cancer cell lines as well as primary tumors. This work identifies SET1A, an H3K4 methyltransferase, and BAT3, a cochaperone recruiter, as binding partners for BORIS, and these proteins bind to the upstream promoter regions of two well-characterized procarcinogenic genes, Myc and BRCA1. RNA interference (RNAi) knockdown of BAT3, as well as SET1A, decreased Myc and BRCA1 gene expression but did not affect the binding properties of BORIS, but RNAi knockdown of BORIS prevented the assembly of BAT3 and SET1A at the Myc and BRCA1 promoters. Finally, chromatin analysis suggested that BORIS and BAT3 exert their effects on gene expression by recruiting proteins such as SET1A that are linked to changes in H3K4 dimethylation. Thus, we propose that BORIS acts as a platform upon which BAT3 and SET1A assemble and exert effects upon chromatin structure and gene expression. C1 [Nguyen, Phuongmai; Bar-Sela, Gil; Sun, Lunching; Bisht, Kheem S.; Gius, David] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Mol Biol, Dept Med,Inst Genet Med, Baltimore, MD 21205 USA. [Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Genet, Dept Med,Inst Genet Med, Baltimore, MD 21205 USA. [Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. [Kohn, Elise] NCI, Pathol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afeinberg@jhu.edu; giusd@mail.nih.gov FU NCI [CA65145]; NIH; CCR FX This work was supported by grant CA65145 (to A.P.F.) from the NCI and also (in part) by the Intramural Research Program of the NIH, the NCI, and the CCR. NR 46 TC 43 Z9 46 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2008 VL 28 IS 21 BP 6720 EP 6729 DI 10.1128/MCB.00568-08 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 359ZS UT WOS:000260027400015 PM 18765639 ER PT J AU Anglesio, MS Arnold, JM George, J Tinker, AV Tothill, R Waddell, N Simms, L Locandro, B Fereday, S Traficante, N Russell, P Sharma, R Birrer, MJ Defazio, A Chenevix-Trench, G Bowtelll, DDL AF Anglesio, Michael S. Arnold, Jeremy M. George, Joshy Tinker, Anna V. Tothill, Richard Waddell, Nic Simms, Lisa Locandro, Bianca Fereday, Sian Traficante, Nadia Russell, Peter Sharma, Raghwa Birrer, Michael J. deFazio, Anna Chenevix-Trench, Georgia Bowtelll, David D. L. CA AOCS Study Grp TI Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors SO MOLECULAR CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; GENE-EXPRESSION PATTERNS; HER2 KINASE DOMAIN; BORDERLINE TUMORS; PROTEIN-KINASE; EPITHELIAL-CELLS; LOW-GRADE; DIFFERENTIAL REGULATION; SOMATIC MUTATIONS; TYROSINE KINASES AB Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis. The mutational profile also differs markedly from that seen in most serous carcinomas. Typically, LMP tumors are associated with KRAS and BRAF mutations. Interrogation of expression profiles in serous LMP tumors suggested overall redundancy of RAS-MAPK pathway mutations and a distinct mechanism of oncogenesis compared with high-grade ovarian carcinomas. Our findings indicate that activating mutation of the RAS-MAPK pathway in serous LMP may be present in >70% of cases compared with similar to 12.5% in serous ovarian carcinomas. In addition to mutations of KRAS (18%) and BRAF (48%) mutations, ERBB2 mutations (6%), but not EGFR, are prevalent among serous LMP tumors. Based on the expression profile signature observed throughout our serous LMP cohort, we propose that RAS-MAPK pathway activation is a requirement of serous LMP tumor development and that other activators of this pathway are yet to be defined. Importantly, as few nonsurgical options exist for treatment of recurrent LMP tumors, therapeutic targeting of this pathway may prove beneficial, especially in younger patients where maintaining fertility is important. (Mol Cancer Res 2008;6(11):1678-90) C1 [Anglesio, Michael S.; George, Joshy; Tothill, Richard; Locandro, Bianca; Fereday, Sian; Traficante, Nadia; Bowtelll, David D. L.; AOCS Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic 8006, Australia. [AOCS Study Grp] Univ Melbourne, Melbourne, Vic, Australia. [Arnold, Jeremy M.; Waddell, Nic; Simms, Lisa; Chenevix-Trench, Georgia; AOCS Study Grp] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Tinker, Anna V.] British Columbia Canc Agcy, Vancouver Ctr, Dept Oncol, Vancouver, BC V5Z 4E6, Canada. [Russell, Peter] Univ Sydney, Dept Pathol, Royal Prince Alfred Hosp, Dept Anat Pathol, Sydney, NSW 2006, Australia. [Sharma, Raghwa] Westmead Hosp, Dept Anat Pathol, Sydney, NSW, Australia. [deFazio, Anna; AOCS Study Grp] Univ Sydney, Westmead Millennium Inst, Westmead Hosp, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. [deFazio, Anna] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia. [Birrer, Michael J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bowtelll, DDL (reprint author), Peter MacCallum Canc Ctr, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia. EM d.bowtell@petermac.org RI deFazio, Anna/D-3939-2013; Bowtell, David/H-1007-2016; Waddell, Nic/H-4929-2015; OI deFazio, Anna/0000-0003-0057-4744; Bowtell, David/0000-0001-9089-7525; Anglesio, Michael/0000-0003-1639-5003; Tothill, Richard/0000-0003-4522-1184 NR 93 TC 52 Z9 54 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2008 VL 6 IS 11 BP 1678 EP 1690 DI 10.1158/1541-7786.MCR-08-0193 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 375SV UT WOS:000261134500003 PM 19010816 ER PT J AU Kinyamu, HK Collins, JB Grissom, SF Hebbar, PB Archer, TK AF Kinyamu, H. Karimi Collins, Jennifer B. Grissom, Sherry F. Hebbar, Pratibha B. Archer, Trevor K. TI Genome Wide Transcriptional Profiling in Breast Cancer Cells Reveals Distinct Changes in Hormone Receptor Target Genes and Chromatin Modifying Enzymes After Proteasome inhibition SO MOLECULAR CARCINOGENESIS LA English DT Article DE proteasome inhibitor; receptors; glucocorticoid; estrogen; gene expression profiling; microarray analysis ID GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; REGULATED TRANSCRIPTION; PROSTATE-CANCER; PROTEIN-DEGRADATION; NUCLEAR RECEPTORS; CERVICAL-CANCER; HUMAN-DISEASES; EXPRESSION; UBIQUITIN AB Steroid hormone receptors, like glucocorticoid (GR) and estrogen receptors (ER), are master regulators of genes that control many biological processes implicated in health and disease. Gene expression is dependent on receptor levels which are tightly regulated by the ubiquitin-proteasome system. Previous studies have shown that proteasome inhibition increases GR, but decreases ER-mediated gene expression. At the gene expression level this divergent role of the proteasome in receptor-dependent transcriptional regulation is not well understood. We have used a genomic approach to examine the impact of proteasome activity on GR- and ER-mediated gene expression in MCF-7 breast cancer cells treated with dexamethasone (DEX) or 17 beta-estradiol (E2), the proteasome inhibitor MG132 (MG) or MG132 and either hormone (MID or ME2) for 24 h. Transcript profiling reveals that inhibiting proteasome activity modulates gene expression by GR and ER in a similar manner in that several GR and ER target genes are upregulated and downregulated after proteasome inhibition. In addition, proteasome inhibition modulates receptor-dependent genes involved in the etiology of a number of human pathological states, including multiple myeloma, leukemia, breast/prostate cancer, HIV/AIDS, and neurodegenerative disorders. Importantly, our analysis reveals that a number of transcripts encoding histone and DNA modifying enzymes, prominently histone/DNA methyltransf erases and demethylases, are altered after proteasome inhibition. As proteasome inhibitors are currently in clinical trials as therapy for multiple myeloma, HIV/AIDS and leukemia, the possibility that some of the target molecules are hormone regulated and chromatin modifying enzymes is intriguing in this era of epigenetic therapy. Published 2008 Wiley-Liss, Inc. C1 [Kinyamu, H. Karimi; Hebbar, Pratibha B.; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer B.; Grissom, Sherry F.] Natl Inst Environm Hlth Sci, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Kinyamu, HK (reprint author), Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233,MD C4-06, Res Triangle Pk, NC 27709 USA. FU NIH; NIEHS FX We are deeply grateful to Dr. Pierre Bushel (Biostatistics Branch, NIEHS) for providing help with the statistical analysis and rewriting the methods section to answer the reviewers concerns. We thank Wendy Jefferson and Sylvia Hewitt for helpful comments in organizing the paper. This research was supported by the Intramural Research Program of NIH and NIEHS. NR 83 TC 18 Z9 18 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 2008 VL 47 IS 11 BP 845 EP 885 DI 10.1002/mc.20440 PG 41 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 371BZ UT WOS:000260808100004 PM 18381591 ER PT J AU McFarland, MA Ellis, CE Markey, SP Nussbaum, RL AF McFarland, Melinda A. Ellis, Christopher E. Markey, Sanford P. Nussbaum, Robert L. TI Proteomics Analysis Identifies Phosphorylation-dependent alpha-Synuclein Protein Interactions SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID SPECTRAL ABUNDANCE FACTORS; MITOCHONDRIAL COMPLEX-I; CORTICAL LEWY BODIES; PARKINSONS-DISEASE; SHOTGUN PROTEOMICS; BRAIN; MICE; SER-129; RELEASE; SYSTEM AB Mutations and copy number variation in the SNCA gene encoding the neuronal protein alpha-synuclein have been linked to familial Parkinson disease ( Thomas, B., and Beal, M. F. ( 2007) Parkinson's disease. Hum. Mol. Genet. 16, R183-R194). The carboxyl terminus of alpha-synuclein can be phosphorylated at tyrosine 125 and serine 129, although only a small fraction of the protein is phosphorylated under normal conditions (Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba, M., Iwatsubo, T., Meijer, L., Kahle, P. J., and Haass, C. ( 2000) Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J. Biol. Chem. 275, 390-397). Under pathological conditions, such as in Parkinson disease, alpha-synuclein is a major component of Lewy bodies, a pathological hallmark of Parkinson disease, and is mostly phosphorylated at Ser-129 ( Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J. P., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X. F., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai, W. P., and Chilcote, T. J. ( 2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281, 29739 29752). Controversy exists over the extent to which phosphorylation of alpha-synuclein and/or the visible protein aggregation in Lewy bodies are steps in disease pathogenesis, are protective, or are neutral markers for the disease process. Here we used the combination of peptide pulldown assays and mass spectrometry to identify and compare protein-protein interactions of phosphorylated and non-phosphorylated alpha-synuclein. We showed that non-phosphorylated alpha-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas alpha-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not. Instead the set of proteins pulled down by phosphorylated alpha-synuclein was highly enriched in certain cytoskeletal proteins, in vesicular trafficking proteins, and in a small number of enzymes involved in protein serine phosphorylation. This targeted comparative proteomics approach for unbiased identification of protein-protein interactions suggests that there are functional consequences when alpha-synuclein is phosphorylated. Molecular & Cellular Proteomics 7: 2123-2137, 2008. C1 [Nussbaum, Robert L.] Univ Calif San Francisco, Div Med Genet, Dept Med, San Francisco, CA 94143 USA. [McFarland, Melinda A.; Markey, Sanford P.] NHGRI, NIMH, Bethesda, MD 20891 USA. [Ellis, Christopher E.] NHGRI, NIH, Bethesda, MD 20891 USA. RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Div Med Genet, Dept Med, Box 0794,513 Parnassus Ave,Rm HSE901E, San Francisco, CA 94143 USA. EM nussbaumr@humgen.ucsf.edu RI McFarland, Melinda/A-1866-2013 FU National Institutes of Health [Z01 MH000279]; Sandler Family Foundation FX We thank Douglas Slotta, Sara Yang, and Anthony J. Makusky for help with data processing; Jeffrey Kowalak and Joanne Connolly for preliminary observations on this project; and Dr. Yien- Ming Kuo and Dr. Valerie Drews for help in preparing and critically reading the manuscript. We thank Nelson Cole for providing some recombinant synucleins and helping us to make others.; This work was supported, in whole or in part, by National Institutes of Health Grant Z01 MH000279 from the intramural programs of the National Institute of Mental Health and by the NHGRI. This work was also supported by the Sandler Family Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 58 TC 72 Z9 73 U1 4 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2008 VL 7 IS 11 BP 2123 EP 2137 DI 10.1074/mcp.M800116-MCP200 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 372HV UT WOS:000260893600005 PM 18614564 ER PT J AU Anderson, SJ Stone, CL Posada-Buitrago, ML Boore, JL Neelam, BA Stephens, RM Luster, DG Frederick, RD Pedley, KF AF Anderson, Sharon J. Stone, Christine L. Posada-Buitrago, Martha Lucia Boore, Jeffrey L. Neelam, Beena A. Stephens, Robert M. Luster, Douglas G. Frederick, Reid D. Pedley, Kerry F. TI Development of simple sequence repeat markers for the soybean rust fungus, Phakopsora pachyrhizi SO MOLECULAR ECOLOGY RESOURCES LA English DT Article DE basidiomycetes; microsatellites; Phakopsora pachyrhizi; soybean rust; SSR AB Twenty-four simple sequence repeat markers were developed for Phakopsora pachyrhizi, a fungal pathogen of soybean (Glycine max) and other legumes. All 24 of the loci were evaluated on 28 isolates of P. pachyrhizi. Twenty-one loci were polymorphic, with allelic diversity ranging from two to eight alleles, and null alleles were observed for eight of the 24 loci. A preliminary screen with the closely related species, P. meibomiae, indicated that these primer pairs are specific to P. pachyrhizi. C1 [Anderson, Sharon J.; Stone, Christine L.; Luster, Douglas G.; Frederick, Reid D.; Pedley, Kerry F.] USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA. [Posada-Buitrago, Martha Lucia; Boore, Jeffrey L.] Joint Genome Inst, Walnut Creek, CA 94598 USA. [Posada-Buitrago, Martha Lucia; Boore, Jeffrey L.] Lawrence Berkeley Natl Lab, US Dept Energy, Walnut Creek, CA USA. [Neelam, Beena A.; Stephens, Robert M.] NCI Frederick, SAIC Frederick Inc, Adv Biomed Comp Ctr, Adv Technol Program, Ft Detrick, MD 21702 USA. RP Pedley, KF (reprint author), USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA. EM kerry.pedley@ars.usda.gov RI Moreira, Eder/B-2309-2010; POSADA, MARTHA/G-7927-2012 NR 8 TC 8 Z9 9 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-098X J9 MOL ECOL RESOUR JI Mol. Ecol. Resour. PD NOV PY 2008 VL 8 IS 6 BP 1310 EP 1312 DI 10.1111/j.1755-0998.2008.02272.x PG 3 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 367BY UT WOS:000260528700027 PM 21586030 ER PT J AU Shen, JS Meng, XL Moore, DF Quirk, JM Shayman, JA Schiffmann, R Kaneski, CR AF Shen, Jin-Song Meng, Xing-Li Moore, David F. Quirk, Jane M. Shayman, James A. Schiffmann, Raphael Kaneski, Christine R. TI Globotriaosylceramide induces oxidative stress and up-regulates cell adhesion molecule expression in Fabry disease endothelial cells SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Fabry disease; alpha-Galactosidase A deficiency; Globotriaosylceramide; Endothelial cells; Reactive oxygen species; Cell adhesion molecule ID ENZYME-REPLACEMENT THERAPY; NITRIC-OXIDE SYNTHASE; CEREBRAL HYPERPERFUSION; SUPEROXIDE GENERATION; AGALSIDASE-ALPHA; ATHEROSCLEROSIS; MICE; GLYCOSPHINGOLIPIDS; DEFICIENCY; CHILDREN AB Fabry disease, an X-linked systemic vasculopathy, is caused by a deficiency of alpha-galactosidase A resulting in globotriaosylceramide (Gb(3)) storage in cells. The pathogenic role of Gb(3) in the disease is not known. Based on previous work, we tested the hypothesis that accumulation of Gb(3) in the vascular endothelium of Fabry disease is associated with increased production of reactive oxygen species (ROS) and increased expression of cell adhesion molecules. Gb(3)-loading resulted in increased intracellular ROS production in cultured vascular endothelial cells in a dose-dependent manner. Increased Gb(3) also induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Reduction of endogenous Gb(3) by treatment of the cells with an inhibitor of glycosphingolipid synthase or alpha-galactosidase A led to decreased expression of adhesion molecules. Plasma from Fabry patients significantly increased ROS generation in endothelial cells when compared with plasma from non-Fabry controls. This effect was not influenced by reduction of intracellular Gb(3). This study provided direct evidence that excess intracellular Gb(3) induces oxidative stress and up-regulates the expression of cellular adhesion molecules in vascular endothelial cells. In addition. other factors in patient's plasma may also contribute to oxidative stress in Fabry vascular endothelial cells. (C) 2008 Elsevier Inc. All rights reserved. C1 [Shen, Jin-Song; Quirk, Jane M.; Schiffmann, Raphael; Kaneski, Christine R.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. [Meng, Xing-Li] NICHHD, Lab Clin Genome, NIH, Bethesda, MD 20892 USA. [Shayman, James A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Shen, Jin-Song; Meng, Xing-Li] Jikei Univ, Sch Med, Inst DNA Med, Dept Gene Therapy, Tokyo, Japan. [Moore, David F.] Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. EM Raphael.schiffmann@baylorhealth.edu OI Kaneski, Christine/0000-0003-1453-2502 FU National Institute of Neurological Disorders and Stroke; NIH FX We thank Drs. R.O. Brady and G.J. Murray for discussions. This work was funded by the Intramural Program of the National Institute of Neurological Disorders and Stroke, NIH. NR 36 TC 77 Z9 81 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2008 VL 95 IS 3 BP 163 EP 168 DI 10.1016/j.ymgme.2008.06.016 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 368DQ UT WOS:000260601900006 PM 18707907 ER PT J AU Tang, JR Donsante, A Desai, V Patronas, N Kaler, SG AF Tang, Jingrong Donsante, Anthony Desai, Vishal Patronas, Nicholas Kaler, Stephen G. TI Clinical outcomes in Menkes disease patients with a copper-responsive ATP7A mutation, G727R SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Copper transport; Neurodevelopment; Gene expression; Menkes disease; Newborn screening ID OCCIPITAL-HORN-SYNDROME; UNFOLDED PROTEIN RESPONSE; TANDEM MASS-SPECTROMETRY; CANDIDATE GENE; NMDA RECEPTOR; TRANSPORTING ATPASE; TRAFFICKING; EXPRESSION; LOCALIZATION; HOMEOSTASIS AB Menkes disease is a fatal neurodegenerative disorder of infancy caused by defects in an X-linked copper transport gene, ATHA. Evidence from a recent clinical trial indicates that favorable response to early treatment of this disorder with copper injections involves mutations that retain some copper transport capacity. In three unrelated infants, we identified the same mutation, G727R, in the second transmembrane segment of ATP7A that complemented a Saccharomyces cerevisiae copper transport mutant. consistent with partial copper transport activity. Quantitative reverse transcription-polymerase chain reaction studies showed approximately normal levels of ATP7A(G727R) transcript in two patients' fibroblasts compared to wild-type controls, but Western blot analyses showed markedly reduced quantities of ATP7A, suggesting post-translational degradation. We confirmed the latter by comparing degradation rates of mutant and wild-type ATP7A via cyclohexamide treatment of cultured fibroblasts; half-life of the G727R mutant was 2.9 h and for the wild-type, 11.4 h. We also documented a X-box binding protein 1 splice variant in G727R cells-known to be associated with the cellular misfolded protein response. Patient A, diagnosed 6 months of age, began treatment at 228 days (7.6 months) of age. At his current age (2.5 years), his overall neurodevelopment remains at a 2- to 4-month level. In contrast, patient B and patient C were diagnosed in the neonatal period, began treatment within 25 days of age, and show near normal neurodevelopment at their current ages, 3 years (patient B), and 7 months (patient C). The poor clinical outcome in patient A with the same missense mutation as patient A and patient B with near normal oucomes, confirms the importance of early medical intervention in Menkes disease and highlights the critical potential benefit of newborn screening for this disorder. Published by Elsevier Inc. C1 [Tang, Jingrong; Donsante, Anthony; Desai, Vishal; Kaler, Stephen G.] NICHHD, Unit Pediat Genet, Program Mol Med, Bethesda, MD 20892 USA. [Patronas, Nicholas] NIH, Imaging Sci Program, Mark O Hatfield Clin Ctr, Bethesda, MD 20892 USA. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Program Mol Med, Bldg 10,Room 10N-313,10 Ctr Dr,MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU NICHD Intramural Research Program FX We are grateful to Sarah Godwin for help in mutation screening, Courtney Holmes and David Goldstein for catecholamine analysis, Christine Kaneski for cell culture, and Olga Protchenko and Caroline Philpott for advice on yeast Western blotting. This work was supported by the NICHD Intramural Research Program. NR 37 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2008 VL 95 IS 3 BP 174 EP 181 DI 10.1016/j.ymgme.2008.06.015 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 368DQ UT WOS:000260601900008 PM 18752978 ER PT J AU Porras, A Kozar, S Russanova, V Salpea, P Hirai, T Sammons, N Mittal, P Kim, JY Ozato, K Romero, R Howard, BH AF Porras, Analia Kozar, Sarah Russanova, Valya Salpea, Paraskevi Hirai, Tazuko Sammons, Nicholas Mittal, Pooja Kim, Ji Young Ozato, Keiko Romero, Roberto Howard, Bruce H. TI Developmental and epigenetic regulation of the human TLR3 gene SO MOLECULAR IMMUNOLOGY LA English DT Article DE Innate immunity; Toll-like receptors; Development; Epigenetics; Chromatin ID TOLL-LIKE RECEPTORS; INNATE IMMUNITY; X-INACTIVATION; CHROMATIN-STRUCTURE; DENDRITIC CELLS; EXPRESSION; MECHANISMS; DISEASE; GAMMA; AGE AB The receptor encoded by the human TLR3 gene recognizes double-strand RNAs (dsRNAs) associated with Viral infection. TLR3 expression is strongly activated upon differentiation of monocytes to dendritic cells, and can be further stimulated by the dsRNA analog polyinosine:polycytosine (PI:C). We report evidence for developmental regulation of the TLR3 gene. In dendritic cells derived from cord blood, both differentiation and PI:C-associated TLR3 transcriptional activation are impaired as compared to cells from adults. Consistent with relative expression patterns, chromatin states and remodeling differ between newborn and adult samples. TLR3 expression in newborn dendritic cells exhibits heterocellularity and allelic imbalance (skewing), features characteristic of cis-acting epigenetic control. These findings reveal a new source for variability in innate immune system function and provide a model for further study of perinatal epigenetic transitions during development. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Porras, Analia; Kozar, Sarah; Russanova, Valya; Salpea, Paraskevi; Hirai, Tazuko; Sammons, Nicholas; Kim, Ji Young; Ozato, Keiko; Howard, Bruce H.] NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. [Mittal, Pooja; Romero, Roberto] NICHHD, Perinatal Res Branch, NIH, Bethesda, MD 20892 USA. RP Howard, BH (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. EM howard@helix.nih.gov RI Salpea, Paraskevi/A-8027-2010 FU NICHD; National Institutes of Health FX We are very grateful to Sandy Field and Nancy Hauff (Perinatology Research Branch), and to Cindy Matthews (Dept. of Transfusion Medicine, National Institutes of Health) for the collection of blood and apheresis specimens. We thank to Vincent Schram in the National Institute of Child Health and Human Development (NICHD) Imaging Facility for assistance with fluorescence imaging experiments. We also thank Michael Doctor and Jonathan Epstein for contributions to graphics and bioinformatics used in this study. This research was supported by the Intramural Research Program of the NICHD, National Institutes of Health. NR 42 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 2008 VL 46 IS 1 BP 27 EP 36 DI 10.1016/j.molimm.2008.06.030 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 371BV UT WOS:000260807700004 PM 18715647 ER PT J AU Sung, MH Bagain, L Chen, Z Karpova, T Yang, X Silvin, C Voss, TC McNally, JG Van Waes, C Gordon, L AF Sung, Myong-Hee Bagain, Lorena Chen, Zhong Karpova, Tatiana Yang, Xinping Silvin, Christopher Voss, Ty C. McNally, James G. Van Waes, Carter Hager, Gordon L. TI Dynamic Effect of Bortezomib on Nuclear Factor-kappa B Activity and Gene Expression in Tumor Cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID INFLAMMATION-ASSOCIATED CANCER; HUMAN HEAD; TRANSCRIPTION FACTORS; FEEDBACK LOOP; TARGET GENES; NECK-CANCER; LIVE CELLS; CARCINOMA; ACTIVATION; OSCILLATIONS AB Nuclear factor-kappa B (NF-kappa B) influences the initiation, progression, and maintenance of diverse cancer types. Despite current therapeutic efforts to block hyperactive NF-kappa B in cancer cells, the in vivo effects of a drug upon this complex pathway are unclear. We monitored NF-kappa B activity and a fast-expressing reporter level simultaneously in head and neck squamous carcinoma cells by quantitative live microscopy. The real-time single cell assay revealed the tumor necrosis factor-alpha-induced oscillation of NF-kappa B was echoed by equally dynamic reporter expression rate. Bortezomib is a proteasome inhibitor whose anticancer action is partly mediated through inhibition of NF-kappa B. When administered to preactivated cells, the drug gave rise to distinct inhibition dynamics, with discrete pulses of reporter induction remaining for hours. These findings suggest that, contrary to a simplistic presumption for a pathway "blockade," the network dynamics and the intracellular pharmacokinetics of the inhibitor must be critically evaluated in developing strategies for optimal intervention of oncogenic pathways. C1 [Sung, Myong-Hee; Karpova, Tatiana; Voss, Ty C.; McNally, James G.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Bagain, Lorena; Chen, Zhong; Yang, Xinping; Van Waes, Carter] Natl Inst Deafness & Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. [Silvin, Christopher] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sung, MH (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Room B602,Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA. EM sungm@mail.nih.gov FU National Institute on Deafness and Other Communication Disorders [Z01-DC-00016]; National Institutes of Health Intramural Research Program for Center for Cancer Research; National Cancer Institute; National Institutes of Health-approved Cooperative Research and Development Agreement with Millennium Pharmaceuticals FX This work was supported by National Institute on Deafness and Other Communication Disorders intramural project Z01-DC-00016 and by the National Institutes of Health Intramural Research Program for Center for Cancer Research, National Cancer Institute. C. V. W. has received bortezomib and clinical trial support under a National Institutes of Health-approved Cooperative Research and Development Agreement with Millennium Pharmaceuticals. NR 39 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2008 VL 74 IS 5 BP 1215 EP 1222 DI 10.1124/mol.108.049114 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362KT UT WOS:000260197300006 PM 18684839 ER PT J AU Yin, X Li, B Chen, H Catt, KJ AF Yin, Xing Li, Bo Chen, Hungdar Catt, Kevin J. TI Differential Signaling Pathways in Angiotensin II- and Epidermal Growth Factor-stimulated Hepatic C9 Cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; FACTOR RECEPTOR TRANSACTIVATION; PROTEIN-KINASE-C; PHOSPHOINOSITIDE 3-KINASE; TYPE-1 RECEPTOR; INDEPENDENT ACTIVATION; REGULATED KINASE-1/2; CAVEOLAE MEMBRANE; EPITHELIAL-CELLS; TYROSINE KINASE AB Caveolin1 (Cav1) is an important component of the plasma-membrane microdomains, such as caveolae/lipid rafts, that are associated with angiotensin II type 1 (AT(1)) and epidermal growth factor (EGF) receptors in certain cell types. The interactions of Cav1 with other signaling molecules that mediate AT(1) receptor function were analyzed in angiotensin II (Ang II)and EGF-stimulated hepatic C9 cells. This study demonstrated that cholesterol-rich domains mediate the actions of early upstream signaling molecules such as Src and intracellular Ca2+ in cells stimulated by Ang II, but not by EGF, and that Cav1 has a scaffolding role in the process of mitogen-activated protein kinase activation. Furthermore, Cav1 phosphorylation by Ang II and EGF was regulated by intracellular Ca2+ and Src, further indicating reciprocal interactions among Cav1, Src, and intracellular Ca2+ through the AT(1) receptor. Phosphorylation of Cav1 and the EGF receptor by Ang II, but not of extracellular signal-regulated kinase 1/2, was dependent on intracellular Ca2+. The phosphatidylinositol 3-kinase inhibitors, 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and wortmannin, differentially modulated both Cav1 and EGF receptor activation by Ang II through intracellular Ca2+. These findings further demonstrate the importance of Cav1 in conjunction with the receptor-mediated signaling pathways involved in cell proliferation and survival. It is clear that differential signaling pathways are operative in Ang II- and EGF-stimulated C9 cells and that cholesterol-enriched microdomains are essential components in cellular signaling processes that are dependent on specific agonists and/or cell types. C1 [Yin, Xing; Chen, Hungdar; Catt, Kevin J.] NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. [Li, Bo] NIDDK, Mol Signalling Lab Bioorgan Chem, NIH, Bethesda, MD USA. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM cattk@mail.nih.gov NR 40 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2008 VL 74 IS 5 BP 1223 EP 1233 DI 10.1124/mol.108.048504 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362KT UT WOS:000260197300007 PM 18687808 ER PT J AU Roy, A Ganguly, A BoseDasgupta, S Das, BB Pal, C Jaisankar, P Majumder, HK AF Roy, Amit Ganguly, Agneyo BoseDasgupta, Somdeb Das, Benu Brata Pal, Churala Jaisankar, Parasuraman Majumder, Hemanta K. TI Mitochondria-Dependent Reactive Oxygen Species-Mediated Programmed Cell Death Induced by 3,3 '-Diindolylmethane through Inhibition of F0F1-ATP Synthase in Unicellular Protozoan Parasite Leishmania donovani SO MOLECULAR PHARMACOLOGY LA English DT Article ID APOPTOSIS-LIKE DEATH; BREAST-CANCER CELLS; TOPOISOMERASE-I; TRYPANOSOME MITOCHONDRIA; DYSKINETOPLASTID CELLS; OXIDATIVE STRESS; ATP SYNTHASE; CYTOCHROME-C; CAMPTOTHECIN; PROMASTIGOTES AB Mitochondria are the principal site for the generation of cellular ATP by oxidative phosphorylation. F0F1-ATP synthase, a complex V of the electron transport chain, is an important constituent of mitochondria-dependent signaling pathways involved in apoptosis. In the present study, we have shown for the first time that 3,3'-diindolylmethane (DIM), a DNA topoisomerase I poison, inhibits mitochondrial F0F1-ATP synthase of Leishmania donovani and induces programmed cell death (PCD), which is a novel insight into the mechanism in protozoan parasites. DIM-induced inhibition of F0F1-ATP synthase activity causes depletion of mitochondrial ATP levels and significant stimulation of mitochondrial reactive oxygen species (ROS) production, followed by depolarization of mitochondrial membrane potential (Delta Psi m). Because Delta Psi m is the driving force for mitochondrial ATP synthesis, loss of Delta Psi m results in depletion of cellular ATP level. The loss of Delta Psi m causes the cellular ROS generation and in turn leads to the oxidative DNA lesions followed by DNA fragmentation. In contrast, loss of Delta Psi m leads to release of cytochrome c into the cytosol and subsequently activates the caspase-like proteases, which lead to oligonucleosomal DNA cleavage. We have also shown that mitochondrial DNA-depleted cells are insensitive to DIM to induce PCD. Therefore, mitochondria are necessary for cytotoxicity of DIM in kinetoplastid parasites. Taken together, our study indicates for the first time that DIM-induced mitochondrial dysfunction by inhibition of F0F1-ATP synthase activity leads to PCD in Leishmania spp. parasites, which could be exploited to develop newer potential therapeutic targets. C1 [Roy, Amit; Ganguly, Agneyo; BoseDasgupta, Somdeb; Majumder, Hemanta K.] Indian Inst Chem Biol, Mol Parasitol Lab, Kolkata 700032, India. [Pal, Churala; Jaisankar, Parasuraman] Indian Inst Chem Biol, Dept Med Chem, Kolkata 700032, India. [Das, Benu Brata] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Majumder, HK (reprint author), Indian Inst Chem Biol, Mol Parasitol Lab, 4 Raja SC Mullick Rd, Kolkata 700032, India. EM hkmajumder@iicb.res.in FU Network Project NWP-38 of Council of Scientific and Industrial Research, Government of India FX This work was supported by the grants from Network Project NWP-38 of Council of Scientific and Industrial Research, Government of India. NR 39 TC 80 Z9 82 U1 3 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2008 VL 74 IS 5 BP 1292 EP 1307 DI 10.1124/mol.108.050161 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362KT UT WOS:000260197300013 PM 18703668 ER PT J AU Borland, MG Foreman, JE Girroir, EE Zolfaghari, R Sharma, AK Amin, S Gonzalez, FJ Ross, AC Peters, JM AF Borland, Michael G. Foreman, Jennifer E. Girroir, Elizabeth E. Zolfaghari, Reza Sharma, Arun K. Amin, Shantu Gonzalez, Frank J. Ross, A. Catharine Peters, Jeffrey M. TI Ligand Activation of Peroxisome Proliferator-Activated Receptor-beta/delta Inhibits Cell Proliferation in Human HaCaT Keratinocytes SO MOLECULAR PHARMACOLOGY LA English DT Article ID DIETARY RETINOIC ACID; SKIN TUMOR PROMOTION; FEMALE SENCAR MICE; PPAR-BETA/DELTA; MOUSE SKIN; CARCINOGENESIS PROTOCOL; MALIGNANT CONVERSION; 9-CIS-RETINOIC ACID; HIGH-RISK; GROWTH AB Although there is strong evidence that ligand activation of peroxisome proliferator-activated receptor (PPAR)-beta/delta induces terminal differentiation and attenuates cell growth, some studies suggest that PPAR beta/delta actually enhances cell proliferation. For example, it was suggested recently that retinoic acid (RA) is a ligand for PPAR beta/delta and potentiates cell proliferation by activating PPAR beta/delta. The present study examined the effect of ligand activation of PPAR beta/delta on cell proliferation, cell cycle kinetics, and target gene expression in human HaCaT keratinocytes using two highly specific PPAR beta/delta ligands [4-[[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl] methyl]thio]-2-methylphenoxy acetic acid (GW0742) and 2-methyl-4-((4-methyl-2-(4-trifluoromethylphenyl)-1,3-thiazol-5- yl)-methylsulfanyl)phenoxy-acetic acid (GW501516)] and RA. Both PPAR beta/delta ligands and RA inhibited cell proliferation of HaCaT keratinocytes. GW0742 and GW501516 increased expression of known PPAR beta/delta target genes, whereas RA did not; RA increased the expression of known retinoic acid receptor/retinoid X receptor target genes, whereas GW0742 did not affect these genes. GW0742, GW501516, and RA did not modulate the expression of 3-phosphoinositide-dependent protein kinase or alter protein kinase B phosphorylation. GW0742 and RA increased annexin V staining as quantitatively determined by flow cytometry. The effects of GW0742 and RA were also examined in wild-type and PPAR beta/delta-null primary mouse keratinocytes to determine the specific role of PPAR beta/delta in modulating cell growth. Although inhibition of keratinocyte proliferation by GW0742 was PPAR beta/delta-dependent, inhibition of cell proliferation by RA occurred in both genotypes. Results from these studies demonstrate that ligand activation of PPAR beta/delta inhibits keratinocyte proliferation through PPAR beta/delta-dependent mechanisms. In contrast, the observed inhibition of cell proliferation in mouse and human keratinocytes by RA is mediated by PPAR beta/delta-independent mechanisms and is inconsistent with the notion that RA potentiates cell proliferation by activating PPAR beta/delta. C1 [Borland, Michael G.; Foreman, Jennifer E.; Girroir, Elizabeth E.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Borland, Michael G.; Foreman, Jennifer E.; Girroir, Elizabeth E.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. [Zolfaghari, Reza; Ross, A. Catharine] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Sharma, Arun K.; Amin, Shantu] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Penn State Canc Inst, Hershey, PA 17033 USA. [Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Bethesda, MD USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU National Science Foundation Graduate Research Fellowship; National Institutes of Health [CA124533, CA90214] FX This work was supported by a National Science Foundation Graduate Research Fellowship and by National Institutes of Health grants CA124533 (to J. M. P.) and CA90214 (to A. C. R.). NR 53 TC 32 Z9 33 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2008 VL 74 IS 5 BP 1429 EP 1442 DI 10.1124/mol.108.050609 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362KT UT WOS:000260197300026 PM 18687807 ER PT J AU Volkow, N Rutter, J Pollock, JD Shurtleff, D Baler, R AF Volkow, N. Rutter, J. Pollock, J. D. Shurtleff, D. Baler, R. TI One SNP linked to two diseases-addiction and cancer: A Double Whammy? Nicotine addiction and lung cancer susceptibility SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID IN-VIVO; ALPHA-3; ASSOCIATION; DEPENDENCE; RECEPTORS; GENES; LOCUS; RNA C1 [Volkow, N.] Natl Inst Drug Abuse, NIH, Off Director, Bethesda, MD 20892 USA. [Rutter, J.; Pollock, J. D.; Shurtleff, D.] Natl Inst Drug Abuse, NIH, Div Basic Neurosci & Behav Res, Bethesda, MD USA. [Baler, R.] Natl Inst Drug Abuse, NIH, Off Sci Policy & Commun, Bethesda, MD USA. RP Volkow, N (reprint author), Natl Inst Drug Abuse, NIH, Off Director, Bethesda, MD 20892 USA. EM balerr@mail.nih.gov RI Pollock, Jonathan/B-1554-2009; OI Rutter, Joni/0000-0002-6502-2361 FU Intramural NIH HHS [Z99 DA999999] NR 17 TC 10 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2008 VL 13 IS 11 BP 990 EP 992 DI 10.1038/mp.2008.71 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 368OS UT WOS:000260632200001 PM 18936755 ER PT J AU Brosh, R Shalgi, R Liran, A Landan, G Korotayev, K Nguyen, GH Enerly, E Johnsen, H Buganim, Y Solomon, H Goldstein, I Madar, S Goldfinger, N Brresen-Dale, AL Ginsberg, D Harris, CC Pilpel, Y Oren, M Rotter, V AF Brosh, Ran Shalgi, Reut Liran, Atar Landan, Gilad Korotayev, Katya Nguyen, Giang Huong Enerly, Espen Johnsen, Hilde Buganim, Yosef Solomon, Hilla Goldstein, Ido Madar, Shalom Goldfinger, Naomi Brresen-Dale, Anne-Lise Ginsberg, Doron Harris, Curtis C. Pilpel, Yitzhak Oren, Moshe Rotter, Varda TI p53-repressed miRNAs are involved with E2F in a feed-forward loop promoting proliferation SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE breast cancer; microarray; miR-106; mir-155; senescence ID CELL-CYCLE PROGRESSION; P53 TUMOR-SUPPRESSOR; GENE-EXPRESSION; MESSENGER-RNA; BREAST-CANCER; COLON-CANCER; MUTANT P53; S-PHASE; MICRORNAS; APOPTOSIS AB Normal cell growth is governed by a complicated biological system, featuring multiple levels of control, often deregulated in cancers. The role of microRNAs (miRNAs) in the control of gene expression is now increasingly appreciated, yet their involvement in controlling cell proliferation is still not well understood. Here we investigated the mammalian cell proliferation control network consisting of transcriptional regulators, E2F and p53, their targets and a family of 15 miRNAs. Indicative of their significance, expression of these miRNAs is downregulated in senescent cells and in breast cancers harboring wild-type p53. These miRNAs are repressed by p53 in an E2F1-mediated manner. Furthermore, we show that these miRNAs silence antiproliferative genes, which themselves are E2F1 targets. Thus, miRNAs and transcriptional regulators appear to cooperate in the framework of a multi-gene transcriptional and post-transcriptional feed-forward loop. Finally, we show that, similarly to p53 inactivation, overexpression of representative miRNAs promotes proliferation and delays senescence, manifesting the detrimental phenotypic consequence of perturbations in this circuit. Taken together, these findings position miRNAs as novel key players in the mammalian cellular proliferation network. C1 [Brosh, Ran; Shalgi, Reut; Liran, Atar; Landan, Gilad; Buganim, Yosef; Solomon, Hilla; Goldstein, Ido; Madar, Shalom; Goldfinger, Naomi; Oren, Moshe; Rotter, Varda] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [Shalgi, Reut; Pilpel, Yitzhak] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Korotayev, Katya; Ginsberg, Doron] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. [Nguyen, Giang Huong; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nguyen, Giang Huong] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Chevy Chase, MD USA. [Enerly, Espen; Brresen-Dale, Anne-Lise] Univ Oslo, Norwegian Radium Hosp, Fac Div, Dept Genet, Oslo, Norway. RP Rotter, V (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM varda.rotter@weizmann.ac.il OI Shalgi, Reut/0000-0002-7589-1798; Brosh, Ran/0000-0001-9714-8623; Goldstein, Ido/0000-0003-0139-1499 FU Flight Attendant Medical Research Institute; EC [502983]; FP7 funding (ONCOMIRS) [201102]; Ben May Charitable Trust; Israel Science Foundation; Yad Abraham Center for Cancer Diagnosis and Therapy; Intramural Research Program; NIH; NCI; CCR; Howard Hughes Medical Institute Grant for Graduate Medical Education FX This study was supported by a Center of Excellence grant from the Flight Attendant Medical Research Institute; EC FP6 funding (contract no. 502983); FP7 funding (ONCOMIRS, agreement 201102); the Ben May Charitable Trust; the Israel Science Foundation and the Yad Abraham Center for Cancer Diagnosis and Therapy. This research was supported in part by the Intramural Research Program, NIH, NCI and CCR. VR is the incumbent of the Norman and Helen Asher Professorial Chair Cancer Research at the Weizmann institute. YP is an incumbent of the Rothstein Career Development Chair in Genetic Diseases. RS is a fellow of the Horowitz Foundation for Complexity Sciences. GHN was supported by the Howard Hughes Medical Institute Grant for Graduate Medical Education. This publication reflects only authors' views. The European Commission is not liable for any use that may be made of the information herein. We thank Agilent Technologies for access to the early version of their miRNA arrays and for their support. NR 66 TC 103 Z9 110 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD NOV PY 2008 VL 4 AR 229 DI 10.1038/msb.2008.65 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379KG UT WOS:000261394500004 PM 19034270 ER PT J AU Dobrikova, EY Broadt, T Poiley-Nelson, J Yang, XY Soman, G Giardina, S Harris, R Gromeier, M AF Dobrikova, Elena Y. Broadt, Trevor Poiley-Nelson, Judith Yang, Xiaoyi Soman, Gopalan Giardina, Steve Harris, Ray Gromeier, Matthias TI Recombinant Oncolytic Poliovirus Eliminates Glioma In Vivo Without Genetic Adaptation to a Pathogenic Phenotype SO MOLECULAR THERAPY LA English DT Article ID RIBOSOMAL ENTRY SITE; ATTENUATED POLIOVIRUS; TRANSGENIC MICE; ATHYMIC MICE; NEUROBLASTOMA; THERAPY; GROWTH; REGION; TUMORS; NEUROVIRULENCE AB Many viruses, either naturally occurring or as a result of genetic manipulation, exhibit conditional replication in transformed cells. This principle is the basis for experimental therapeutic approaches exploiting the oncolytic potential of such agents without the danger of collateral damage to resistant normal tissues. One of the potential obstacles to these approaches is the possibility of genetic adaptation of oncolytic viruses upon replication in susceptible tumor tissues. Genetic variation can reverse genetic manipulations of parental viral genomes that determine attenuation of virulence, selective tumor cell tropism or other desirable traits. Alternatively, it may convey new properties not originally associated with parental strains, e. g., adaptation to a human host range. We examined genetic stability of an oncolytic nonpathogenic poliovirus recombinant considered for therapy of recurrent glioblastoma multiforme (GBM). This was done by serial passage experiments in glioma xenografts in vivo and investigation of phenotypic and genotypic markers of attenuation. Intratumoral inoculation of oncolytic poliovirus produced efficient tumor regress and elimination without altering temperature-sensitive growth, selective cytotoxicity, or genetic markers of attenuation of virus recovered from inoculated animals. Our studies demonstrate that active viral oncolysis of malignant glioma does not alter the conditional replication properties of oncolytic nonpathogenic poliovirus recombinants. C1 [Dobrikova, Elena Y.; Gromeier, Matthias] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. [Broadt, Trevor; Poiley-Nelson, Judith; Yang, Xiaoyi; Soman, Gopalan; Giardina, Steve; Harris, Ray] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Gromeier, M (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. EM grome001@mc.duke.edu FU PHS [NS20023, CA124756]; Alex's Lemonade Stand Foundation; Developmental Therapeutics Program; Division of Cancer Treatment and Diagnosis; National Cancer Institute; National Institutes of Health FX We gratefully acknowledge A. Nomoto (University of Tokyo, Japan) for providing the genomic complementary DNA clone of poliovirus type 1 (Sabin) used to generate PVS-RIPO. This work was supported by the PHS grants NS20023 (to M. G.), CA124756 (to M. G.), and Alex's Lemonade Stand Foundation. This project has been supported in whole or in part through the NCI-RAID Program of the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or any organization imply endorsement by the US Government. NR 33 TC 28 Z9 28 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2008 VL 16 IS 11 BP 1865 EP 1872 DI 10.1038/mt.2008.184 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366HY UT WOS:000260472600017 PM 18766173 ER PT J AU Kelsall, B AF Kelsall, B. TI Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages SO MUCOSAL IMMUNOLOGY LA English DT Review ID REGULATORY T-CELLS; FOLLICLE-ASSOCIATED EPITHELIUM; INFLAMMATORY-BOWEL-DISEASE; MURINE PEYERS PATCH; ORAL SALMONELLA INFECTION; TOLL-LIKE RECEPTOR-5; TRANS-RETINOIC ACID; LAMINA-PROPRIA; TGF-BETA; IMMUNE-RESPONSES AB Mucosal immune responses must be tightly controlled, particularly in the intestine. As members of the mononuclear phagocyte family, dendritic cells (DCs) and macrophages are well represented in intestinal tissues and have developed unique functional niches. This review will focus on recent findings on antigen uptake and processing in the intestine and the role of DCs in the imprinting of homing receptors on T and B cells, the induction of immunoglobulin A B-cell responses, and the differentiation of regulatory T cells. It will also address the unique phenotype of intestinal macrophages and briefly what is known regarding the relationships between these cell types. C1 NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Kelsall, B (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Kelsall@nih.gov FU Intramural NIH HHS [Z01 AI000833-10] NR 123 TC 76 Z9 79 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 IS 6 BP 460 EP 469 DI 10.1038/mi.2008.61 PG 10 WC Immunology SC Immunology GA 366HL UT WOS:000260471300007 PM 19079213 ER PT J AU Udey, MC Nagao, K AF Udey, M. C. Nagao, K. TI Characteristics and functions of murine cutaneous dendritic cells: a synopsis of recent developments SO MUCOSAL IMMUNOLOGY LA English DT Review ID EPIDERMAL LANGERHANS CELLS; STEADY-STATE; CONTACT HYPERSENSITIVITY; BONE-MARROW; NULL MICE; T-CELLS; IN-VIVO; SKIN; LANGERIN/CD207; IDENTIFICATION AB Cutaneous accessory cells include dendritic cells (DCs) and macrophages. Heterogeneity, plasticity, and responsiveness to local environmental cues are hallmarks of both types of cells. Until recently, results of studies of cells that had been extracted from tissues or propagated in vitro provided the foundation for most conceptual frameworks. The availability of a variety of spontaneously occurring and genetically engineered mice has facilitated in vivo studies that have provided new insights into the developmental and functional aspects of DCs in skin and other tissues. In several instances, results of these in vivo studies have been very surprising. Existing paradigms have been modified or debunked, and new hypotheses have been generated. We can anticipate that detailed understanding of the biology of individual cutaneous accessory cells and their relationships with each other will continue to accumulate as these types of studies are actively pursued. C1 [Udey, M. C.; Nagao, K.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM udey@helix.nih.gov RI Nagao, Keisuke/J-5116-2013 OI Nagao, Keisuke/0000-0002-7005-3138 FU Intramural Program of the NIH; Center for Cancer Research; NCI FX We thank Miriam Merad for helpful discussions and for allowing us to review and cite materials that were in press when this paper was prepared. This study was supported by the Intramural Program of the NIH, Center for Cancer Research, NCI. NR 32 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 IS 6 BP 470 EP 474 DI 10.1038/mi.2008.37 PG 5 WC Immunology SC Immunology GA 366HL UT WOS:000260471300008 PM 19079214 ER PT J AU Macal, M Sankaran, S Chun, TW Reay, E Flamm, J Prindiville, TJ Dandekar, S AF Macal, M. Sankaran, S. Chun, T-W Reay, E. Flamm, J. Prindiville, T. J. Dandekar, S. TI Effective CD4+T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses SO MUCOSAL IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; TYPE-1 INFECTION; HIV-1-INFECTED SUBJECTS; ANTIVIRAL THERAPY; CCR5 EXPRESSION; MUCOSAL REPAIR; MEMORY; REPLICATION; PERSISTENCE AB Human immunodeficiency virus (HIV) infection leads to severe CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) that persists despite the initiation of highly active antiretroviral therapy (HAART). It is not known whether restoration of gut mucosal CD4+ T cells and their functions is feasible during therapy and how that relates to immune correlates and viral reservoirs. Intestinal biopsies and peripheral blood samples from HIV-infected patients who were either HAART naive or on long-term HAART were evaluated. Our data demonstrated that gut CD4+ T-cell restoration ranged from modest (<50%) to high (>50%), compared with uninfected controls. Despite persistent CD4+ T-cell proviral burden and residual immune activation in GALT during HAART, effective CD4+ T-cell restoration (>50%) was achieved, which was associated with enhanced Th17 CD4+ T-cell accumulation and polyfunctional anti-HIV cellular responses. Our findings suggest that a threshold of >50% CD4+ T-cell restoration may be sufficient for polyfunctional HIV-specific T cells with implications in the evaluation of vaccines and therapeutics. C1 [Macal, M.; Sankaran, S.; Reay, E.; Dandekar, S.] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Chun, T-W] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Flamm, J.] Kaiser Permanente Med Grp, Sacramento, CA USA. [Prindiville, T. J.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. RP Dandekar, S (reprint author), Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. EM sdandekar@ucdavis.edu FU National Institute of Health (NIH) [R01 DK61297, AIO43274, T32 AI-60555] FX We thank UCDMC GI and J St Clinic staff, California HIV AIDS Research Program CH5-D-606, Dr Jerome Braun for statistical advice, Dr Michael George for paper review, and patients for their participation. Study support was provided by the National Institute of Health (NIH) R01 DK61297 and by NIH supplemental award AIO43274 and T32 AI-60555 for primary author. NR 45 TC 111 Z9 116 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 IS 6 BP 475 EP 488 DI 10.1038/mi.2008.35 PG 14 WC Immunology SC Immunology GA 366HL UT WOS:000260471300009 PM 19079215 ER PT J AU Vaccari, M Boasso, A Ma, ZM Cecchinato, V Venzon, D Doster, MN Tsai, WP Shearer, GM Fuchs, D Felber, BK Pavlakis, GN Miller, CJ Franchini, G AF Vaccari, M. Boasso, A. Ma, Z-M Cecchinato, V. Venzon, D. Doster, M. N. Tsai, W. P. Shearer, G. M. Fuchs, D. Felber, B. K. Pavlakis, G. N. Miller, C. J. Franchini, G. TI CD4(+) T-cell loss and delayed expression of modulators of immune responses at mucosal sites of vaccinated macaques following SIVmac251 infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOID-TISSUE; RHESUS-MONKEYS; SIV INFECTION; ANTIRETROVIRAL THERAPY; SYSTEMIC VACCINATION; TYPE-1 INFECTION; TGF-BETA; MEMORY AB Systemic immunization of macaques with a combination of DNA-poxvirus-based vaccines confers protection from high level of both systemic and mucosal viral replication following rectal exposure to the pathogenic SIVmac251. Here we investigated early post-infection events in rectal and vaginal tissues, and found that the loss of CCR5(+) CD4(+) T cells was equivalent in vaccinated and control macaques, despite a three logs reduction at mucosal sites of simian immunodeficiency virus (SIV) RNA in the vaccinated group. Even though a normal CD4(+) T cell number is not reconstituted at mucosal sites in either group, vaccination appeared to confer a better preservation of the CD4(+) CCR5(+) T cells that replenish these sites. Analysis of rectal tissues RNA following challenge exposure demonstrated a decreased expression in vaccinated macaques of transforming growth factor-beta, cytotoxic T lymphocyte antigen-4, FoxP3, and indoleamine 2,3-dioxygenase, an immune suppressive enzyme expressed by dendritic cells that converts tryptophan to kynurenine and limits T-cell responses. Accordingly, the ratio of kynurenine and tryptophan in the plasma was significantly reduced in the vaccinated animals respect to the controls. Thus, preexisting adaptive immune responses induced by these vaccine modalities, although they do not protect from CD4(+) T-cell depletion, nevertheless, they contain SIVmac251 replication and delay expression of markers of T-cell activation and/or suppression at mucosal sites. C1 [Vaccari, M.; Cecchinato, V.; Doster, M. N.; Tsai, W. P.; Franchini, G.] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Boasso, A.; Shearer, G. M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Ma, Z-M] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Venzon, D.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Fuchs, D.] Innsbruck Med Univ, Div Biol Chem, Bioctr, Innsbruck, Austria. [Felber, B. K.] NCI, Human Retrovirus Pathogenesis Sect, NIH, Frederick, MD 21701 USA. [Pavlakis, G. N.] NCI, Human Retrovirus Sect, NIH, Frederick, MD 21701 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX We thank P. D. Markham, S. Orndorff, D. Weiss, and J. Treece of Advanced BioScience Laboratories, Kensington, MD. We thank D. Panicali from Therion for constructing and providing us the recombinant poxviruses. We also thank Steven Snodgrass, Ryan Kelly, and Teresa Habina for the editorial assistance. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 43 TC 21 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 IS 6 BP 497 EP 507 DI 10.1038/mi.2008.60 PG 11 WC Immunology SC Immunology GA 366HL UT WOS:000260471300011 PM 19079217 ER PT J AU Fichtner-Feigl, S Strober, W Geissler, EK Schlitt, HJ AF Fichtner-Feigl, S. Strober, W. Geissler, E. K. Schlitt, H-J TI Cytokines mediating the induction of chronic colitis and colitis-associated fibrosis SO MUCOSAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of Intestinal Inflammation CY OCT, 2007 CL Dresden, GERMANY SP Falk Fdn ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; IL-13; RECEPTOR AB To investigate the immunopathogenesis of inflammation-associated fibrosis we analyzed the chronic colitis and late-developing fibrosis occurring in BALB/c mice administered weekly doses of intrarectal trinitrobenzene sulfonic acid (TNBS). We showed first in this model that an initial T helper type 1 response involving interleukin (IL)-12p70 and interferon-gamma subsides after 3 weeks to be supplanted by an IL-23/IL-25 response beginning after 4-5 weeks. This evolution is followed by gradually increasing production of IL-17 and cytokines ordinarily seen in a T helper type 2 response, particularly IL-13, which reaches a plateau at 8-9 weeks. We then show that IL-13 production results in the induction of an IL-13 receptor formerly thought to function only as a decoy receptor, IL-13R alpha(2), and this receptor is critical to the production of tumor growth factor (TGF)-beta(1) and the onset of fibrosis. Thus, if IL-13 signaling through this receptor is blocked by administration of soluble IL-13R alpha(2)-Fc, or by administration of IL-13R alpha(2)-specific siRNA, TGF-beta(1) is not produced and fibrosis does not occur. These studies show that in chronic TNBS colitis, fibrosis is dependent on the development of an IL-13 response that acts through a novel cell-surface-expressed IL-13 receptor to induce TGF-beta(1). C1 [Fichtner-Feigl, S.; Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Fichtner-Feigl, S.; Geissler, E. K.; Schlitt, H-J] Univ Regensburg, Dept Surg, Regensburg, Germany. RP Fichtner-Feigl, S (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM stefan.fichtner@klinik.uni-regensburg.de RI Geissler, Edward/R-4131-2016 FU Intramural NIH HHS [ZIA AI000432-25] NR 12 TC 29 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 SU 1 BP S24 EP S27 DI 10.1038/mi.2008.41 PG 4 WC Immunology SC Immunology GA 366HN UT WOS:000260471500006 PM 19079223 ER PT J AU Fuss, IJ Strober, W AF Fuss, I. J. Strober, W. TI The role of IL-13 and NK T cells in experimental and human ulcerative colitis SO MUCOSAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of Intestinal Inflammation CY OCT, 2007 CL Dresden, GERMANY SP Falk Fdn ID ANTIGEN PRESENTATION; OXAZOLONE COLITIS; MODEL AB Recent studies that have evaluated the immunologic factors that mediate the development of the two forms of inflammatory bowel disease, namely Crohn's disease and ulcerative colitis (UC), have suggested that these diseases are because of disparate immune responses. Although Crohn's disease has been characterized as a dysregulation of the T helper (Th)1/Th17 pathways more recent evidence has emerged that UC pathogenesis is associated with a nonclassical NK (natural killer) T cell producing an atypical Th2 (interleukin (IL)-13) response. In the following review the insights gained from both animal models and human studies as to the function that IL-13 and NK T cells have in the pathogenesis of UC will be discussed. C1 [Fuss, I. J.; Strober, W.] NIH, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA. RP Fuss, IJ (reprint author), NIH, Mucosal Immun Sect, Host Def Lab, Bldg 10, Bethesda, MD 20892 USA. EM ifuss@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000354-25] NR 12 TC 46 Z9 47 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 SU 1 BP S31 EP S33 DI 10.1038/mi.2008.40 PG 3 WC Immunology SC Immunology GA 366HN UT WOS:000260471500008 PM 19079225 ER PT J AU Kitani, A Xu, L AF Kitani, A. Xu, L. TI Regulatory T cells and the induction of IL-17 SO MUCOSAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of Intestinal Inflammation CY OCT, 2007 CL Dresden, GERMANY SP Falk Fdn ID GROWTH-FACTOR-BETA; TGF-BETA; CUTTING EDGE; HELPER-CELLS; DIFFERENTIATION; INTERLEUKIN-17; COLITIS; LINEAGE; CURE AB T helper (Th)17 cells have been shown to play a role in the pathogenesis of inflammatory and autoimmune diseases including inflammatory bowel diseases (IBD). It is now well established that although transforming growth factor (TGF)-beta alone induces FoxP3(+) regulatory T (Treg) cells, TGF-beta and interleukin (IL)-6, acting in concert, induce differentiation of mouse naive T cells into Th17. As we previously showed that CD4(+)CD25(+)Foxp3(+) "natural" Treg cells express cell surface or secrete TGF-beta, we examined whether Treg cells serve to induce Th17 differentiation. We found that upon activation, Treg cells induce CD4(+)CD25(-) naive T cells or Treg cells themselves to differentiate into Th17 in the presence of IL-6 alone without exogenous addition of TGF-beta. We also found that TGF-beta is also produced by dendritic cells that are in contact with Treg cells. Although Treg cells are effectively recruited at inflamed mucosa in patients with IBD, it is possible that Treg cells may have undesirable effects through their ability to differentiate into pathogenic Th17 in the presence of IL-6 and/or IL-23 at sites of inflammation. Further study of the relationship between Treg cells and Th17 cells in the inflamed tissue in IBD is important for possible Treg cell-mediated therapeutic applications. C1 [Kitani, A.; Xu, L.] NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA. RP Kitani, A (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, Bethesda, MD 20892 USA. EM akitani@niaid.nih.gov NR 18 TC 30 Z9 36 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 SU 1 BP S43 EP S46 DI 10.1038/mi.2008.51 PG 4 WC Immunology SC Immunology GA 366HN UT WOS:000260471500011 PM 19079228 ER PT J AU Strober, W Kitani, A Fuss, I Asano, N Watanabe, T AF Strober, W. Kitani, A. Fuss, I. Asano, N. Watanabe, T. TI The molecular basis of NOD2 susceptibility mutations in Crohn's disease SO MUCOSAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of Intestinal Inflammation CY OCT, 2007 CL Dresden, GERMANY SP Falk Fdn ID COLITIS; INDUCTION; RESPONSES; MICE AB Nucleotide oligomerization domain (NOD) 2 is a member of the NOD-like receptor family of proteins that initiate inflammatory responses when exposed to ligands derived from bacterial components that gain access to the intracellular milieu. It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (CARD15) that lead to impaired NOD2 function, are susceptibility factors in Crohn's disease, a condition marked by excessive inflammatory responses to normal bacterial flora. In an initial series of studies conducted in our laboratory to better define NOD2 function and to resolve this paradox we showed that NOD2 activation by its ligand, muramyl dipeptide (MDP) ordinarily downregulates responses to Toll-like receptor (TLR) stimulation, and thus cells lacking NOD2 mount increased responses to such stimulation. This fits with the fact that mice bearing an NOD2 transgene, and thus having cells with increased NOD2 function display decreased responses to TLR stimulation and are resistant to experimental colitis induction. In further studies, we showed that prestimulation of cells with NOD2 ligand renders them unresponsive to TLR stimulation, because such prestimulation results in the elaboration of inhibitory factor (IRF4), an inhibitor of TLR-induced inflammatory pathways. Furthermore, administration of MDP to normal mice induces IRF4 and prevents experimental colitis. These studies strongly suggest that NOD2 polymorphisms are associated with Crohn's disease because they lead to a decrease in the negative regulation of TLR responses occurring in the normal gut, and thus a pathologic increase in responses to the normal flora. The finding that MDP administration prevents experimental colitis opens the door to the possibility that such treatment might quell Crohn's disease relapses in patients without NOD2 abnormalities. C1 [Strober, W.; Kitani, A.; Fuss, I.; Asano, N.; Watanabe, T.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Watanabe, T.] Kyoto Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Kyoto, Japan. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov OI Asano, Naoki/0000-0003-4452-8459 FU Intramural NIH HHS [Z01 AI000354-25] NR 8 TC 53 Z9 54 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 SU 1 BP S5 EP S9 DI 10.1038/mi.2008.42 PG 5 WC Immunology SC Immunology GA 366HN UT WOS:000260471500002 PM 19079230 ER PT J AU Strober, W Zeitz, M Blumberg, RS AF Strober, W. Zeitz, M. Blumberg, R. S. TI Preface SO MUCOSAL IMMUNOLOGY LA English DT Editorial Material C1 [Strober, W.] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Zeitz, M.] Charite Univ Med Berlin, Med Klin 1, Berlin, Germany. [Blumberg, R. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Gastroenterol Div, Boston, MA 02115 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2008 VL 1 SU 1 BP S1 EP S4 DI 10.1038/mi.2008.58 PG 4 WC Immunology SC Immunology GA 366HN UT WOS:000260471500001 PM 19079219 ER PT J AU Miller, DH Weinshenker, BG Filippi, M Banwell, BL Cohen, JA Freedman, MS Galetta, SL Hutchinson, M Johnson, RT Kappos, L Kira, J Lublin, FD McFarland, HF Montalban, X Panitch, H Richert, JR Reingold, SC Polman, CH AF Miller, D. H. Weinshenker, B. G. Filippi, M. Banwell, B. L. Cohen, J. A. Freedman, M. S. Galetta, S. L. Hutchinson, M. Johnson, R. T. Kappos, L. Kira, J. Lublin, F. D. McFarland, H. F. Montalban, X. Panitch, H. Richert, J. R. Reingold, S. C. Polman, C. H. TI Differential diagnosis of suspected multiple sclerosis: a consensus approach SO MULTIPLE SCLEROSIS JOURNAL LA English DT Review DE diagnosis; differential diagnosis; multiple sclerosis ID DEVICS-NEUROMYELITIS-OPTICA; CLINICALLY ISOLATED SYNDROMES; ACUTE DISSEMINATED ENCEPHALOMYELITIS; MAGNETIZATION-TRANSFER; IMAGING CHANGES; IGG PREDICTS; MRI FINDINGS; FOLLOW-UP; NMO-IGG; CRITERIA AB Background and objectives Diagnosis of multiple sclerosis ( MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. Multiple Sclerosis 2008; 14: 1157 1174. http://msj.sagepub. com C1 [Miller, D. H.] UCL, NMR Res Unit, Inst Neurol, Dept Inflammat, London WC1E 6BT, England. [Weinshenker, B. G.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. [Filippi, M.] Osped San Rafaele, Dept Neurol, Neuroimaging Res Unit, Milan, Italy. [Banwell, B. L.] Hosp Sick Children, Dept Paediat, Div Neurol, Toronto, CA USA. [Cohen, J. A.] Cleveland Clin, Mellen Ctr, Cleveland, OH 44106 USA. [Freedman, M. S.] Univ Ottawa, Ottawa Hosp, Dept Med Neurol, MS Res Unit, Ottawa, CA USA. [Galetta, S. L.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Hutchinson, M.] St Vincents Univ Hosp, Dept Neurol, Dublin 4, Ireland. [Johnson, R. T.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Kappos, L.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland. [Kira, J.] Kyushu Univ, Dept Neurol, Kyushu, Japan. [Lublin, F. D.] Mt Sinai Sch Med, Corrine Goldsmith Dickinson Ctr Multiple Sclerosi, New York, NY USA. [McFarland, H. F.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Montalban, X.] Hosp Univ Hebron, Unitat Neuroimmunol Clin, Barcelona, Spain. [Panitch, H.] Univ Vermont, Coll Med, Neurol Serv, Burlington, VT USA. [Richert, J. R.; Reingold, S. C.] Natl Multiple Sclerosis Soc, Res & Clin Programs Dept, New York, NY USA. [Reingold, S. C.] Sci & Clin Review Associates LLC, New York, NY USA. [Polman, C. H.] UCL, Inst Neurol, Dept Neuroinflammat, London WC1E 6BT, England. RP Polman, CH (reprint author), Free Univ Amsterdam, Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. EM ch.polman@vumc.nl OI hutchinson, michael/0000-0002-8675-1723 FU National Multiple Sclerosis Society (US) FX The authors gratefully acknowledge constructive criticism provided in review of an earlier version of the manuscript by Drs Sten Fredrikson (Copenhagen), Andrew Goodman (Rochester, NY), Catherine Lubetzki (Paris), John Newsom-Davis (Oxford, deceased), Paul O'Connor (Toronto), Richard Rudick (Cleveland), and Jack Simon (Portland, OR). The work of the Task Force was supported by the National Multiple Sclerosis Society (US). NR 62 TC 260 Z9 275 U1 1 U2 19 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD NOV PY 2008 VL 14 IS 9 BP 1157 EP 1174 DI 10.1177/1352458508096878 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 364MR UT WOS:000260340300003 PM 18805839 ER PT J AU O'Brien, EP Stan, G Thirumalai, D Brooks, BR AF O'Brien, Edward P. Stan, George Thirumalai, D. Brooks, Bernard R. TI Factors Governing Helix Formation in Peptides Confined to Carbon Nanotubes SO NANO LETTERS LA English DT Article ID 4-HELIX BUNDLE PROTEIN; GLOBULAR-PROTEINS; EXIT TUNNEL; SECONDARY STRUCTURE; ALPHA-HELICES; NATIVE-STATE; RIBOSOME; STABILITY; ENHANCEMENT; SIMULATIONS AB The effect of confinement on the stability and dynamics of peptides and proteins is relevant in the context of a number of problems in biology and biotechnology. We have examined the stability of different helix-forming sequences upon confinement to a carbon nanotube using Langevin dynamics simulations of a coarse-grained representation of the polypeptide chain. We show that the interplay of several factors that include sequence, solvent conditions, strength (lambda) of nanotube-peptide interactions, and the nanotube diameter (D) determines confinement-induced stability of helicies. In agreement with predictions based on polymer theory, the helical state is entropically stabilized for all sequences when the interaction between the peptide and the nanotube is weakly hydrophobic and D is small. However, there is a strong sequence dependence as the strength of the lambda increases. For an amphiphilic sequence, the helical stability increases with lambda, whereas for polyalanine the diagram of states is a complex function of lambda and D. In addition, decreasing the size of the "hydrophobic patch" lining the nanotube, which mimics the chemical heterogeneity of the ribosome tunnel, increases the helical stability of the polyalanine sequence. Our results provide a framework for interpreting a number of experiments involving the structure formation of peptides in the ribosome tunnel as well as transport of biopolymers through nanotubes. C1 [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [O'Brien, Edward P.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Stan, George] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. [Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. EM thirum@glue.umd.edu RI O'Brien, Edward/C-3587-2015 FU NSF [05-14056]; American Heart Association; NIH, National Heart Lung and Blood Institute; NIH GPP Biophysics FX The authors thank Vincent Crespi for a computer program to generate atomic coordinates of carbon nanotubes. This work was supported in part by grants from the NSF (05-14056) to D.T., Scientific Development Grant from the American Heart Association to G.S., the Intramural Research Program of the NIH, National Heart Lung and Blood Institute, to B.R.B., and a NIH GPP Biophysics Fellowship to E.P.O. NR 36 TC 28 Z9 28 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD NOV PY 2008 VL 8 IS 11 BP 3702 EP 3708 DI 10.1021/nl8019328 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 372FX UT WOS:000260888600027 PM 18817452 ER PT J AU Naetar, N Korbei, B Kozlov, S Kerenyi, MA Dorner, D Kral, R Gotic, I Fuchs, P Cohen, TV Bittner, R Stewart, CL Foisner, R AF Naetar, Nana Korbei, Barbara Kozlov, Serguei Kerenyi, Marc A. Dorner, Daniela Kral, Rosana Gotic, Ivana Fuchs, Peter Cohen, Tatiana V. Bittner, Reginald Stewart, Colin L. Foisner, Roland TI Loss of nucleoplasmic LAP2 alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation SO NATURE CELL BIOLOGY LA English DT Article ID STEM-CELL DIFFERENTIATION; LAMIN-A; ERYTHROPOIESIS; RB; PROTEINS; MOUSE; GENE; PROLIFERATION; ASSOCIATION; EXPRESSION AB Lamina-associated polypeptide (LAP) 2 alpha is a chromatin-associated protein that binds A-type lamins(1,2). Mutations in both LAP2 alpha and A-type lamins are linked to human diseases called laminopathies(3), but the molecular mechanisms are poorly understood. The A-type lamin-LAP2a complex interacts with and regulates retinoblastoma protein (pRb)(4,5), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2a complex with the use of LAP2 alpha-deficient mice. We show that LAP2a loss causes relocalization of nucleoplasmic A-type lamins to the nuclear envelope and impairs pRb function. This causes inefficient cell-cycle arrest in dense fibroblast cultures and hyperproliferation of epidermal and erythroid progenitor cells in vivo, leading to tissue hyperplasia. Our results support a disease-relevant model(6) in which LAP2a defines A-type lamin localization in the nucleoplasm, which in turn affects pRb-mediated regulation of progenitor cell proliferation and differentiation in highly regenerative tissues. C1 [Naetar, Nana; Korbei, Barbara; Kerenyi, Marc A.; Dorner, Daniela; Kral, Rosana; Gotic, Ivana; Fuchs, Peter; Foisner, Roland] Med Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria. [Naetar, Nana; Korbei, Barbara; Kerenyi, Marc A.; Dorner, Daniela; Kral, Rosana; Gotic, Ivana; Fuchs, Peter; Foisner, Roland] Univ Vienna, A-1030 Vienna, Austria. [Kozlov, Serguei; Cohen, Tatiana V.; Stewart, Colin L.] NCI, Adv BioSci Labs, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Kerenyi, Marc A.] Vienna Bioctr, Inst Mol Pathol, A-1030 Vienna, Austria. [Bittner, Reginald] Med Univ Vienna, Neuromuscular Res Ctr, Ctr Anat & Cell Biol, A-1090 Vienna, Austria. RP Foisner, R (reprint author), Med Univ Vienna, Max F Perutz Labs, Dr Bohr Gasse 9, A-1030 Vienna, Austria. EM roland.foisner@meduniwien.ac.at OI Korbei, Barbara/0000-0002-0439-0435; Fuchs, Peter/0000-0003-3933-7674 FU Austrian Science Research Fund [FWF P17871]; European Commission [LSHM-CT-2005-018690]; L'Oreal/UNESCO/OADW/BMWF FX We thank W. Muller for the Cre-deleter mouse strain, Larry Gerace for the genomic BAC clone, T. Jacks for triple knockout mouse embryonic fibroblasts, P. Luvalle for providing paws from lamin A/C-deficient mice, K. Biadasiewicz for expert technical assistance, and H. Beug and E. W. Mullner for helpful discussions. This study was supported by grants from the Austrian Science Research Fund (FWF P17871) and the EURO-Laminopathies research project of the European Commission (contract LSHM-CT-2005-018690) to R. F. and a postdoctoral fellowship from L'Oreal/UNESCO/OADW/BMWF to N. N. NR 33 TC 69 Z9 70 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2008 VL 10 IS 11 BP 1341 EP U213 DI 10.1038/ncb1793 PG 32 WC Cell Biology SC Cell Biology GA 367XU UT WOS:000260586700017 PM 18849980 ER PT J AU Merino, JG Latour, LL AF Merino, Jose G. Latour, Lawrence L. TI The Boston Acute Stroke Imaging Scale: ready for use in clinical practice? SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material DE acute stroke; imaging; MRI; prognosis ID ACUTE ISCHEMIC-STROKE AB This Practice Point commentary discusses a report by Torres-Mozqueda et al. on newly developed classification instrument for predicting outcome after stroke, the Boston Acute Stroke Imaging Scale (BASIS). This tool incorporates imaging data on the patency of the vasculature and the parenchyma and classifies ischemic strokes as major (if large vessels are occluded or parenchymal changes are present) or minor (all others). When testing the scale, the authors looked at short-term outcome at the time of hospital discharge; patients classified with major stroke by BASIS had a higher mortality and longer hospital stay and were more likely to be discharged to a rehabilitation facility than patients with minor stroke. The authors concluded that BASIS can predict outcome after stroke. We point to several shortcomings in the study methodology and argue that, although BASIS has potential as a prognostic tool, further studies are needed before it can be widely used. C1 [Merino, Jose G.] Suburban Hosp, Stroke Program, Bethesda, MD 20814 USA. [Latour, Lawrence L.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. RP Merino, JG (reprint author), Suburban Hosp, Stroke Program, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA. EM merinoj@ninds.nih.gov OI Merino, Jose/0000-0002-6676-0008 NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD NOV PY 2008 VL 4 IS 11 BP 592 EP 593 DI 10.1038/ncpneuro0919 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 367ZS UT WOS:000260591700005 PM 18825146 ER PT J AU Ahmed, ZM Masmoudi, S Kalay, E Belyantseva, IA Mosrati, MA Collin, RWJ Riazuddin, S Hmani-Aifa, M Venselaar, H Kawar, MN Tlili, A van der Zwaag, B Khan, SY Ayadi, L Riazuddin, SA Morell, RJ Griffith, AJ Charfedine, I Caylan, R Oostrik, J Karaguzel, A Ghorbel, A Riazuddin, S Friedman, TB Ayadi, H Kremer, H AF Ahmed, Zubair M. Masmoudi, Saber Kalay, Ersan Belyantseva, Inna A. Mosrati, Mohamed Ali Collin, Rob W. J. Riazuddin, Saima Hmani-Aifa, Mounira Venselaar, Hanka Kawar, Mayya N. Tlili, Abdelaziz van der Zwaag, Bert Khan, Shahid Y. Ayadi, Leila Riazuddin, S. Amer Morell, Robert J. Griffith, Andrew J. Charfedine, Ilhem Caylan, Refik Oostrik, Jaap Karaguzel, Ahmet Ghorbel, Abdelmonem Riazuddin, Sheikh Friedman, Thomas B. Ayadi, Hammadi Kremer, Hannie TI Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans SO NATURE GENETICS LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; OUTER HAIR-CELLS; HEARING IMPAIRMENT; CORTICAL LATTICE; LOCUS DFNB63; GENOME-WIDE; EAR; TRANSCRIPTION; LOCALIZATION; METHYLATION AB Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness(1-3). We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes(4). We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents. C1 [Kalay, Ersan; Collin, Rob W. J.; Oostrik, Jaap; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. [Kalay, Ersan; Collin, Rob W. J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. [Ahmed, Zubair M.; Belyantseva, Inna A.; Riazuddin, Saima; Kawar, Mayya N.; Morell, Robert J.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD 20850 USA. [Masmoudi, Saber; Mosrati, Mohamed Ali; Hmani-Aifa, Mounira; Tlili, Abdelaziz; Ayadi, Leila; Ayadi, Hammadi] Ctr Biotechnol, Unite Cibles Diagnost & Therapie, Sfax 3018, Tunisia. [Kalay, Ersan; Karaguzel, Ahmet] Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey. [Venselaar, Hanka] Radboud Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6500 HB Nijmegen, Netherlands. [van der Zwaag, Bert] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, NL-3584 CG Utrecht, Netherlands. [Khan, Shahid Y.; Riazuddin, S. Amer; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Rockville, MD 20850 USA. [Charfedine, Ilhem; Ghorbel, Abdelmonem] CHU Habib Bourguiba Sfax, Serv ORL, Sfax 3029, Tunisia. [Caylan, Refik] Karadeniz Tech Univ, Fac Med, Dept Otorhinolaryngol, TR-61080 Trabzon, Turkey. [Kremer, Hannie] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands. [Kremer, Hannie] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. RP Kremer, H (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. EM friedman@nidcd.nih.gov; directeur.general@cbs.rnrt.tn; H.Kremer@antrg.umcn.nl RI Kremer, Hannie/F-5126-2010; Collin, Rob/N-3575-2014; Oostrik, Jaap/A-1703-2016; SHEIKH, RIAZUDDIN/L-2406-2015; Venselaar, Hanka/D-2009-2016; OI Kremer, Hannie/0000-0002-0841-8693; Morell, Robert/0000-0003-1537-7356 FU NIDCD/NIH [ZO1DC00035-06, ZO1DC000060, ZO1DC000064]; European Commission FP6 Integrated Project EUROHEAR [LSHG-CT-20054-512063:2]; Heinsius Houbolt Foundation; Karadeniz Technical University Research Fund [2002.114.001.3, 2006.114.001.1]; Le Ministere de l'Enseignement Superieur; de la Recherche Scientifique et de la Technologie, Tunisia; Higher Education Commission and the Ministry of Science and Technology in Islamabad, Pakistan FX We thank the families for their participation in this study, which was supported by NIDCD/NIH (intramural research fund ZO1DC00035-06 and ZO1DC00035-06 to T.B.F., ZO1DC000060 and ZO1DC000064 to A.J.G.), funds from the European Commission FP6 Integrated Project EUROHEAR (contract number LSHG-CT-20054-512063:2), the Heinsius Houbolt Foundation and the Karadeniz Technical University Research Fund (contract numbers 2002.114.001.3 and 2006.114.001.1). In Tunisia work was also funded by Le Ministere de l'Enseignement Superieur, de la Recherche Scientifique et de la Technologie, Tunisia. In Pakistan the Higher Education Commission and the Ministry of Science and Technology in Islamabad, Pakistan supported this project. We thank B. Ploplis, M. Ansari, A. Lagziel, E. Boger, S. Kitajiri, E. van Wijk, T. Peters and H. Spierenburg for their technical help and G. Vriend, F. Cremers, H. Brunner and C. Cremers for discussion. We also thank J. Bird, D. Drayna, M. Meisler and S. Sullivan for advice and comments in preparing the manuscript. We thank the Southwest National Primate Research Center, San Antonio, Texas for providing brain tissue samples from chimpanzee and baboon, and the Duke Lemur Center, Durham, North Carolina for brain tissue samples from a lemur. NR 30 TC 28 Z9 39 U1 6 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2008 VL 40 IS 11 BP 1335 EP 1340 DI 10.1038/ng.245 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 366RQ UT WOS:000260501500027 PM 18953341 ER PT J AU Rahimov, F Marazita, ML Visel, A Cooper, ME Hitchler, MJ Rubini, M Domann, FE Govil, M Christensen, K Bille, C Melbye, M Jugessur, A Lie, RT Wilcox, AJ Fitzpatrick, DR Green, ED Mossey, PA Little, J Steegers-Theunissen, RP Pennacchio, LA Schutte, BC Murray, JC AF Rahimov, Fedik Marazita, Mary L. Visel, Axel Cooper, Margaret E. Hitchler, Michael J. Rubini, Michele Domann, Frederick E. Govil, Manika Christensen, Kaare Bille, Camille Melbye, Mads Jugessur, Astanand Lie, Rolv T. Wilcox, Allen J. Fitzpatrick, David R. Green, Eric D. Mossey, Peter A. Little, Julian Steegers-Theunissen, Regine P. Pennacchio, Len A. Schutte, Brian C. Murray, Jeffrey C. CA NISC Comparative Sequencing Pr TI Disruption of an AP-2 alpha binding site in an IRF6 enhancer is associated with cleft lip SO NATURE GENETICS LA English DT Article ID OROFACIAL CLEFTS; ORAL CLEFTS; PALATE; GENE; POPULATION; SEQUENCES; POLYMORPHISMS; CONTRIBUTES; EXPRESSION; MUTATIONS AB Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P)(1) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6)(2). Here, we use multispecies sequence comparisons to identify a common SNP (rs642961, G>A) in a newly identified IRF6 enhancer. The A allele is significantly overtransmitted (P = 1 x 10(-11)) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays demonstrate that the risk allele disrupts the binding site of transcription factor AP-2a and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2a in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder. C1 [Rahimov, Fedik; Schutte, Brian C.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Marazita, Mary L.; Cooper, Margaret E.; Govil, Manika] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15219 USA. [Visel, Axel; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genome Div, Berkeley, CA 94720 USA. [Hitchler, Michael J.; Domann, Frederick E.] Univ Iowa, Dept Radiat Oncol, Iowa City, IA 52242 USA. [Rubini, Michele] Univ Ferrara, Med Genet Unit, Dept Expt Diagnost Med, I-44100 Ferrara, Italy. [Christensen, Kaare; Bille, Camille] Univ So Denmark, Inst Publ Hlth, Ctr Prevent Congenital Malinformat, DK-5000 Odense C, Denmark. [Melbye, Mads] Danish Epidemiol Sci Ctr, State Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Jugessur, Astanand; Lie, Rolv T.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, N-5018 Bergen, Norway. [Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Fitzpatrick, David R.] Western Gen Hosp, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Green, Eric D.; NISC Comparative Sequencing Pr] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparative Sequencing Pr] NHGRI, US Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Mossey, Peter A.] Univ Dundee, Dent Hosp & Sch, Dundee DD1 4HR, Scotland. [Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. [Steegers-Theunissen, Regine P.] Univ Med Ctr, NL-3015 GD Rotterdam, Netherlands. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, 2182 ML,S Grand Ave, Iowa City, IA 52242 USA. EM jeff-murray@uiowa.edu RI Visel, Axel/A-9398-2009; Christensen, Kaare/C-2360-2009; FitzPatrick, David/C-7301-2013; Rahimov, Fedik/H-2685-2013; OI Visel, Axel/0000-0002-4130-7784; Christensen, Kaare/0000-0002-5429-5292; Mossey, Peter/0000-0002-9914-6901; Wilcox, Allen/0000-0002-3376-1311 FU National Institutes of Health (NIH) [P50 DE16215, P30 ES05605, R37 DE08559, R01-DE13513, 1 UL1 RR024979-01, R01-CA73612, R01-HG003988]; Intramural Research Program of the National Human Genome Research Institute; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences; European Commission FP5; EUROCRAN [QLG1-CT-2000-01019]; American Heart Association; [DE-AC02-05CH11231]; [T32 CA078586] FX We would like to thank A. Kinoshita, K. Frees, A. Mansilla, J. L'Heureux, M. Johnson, H. Morrison, G. Wehby, N. Rorick, K. Bedell and L. Powers for technical assistance and S. McConnell, D. Benton and M. DeVore for their administrative assistance. We would also like to thank A. Klingelhutz (University of Iowa) for kindly providing us with HFK cell line. This work was supported by grants from the National Institutes of Health (NIH): P50 DE16215 (J.C.M., M.L.M., B.C.S.), P30 ES05605 (J.C.M.), R37 DE08559 (J.C.M., M.L.M.), R01-DE13513 (B.C.S.), 1 UL1 RR024979-01 (J.C.M., B.C.S.), R01-CA73612 (F.E.D.), R01-HG003988 administered under Department of Energy Contract DE-AC02-05CH11231 (L.A.P.) as well as by the Intramural Research Program of the National Human Genome Research Institute (E.D.G.), in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (A.J.W.), and European Commission FP5: EUROCRAN Project (contract no. QLG1-CT-2000-01019) (M.R., P.A.M., J.L., R.P.S.-T.). A.V. was supported by the American Heart Association. M.J.H. received salary support from T32 CA078586. NR 30 TC 222 Z9 235 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2008 VL 40 IS 11 BP 1341 EP 1347 DI 10.1038/ng.242 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 366RQ UT WOS:000260501500028 PM 18836445 ER PT J AU Jeong, Y Leskow, FC El-Jaick, K Roessler, E Muenke, M Yocum, A Dubourg, C Li, X Geng, X Oliver, G Epstein, DJ AF Jeong, Yongsu Leskow, Federico Coluccio El-Jaick, Kenia Roessler, Erich Muenke, Maximilian Yocum, Anastasia Dubourg, Christele Li, Xue Geng, Xin Oliver, Guillermo Epstein, Douglas J. TI Regulation of a remote Shh forebrain enhancer by the Six3 homeoprotein SO NATURE GENETICS LA English DT Article ID VENTRAL FOREBRAIN; EYE DEVELOPMENT; GENE; EXPRESSION; MUTATIONS; REPRESSION; MEMBERS; FAMILY; RISK; FACE AB In humans, SHH haploinsufficiency results in holoprosencephaly (HPE), a defect in anterior midline formation(1,2). Despite the importance of maintaining SHH transcript levels above a critical threshold, we know little about the upstream regulators of SHH expression in the forebrain. Here we describe a rare nucleotide variant located 460 kb upstream of SHH in an individual with HPE that resulted in the loss of Shh brain enhancer-2 (SBE2) activity in the hypothalamus of transgenic mouse embryos. Using a DNA affinity-capture assay, we screened the SBE2 sequence for DNA-binding proteins and identified members of the Six3 and Six6 homeodomain family as candidate regulators of Shh transcription. Six3 showed reduced binding affinity for the mutant compared to the wild-type SBE2 sequence. Moreover, Six3 with HPE-causing alterations failed to bind and activate SBE2. These data suggest a direct link between Six3 and Shh regulation during normal forebrain development and in the pathogenesis of HPE. C1 [Jeong, Yongsu; Leskow, Federico Coluccio; Epstein, Douglas J.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [El-Jaick, Kenia; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Yocum, Anastasia] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Dubourg, Christele] Univ Rennes 1, CNRS, UMR 6061, F-35043 Rennes, France. [Li, Xue] Harvard Univ, Sch Med, Childrens Hosp, Dept Urol Surg, Boston, MA 02115 USA. [Geng, Xin; Oliver, Guillermo] St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. RP Epstein, DJ (reprint author), Univ Penn, Sch Med, Dept Genet, 415 Curie Blvd, Philadelphia, PA 19104 USA. EM epsteind@mail.med.upenn.edu OI Jeong, Yongsu/0000-0002-0008-9928 FU NINDS [R01 NS39421, R01 NS052386]; March of Dimes [1-FY05-112]; Pew Scholar Award in the Biomedical Sciences; Cancer Center [CA-21765]; American Lebanese Syrian Associated Charities (ALSAC); Division of Intramural Research; National Human Genome Research Institute; National Institutes of Health FX We thank the families for their participation in these studies. We also thank J. Richa and his staff at the University of Pennsylvania Transgenic and Mouse Chimeric Facility for their assistance in transgenic mouse production. We are grateful to V. Cheung, D. Kessler and T. Kadesch for their helpful comments on the manuscript. We are also grateful to K. Ewens and W. Ankener (R. Spielman laboratory) for the control human genotyping data and P. Bovolenta (Instituto Cajal, CSIC, Madrid, Spain) for kindly providing the human Six3 and Six6 expression constructs. This work was supported by NIH grants R01 NS39421 from NINDS (D.J.E.), R01 NS052386 (G.O.), March of Dimes grant # 1-FY05-112 (D.J.E.), a Pew Scholar Award in the Biomedical Sciences (D.J.E.), Cancer Center Support CA-21765 (G.O.), the American Lebanese Syrian Associated Charities (ALSAC) (G.O.) and the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health (M.M.). NR 30 TC 82 Z9 85 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2008 VL 40 IS 11 BP 1348 EP 1353 DI 10.1038/ng.230 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 366RQ UT WOS:000260501500029 PM 18836447 ER PT J AU Feng, CG Zheng, LX Jankovic, D Bafica, A Cannons, JL Watford, WT Chaussabel, D Hieny, S Caspar, P Schwartzberg, PL Lenardo, MJ Sher, A AF Feng, Carl G. Zheng, Lixin Jankovic, Dragana Bafica, Andre Cannons, Jennifer L. Watford, Wendy T. Chaussabel, Damien Hieny, Sara Caspar, Patricia Schwartzberg, Pamela L. Lenardo, Michael J. Sher, Alan TI The immunity-related GTPase Irgm1 promotes the expansion of activated CD4(+) T cell populations by preventing interferon-gamma-induced cell death SO NATURE IMMUNOLOGY LA English DT Article ID MYCOBACTERIUM-AVIUM INFECTION; RECEPTOR-BETA CHAIN; IFN-GAMMA; CYTOKINE SIGNALING-1; MICE DEFICIENT; T(H)1 CELLS; IN-VIVO; AUTOPHAGY; LRG-47; TUBERCULOSIS AB Mice deficient in the interferon-gamma (IFN-gamma)-inducible, immunity-related GTPase Irgm1 have defective host resistance to a variety of intracellular pathogens. This greater susceptibility to infection is associated with impaired IFN-gamma-dependent macrophage microbicidal activity in vitro. Here we show that Irgm1 also regulated the survival of mature effector CD4(+) T lymphocytes by protecting them from IFN-gamma-induced autophagic cell death. Mice deficient in both IFN-gamma and Irgm1 were 'rescued' from the lymphocyte depletion and greater mortality that occurs in mice singly deficient in Irgm1 after mycobacterial infection. Our studies identify a feedback mechanism in the T helper type 1 response that limits the detrimental effects of IFN-gamma on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-gamma. C1 [Feng, Carl G.; Jankovic, Dragana; Bafica, Andre; Hieny, Sara; Caspar, Patricia; Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Watford, Wendy T.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Chaussabel, Damien] Baylor Inst Immunol Res, Dallas, TX 75204 USA. RP Feng, CG (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM cfeng@niaid.nih.gov RI Vacinas, Inct/J-9431-2013 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health, Department of Health and Human Services FX We thank G. Taylor ( Duke University) for Irgm1-/- mice backcrossed more than 12 times to C57BL/6 mice; S. White, C. Henry and C. Eigsti for technical assistance; J. Zhu and L. Yu for advice and discussions; K. Nagashima ( Electron Microscope Facility, Image Analysis Laboratory, Science Applications International Corporation-National Cancer Institute, Frederick) for the electron microscopy studies; A. Cheever ( Biomedical Research Institute) for assessing tissue fibrosis and pathology in S. mansoni infection experiments; R. Donnelly ( Center for Biologics Evaluation and Research, Food and Drug Administration) for initial help in measuring STAT1 phosphorylation; and H. Young and D. L. Barber for critical reading of the manuscript. Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. NR 49 TC 75 Z9 75 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2008 VL 9 IS 11 BP 1279 EP 1287 DI 10.1038/ni.1653 PG 9 WC Immunology SC Immunology GA 363EA UT WOS:000260248600015 PM 18806793 ER PT J AU Liao, W Schones, DE Oh, J Cui, YZ Cui, KR Roh, TY Zhao, K Leonard, WJ AF Liao, Wei Schones, Dustin E. Oh, Jangsuk Cui, Yongzhi Cui, Kairong Roh, Tae-Young Zhao, Keji Leonard, Warren J. TI Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression SO NATURE IMMUNOLOGY LA English DT Article ID TH2 DIFFERENTIATION; IL-4 RECEPTOR; CELL-PROLIFERATION; UP-REGULATION; STAT5; RESPONSES; MECHANISMS; GENE; MICE; SUFFICIENT AB T helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T(H)2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor alpha-chain (IL-4R alpha), was essential for inducing and maintaining IL-4R alpha expression. Although IL-4 induced IL-4R alpha expression, T cell receptor-induced IL-4R alpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4R alpha expression restored the T(H)2 differentiation of Il2(-/-) cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with T(H)2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells. C1 [Liao, Wei; Schones, Dustin E.; Oh, Jangsuk; Cui, Kairong; Roh, Tae-Young; Zhao, Keji; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Cui, Yongzhi] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Division of Intramural Research of the National Heart, Lung, and Blood Institute, National Institutes of Health FX We thank P. Ryan (National Heart, Lung and Blood Institute, National Institutes of Health) for Il4-/- mice; J. X. Lin (National Heart, Lung and Blood Institute, National Institutes of Health) for discussions and real-time PCR primers; J. F. Zhu, H. H. Xue, H. P. Kim and R. Spolski for discussions and technical assistance; L. Hennighausen for support and discussions; and X. Shirley Liu for the 'model-based analysis of ChiP-seq' algorithm. Supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 41 TC 120 Z9 121 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2008 VL 9 IS 11 BP 1288 EP 1296 DI 10.1038/ni.1656 PG 9 WC Immunology SC Immunology GA 363EA UT WOS:000260248600016 PM 18820682 ER PT J AU Zhang, FP Meng, GX Strober, W AF Zhang, Fuping Meng, Guangxun Strober, Warren TI Interactions among the transcription factors Runx1, ROR gamma t and Foxp3 regulate the differentiation of interleukin 17-producing T cells SO NATURE IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; GENE-EXPRESSION; IFN-GAMMA; BINDING-SITE; RECEPTOR; IL-21; SUSCEPTIBILITY; INDUCTION; ARTHRITIS AB The molecular mechanisms underlying the differentiation of interleukin 17-producing T helper cells (T-H-17 cells) are still poorly understood. Here we show that optimal transcription of the gene encoding interleukin 17 (Il17) required a 2-kilobase promoter and at least one conserved noncoding (enhancer) sequence, CNS-5. Both cis-regulatory elements contained regions that bound the transcription factors ROR gamma t and Runx1. Runx1 influenced T-H-17 differentiation by inducing ROR gamma t expression and by binding to and acting together with ROR gamma t during Il17 transcription. However, Runx1 also interacts with the transcription factor Foxp3, and this interaction was necessary for the negative effect of Foxp3 on T-H-17 differentiation. Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with ROR gamma t regulates T-H-17 differentiation. C1 [Zhang, Fuping; Meng, Guangxun; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov OI 孟, 广勋/0000-0002-4253-9675 FU Intramural NIH HHS [Z01 AI000354-25, Z01 AI000432-23] NR 37 TC 273 Z9 287 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2008 VL 9 IS 11 BP 1297 EP 1306 DI 10.1038/ni.1663 PG 10 WC Immunology SC Immunology GA 363EA UT WOS:000260248600017 PM 18849990 ER PT J AU Strauss, JF De Paolo, LV AF Strauss, Jerome F., III De Paolo, Louis V. TI Funding for the reproductive sciences in the US SO NATURE MEDICINE LA English DT Editorial Material ID ANIMAL REPRODUCTION; AGRICULTURE; TECHNOLOGY; PRIORITIES; BIOLOGY C1 [Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA. [De Paolo, Louis V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD NOV PY 2008 VL 14 IS 11 SU S BP 1214 EP 1217 DI 10.1038/nm1108-1214 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 397FU UT WOS:000262649100032 PM 18989308 ER PT J AU Strauss, JF De Paolo, LV AF Strauss, Jerome F., III De Paolo, Louis V. TI Funding for the reproductive sciences in the US SO NATURE MEDICINE LA English DT Editorial Material ID ANIMAL REPRODUCTION; AGRICULTURE; TECHNOLOGY; PRIORITIES; BIOLOGY C1 [Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23298 USA. [De Paolo, Louis V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Sch Med, 1101 E Marshall St, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD NOV PY 2008 VL 14 IS 11 BP 1214 EP 1217 DI 10.1038/nm1108-1214 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 370GR UT WOS:000260751200039 PM 18989308 ER PT J AU Ozato, K Shin, DM Chang, TH Morse, HC AF Ozato, Keiko Shin, Dong-Mi Chang, Tsung-Hsien Morse, Herbert C., III TI TRIM family proteins and their emerging roles in innate immunity SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID INTERFERON REGULATORY FACTOR-8; RET FINGER PROTEIN; PROMYELOCYTIC LEUKEMIA PROTEIN; RESTRICTION FACTOR TRIM5-ALPHA; TRIPARTITE MOTIF PROTEINS; NUCLEAR-BODY FORMATION; E3 UBIQUITIN LIGASE; RING-FINGER; RETROVIRAL RESTRICTION; ANTIVIRAL DEFENSE AB The superfamily of tripartite motif-containing ( TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence. C1 [Ozato, Keiko; Chang, Tsung-Hsien] NICHHD, Program Genom & Differentiat, NIH, Bethesda, MD 20892 USA. [Shin, Dong-Mi; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Ozato, K (reprint author), NICHHD, Program Genom & Differentiat, NIH, Bethesda, MD 20892 USA. EM ozatok@nih.gov; hmorse@mail.nih.gov RI Liu, FL/D-1795-2009; OI Morse, Herbert/0000-0002-9331-3705 FU National Institutes of Health; National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases FX We thank J. Weddle for his assistance in the preparation of this manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases. NR 127 TC 299 Z9 316 U1 6 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2008 VL 8 IS 11 BP 849 EP 860 DI 10.1038/nri2413 PG 12 WC Immunology SC Immunology GA 364CE UT WOS:000260313000010 PM 18836477 ER PT J AU Redd, AD Quinn, TC AF Redd, Andrew D. Quinn, Thomas C. TI CD4 immunodiagnostics for HIV in the developing world FOREWORD SO NATURE REVIEWS MICROBIOLOGY LA English DT Editorial Material ID TOTAL LYMPHOCYTE COUNT; ANTIRETROVIRAL THERAPY AB This supplement on evaluating CD4 diagnostics for HIV is the fourth in a series of user-friendly operational guides explaining how to conduct evaluations of diagnostic tests for infectious diseases that are of public health importance in the developing world. Here, Andrew Redd and Thomas Quinn introduce the supplement. C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Redd, AD (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tquinn@jhmi.edu RI Redd, Andrew/D-1802-2010 NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD NOV PY 2008 VL 6 IS 11 SU S BP S1 EP S1 DI 10.1038/nrmicro1996 PG 1 WC Microbiology SC Microbiology GA 372EE UT WOS:000260883800001 PM 22745948 ER PT J AU Wang, WD AF Wang, Weidong TI A major switch for the Fanconi anemia DNA damage-response pathway SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID REPLICATION FORKS; PROTEIN; REPAIR; COMPLEX; FANCD2 AB The Fanconi anemia pathway is part of the DNA-damage network including breast cancer-susceptibility proteins BRCA1 and BRCA2. This pathway is activated by the ataxia telangiectasia and Rad3-related (ATR) kinase, but the underlying mechanism remains unclear. A new study demonstrates that a major switch activating the pathway is the ATR-dependent phosphorylation of FANCI. C1 NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, Room 10B113,251 Bayview Blvd, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov FU Intramural NIH HHS NR 15 TC 13 Z9 13 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2008 VL 15 IS 11 BP 1128 EP 1130 DI 10.1038/nsmb1108-1128 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 368QV UT WOS:000260638500002 PM 18985065 ER PT J AU Yang, W AF Yang, Wei TI An equivalent metal ion in one- and two-metal-ion catalysis SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; T4 ENDONUCLEASE VII; ACTIVE-SITE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; POLYMERASE-I; SUBSTRATE-SPECIFICITY; CONJUGATIVE RELAXASE; ANGSTROM RESOLUTION; 3'-5' EXONUCLEASE AB Nucleotidyl-transfer enzymes, which synthesize, degrade and rearrange DNA and RNA, often depend on metal ions for catalysis. All DNA and RNA polymerases, MutH-like or RNase H-like nucleases and recombinases, and group I introns seem to require two divalent cations to form a complete active site. The two-metal-ion mechanism has been proposed to orient the substrate, facilitate acid-base catalysis and allow catalytic specificity to exceed substrate binding specificity attributable to the stringent metal-ion (Mg2+ in particular) coordination. Not all nucleotidyl-transfer enzymes use two metal ions for catalysis, however. The beta beta alpha-Me and HUH nucleases depend on a single metal ion in the active site for the catalysis. All of these one- and two metal ion-dependent enzymes generate 5'- phosphate and 3'-OH products. Structural and mechanistic comparisons show that these seemingly unrelated nucleotidyl-transferases share a functionally equivalent metal ion. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B1-03, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU US National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX I thank C. Biertumpfel, C. Larkin and M. Nowotny for stimulating discussion, and B. Craigie, F. Dyda, D. Leahy and H. Yuan for critical reading of the manuscript. This research was supported by the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 50 TC 47 Z9 48 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2008 VL 15 IS 11 BP 1228 EP 1231 DI 10.1038/nsmb.1502 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 368QV UT WOS:000260638500023 PM 18953336 ER PT J AU Roschke, A Glebov, OK Lababidi, S Gehlhaus, KS Weinstein, JN Kirsch, IR AF Roschke, Anna Glebov, Oleg K. Lababidi, Samir Gehlhaus, Kristen S. Weinstein, John N. Kirsch, Ilan R. TI Chromosomal Instability Is Associated with Higher Expression of Genes Implicated in Epithelial-Mesenchymal Transition, Cancer Invasiveness, and Metastasis and with Lower Expression of Genes Involved in Cell Cycle Checkpoints, DNA Repair, and Chromatin Maintenance SO NEOPLASIA LA English DT Article ID MITOTIC CHECKPOINT; BREAST-CANCER; NEOPLASTIC TRANSFORMATION; KARYOTYPIC COMPLEXITY; LUNG-CANCER; HBUB1; PROGRESSION; MICROARRAY; INACTIVATION; PHENOTYPES AB Chromosomal instability-a hallmark of epithelial cancers-is an ongoing process that results in aneuploidy and karyotypic heterogeneity of a cancer cell population. Previously, we stratified cancer cell lines in the NCI-60 drug discovery panel based on their karyotypic complexity and heterogeneity. Using this stratification in conjunction with drug response data for the cell lines allowed us to identify classes of chemical compounds whose growth-inhibitory activity correlates with karyotypic complexity and chromosomal instability. In this article, we asked the question: What are the biological processes, pathways, or genes associated with chromosomal instability of cancer cells? We found that increased instability of the chromosomal content in a cancer cell population, particularly, persistent gains and losses of chromosomes, is associated with elevated expression of genes involved with aggressive cellular behavior, including invasion-and metastasis-associated changes in cell communication, adhesion, motility, and migration. These same karyotypic features are negatively correlated with the expression of genes involved in cell cycle checkpoints, DNA repair, and chromatin maintenance. C1 [Roschke, Anna] NCI, Ctr Canc Res, NNMC, Bethesda, MD 20889 USA. RP Roschke, A (reprint author), NCI, Ctr Canc Res, NNMC, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM roschkea@mail.nih.gov NR 43 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 1522-8002 EI 1476-5586 J9 NEOPLASIA JI Neoplasia PD NOV PY 2008 VL 10 IS 11 BP 1222 EP U72 DI 10.1593/neo.08682 PG 26 WC Oncology SC Oncology GA 358AX UT WOS:000259889800007 PM 18953431 ER PT J AU Duffy, KB Spangler, EL Devan, BD Guo, ZH Bowker, JL Janas, AM Hagepanos, A Minor, RK DeCabo, R Mouton, PR Shukitt-Hale, B Joseph, JA Ingram, DK AF Duffy, Kara B. Spangler, Edward L. Devan, Bryan D. Guo, Zhihong Bowker, Jonna L. Janas, Anne M. Hagepanos, Adrienne Minor, Robin K. DeCabo, Rafael Mouton, Peter R. Shukitt-Hale, Barbara Joseph, James A. Ingram, Donald K. TI A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats SO NEUROBIOLOGY OF AGING LA English DT Article DE flavanoid; neurotoxicity; nutrition; memory; glutamate; hippocampus; Alzheimer's disease ID RADICAL ABSORBENCY CAPACITY; ACTIVATED PROTEIN-KINASE; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; AGED RATS; MEMORY CONSOLIDATION; ANTIOXIDANT CAPACITY; BEHAVIORAL DEFICITS; LIPID-PEROXIDATION; KAINIC ACID AB Young male Fischer-344 rats were fed a diet containing 2% blueberry (BB) extract or control diet for at least 8 weeks and then received bilateral hippocampal injections of kainic acid (KA 200 ng/0.5 mu l) or phosphate buffered saline (PBS). One week later rats were trained in one-way active footshock avoidance in a straight runway followed the next day by training in a footshock motivated 14-unit T-maze with documented sensitivity to hippocampal glutamatergic manipulations. Based on analyses of several performance variables, KA-treated rats exhibited clearly impaired learning performance; however. the BB diet significantly reduced this impairment. Supporting the behavioral findings. stereological assessment of CA1 pyramidal neurons documented greater neuronal loss in KA-treated controls compared to KA-treated rats on the BB diet. In an in vitrio experiment, FaO cells grown in medium supplemented with serum from BB-fed rats had enhanced viability after exposure to hydrogen peroxide. These findings suggest that BB supplementation may protect against neurodegeneration and cognitive impairment mediated by excitotoxicity and oxidative stress. Published by Elsevier Inc. C1 [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. [Duffy, Kara B.; Spangler, Edward L.; Devan, Bryan D.; Bowker, Jonna L.; Janas, Anne M.; Minor, Robin K.; DeCabo, Rafael; Mouton, Peter R.; Ingram, Donald K.] NIA, Lab Expt Geront, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Guo, Zhihong; Hagepanos, Adrienne] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Shukitt-Hale, Barbara; Joseph, James A.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Ingram, DK (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM Donald.Ingram@pbrc.edu 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 National Institute on Aging; National Institutes of Health; United States Department of Agriculture; NASA [NAG9-1529]; U.S. Highbush Blueberry Council (USHBC); Wild Blueberry Association of North America (WBANA) FX This research was supported in part by funds from the Intramural Research Program of the National Institute on Aging, National Institutes of Health, and also in part by the United States Department of Agriculture and NASA Grant NAG9-1529 to J.A. Joseph. The laboratory of J.A. Joseph also receives research support from the U.S. Highbush Blueberry Council (USHBC) and the Wild Blueberry Association of North America (WBANA). NR 72 TC 52 Z9 59 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2008 VL 29 IS 11 BP 1680 EP 1689 DI 10.1016/j.neurobiolaging.2007.04.002 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 356JP UT WOS:000259774800007 PM 17524525 ER PT J AU Basselin, M Chang, L Chen, M Bell, JM Rapoport, SI AF Basselin, Mireille Chang, Lisa Chen, Mei Bell, Jane M. Rapoport, Stanley I. TI Chronic administration of valproic acid reduces brain NMDA signaling via arachidonic acid in unanesthetized rats SO NEUROCHEMICAL RESEARCH LA English DT Article DE valproic acid; NMDA; arachidonic acid; bipolar disorder; phospholipase A(2); prostaglandin E2 ID EXCITATORY AMINO-ACIDS; D-ASPARTATE RECEPTORS; DNA-BINDING ACTIVITY; BIPOLAR DISORDER; SODIUM-VALPROATE; CHRONIC LITHIUM; IN-VIVO; MOOD STABILIZERS; ANTIEPILEPTIC DRUGS; PHOSPHOLIPASE A(2) AB Evidence that brain glutamatergic activity is pathologically elevated in bipolar disorder suggests that mood stabilizers are therapeutic in the disease in part by downregulating glutamatergic activity. Such activity can involve the second messenger, arachidonic acid (AA, 20:4n-6). We tested this hypothesis with regard to valproic acid (VPA), when stimulating glutamatergic N-methyl-D-aspartate (NMDA) receptors in rat brain and measuring AA and related responses. An acute subconvulsant dose of NMDA (25 mg/kg i.p.) or saline was administered to unanesthetized rats that had been treated i.p. daily with VPA (200 mg/kg) or vehicle for 30 days. Quantitative autoradiography following intravenous [1-(14)C] AA infusion was used to image regional brain AA incorporation coefficients k*, markers of AA signaling. In chronic vehicle-pretreated rats, NMDA compared with saline significantly increased k* in 41 of 82 examined brain regions, many of which have high NMDA receptor densities, and also increased brain concentrations of the AA metabolites, prostaglandin E(2) (PGE(2)) and thromboxane B(2) (TXB(2)). VPA pretreatment reduced baseline concentrations of PGE2 and TXB2, and blocked the NMDA induced increases in k* and in eicosanoid concentrations. These results, taken with evidence that carbamazepine and lithium also block k* responses to NMDA in rat brain, suggest that mood stabilizers act in bipolar disorder in part by downregulating glutamatergic signaling involving AA. C1 [Basselin, Mireille; Chang, Lisa; Chen, Mei; Bell, Jane M.; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S126,MSC 0947,9 Mem Dr, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov FU Intramural Research Program of the National Institute on Aging FX This research was supported by the Intramural Research Program of the National Institute on Aging. None of the authors has a financial or other conflict of interest related to this work. NR 96 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2008 VL 33 IS 11 BP 2229 EP 2240 DI 10.1007/s11064-008-9700-2 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 352GG UT WOS:000259483300008 PM 18461450 ER PT J AU Chang, YC Kim, HW Rapoport, SI Rao, JS AF Chang, Yunyoung C. Kim, Hyung-Wook Rapoport, Stanley I. Rao, Jagadeesh S. TI Chronic NMDA administration increases neuroinflammatory markers in rat frontal cortex: Cross-talk between excitotoxicity and neuroinflammation SO NEUROCHEMICAL RESEARCH LA English DT Article DE excitotoxicity; neuroinflammation; interleukin-1beta; tumor necrosis factor alpha; interleukin-10; glial fibrillary acidic protein; inducible nitric oxide synthase; brain ID D-ASPARTATE RECEPTOR; ARACHIDONIC-ACID METABOLISM; MESSENGER-RNA EXPRESSION; NITRIC-OXIDE SYNTHASE; DNA-BINDING ACTIVITY; PROTEIN-KINASE-II; PHOSPHOLIPASE A(2); TRANSCRIPTION FACTOR; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE AB Chronic N-Methyl-D-aspartate (NMDA) administration, a model of excitotoxicity, and chronic intracerebroventricular lipopolysaccharide infusion, a model of neuroinflammation, are reported to upregulate arachidonic acid incorporation and turnover in rat brain phospholipids as well as enzymes involved in arachidonic acid metabolism. This suggests cross-talk between signaling pathways of excitotoxicity and of neuroinflammation, involving arachidonic acid. To test whether chronic NMDA administrations to rats can upregulate brain markers of neuroinflammation, NMDA (25 mg/kg i. p.) or vehicle (1 ml saline/kg i. p.) was administered daily to adult male rats for 21 days. Protein and mRNA levels of cytokines and other inflammatory markers were measured in the frontal cortex using immunoblot and realtime PCR. Compared with chronic vehicle, chronic NMDA significantly increased protein and mRNA levels of interleukin-1beta, tumor necrosis factor alpha, glial fibrillary acidic protein and inducible nitric oxide synthase. Chronic NMDA receptor overactivation results in increased levels of neuro-inflammatory markers in the rat frontal cortex, consistent with cross-talk between excitotoxicity and neuroinflammation. As both processes have been reported in a number of human brain diseases, NMDA receptor inhibitors might be of use in treating neuroinflammation in these diseases. C1 [Chang, Yunyoung C.; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Kim, Hyung-Wook/B-6308-2009; Rao, Jagadeesh/C-1250-2009 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 48 TC 38 Z9 39 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2008 VL 33 IS 11 BP 2318 EP 2323 DI 10.1007/s11064-008-9731-8 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 352GG UT WOS:000259483300019 PM 18500552 ER PT J AU Taniura, S Kamitani, H Watanabe, T Eling, TE AF Taniura, Seijiro Kamitani, Hideki Watanabe, Takashi Eling, Thomas E. TI Induction of Cyclooxygenase-2 Expression by Interleukin-1 beta in Human Glioma Cell Line, U87MG SO NEUROLOGIA MEDICO-CHIRURGICA LA English DT Article DE cyclooxygenase-2; interleukin-1 beta; glioma ID HUMAN GLIOBLASTOMA CELLS; SQUAMOUS CARCINOMA-CELLS; PROGNOSTIC-SIGNIFICANCE; GENE-EXPRESSION; P53; APOPTOSIS; PROTEIN; INHIBITION; ASTROCYTES; CANCER AB Cyclooxygenase-2 (COX-2) is up-regulated in most high-grade gliomas, and high COX-2 expression is associated with aggressive character and poor prognosis. However, the effect of COX-2 in human glioma cell lines is not well known. This study examined the effect of several stimuli, including interleukin-1 beta (IL-1 beta) and carcinogens, on COX-2 induction in normal astrocyte cells and human glioma cell lines U87MG, A172, and T98G. IL-1 beta-induced COX-2 expression strongly at both protein and messenger ribonucleic acid levels in only the U87MG cells of the glioma cell lines. Furthermore, carcinogen induced COX-2 expression. Similar findings were also observed in normal human astrocyte cells. The U87MG glioma cell line is a good model for COX-2 induction in glioma cell lines. C1 [Taniura, Seijiro; Kamitani, Hideki; Watanabe, Takashi] Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurosurg, Yonago, Tottori 683, Japan. [Eling, Thomas E.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Taniura, S (reprint author), Takashima Hosp, Dept Neurosurg, 6 Nishi Cho, Tottori 6830826, Japan. EM taniura@sanmedia.or.jp FU Intramural NIH HHS [Z01 ES010016-09] NR 34 TC 3 Z9 3 U1 0 U2 0 PU JAPAN NEUROSURGICAL SOC PI TOKYO PA C/O AKAMON-MAE IWATA BLDG, 5-27-8 HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0470-8105 J9 NEUROL MED-CHIR JI Neurol. Med.-Chir. PD NOV PY 2008 VL 48 IS 11 BP 500 EP 505 DI 10.2176/nmc.48.500 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 372UZ UT WOS:000260928800011 PM 19029777 ER PT J AU Murphy, DL Fox, MA Timpano, KR Moya, PR Ren-Patterson, R Andrews, AM Holmes, A Lesch, KP Wendland, JR AF Murphy, Dennis L. Fox, Meredith A. Timpano, Kiara R. Moya, Pablo R. Ren-Patterson, Renee Andrews, Anne M. Holmes, Andrew Lesch, Klaus-Peter Wendland, Jens R. TI How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems SO NEUROPHARMACOLOGY LA English DT Review DE Homeostasis; Serotonin transporter; Anxiety; Obsessive-compulsive disorder; Depression; Epistasis ID OBSESSIVE-COMPULSIVE DISORDER; KNOCK-OUT MICE; POSITRON-EMISSION-TOMOGRAPHY; IRRITABLE-BOWEL-SYNDROME; PRIMARY PULMONARY-HYPERTENSION; DEFICIT HYPERACTIVITY DISORDER; 5-HT2A PROMOTER POLYMORPHISM; CATECHOL O-METHYLTRANSFERASE; ANTIDEPRESSANT-INDUCED MANIA; BIOGENIC-AMINE TRANSPORTERS AB Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct serotonergic gene manipulation (gene deletion or overexpression) in mice and other species: an evaluation of some phenotypes related to functional human serotonergic gene variants, particularly in SLC6A4, the serotonin transporter gene: and finally, a consideration of the pharmacogenomics of serotonergic drugs with respect to both their therapeutic actions and side effects. The serotonin transporter (SERT) has been the most comprehensively studied of the serotonin system molecular components, and will be the primary focus of this review. We provide in-depth examples of gene-based discoveries primarily related to SLC6A4 that have clarified serotonin's many important homeostatic functions in humans, non-human primates, mice and other species. Published by Elsevier Ltd. C1 [Murphy, Dennis L.; Fox, Meredith A.; Timpano, Kiara R.; Moya, Pablo R.; Wendland, Jens R.] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Timpano, Kiara R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ren-Patterson, Renee] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Andrews, Anne M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Andrews, Anne M.] Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. [Wendland, Jens R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM dennismurphy@mail.nih.gov RI Andrews, Anne/B-4442-2011; Wendland, Jens/A-1809-2012; Timpano, Kiara/C-8760-2012; Lesch, Klaus-Peter/J-4906-2013; OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X; Timpano, Kiara/0000-0002-0665-8722 FU NIMH, NIH; NARSAD 2007 Young Investigator Award; NIMH Division of Intramural Research Programs Julius Axelrod Memorial Fellowship Training Award FX This research was supported by the Intramural Research Program of the NIMH, NIH. Jens R. Wendland, M.D. was also supported by a NARSAD 2007 Young Investigator Award and an NIMH Division of Intramural Research Programs Julius Axelrod Memorial Fellowship Training Award. The authors are also grateful to Theresa B. DeGuzman, Teresa Tolliver, Su-Jan Huang and Justin LaPorte for their assistance in these studies. NR 290 TC 124 Z9 128 U1 7 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2008 VL 55 IS 6 BP 932 EP 960 DI 10.1016/j.neuropharm.2008.08.034 PG 29 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 373OX UT WOS:000260982700003 PM 18824000 ER PT J AU Childs, E Hohoff, C Deckert, J Xu, K Badner, J de Wit, H AF Childs, Emma Hohoff, Christa Deckert, Juergen Xu, Ke Badner, Judith de Wit, Harriet TI Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE caffeine; adenosine; dopamine; polymorphism; single nucleotide; anxiety ID ADENOSINE A(2A) RECEPTOR; PROMOTER REGION; GENE; DOPAMINE; WITHDRAWAL; DISCRIMINATION; DISEQUILIBRIUM; IDENTIFICATION; SCHIZOPHRENIA; AMPHETAMINE AB Caffeine produces mild psychostimulant and sometimes anxiogenic effects by antagonizing adenosine at A(1) and A(2A) receptors, and perhaps through interactions with other transmitter systems. Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study, we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD(2)) receptors. Healthy male and female individuals (n = 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times after capsules were consumed. At the 150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety ( Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3'-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine. C1 [Childs, Emma; Badner, Judith; de Wit, Harriet] Univ Chicago, Dept Psychiat, Chicago, IL 60657 USA. [Hohoff, Christa; Deckert, Juergen] Univ Munster, Dept Psychiat, Munster, Germany. [Deckert, Juergen] Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany. [Xu, Ke] NIAAA, Sect Human Neurogenet, Neurogenet Lab, NIH, Bethesda, MD USA. RP Childs, E (reprint author), Univ Chicago, Dept Psychiat, 5841 S Maryland Ave MC3077, Chicago, IL 60657 USA. EM echilds@yoda.bsd.uchicago.edu RI Childs, Emma/K-6775-2014; OI Childs, Emma/0000-0003-1747-5208; de Wit, Harriet/0000-0002-7211-8994 FU NIDA [DA02812]; General Clinical Research Center [USPHS MO1RR000555] FX This research was supported by NIDA (DA02812) and the General Clinical Research Center (USPHS MO1RR000555). We thank Michelle Dassinger, Liz Young, Lisa Vicini, Maliha Darugar, and Kathrin Schwarte for their technical assistance. NR 44 TC 80 Z9 82 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2008 VL 33 IS 12 BP 2791 EP 2800 DI 10.1038/npp.2008.17 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 359SB UT WOS:000260007300001 PM 18305461 ER PT J AU Justinova, Z Munzar, P Panlilio, LV Yasar, S Redhi, GH Tanda, G Goldberg, SR AF Justinova, Zuzana Munzar, Patrik Panlilio, Leigh V. Yasar, Sevil Redhi, Godfrey H. Tanda, Gianluigi Goldberg, Steven R. TI Blockade of THC-Seeking Behavior and relapse in monkeys by the cannabinoid CB(1)-Receptor antagonist rimonabant SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cannabinoids; drug seeking; reinstatement; rimonabant; second-order schedule; self-administration ID CB1 RECEPTOR ANTAGONIST; SQUIRREL-MONKEYS; 2ND-ORDER SCHEDULES; DRUG-SEEKING; DELTA(9)-TETRAHYDROCANNABINOL THC; FIXED-RATIO; COCAINE; HEROIN; REINFORCEMENT; INJECTION AB Accumulating evidence suggests the endocannabinoid system modulates environmental cues' ability to induce seeking of drugs, including nicotine and alcohol. However, little attention has been directed toward extending these advances to the growing problem of cannabis use disorders. Therefore, we studied intravenous self-administration of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, using a second-order schedule of drug seeking. Squirrel monkeys' lever responses produced only a brief cue light until the end of the session, when the final response delivered THC along with the cue. When a reinstatement procedure was used to model relapse following a period of abstinence, THC-seeking behavior was robustly reinstated by the cue or by pre-session administration of THC, other cannabinoid agonists, or morphine, but not cocaine. The cannabinoid antagonist rimonabant blocked cue-induced drug seeking, THC-induced drug seeking, and the direct reinforcing effects of THC. Thus, rimonabant and related medications might be effective as treatments for cannabinoid dependence. C1 [Justinova, Zuzana; Munzar, Patrik; Panlilio, Leigh V.; Redhi, Godfrey H.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Dept Hlth & Human Serv, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Munzar, Patrik] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Tanda, Gianluigi] Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch,Dept Hlth & Human Se, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch,Dept Hlth & Human Serv, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484 FU Intramural Research Program of the National Institute on Drug Abuse; NIH; DHHS FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH, DHHS. We thank Eric Thorndike for programming assistance and Kathleen Stillwell and Dr Ira Baum for excellent surgical assistance with catheter implantation and maintenance. NR 36 TC 44 Z9 44 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2008 VL 33 IS 12 BP 2870 EP 2877 DI 10.1038/npp.2008.21 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 359SB UT WOS:000260007300008 PM 18305459 ER PT J AU Rex, EB Rankin, ML Ariano, MA Sibley, DR AF Rex, Elizabeth B. Rankin, Michele L. Ariano, Marjorie A. Sibley, David R. TI Ethanol regulation of D-1 dopamine receptor signaling is mediated by protein kinase c in an isozyme-specific manner SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ethanol; dopamine; PKC; D-1 receptor; DARPP-32; phosphorylation ID VENTRAL TEGMENTAL AREA; AGONIST-INDUCED DESENSITIZATION; CENTRAL-NERVOUS-SYSTEM; NULL MUTANT MICE; IN-VIVO; NUCLEUS-ACCUMBENS; ADENYLYL-CYCLASE; DORSAL STRIATUM; NMDA RECEPTORS; RAT-BRAIN AB Ethanol consumption potentiates dopaminergic signaling that is partially mediated by the D-1 dopamine receptor; however, the mechanism(s) underlying ethanol-dependent modulation of D-1 signaling is unclear. We now show that ethanol treatment of D-1 receptor-expressing cells decreases D-1 receptor phosphorylation and concurrently potentiates dopamine-stimulated cAMP accumulation. Protein kinase C (PKC) inhibitors mimic the effects of ethanol on D-1 receptor phosphorylation and dopamine-stimulated cAMP levels in a manner that is non-additive with ethanol treatment. Ethanol was also found to modulate specific PKC activities as demonstrated using in vitro kinase assays where ethanol treatment attenuated the activities of lipid-stimulated PKC gamma and PKC delta in membrane fractions, but did not affect the activities of PKC alpha, PKC beta(1), or PKC epsilon. Importantly, ethanol treatment potentiated D-1 receptor-mediated DARPP-32 phosphorylation in rat striatal slices, supporting the notion that ethanol enhances D-1 receptor signaling in vivo. These findings suggest that ethanol inhibits the activities of specific PKC isozymes, resulting in decreased D-1 receptor phosphorylation and enhanced dopaminergic signaling. C1 [Rex, Elizabeth B.; Rankin, Michele L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. [Rex, Elizabeth B.] NIAAA, NIH, Rockville, MD 20852 USA. [Ariano, Marjorie A.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Dept Neurosci, N Chicago, IL USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04, Bethesda, MD 20892 USA. EM sibley@helix.nih.gov FU NINDS FX We thank David Cabrera for technical support and Dr David Lovinger for reading the manuscript. MLR was supported by a NINDS Competitive Fellowship. NR 53 TC 15 Z9 16 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2008 VL 33 IS 12 BP 2900 EP 2911 DI 10.1038/npp.2008.16 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 359SB UT WOS:000260007300011 PM 18288091 ER PT J AU Liu, ZH Shin, R Ikemoto, S AF Liu, Zhong-Hua Shin, Rick Ikemoto, Satoshi TI Dual role of medial A10 dopamine neurons in affective encoding SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ventral tegmental area; substantia nigra; nucleus accumbens; incentive motivation; conditioned place preference; avoidance ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS SHELL; CONDITIONED PLACE PREFERENCE; OLFACTORY TUBERCLE; EXTRACELLULAR DOPAMINE; RECEPTOR ANTAGONISTS; WITHDRAWAL SYNDROME; AVERSIVE STIMULI; TASTE-AVERSION; BASAL GANGLIA AB Increasing evidence suggests that the activation of medial A10 neurons mediates positive affective encoding. However, little is known about the functions of the inhibition of midbrain dopamine neurons. Here we show evidence suggesting that the inhibition of medial A10 neurons mediates a negative affective state, leading to negative affective encoding, whereas blunting the activation of medial A10 neurons disrupts positive affective encoding involving food reward. We used a microinjection procedure, in which the D(2) dopamine receptor agonist quinpirole was administered into the cell body region of the dopamine neurons, a procedure that reduces dopamine cell firing. Microinjections of quinpirole into the posteromedial ventral tegmental area, but not its more lateral counterparts, led to conditioned place aversion. Quinpirole administration to this site also decreased food intake and basal dopamine concentration in the ventromedial striatum, a major projection area of medial A10 neurons. In addition, moderate quinpirole doses that did not lead to conditioned place aversion or disrupt food intake abolished food-conditioned place preference, suggesting that blunting dopamine impulse activity in response to food reward disrupts positive affective encoding in associated external stimuli. Our data support the hypothesis that activation of medial A10 dopamine neurons mediates a positive affective state, leading to positive affective encoding, while their inhibition mediates a negative affective state, leading to negative affective encoding. Together with previous findings, we propose that medial A10 neurons are an important component of the mechanism via which animals learn to avoid negative incentive stimuli. C1 [Liu, Zhong-Hua; Shin, Rick; Ikemoto, Satoshi] Natl Inst Drug Abuse, Behav Neurosci Res Branch, NIH, US Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), Natl Inst Drug Abuse, Behav Neurosci Res Branch, NIH, US Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@mail.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 FU Intramural Research Program of National Institute on Drug Abuse; National Institutes of Health FX The present research was supported by the Intramural Research Program of National Institute on Drug Abuse, National Institutes of Health. We thank Drs Bin Wang, Roy Wise, and Zhi-Bing You for their help with microdialysis and Mary Pfeiffer and Emily Wentzell for editorial assistance. NR 76 TC 33 Z9 33 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2008 VL 33 IS 12 BP 3010 EP 3020 DI 10.1038/npp.2008.4 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 359SB UT WOS:000260007300020 PM 18256592 ER PT J AU Toscano, CD Kingsley, PJ Marnett, LJ Bosetti, F AF Toscano, Christopher D. Kingsley, Philip J. Marnett, Lawrence J. Bosetti, Francesca TI NMDA-induced seizure intensity is enhanced in COX-2 deficient mice SO NEUROTOXICOLOGY LA English DT Article DE N-Methyl-D-aspartate; Prostaglandin; Excitotoxicity; Lindane; Kainate; Fluoro Jade B ID ACID-INDUCED SEIZURE; NEURONAL CELL-DEATH; KAINIC ACID; CYCLOOXYGENASE-2 EXPRESSION; SELECTIVE INHIBITORS; RAT HIPPOCAMPUS; BRAIN-INJURY; RECEPTORS; LINDANE; LIPOPOLYSACCHARIDE AB Pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not COX-1, has been shown to increase susceptibility to kainic acid (KA)-induced excitotoxicity. However, it is unclear if susceptibility to excitotoxins that act through other neurotransmitter receptors is altered by COX-2 inhibition. To further understand the involvement of COX-2 in regulating susceptibility to excitotoxicity, we investigated the effect of COX-2 deletion on excitotoxicity induced by peripheral injection of Nmethyl-D-aspartate (NMDA, a specific agonist of the NMDA receptors) or lindane (a GABA(A) receptor antagonist). COX-2(-/-) mice injected intraperitoneally with NMDA (50-100 mg/kg) exhibited significantly increased median seizure intensity when compared to COX-2(+/+) mice. Further, COX-2(-/-) mice exposed to NMDA showed neuronal damage, detected by Fluoro Jade B (FJB) staining, in the CA3 region of the hippocampus. There was no FJB staining nor any significant difference in median or maximal seizure intensity in COX-2(+/+) and COX-2(-/-) mice exposed to lindane. LC-MS/MS analysis of brain prostaglandin profile in COX-2(-/-) mice demonstrated a significant increase in PGF(2 alpha), TXB(2), PGE(2) and PGD(2) expression 1 h after administration of an excitotoxic dose of KA, but not of NMDA. Our findings demonstrate that COX-2 regulates susceptibility to KA and NMDA excitotoxicity, which directly activate glutamatergic neurotransmission, but not to lindane, which indirectly alters glutamatergic neurotransmission. Furthermore, increased levels of prostaglandins after seizures are associated with consistent manifestation of neuronal damage. Published by Elsevier B.V. C1 [Toscano, Christopher D.; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. [Kingsley, Philip J.; Marnett, Lawrence J.] Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Bldg 9,Room 1S126,MSC 0947, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU NIH [GM15431]; National Institute on Aging [Z01AG000423-04] FX The authors would like to thank Dr. Robert Langenbach for supplying the cyclooxygenase-2 knockout mice and Drs. Saba Aid and Sang-Ho Choi for their helpful discussions and technical advice. This research was supported by the Intramural Research Program of the NIH, National Institute on Aging (Z01AG000423-04; CDT, FB) and by NIH grant # GM15431 (LJM). NR 33 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD NOV PY 2008 VL 29 IS 6 BP 1114 EP 1120 DI 10.1016/j.neuro.2008.08.008 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 381QU UT WOS:000261551800025 PM 18834901 ER PT J AU Li, SK Lizak, MJ Jeong, EK AF Li, S. Kevin Lizak, Martin J. Jeong, Eun-Kee TI MRI in ocular drug delivery SO NMR IN BIOMEDICINE LA English DT Review DE MRI; eye; ocular; drug delivery; contrast agent ID BLOOD-RETINAL BARRIER; CONTRAST-ENHANCED MRI; NUCLEAR-MAGNETIC-RESONANCE; POSTERIOR SEGMENT; HUMAN EYE; HIGH-RESOLUTION; AQUEOUS-HUMOR; RABBIT EYE; TRANSTYMPANIC IONTOPHORESIS; PHARMACEUTICAL RESEARCH AB Conventional pharmacokinetic method for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology present some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. Copyright (C) 2008 John Wiley & Sons. Ltd. C1 [Li, S. Kevin] Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA. [Lizak, Martin J.] NINDS, NIH, Bethesda, MD 20892 USA. [Jeong, Eun-Kee] Univ Utah, Dept Radiol, Salt Lake City, UT 84108 USA. [Jeong, Eun-Kee] Univ Utah, Utah Ctr Adv Imaging Res, Salt Lake City, UT 84108 USA. RP Li, SK (reprint author), Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA. EM kevin.li@uc.edu OI Li, Kevin/0000-0001-8626-9630 FU NIH [EN 015181] FX We thank Sarah A. Molokhia and Stephanie H. Kim for providing the MR data in this review, and Drs Hyuncheol Kim. Jinsong Hao, and Yanhui Zhano for their help. Some Unpublished MR data were obtained from Studies supported by NIH Grant EN 015181. NR 113 TC 16 Z9 17 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD NOV PY 2008 VL 21 IS 9 SI SI BP 941 EP 956 DI 10.1002/nbm.1230 PG 16 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 375TM UT WOS:000261136200003 PM 18186077 ER PT J AU Shakes, LA Malcolm, TL Allen, KL De, S Harewood, KR Chatterjee, PK AF Shakes, Leighcraft A. Malcolm, Tennison L. Allen, Kevin L. De, Supriyo Harewood, Ken R. Chatterjee, Pradeep K. TI Context dependent function of APPb enhancer identified using enhancer trap-containing BACs as transgenes in zebrafish SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOMES; AMYLOID PRECURSOR PROTEIN; CONSERVED NONCODING ELEMENTS; ALZHEIMERS-DISEASE; IN-VIVO; ESCHERICHIA-COLI; GENE-EXPRESSION; BETA-GLOBIN; HOMOLOGOUS RECOMBINATION; NESTED DELETIONS AB An enhancer within intron 1 of the amyloid precursor protein gene (APPb) of zebrafish is identified functionally using a novel approach. Bacterial artificial chromosomes (BACs) were retrofitted with enhancer traps, and expressed as transgenes in zebrafish. Expression from both transient assays and stable lines were used for analysis. Although the enhancer was active in specific nonneural cells of the notochord when placed with APPb gene promoter proximal elements its function was restricted to, and absolutely required for, specific expression in neurons when juxtaposed with additional far-upstream promoter elements of the gene. We demonstrate that expression of green fluorescent protein fluorescence resembling the tissue distribution of APPb mRNA requires both the intron 1 enhancer and 28 kb of DNA upstream of the gene. The results indicate that tissue-specificity of an isolated enhancer may be quite different from that in the context of its own gene. Using this enhancer and upstream sequence, polymorphic variants of APPb can now more closely recapitulate the endogenous pattern and regulation of APPb expression in animal models for Alzheimers disease. The methodology should help functionally map multiple noncontiguous regulatory elements in BACs with or without gene-coding sequences. C1 [Shakes, Leighcraft A.; Malcolm, Tennison L.; Allen, Kevin L.; Harewood, Ken R.; Chatterjee, Pradeep K.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. [Malcolm, Tennison L.; Chatterjee, Pradeep K.] N Carolina Cent Univ, Dept Chem, Durham, NC 27707 USA. [Allen, Kevin L.; Harewood, Ken R.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. [De, Supriyo] NIA, Gene Express & Genom Unit, NIH, Triad Technol Ctr, Baltimore, MD 21224 USA. RP Chatterjee, PK (reprint author), N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. EM pchatterjee@nccu.edu OI De, Supriyo/0000-0002-2075-7655 FU MBRS-SCORE [608049]; NIGMS and EXPORT [1P20 MD00175-01]; National Institute of Health; North Carolina Biotechnology Center; National Institutes of Health-NCMH HD FX MBRS-SCORE (# SO 608049); NIGMS and EXPORT (#1P20 MD00175-01); National Institute of Health; North Carolina Biotechnology Center. Funding for open access charge: National Institutes of Health-NCMH& HD. NR 74 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2008 VL 36 IS 19 BP 6237 EP 6248 DI 10.1093/nar/gkn628 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373PA UT WOS:000260983000028 PM 18832376 ER PT J AU Abes, R Moulton, HM Clair, P Yang, ST Abes, S Melikov, K Prevot, P Youngblood, DS Iversen, PL Chernomordik, LV Lebleu, B AF Abes, Rachida Moulton, Hong M. Clair, Philippe Yang, Sung-Tae Abes, Said Melikov, Kamran Prevot, Paul Youngblood, Derek S. Iversen, Patrick L. Chernomordik, Leonid V. Lebleu, Bernard TI Delivery of steric block morpholino oligomers by (R-X-R)(4) peptides: structure-activity studies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EFFICIENT SPLICING CORRECTION; CELL-PENETRATING PEPTIDES; DYSTROPHIN EXPRESSION; VIRUS-INFECTIONS; MDX MOUSE; IN-VITRO; OLIGONUCLEOTIDES; TRANSPORTERS; INHIBITION; STABILITY AB Redirecting the splicing machinery through the hybridization of high affinity, RNase H-incompetent oligonucleotide analogs such as phosphoramidate morpholino oligonucleotides (PMO) might lead to important clinical applications. Chemical conjugation of PMO to arginine-rich cell penetrating peptides (CPP) such as (R-Ahx-R)(4) (with Ahx standing for 6-aminohexanoic acid) leads to sequence-specific splicing correction in the absence of endosomolytic agents in cell culture at variance with most conventional CPPs. Importantly, (R-Ahx-R)(4) PMO conjugates are effective in mouse models of various viral infections and Duchenne muscular dystrophy. Unfortunately, active doses in some applications might be close to cytotoxic ones thus presenting challenge for systemic administration of the conjugates in those clinical settings. Structure activity relationship studies have thus been undertaken to unravel CPP structural features important for the efficient nuclear delivery of the conjugated PMO and limiting steps in their internalization pathway. Affinity for heparin (taken as a model heparan sulfate), hydrophobicity, cellular uptake, intracellular distribution and splicing correction have been monitored. Spacing between the charges, hydrophobicity of the linker between the Arg-groups and Arg-stereochemistry influence splicing correction efficiency. A significant correlation between splicing correction efficiency, affinity for heparin and ability to destabilize model synthetic vesicles has been observed but no correlation with cellular uptake has been found. Efforts will have to focus on endosomal escape since it appears to remain the limiting factor for the delivery of these splice-redirecting ON analogs. C1 [Abes, Rachida; Clair, Philippe; Abes, Said; Prevot, Paul; Lebleu, Bernard] Univ Montpellier 2, CNRS, UMR 5235, F-34095 Montpellier 5, France. [Moulton, Hong M.; Youngblood, Derek S.; Iversen, Patrick L.] AVI BioPharma, Corvallis, OR 97333 USA. [Yang, Sung-Tae; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Lebleu, B (reprint author), Univ Montpellier 2, CNRS, UMR 5235, Pl Eugene Bataillon, F-34095 Montpellier 5, France. EM bernard.lebleu@univ-montp2.fr RI Melikov, Kamran/A-6604-2009 FU AFM and ARC; Ligue Regionale de Lutte contre le Cancer; EEC post-doctoral fellowship; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health [HD001501-17]; Centre National de la Recherche Scientifique FX AFM and ARC (B. L.); Ligue Regionale de Lutte contre le Cancer, PhD fellowships (S. A. and R. A.); EEC post-doctoral fellowship (P. C.); Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (S.-T.Y., K. M. and L. V. C.); National Institutes of Health (HD001501-17 L. V. C.). Funding for open access charge: Centre National de la Recherche Scientifique. NR 27 TC 52 Z9 58 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2008 VL 36 IS 20 BP 6343 EP 6354 DI 10.1093/nar/gkn541 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373NA UT WOS:000260977500009 PM 18796528 ER EF