FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wang, S Ziman, B Bodi, I Rubio, M Zhou, YY D'Souza, K Bishopric, NH Schwartz, A Lakatta, EG AF Wang, Su Ziman, Bruce Bodi, Ilona Rubio, Marta Zhou, Ying-Ying D'Souza, Karen Bishopric, Nanette H. Schwartz, Arnold Lakatta, Edward G. TI Dilated Cardiomyopathy with Increased SR Ca2+ Loading Preceded by a Hypercontractile State and Diastolic Failure in the alpha(1C)TG Mouse SO PLOS ONE LA English DT Article AB Mice over-expressing the alpha(1)-subunit (pore) of the L-type Ca2+ channel (alpha(1C)TG) by 4months (mo) of age exhibit an enlarged heart, hypertrophied myocytes, increased Ca2+ current and Ca2+ transient amplitude, but a normal SR Ca2+ load. With advancing age (8-11 mo), some mice demonstrate advanced hypertrophy but are not in congestive heart failure (NFTG), while others evolve to frank dilated congestive heart failure (FTG). We demonstrate that older NFTG myocytes exhibit a hypercontractile state over a wide range of stimulation frequencies, but maintain a normal SR Ca2+ load compared to age matched non-transgenic (NTG) myocytes. However, at high stimulation rates (2-4 Hz) signs of diastolic contractile failure appear in NFTG cells. The evolution of frank congestive failure in FTG is accompanied by a further increase in heart mass and myocyte size, and phospholamban and ryanodine receptor protein levels and phosphorylation become reduced. In FTG, the SR Ca2+ load increases and Ca2+ release following excitation, increases further. An enhanced NCX function in FTG, as reflected by an accelerated relaxation of the caffeine-induced Ca2+ transient, is insufficient to maintain a normal diastolic Ca2+ during high rates of stimulation. Although a high SR Ca2+ release following excitation is maintained, the hypercontractile state is not maintained at high rates of stimulation, and signs of both systolic and diastolic contractile failure appear. Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca2+ loading or release, as occurs in some other cardiomyopathic models. C1 [Wang, Su; Ziman, Bruce; Zhou, Ying-Ying; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD USA. [Bodi, Ilona; Rubio, Marta; D'Souza, Karen; Schwartz, Arnold] Univ Cincinnati, Coll Med, Dept Surg, Inst Mol Pharmacol & Biophys, Cincinnati, OH 45221 USA. [Bishopric, Nanette H.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol Med & Pediat, Miami, FL USA. RP Wang, S (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD USA. EM schwara@email.uc.edu; LakattaE@grc.nia.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Aging [R01 HL079599, T-32 HL07382] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and in part by R01 HL079599 (AS), and T-32 HL07382 (AS). NR 36 TC 16 Z9 16 U1 0 U2 1 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 JAN 6 PY 2009 VL 4 IS 1 AR e4133 DI 10.1371/journal.pone.0004133 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437FV UT WOS:000265473100007 PM 19125184 ER PT J AU Zhang, LL Lee, SY Beznoussenko, GV Peters, PJ Yang, JS Gilbert, HY Brass, AL Elledge, SJ Isaacs, SN Moss, B Mironov, A Hsu, VW AF Zhang, Leiliang Lee, Stella Y. Beznoussenko, Galina V. Peters, Peter J. Yang, Jia-Shu Gilbert, Hui-ya Brass, Abraham L. Elledge, Stephen J. Isaacs, Stuart N. Moss, Bernard Mironov, Alexander Hsu, Victor W. TI A role for the host coatomer and KDEL receptor in early vaccinia biogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COPI; morphogenesis ID FUNCTIONAL GENOMIC SCREEN; ENDOPLASMIC-RETICULUM; COPI VESICLES; MEMBRANE; VIRUS; PROTEIN; TRANSPORT; REVEALS; ARF1; MORPHOGENESIS AB Members of the poxvirus family have been investigated for their applications as vaccines and expression vectors and, more recently, because of concern for their potential as biological weapons. Vaccinia virus, the prototypic member, evolves through multiple forms during its replication. Here, we show a surprising way by which vaccinia hijacks coatomer for early viral biogenesis. Whereas coatomer forms COPI vesicles in the host early secretory system, vaccinia formation bypasses this role of coatomer, but instead, depends on coatomer interacting with the host KDEL receptor. To gain insight into the viral roles of these two host proteins, we have detected them on the earliest recognized viral forms. These findings not only suggest insights into early vaccinia biogenesis but also reveal an alternate mechanism by which coatomer acts. C1 [Zhang, Leiliang; Lee, Stella Y.; Yang, Jia-Shu; Gilbert, Hui-ya; Hsu, Victor W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Zhang, Leiliang; Lee, Stella Y.; Yang, Jia-Shu; Gilbert, Hui-ya; Hsu, Victor W.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Beznoussenko, Galina V.; Mironov, Alexander] Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy. [Peters, Peter J.] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands. [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Genet, Howard Hughes Med Inst,Ctr Genet & Genom, Boston, MA 02115 USA. [Brass, Abraham L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Isaacs, Stuart N.] Univ Penn, Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hsu, VW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu FU National Institutes of Health; Telethon Italy; Harvard University Center for AIDS Research FX We thank Jian Li and Ming Bai for advice and Erik Bos for technical assistance. This work was supported by grants from the National Institutes of Health ( to V. W. H. and S.N.I.), Telethon Italy ( to A. M.), and the Harvard University Center for AIDS Research ( to A. L. B.). S. J. E. is an Investigator of the Howard Hughes Medical Institute. NR 29 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 JAN 6 PY 2009 VL 106 IS 1 BP 163 EP 168 DI 10.1073/pnas.0811631106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391WC UT WOS:000262263900032 PM 19109439 ER PT J AU Chadman, KK Yang, M Crawley, JN AF Chadman, Kathryn K. Yang, Mu Crawley, Jacqueline N. TI Criteria for Validating Mouse Models of Psychiatric Diseases SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE mouse; model; behavior; phenotyping ID VISIBLE BURROW SYSTEM; CHRONIC SOCIAL STRESS; TAIL SUSPENSION TEST; ELEVATED PLUS-MAZE; TESTICULAR 11-BETA-HYDROXYSTEROID DEHYDROGENASE; RECEPTOR SUBTYPES MEDIATE; BEHAVIORAL-TEST BATTERIES; MUTANT MICE DISPLAY; BTBR-T+TF/J MICE; WILD HOUSE MICE AB Animal models of human diseases are in widespread use for biomedical research. Mouse models with a mutation in a single gene or multiple genes are excellent research tools for understanding the role of a specific gene in the etiology of a human genetic disease. Ideally, the mouse phenotypes will recapitulate the human phenotypes exactly. However, exact matches are rare, particularly in mouse models of neuropsychiatric disorders. This article summarizes the current strategies for optimizing the validity of a mouse model of a human brain dysfunction. We address the common question raised by molecular geneticists and clinical researchers in psychiatry, "what is a 'good enough' mouse model"? Published 2008 Wiley-Liss, Inc. C1 [Chadman, Kathryn K.] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Chadman, KK (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bldg 35 Room IC-909,Mail Stop 3730, Bethesda, MD 20892 USA. EM chadmank@mail.nih.gov FU National Institute of Mental Health FX Supported by the National Institute of Mental Health Intramural Research Program. NR 145 TC 45 Z9 46 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2009 VL 150B IS 1 BP 1 EP 11 DI 10.1002/ajmg.b.30777 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 402XR UT WOS:000263046900001 PM 18484083 ER PT J AU Wang, Y Samuels, JF Chang, YC Grados, MA Greenberg, BD Knowles, JA McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Hoehn-Saric, R Pinto, A Fyer, AJ Piacentini, J Pauls, DL Bienvenu, OJ Riddle, M Shugart, YY Liang, KY Nestadt, G AF Wang, Y. Samuels, J. F. Chang, Y. C. Grados, M. A. Greenberg, B. D. Knowles, J. A. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Hoehn-Saric, R. Pinto, A. Fyer, A. J. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Riddle, M. Shugart, Y. Y. Liang, K. Y. Nestadt, G. TI Gender Differences in Genetic Linkage and Association on 11p15 in Obsessive-Compulsive Disorder Families SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; linkage; association; OCD; gender ID TANDEM DUPLICATION POLYMORPHISM; COMPLEX SEGREGATION ANALYSIS; DOPAMINE-D4 RECEPTOR GENE; DRD4 GENE; CHILDREN; ADHD; SUSCEPTIBILITY; LOCUS; IDENTIFICATION; ADOLESCENTS AB Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KAC(all) = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KAC(all) = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD. (c) 2008 Wiley-Liss, Inc. C1 [Wang, Y.; Samuels, J. F.; Grados, M. A.; Hoehn-Saric, R.; Bienvenu, O. J.; Riddle, M.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Chang, Y. C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, J. A.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Pinto, A.; Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Shugart, Y. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. [Liang, K. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Mental Health NIMH [R01 MH50214, K23MH64543, 7K23MHO66284]; James E. Marshall OCD Foundation; NIH [OPD-GCRC RR 00052]; NCRR FX This study is supported by NIMH R01 MH50214 to GN, K23MH64543 to OJB, and 7K23MHO66284 to MAG from the National Institute of Mental Health, and funding from the James E. Marshall OCD Foundation, and NIH, NCRR, OPD-GCRC RR 00052 from the National Institutes of Health. We are grateful to the numerous individuals and families who generously donated their time and resources. We thank David Houseman, MID, Kathleen Merikangas, PhD, Ann Pulver, PhD, and Alec Wilson, Phl), for consultation; and clinicians and coordinators at each site: Providence (Maria Mancebo, Phl), Richard Marsland, RN, Shirley Yen, PhD); New York (Rence Goodwin, PhD, Joshua Lipsitz, PhD); Baltimore (Laura Eisen, BS; Karan Lamb, PsyD, Tracey Lichner, PhD, Yungmei Leong, Phl); Krista Vermillion, BA); Boston (Dan Geller, MD, Anne Chosak, Phl), Michelle Wedig, BS, Evelyn Stewart, MD, Michael Jenike, MD, Beth Gershuny, Phl), Sabine Wilhelm, PhD); Bethesda (Lucy Justement, Diane Kazuba, V Holland LaSafle-Ricci, Theresa B DeGuzman); Los Angeles (R Lindsey Bergman, PhD, Susanna Chang, PhD, Audra Langley, Phl), Arnanda Pearlrnan, BA). NR 66 TC 16 Z9 17 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2009 VL 150B IS 1 BP 33 EP 40 DI 10.1002/ajmg.b.30760 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 402XR UT WOS:000263046900004 PM 18425788 ER PT J AU Lipsky, RH Hu, XZ Goldman, D AF Lipsky, Robert H. Hu, Xian-Zhang Goldman, David TI Additional Functional Variation at the SLC6A4 Gene SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Letter C1 [Lipsky, Robert H.; Hu, Xian-Zhang; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. RP Lipsky, RH (reprint author), 5625 Fishers Lane,Room 3S32, Rockville, MD 20852 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473 FU Intramural NIH HHS [Z01 AA000306-02] NR 0 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2009 VL 150B IS 1 BP 153 EP 153 DI 10.1002/ajmg.b.30766 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 402XR UT WOS:000263046900020 PM 18444253 ER PT J AU Negus, SS Bear, AE Folk, JE Rice, KC AF Negus, S. Stevens Bear, Ashley E. Folk, John E. Rice, Kenner C. TI Role of delta opioid efficacy as a determinant of mu/delta opioid interactions in rhesus monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Delta opioid receptor; Mu opioid receptor; Interaction; Antinociception; Efficacy; Rhesus monkey ID MU-MEDIATED ANTINOCICEPTION; SPRAGUE-DAWLEY RATS; AGONIST SNC80; THERMAL NOCICEPTION; RECEPTOR; MORPHINE; LIGANDS; BINDING; TRAFFICKING; COMBINATION AB Delta opioid agonists can selectively enhance the antinociceptive effects of mu opioid agonists without enhancing some other, potentially undesirable mu agonist effects. However, the degree of delta receptor efficacy required to produce this profile of interactions is unknown. To address this issue, the present study examined interactions produced by the mu agonist fentanyl and the intermediate-efficacy delta opioid MSF61 in rhesus monkeys. For comparison, interactions were also examined between fentanyl and the relatively high-efficacy delta agonist SNC243A and the delta antagonist naltrindole, which has negligible efficacy at delta receptors. Two different behavioral procedures were used: (a) a warm-water tail-withdrawal assay of thermal nociception, and (b) an assay of schedule-controlled responding for food reinforcement. Drug interactions within each procedure were evaluated using dose-addition analysis to compare experimental results with expected additivity. Drug interactions across procedures were evaluated using dose-ratio analysis to assess relative potencies to produce antinociception vs. response-rate suppression. As expected, dose-addition analysis found that fentanyl/SNC243A interactions were superadditive in the assay of antinociception but additive in the assay of schedule-controlled responding. Conversely, fentanyl/MSF61 interactions were generally additive in both procedures, and fentanyl/naltrindole interactions were additive or subadditive in both procedures. Dose-ratio analysis found that fentanyl alone produced antinociception and rate suppression with similar potencies. Some fentanyl/SNC243A mixtures produced antinociception with up to 4-fold greater potency than rate-suppression. However, fentanyl/MSF61 and fentanyl/naltrindole mixtures produced antinociception with lower potency than rate suppression. These results suggest that relatively high delta receptor efficacy is required for mu/delta antinociceptive synergy. (C) 2008 Elsevier B.V. All rights reserved. C1 [Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Negus, S. Stevens; Bear, Ashley E.; Folk, John E.] Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA. [Rice, Kenner C.] NIAAA, NIH, DHHS, Bethesda, MD USA. RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA. EM ssnegus@vcu.edu FU National Institute on Drug Abuse [Grant RO1-DA11460]; National Institutes of Health; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by Grant RO1-DA11460 from the National Institute on Drug Abuse, National Institutes of Health. A portion of this work was also supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. The authors would like to thank Joe Pocher, D.V.M., for expert veterinary assistance. NR 44 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 5 PY 2009 VL 602 IS 1 BP 92 EP 100 DI 10.1016/j.ejphar.2008.11.004 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 401WD UT WOS:000262972300015 PM 19027735 ER PT J AU De Silva, FS Paran, N Moss, B AF De Silva, Frank S. Paran, Nir Moss, Bernard TI Products and substrate/template usage of vaccinia virus DNA primase SO VIROLOGY LA English DT Article DE Poxvirus DNA primase; Poxvirus DNA replication; Poxvirus enzymes ID MOUSE L-CELLS; VIRAL-DNA; HETERODIMERIC PRIMASE; D5 PROTEIN; REPLICATION; SEQUENCE; RNA; POLYMERASE; INITIATION; GENOME AB Vaccinia virus encodes a 90-kDa protein conserved in all poxviruses, with DNA primase and nucleoside triphosphatase activities. DNA primase products, synthesized with a single stranded phi X174 DNA template, were resolved as dinucleotides and long RNAs on denaturing polyacrylamide and agarose gels. Following phosphatase treatment, the dinucleotides GpC and ApC in a 4:1 ratio were identified by nearest neighbor analysis in which (32)P Was transferred from [alpha-(32)P]CTP to initiating purine nucleotides. Differences in the nucleotide binding sites for initiation and elongation were suggested by the absence of CpC and UpC dinucleotides as well as the inability of deoxynucleotides to mediate primer synthesis despite their incorporation into mixed RNA/DNA primers. Strong primase activity was detected with an oligo(dC) template. However, there was only weak activity with an oligo(dT) template and none with oligo(dA) or oligo (dG). The absence of stringent template specificity is consistent with a role for the enzyme in priming DNA synthesis at the replication fork. (c) Published by Elsevier Inc. C1 [De Silva, Frank S.; Paran, Nir; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, National Institute of Allergy and infectious Diseases, National Institutes of Health FX The work was supported by the Division of Intramural Research, National Institute of Allergy and infectious Diseases, National Institutes of Health. NR 37 TC 7 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2009 VL 383 IS 1 BP 136 EP 141 DI 10.1016/j.virol.2008.10.008 PG 6 WC Virology SC Virology GA 394LD UT WOS:000262447300017 PM 19007959 ER PT J AU Chen, R Holmes, EC AF Chen, Rubing Holmes, Edward C. TI Frequent inter-species transmission and geographic subdivision in avian influenza viruses from wild birds SO VIROLOGY LA English DT Article DE Avian influenza virus; Migration; Phylogeny; Population structure; Epidemiology ID A VIRUSES; DUCKS; EVOLUTION; ECOLOGY; DYNAMICS AB Revealing the factors that shape the genetic structure of avian influenza viruses (AIVs) in wild bird populations is essential to understanding their evolution. However, the relationship between epidemiological dynamics and patterns of genetic diversity in AIV is not well understood, especially at the continental scale. To address this question, we undertook a phylogeographic analysis of complete genome sequences of AIV sampled from wild birds in North America. In particular, we asked whether host species, geographic location or sampling time played the major role in shaping patterns of viral genetic diversity. Strikingly, our analysis revealed no strong species effect, yet a significant viral clustering by time and place of sampling, as well as the circulation of multiple viral lineages in single locations. These results suggest that AIVs can readily infect many of the bird species that share breeding/feeding areas. (c) 2008 Elsevier Inc. All rights reserved. C1 [Chen, Rubing; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu RI Chen, Rubing/A-2276-2010; Chen, Rubing/F-2314-2011; OI Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [R01 GM080533, R01 GM080533-02] NR 28 TC 43 Z9 45 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2009 VL 383 IS 1 BP 156 EP 161 DI 10.1016/j.virol.2008.10.015 PG 6 WC Virology SC Virology GA 394LD UT WOS:000262447300020 PM 19000628 ER PT J AU Martin, MV Churchill, JD Dong, HX Wozniak, DF Cheverud, JM Csernansky, JG AF Martin, Maureen V. Churchill, James D. Dong, Hongxin Wozniak, David F. Cheverud, James M. Csernansky, John G. TI Genetic influences on hippocampal structure and function in recombinant inbred mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Hippocampus; QTL; Structure/function relationships; Recombinant inbred mice ID RADIAL-ARM MAZE; WORKING-MEMORY IMPAIRMENTS; QUANTITATIVE TRAIT LOCI; SCHIZOPHRENIC-PATIENTS; SPATIAL WORKING; BRAIN STRUCTURE; STARTLE REFLEX; ANIMAL-MODELS; VOLUME; INDIVIDUALS AB Previously, we identified separate genetic influences on ventral versus dorsal hippocampal volume in BXD recombinant inbred mice [Martin MV, Dong HX, Vallera D, Lu L, Williams RW, Rosen GD, et al. Independent quantitative trait loci influence ventral and dorsal hippocampal volume in recombinant inbred strains of mice. Genes Brain Behav 2006:5:614-23]. Based on genotype at genetic markers associated with ventral hippocampal volume, we evaluated BXD mouse strains with relatively small versus large ventral hippocampal volumes using numerous behavioral paradigms known to rely upon hippocampal function and several other tasks that tap into behaviors analogous to those often impaired in schizophrenia. We observed a relationship between genotype at markers known to influence ventral hippocampal volume and working memory at an intermediate memory load. There was no association between genotype at markers known to influence ventral hippocampal volume and spatial reference memory, prepulse inhibition, or elevated plus maze performance. The relevance of these findings for understanding the pathophysiology of schizophrenia are discussed, including the possibility that genetic predisposition toward anterior hippocampal volume reductions and working memory deficits in schizophrenia may be related through a shared genetic locus. (C) 2008 Elsevier B.V. All rights reserved. C1 [Martin, Maureen V.; Csernansky, John G.] Univ Calif Irvine, Irvine, CA 92697 USA. [Martin, Maureen V.; Dong, Hongxin; Wozniak, David F.; Csernansky, John G.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Cheverud, James M.; Csernansky, John G.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Churchill, James D.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Dong, Hongxin; Csernansky, John G.] Psychiat & Behav Sci NW Feinberg Sch Med, Chicago, IL USA. [Churchill, James D.] NIMH, Res Training & Career Dev Off, Div Neurosci & Basci Behav Sci, NIH,DHHS, Bethesda, MD 20892 USA. RP Csernansky, JG (reprint author), Univ Calif Irvine, 837 Hlth Sci Rd,Zot 4260, Irvine, CA 92697 USA. EM jgc@northwestern.edu FU NIH [MH071616]; Washington University (DFW) [P30 NS057105] FX This work was supported by NIH grants MH071616 (JGC/JMC) and the Neuroscience Blueprint Core Grant P30 NS057105 to Washington University (DFW). NR 55 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 3 PY 2009 VL 196 IS 1 BP 78 EP 83 DI 10.1016/j.bbr.2008.07.029 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 386EM UT WOS:000261865100011 PM 18721828 ER PT J AU Herbeuval, JP Nilsson, J Boasso, A Hardy, AW Vaccari, M Cecchinato, V Valeri, V Franchini, G Andersson, J Shearer, GM AF Herbeuval, Jean-Philippe Nilsson, Jakob Boasso, Adriano Hardy, Andrew W. Vaccari, Monica Cecchinato, Valentina Valeri, Valerio Franchini, Genoveffa Andersson, Jan Shearer, Gene M. TI HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques SO AIDS LA English DT Article DE antiretroviral therapy; apoptosis; death ligands; death receptors; HIV-1; lymphoid tissue; macaques; simian immunodeficiency virus; tumor necrosis factor-related apoptosis-inducing ligand; type I interferon ID APOPTOSIS-INDUCING LIGAND; ACTIVE ANTIRETROVIRAL THERAPY/; PLASMACYTOID DENDRITIC CELLS; CD4(+) T-CELLS; HIV-1-INFECTED PATIENTS; TRAIL; ACTIVATION; EXPRESSION; IMPACT AB Objective: To determine how antiretroviral therapy (ART) or HAART affects the expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and simian immunodeficiency virus-infected macaques. Methods: We analyzed the mRNA expression of death molecules [tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL] and their receptors(DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV positive), HIV-infected patients receiving HAART and HIV- uninfected (HIV negative) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from simian immunodeficiency virus-infected macaques before and after ART. Results: Expression of TRAIL, FasL, DR5 and Fas was elevated in circulating CD4(+) T cells from a group of HIV-positive patients as compared with that from both HIV-negative donors and HAART patients. In a different study group, I-RAIL, FasL, DR5 and Fas were increased in tonsils of HIV-positive patients as compared with I-IN-negative donors and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas as compared with HIV-positive patients. Similarly, data obtained in a longitudinal study of simian immunodeficiency virus-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood but only TRAIL and not DR5 in lymph nodes from the same animals. Conclusion: These findings suggest that HAART or ART is ineffective in reducing the expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4+ T cells in lymphoid tissue. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Herbeuval, Jean-Philippe; Boasso, Adriano; Hardy, Andrew W.; Shearer, Gene M.] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Herbeuval, Jean-Philippe] Univ Paris 05, CNRS, UMR 8147, Paris, France. [Nilsson, Jakob; Andersson, Jan] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. [Vaccari, Monica; Cecchinato, Valentina; Valeri, Valerio; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, CCR, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM shearerg@mail.nih.gov OI Nilsson, Jakob/0000-0001-5091-8133; Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS NR 23 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2009 VL 23 IS 1 BP 35 EP 40 DI 10.1097/QAD.0b013e32831cb907 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 390XS UT WOS:000262197600006 PM 19050384 ER PT B AU Nelson, SJ AF Nelson, Stuart J. GP IEEE TI Medical Terminologies That Work The Example of MeSH SO 2009 10TH INTERNATIONAL SYMPOSIUM ON PERVASIVE SYSTEMS, ALGORITHMS, AND NETWORKS (ISPAN 2009) LA English DT Proceedings Paper CT 10th International Symposium on Pervasive Systems, Algorithms, and Networks CY DEC 14-16, 2009 CL Kaohsiung, TAIWAN DE terminologies; identifiers; relationships; medical informatics AB One description of medical informatics is as a disciplined search for methods to answer a question that a physician might pose: "What is the experience with patients like mine?" The difficulty in practicing high quality medicine has resulted in a strong professional emphasis in clinical practice of evidence-based medicine. This emphasis on evidence-based medicine relies primarily on literature review, and has largely ignored the fundamental problems of identifying patients similar to the patient at hand and exploring their experience. Standard terminologies are an important tool for humans and machines to recognize and to describe similar patients and to measure outcomes. Other tools, such as suitable outcome and similarity measures, are not within the scope of this paper, but clearly are other major concerns. Despite efforts over many years, there are few examples of standard terminologies that have been instituted into working systems. Lessons from the success of the Medical Subject Headings, used to index the world's biomedical literature in MEDLINE, have led to the formulation of several principles in building terminologies that work. Essentials include starting with a simple user and information model, evolving as user needs indicate, and understanding the interaction between systems, information models, and terminology. Update models and managing changing terminology pose significant challenges. Overall, making terminologies that work is a complex engineering process. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Nelson, SJ (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM nelsonst@mail.nih.gov NR 6 TC 9 Z9 9 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5403-7 PY 2009 BP 380 EP 384 DI 10.1109/I-SPAN.2009.84 PG 5 WC Computer Science, Hardware & Architecture; Computer Science, Theory & Methods SC Computer Science GA BVC20 UT WOS:000291013200065 ER PT S AU Lillywhite, K Lee, DJ Antani, S Zhang, D Long, R AF Lillywhite, Kirt Lee, Dah-Jye Antani, Sameer Zhang, Dong Long, Rodney GP IEEE TI Lessons Learned in Developing a Low-cost High Performance Medical Imaging Cluster SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE AB This paper explores the usefulness of the Sony Play Station 3 (PS3) for medical image processing. Medical image processing often entails dealing with a large number of high resolution images, requiring a large amount of computational power to process. The PS3 is powered by the Cell Broadband Engine, a microprocessor created by IBM, capable of rapid numeric computation with low power requirements that has helped the unit to become a popular gaming unit. The unit can be repurposed as a low-cost high performance computing platform. In order to demonstrate the computational abilities of the PS3, several basic image processing tasks are implemented and compared with desktop PCs, equipped with general-purpose microprocessors. This article describes lessons learned in the process of building some fundamental image processing tasks. The article also describes the architecture of the Cell Broadband Engine and provides information about developing applications given the architecture. The article also provides an introduction to setting up a high-performance image processing environment with, a cluster of such relatively inexpensive PS3 units. C1 [Lillywhite, Kirt; Lee, Dah-Jye] Brigham Young Univ, Dept Elect & Comp Eng, Provo, UT 84602 USA. [Antani, Sameer; Long, Rodney] Natl Inst Hlth, Natl Lib Med, Bethesda, MD USA. [Zhang, Dong] Sun Yat Sen Univ, Sch Informat Sci & Technol, Guangzhou 510275, Guangdong, Peoples R China. RP Lillywhite, K (reprint author), Brigham Young Univ, Dept Elect & Comp Eng, Provo, UT 84602 USA. EM kirt.lillywhite@gmail.com; djlee@ee.byu.edu; antani@nlm.nih.gov; zhangd@mail.sysu.edu.cn; long@nlm.nih.gov FU National Library of Medicine (NLM) [276200800412]; Lister Hill National Center for Biomedical Communications; National Library of Medicine (NLM); National Institutes of Health (NIH) FX This work research was supported in part by the National Library of Medicine (NLM) under Grant contract HHSN 276200800412 and intramural research funds of the Lister Hill National Center for Biomedical Communications, the National Library of Medicine (NLM), and the National Institutes of Health (NIH). NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 13 EP + PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800004 ER PT S AU Kim, J Le, DX Thoma, GR AF Kim, Jongwoo Le, Daniel X. Thoma, George R. GP IEEE TI Inferring Grant Support Types from Online Biomedical Articles SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE AB The category of institution or organization underwriting the research reported in a scientific article is a required field (Grant Support type) in the bibliographic record of that article in the MEDLINE database. We describe a system based on a combination of a Naive Bayes classifier and heuristic rules that automatically infers the Grant Support types from article text. Testing the performance of the system on 2,000 biomedical articles shows Precision, Recall, and F-Measure exceeding 95%. C1 [Kim, Jongwoo; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jongkim@mail.nih.gov; danle@mail.nih.gov; gthoma@mail.nih.gov NR 11 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 48 EP 53 PG 6 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800010 ER PT S AU Young, L Tu, SW Tennakoon, L Vismer, D Astakhov, V Gupta, A Grethe, JS Martone, ME Das, AK McAuliffe, MJ AF Young, Lynn Tu, Samson W. Tennakoon, Lakshika Vismer, David Astakhov, Vadim Gupta, Amarnath Grethe, Jeffrey S. Martone, Maryann E. Das, Amar K. McAuliffe, Matthew J. GP IEEE TI Ontology Driven Data Integration for Autism Research SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID SPECTRUM AB Autism Spectrum Disorder is an inherently complex phenomenon requiring large studies of many different types to further understanding of its causes. The National Database for Autism Research (NDAR) is being constructed to aid in this effort by providing a means for researchers to share and integrate data. An autism ontology drafted by a group at Stanford is being incorporated for use by NDAR to allow semantic data integration. The architecture upon which NDAR is built - the UCSD Developed Data Integration Environment - supports the use of this autism ontology, including annotation of data with ontological concepts and ontology enhanced queries on databases, both central and federated. C1 [Young, Lynn; Vismer, David; McAuliffe, Matthew J.] US Natl Inst Hlth, Div Computat Biosci, CIT, Bethesda, MD 20892 USA. [Tu, Samson W.; Tennakoon, Lakshika; Das, Amar K.] Stanford Univ, Ctr Biomed Informat Res, Stanford, CA 94305 USA. [Astakhov, Vadim; Gupta, Amarnath; Grethe, Jeffrey S.; Martone, Maryann E.] Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA. RP Young, L (reprint author), US Natl Inst Hlth, Div Computat Biosci, CIT, Bethesda, MD 20892 USA. EM lynny@mail.nih.gov; swt@stanford.edu; lakshika@stanford.edu; vismerd@mail.nih.gov; astakhov@ncmir.ucsd.edu; gupta@sdsc.edu; jgrethe@ncmir.ucsd.edu; maryann@ncmir.ucsd.edu; das@stanford.edu; mcmatt@mail.nih.gov FU NIH, Center for Information Technology (LY, DV, MJM); NLM (SWT, LT, AKD) [1P41LM007885]; NINDS [RO1NS058296]; NCRR [RR04050]; (VA,AG, JSG, and MEM) [RR08605] FX William Bug (1961-2008) was instrumental in this project. This work was supported by 1) the Intramural Research Program of the NIH, Center for Information Technology (LY, DV, MJM), 2) NLM 1P41LM007885 (SWT, LT, AKD), and 3) NINDS RO1NS058296, NCRR RR04050, and RR08605 (VA,AG, JSG, and MEM) NR 14 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 54 EP + PG 3 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800011 ER PT S AU Xue, ZY Antani, S Long, LR Thoma, GR AF Xue, Zhiyun Antani, Sameer Long, L. Rodney Thoma, George R. GP IEEE TI A System for Searching Uterine Cervix Images by Visual Attributes SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID RETRIEVAL AB Content-based indexing and retrieval is gaining increasing interest in the medical domain with the growing size of medical image databases. We present here a Web-accessible retrieval system for searching for similar uterine cervix images based on their visual characteristics. The system operates on a subset of a large database created for archiving patient records collected by two key projects in cervical cancer research. It was developed to bridge the "gaps" that hold back the practical adoption of most CBIR systems. This collaboration between engineers and gynecological experts promises to provide a new biomedical resource beyond current text-based searching tools. C1 [Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bethesda, MD 20892 USA. EM xuez@mail.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 96 EP 100 PG 5 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800017 ER PT S AU Guan, HY Antani, S Long, LR Thoma, GR AF Guan, Haiying Antani, Sameer Long, L. Rodney Thoma, George R. GP IEEE TI Comparative Study of Spine Vertebra Shape Retrieval using Learning-based Feature Selection SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID PATTERN-RECOGNITION; GRAPHS AB Feature extraction and selection are two important steps for shape retrieval. Given a data set, a set of features which describe the shape property from different aspects are extracted. Our goal is a learning-based methodology to select the features for improving retrieval performance. Our approach uses both global and local feature descriptors. The global shape features include geometric ones (elongation, eccentricity, roughness, and compactness), Fourier descriptors with complex coordinates, Fourier descriptors with Centroid Contour Distance Curve, Coefficients of Fourier Expansion of Bent function, moment invariants, and local shape features that include turn angle and Distance Across the Shape. We propose a learning-based feature selection algorithm as a strategy for optimizing retrieval performance. We provide results from the vertebra shape dataset created from our database containing spine x-rays from the National Health and Nutrition Examination Survey (NHANES II). Finally, we compare the retrieval performances of feature descriptors on "whole shape" and "corner shape" datasets. The experimental results show that various feature descriptors perform differently on different datasets, and that feature selection schemes improve the retrieval performance significantly. C1 [Guan, Haiying; Antani, Sameer; Long, L. Rodney; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Guan, HY (reprint author), NIH, US Natl Lib Med, Bethesda, MD 20892 USA. EM guanh@mail.nih.gov; santani@mail.nih.gov; rlong@mail.nih.gov; gthoma@mail.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 139 EP 145 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800024 ER PT S AU Wilhelm, M Nutter, B Long, R Antani, S AF Wilhelm, Matthew Nutter, Brian Long, Rodney Antani, Sameer GP IEEE TI Linear Array Image Analysis For Automated Detection of Human Papillomavirus SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE AB Persistent infections with carcinogenic Human Papillomavirus (HPV) are a necessary cause for cervical cancer, which is the fifth most deadly cancer for women worldwide. Approximately 20 million Americans are currently infected with HP V but only a subset will develop cervical cancer. While a negative HPV test indicates a very low risk for cervical cancer, a positive test cannot discriminate between an innocuous transient infection and a prevalent cancer. Additional information such as HPV genotype and HPV viral load is thought to improve the predictive ability of which women will develop cervical cancer. The visual interpretation of hybridization-strip-based HPV genotyping results, however, is heterogeneous and poorly standardized. This has led to work toward the development of a robust automated image analysis package for HPV genotyping strips. C1 [Wilhelm, Matthew; Nutter, Brian] Texas Tech Univ, Dept Elect & Comp Engn, Lubbock, TX 79409 USA. [Long, Rodney; Antani, Sameer] NIH, Lister Hill Nat Cen Biomed Comm, Natl Lib Med, Bethesda, MD 20892 USA. RP Wilhelm, M (reprint author), Texas Tech Univ, Dept Elect & Comp Engn, Lubbock, TX 79409 USA. EM brian.nutter@ttu.edu FU U.S. National Institutes of Health; National Library of Medicine; Lister Hill National Center for Biomedical Communications [HHSN276200800411P] FX The authors gratefully acknowledge the contribution of HPV data from the Study to Understand Cervical Cancer Early Endpoints and Determinants(SUCCEED), provided by Terence Dunn and R. Andy Allen, of the University of Oklahoma Health Sciences Center. We also thank Dr. Nicolas Wentzensen and Sophia Wang of the National Cancer Institute for this data, and for their review of, and contributions to, this paper. This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Library of Medicine, and Lister Hill National Center for Biomedical Communications, Contract No. HHSN276200800411P. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 284 EP + PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800047 ER PT S AU Senseney, J Hemler, PF McAuliffe, MJ AF Senseney, Justin Hemler, Paul F. McAuliffe, Matthew J. GP IEEE TI Automated Segmentation of Computed Tomography Images SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID OVERWEIGHT; OBESITY; HEALTH; RISK AB An image analysis, visualization, and segmentation system has been developed to assist researchers participating in a world-wide imaging study led by the National Institute on Aging to determine risk factors contributing to chronic osteoarthritis. The system provides a sophisticated but simple to use interface that directs the segmentation of muscle, fat, and other tissues of interest in thigh and abdomen computed tomography images. C1 [Senseney, Justin; McAuliffe, Matthew J.] NIH, BIRSS, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. [Hemler, Paul F.] Hampden Sydney Coll, Dept Math & Comp Sci, Hampden Sydney, VA 23943 USA. RP Senseney, J (reprint author), NIH, BIRSS, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM senseneyj@mail.nih.gov; phemler@hsc.edu; mcmatt@exchange.nih.gov FU Intramural Research Program of the National Institutes of Health; Center for Information Technology at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institutes of Health and the Center for Information Technology at the National Institutes of Health. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 311 EP + PG 3 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800051 ER PT S AU Hart, AF Mattmann, CA Tran, JJ Crichton, DJ Hughes, JS Kincaid, H Kelly, S Anton, K Johnsey, D Patriotis, C AF Hart, Andrew F. Mattmann, Chris A. Tran, John J. Crichton, Daniel J. Hughes, J. Steven Kincaid, Heather Kelly, Sean Anton, Kristen Johnsey, Donald Patriotis, Christos GP IEEE TI Enabling Effective Curation of Cancer Biomarker Research Data SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID MEDLINE AB The dramatic increase in data in the area of cancer research has elevated the importance of effectively managing the quality and consistency of research results from multiple providers. The U.S. National Cancer Institute's Early Detection Research Network (EDRN) is a prime example of a virtual organization, sponsoring distributed, collaborative work at dozens of institutions around the country. As part of a comprehensive informatics infrastructure, The NASA Jet Propulsion Laboratory, in collaboration with Dartmouth Medical School, has developed a web application for the curation of cancer biomarker research results. In this paper, we describe and evaluate the application in the context of the EDRN content management process, and detail our experience using the tool in an operational environment to capture and annotate biomarker research data generated by the EDRN. C1 [Hart, Andrew F.; Mattmann, Chris A.; Tran, John J.; Crichton, Daniel J.; Hughes, J. Steven; Kincaid, Heather; Kelly, Sean] CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA. [Anton, Kristen] Dartmouth Med Sch, Biostat & Epidemiol, Lebanon, NH 03766 USA. [Johnsey, Donald; Patriotis, Christos] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hart, AF (reprint author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA. EM ahart@jpl.nasa.gov; mattmann@jpl.nasa.gov; jtran@jpl.nasa.gov; crichton@jpl.nasa.gov; jshughes@jpl.nasa.gov; kincaid@jpl.nasa.gov; kelly@jpl.nasa.gov; kristen.anton@dartmouth.edu; johnseyd@mail.nih.gov; patriotisc@mail.nih.gov FU Jet Propulsion Laboratory; National Aeronautics and Space Administration FX This effort was supported by the Jet Propulsion Laboratory, managed by the California Institute of Technology under a contract with the National Aeronautics and Space Administration. The authors would like to thank Donald Johnsey, Christos Patriotis, and Sudhir Srivastava and the NCI leadership as a whole for their collaborative guidance and support. NR 15 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2372-9198 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 408 EP + PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800067 ER PT S AU Rahman, MM Antani, SK Thoma, GR AF Rahman, Md Mahmudur Antani, Sameer K. Thoma, George R. GP IEEE TI A Medical Image Retrieval Framework in Correlation Enhanced Visual Concept Feature Space SO 2009 22ND IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 22nd IEEE International Symposium on Computer-Based Medical Systems CY AUG 03-04, 2009 CL Albuquerque, NM SP IEEE ID SYSTEMS AB This paper presents a medical image retrieval framework that uses visual concepts in a feature space employing statistical models built using a probabilistic multi-class support vector machine (SVM). The images are represented using concepts that comprise color and texture patches from local image regions in a multi-dimensional feature space. A major limitation of concept feature representation is that the structural relationship or spatial ordering between concepts are ignored. We present a feature representation scheme as visual concept structure descriptor (VCSD) that overcomes this challenge and captures both the concept frequency similar to a color histogram and the local spatial relationships of the concepts. A probabilistic framework makes the descriptor robust against classification and quantization errors. Evaluation of the proposed image retrieval framework on a biomedical image dataset with different imaging modalities validates its benefits. C1 [Rahman, Md Mahmudur; Antani, Sameer K.; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Rahman, MM (reprint author), NIH, US Natl Lib Med, Bethesda, MD 20892 USA. EM rahmanmm@mail.nih.gov; santani@mail.nih.gov; gthoma@mail.nih.gov NR 11 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-7125 BN 978-1-4244-4879-1 J9 COMP MED SY PY 2009 BP 429 EP 432 PG 4 WC Computer Science, Information Systems; Health Care Sciences & Services SC Computer Science; Health Care Sciences & Services GA BPJ31 UT WOS:000278974800071 ER PT B AU Taboas, JM Connor, SK Tuan, RS AF Taboas, J. M. Connor, S. K. Tuan, R. S. GP IEEE TI Constitutive Bcl-2 Over-expression Triggers an Anabolic Response in Chondrocytes, with Partial Abatement of IL-1 beta Catabolic Effects SO 2009 35TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE LA English DT Proceedings Paper CT 35th Annual Northeast Bioengineering Conference CY APR 03-05, 2009 CL Cambridge, MA ID DEACETYLASE AB We are interested in engineering cartilage that is resistant to arthritic disease. We hypothesized that suppression of terminal differentiation pathways would lead to decreased chondrocyte catabolic response to inflammatory cytokines and used a Bcl-2 over-expression gene therapy approach targeting chondrocyte apoptosis. Retrovirally transduced chondrocytes were cultured in 1.25% alginate hydrogels and subjected to interleukin 1 beta (IL-1 beta) stimulation (5 ng/ml) over one month. In the absence of IL-1 beta, Bcl-2 therapy induced a pro-chondrogenic effect, increasing anabolic gene expression and glycosaminoglycan (GAG) accumulation while decreasing injury markers. Though Bcl-2 continued to increase anabolic markers and tissue inhibitors of matrix metalloproteinases (MMPs) under IL-1 beta stimulation, it did not override the overall IL-1 beta suppression of cell number and anabolic markers. Bcl-2 further augmented MMP expression and total GAG loss with IL-1 beta. However under long term IL-I beta stimulation, Bcl-2 abrogated the expression of hypertrophic markers such as collagen type X. Thus, elucidation of the mechanism driving the beneficial aspects of Bcl-2 over-expression and developing conditionally regulated anti-apoptotic gene therapy may prove therapeutic in engineering cartilage that is resistant to disease. C1 [Taboas, J. M.; Connor, S. K.; Tuan, R. S.] NIAMS, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. RP Taboas, JM (reprint author), NIAMS, Cartilage Biol & Orthopaed Branch, 50 South Dr,Rm 1139, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4362-8 PY 2009 BP 66 EP 67 PG 2 WC Engineering, Biomedical SC Engineering GA BKP77 UT WOS:000268886300030 ER PT S AU Wang, SJ Yao, JH Liu, JM Petrick, N Summers, RM AF Wang, Shijun Yao, Jianhua Liu, Jiamin Petrick, Nicholas Summers, Ronald M. GP IEEE TI Registration of Prone and Supine CT Colonography Scans Based on Correlation Optimized Warping and Canonical Correlation Analysis SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB In this paper, we propose an automated method for colon registration from supine and prone scans. Four anatomical salient points on the colon are distinguished first. Then correlation optimized warping (COW) method is applied to the segments defined by the anatomical landmarks to find better global registration based on local correlation of segments. To utilize more features along the colon centerline, we extended the COW method by embedding canonical correlation analysis into it for correlation calculation of colon segments. To verify the effectiveness of the proposed method, we tested the algorithm on a CTC dataset of 19 patients with 23 polyps. Experimental results show that by using our method, the estimation error of polyp location could be reduced 68.5% (from 41.6mm to 13.1mm on average) compared to a traditional dynamic warping algorithm. C1 [Wang, Shijun; Yao, Jianhua; Liu, Jiamin; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room B2S-231 MSC 1182, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room B2S-231 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. We thank Drs. Perry Pickhardt, J. Richard Choi and William Schindler for providing CT colonography data. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 81 EP + DI 10.1109/IEMBS.2009.5334691 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543600022 ER PT S AU Battapady, H Lin, P Fei, DY Huang, DD Bai, O AF Battapady, Harsha Lin, Peter Fei, Ding-Yu Huang, Dandan Bai, Ou GP IEEE TI Single Trial Detection of Human Movement Intentions from SAM-Filtered MEG Signals for a High Performance Two-Dimensional BCI SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID EVENT-RELATED DESYNCHRONIZATION; BRAIN-COMPUTER-INTERFACE; CORTICAL POTENTIALS; EEG; COMMUNICATION AB The objective of this research is to explore whether a two-dimensional BCI can be achieved by reliably decoding single-trial magneto-encephalography (MEG) signal associated with sustaining or ceasing right and left hand movements. Seven naive subjects participated in the study. Signals were recorded from 275-channel MEG and synthetic aperture magnetometry (SAM) was employed. The multi-class classification for four-directional control was evaluated offline from 10-fold cross-validation using direct-decision tree classifier and genetic algorithm based Mahalanobis linear distance. Beta band (15-30Hz) event-related desynchronization and event related synchronization were observed in right and left hand movement related motor areas for physical movements as well as motor imagery. The cross-validation accuracy for the proposed four-direction classification from SAM-filtered MEG signal was as high as 95-97% for physical movements and 86-87% for motor imagery. The high classification accuracy suggests that a reliable high performance two-dimensional BC! can be achieved from single trial detection of human natural movement intentions from SAM-filtered MEG signals, where user may not need extensive training. C1 [Battapady, Harsha; Fei, Ding-Yu; Huang, Dandan; Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA. [Lin, Peter] Natl Inst Hlth, Natl Inst Neurol Disorders, Human Motor Control Sec, Bethesda, MD 20892 USA. RP Battapady, H (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM linpe@ninds.nih.gov; obai@vcu.edu NR 15 TC 2 Z9 2 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 524 EP + DI 10.1109/IEMBS.2009.5333632 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543600134 ER PT S AU Sikdar, S Lebiedowska, M Eranki, A Garmirian, L Damiano, D AF Sikdar, Siddhartha Lebiedowska, Maria Eranki, Avinash Garmirian, Lindsay Damiano, Diane GP IEEE TI Measurement of Rectus Femoris Muscle Velocities During Patellar Tendon Jerk Using Vector Tissue Doppler Imaging SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc DE Ultrasonography; pulsed Doppler; vector Doppler; reflex; stretch; neuromuscular diseases ID CONTRACTION; REFLEXES; HUMANS AB We have developed a vector tissue Doppler imaging (TDI) system based on a clinical scanner that can be used to measure muscle velocities independent of the direction of motion. This method overcomes the limitations of conventional Doppler ultrasound, which can only measure velocity components along the ultrasound beam. In this study, we utilized this method to investigate the rectus femoris muscle velocities during a patellar tendon jerk test. Our goal was to investigate whether the muscle elongation velocities during a brisk tendon tap fall within the normal range of velocities that are expected due to rapid stretch of limb segments. In a preliminary study, we recruited six healthy volunteers (three men and three women) following informed consent. The stretch reflex response to tendon tap was evaluated by measuring: (1) the tapping force using an accelerometer instrumented to the neurological hammer (2) the angular velocities of the knee extension and flexion using a electrogoniometer (3) reflex activation using electromyography (EMG) and (4) muscle elongation, extension and flexion velocities using vector TDI. The passive joint angular velocity was linearly related to the passive muscle elongation velocity (R-2=0.88). The maximum estimated joint angular velocity corresponding to muscle elongation due to tendon tap was less than 8.25 radians/s. This preliminary study demonstrates the feasibility of vector TDI for measuring longitudinal muscle velocities and indicates that the muscle elongation velocities during a clinical tendon tap test are within the normal range of values for rapid limb stretch encountered in daily life. With further refinement, vector TDI could become a powerful method for quantitative evaluation of muscle motion in musculoskeletal disorders. C1 [Sikdar, Siddhartha; Eranki, Avinash] George Mason Univ, Fairfax, VA 22030 USA. [Lebiedowska, Maria; Eranki, Avinash; Garmirian, Lindsay; Damiano, Diane] Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. RP Sikdar, S (reprint author), George Mason Univ, Fairfax, VA 22030 USA. EM ssikdar@gmu.edu RI CHASSAGNE, Fanette/B-7212-2012; Damiano, Diane/B-3338-2010 OI Damiano, Diane/0000-0002-2770-5356 NR 10 TC 3 Z9 3 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 2963 EP 2966 DI 10.1109/IEMBS.2009.5332500 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543602106 ER PT S AU Wang, ST Frenkel, V Zderic, V AF Wang, Shutao Frenkel, Victor Zderic, Vesna GP IEEE TI Preliminary optimization of non-destructive high intensity focused ultrasound exposures for hyperthermia applications SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID MEDIATED DELIVERY; THERMAL THERAPY; SOLID TUMORS; IN-VIVO; LIPOSOMES; DRUGS; MODEL AB Due to its high degree of accuracy and non-invasive implementation, pulsed-high intensity focused ultrasound (HIFU) is a promising modality for hyperthermia applications as adjuvant therapy for cancer treatment. However, the relatively small focal region of the HIFU beam could result in prohibitively long treatment times for large targets requiring multiple exposures. In this work, finite element analysis modeling was used to simulate focused ultrasound propagation and the consequent induction of hyperthermia. The accuracy of the simulations was first validated with thermocouple measurements in hydrogel phantoms. More advanced simulations of in vivo applications using single HIFU exposures were then done incorporating complex, multi-layered tissue composition and variable perfusion for an in vivo murine xenograft tumor model. The results of this study describe the development of a preliminary methodology for optimizing spatial application of hyperthermia, through the evaluation of different HIFU exposures. These types of simulations, and their validations in vivo, may help minimize treatment durations for pulsed-HIFU induced hyperthermia and facilitate the translation of these exposures into the clinic. C1 [Wang, Shutao; Zderic, Vesna] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. [Frenkel, Victor] Natl Inst Hlth, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Wang, ST (reprint author), George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. EM kevinwst@gwmail.gwu.edu; vfrenkel@cc.nih.gov; zderic@gwu.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 3055 EP 3059 DI 10.1109/IEMBS.2009.5333582 PG 5 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543602129 ER PT S AU Tan, S Yao, JH Yao, L Ward, MM AF Tan, Sovira Yao, Jianhua Yao, Lawrence Ward, Michael M. GP IEEE TI Precision of Syndesmophyte Volume Measurement for Ankylosing Spondylitis: a Phantom Study Using High Resolution CT SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB Ankylosing Spondylitis is a disease characterized by abnormal bone structures (syndesmophytes) growing at intervertebral disk spaces (IDS). The growth of syndesmophytes is typically monitored by visual inspection of radiographs. The limitations inherent to the modality (2D projection of a 3D object) and rater (qualitative human judgment) entail a possibly important loss in sensitivity. We previously presented a method designed to overcome both limitations: a computer algorithm that quantitatively measures syndesmophytes in the 3D space of a high-resolution computed tomography scan. To establish the method's usefulness for longitudinal studies, it is necessary to assess its precision (repeatability) which can be affected by the limitations of both the algorithm itself and the imaging modality. To this end, an anthropomorphic vertebral phantom with syndesmophytes in 4 IDSs was manufactured. It was scanned 22 times with varying positions and resolutions. The syndesmophyte volumes extracted by our algorithm have an average coefficient of variation of 1.6% per IDS and 0.85% for the total. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. [Yao, Jianhua; Yao, Lawrence] Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM tanso@mail.nih.gov FU Intramural Research Program of the NIH; NIAMS; CC FX This research was supported by the Intramural Research Program of the NIH, NIAMS and CC. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 3577 EP 3580 DI 10.1109/IEMBS.2009.5335439 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543602260 ER PT S AU Tan, S Yao, JH Ward, MM Summers, RM AF Tan, Sovira Yao, Jianhua Ward, Michael M. Summers, Ronald M. GP IEEE TI Linear Measurement of Polyps in CT Colonography Using Level Sets on 3D Surfaces SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID COLONIC POLYPS AB CT colonography has emerged as a minimally invasive alternative to optical colonoscopy for the screening of polyps which are the precursors to colon cancer. Accurate polyp measurement is crucial as the size of a polyp is considered an indication of its potential for malignancy. We present a novel method for the automatic measurement of polyps. It is based on a level set algorithm capable of evolving on the surface of a 3D object represented by a triangular mesh. It is guided by curvature features and is capable of segmenting the polyp neck, that is, the ridgeline/crestline formed around the polyp by its merging to the colon wall. Our method was validated on 40 polyp surfaces obtained from real clinical data. A 3D manual measurement was used as the reference standard. A correlation of 0.825 was found between polyp measurements from our new method and the reference standard. C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. [Yao, Jianhua; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM tanso@mail.nih.gov; rms@nih.gov FU Intramural Research Program of the NIH; NIAMS; CC FX This research was supported by the Intramural Research Program of the NIH, NIAMS and CC. NR 14 TC 2 Z9 2 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 3617 EP 3620 DI 10.1109/IEMBS.2009.5334027 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543602270 ER PT S AU Huang, DD Lin, P Fei, DY Chen, XD Bai, O AF Huang, Dandan Lin, Peter Fei, Ding-Yu Chen, Xuedong Bai, Ou GP IEEE TI EEG-Based Online Two-Dimensional Cursor Control SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID BRAIN-COMPUTER-INTERFACE; EVENT-RELATED DESYNCHRONIZATION; FINGER MOVEMENTS; COMMUNICATION; HUMANS AB This study aims to explore whether human intentions to move or cease to move right and left hands can provide four spatiotemporal patterns in single-trial non-invasive EEG signals to achieve a two-dimensional cursor control. Subjects performed motor tasks by either physical movement or motor imagery. Spatial filtering, temporal filtering, feature selection and classification methods were explored to support accurate computer pattern recognition. The performance was evaluated by both offline classification and online two-dimensional cursor control. Event-related desynchronization (ERD) and post-movement event-related synchronization (ERS) were observed on the contralateral hemisphere to the moving hand for both physical movement and motor imagery. The offline classification of four motor tasks provided 10-fold cross-validation accuracy as high as 88% for physical movement and 73% for motor imagery. Subjects participating in experiments with physical movement were able to complete the online game with the average accuracy of 85.5 +/- 4.65%; Subjects participating in motor imagery study also completed the game successfully. The proposed brain-computer interface (BCI) provided a new practical multi-dimensional method by noninvasive EEG signal associated with human natural behavior, which does not need long-term training. C1 [Huang, Dandan; Fei, Ding-Yu; Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23284 USA. [Lin, Peter] NIH, Natl Inst Neurol Disorder, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. [Chen, Xuedong] Huazhong Univ, Sch Mech Sci & Engn, Wuhan, Peoples R China. RP Huang, DD (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23284 USA. EM linpe@ninds.nih.gov; chenxd@mail.hust.edu.cn; obai@vcu.edu NR 15 TC 3 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 4547 EP + DI 10.1109/IEMBS.2009.5332722 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543603231 ER PT S AU Apostolova, E Channin, DS Demner-Fushman, D Furst, J Lytinen, S Raicu, D AF Apostolova, Emilia Channin, David S. Demner-Fushman, Dina Furst, Jacob Lytinen, Steven Raicu, Daniela GP IEEE TI Automatic Segmentation of Clinical Texts SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB Clinical narratives, such as radiology and pathology reports, are commonly available in electronic form. However, they are also commonly entered and stored as free text. Knowledge of the structure of clinical narratives is necessary for enhancing the productivity of healthcare departments and facilitating research. This study attempts to automatically segment medical reports into semantic sections. Our goal is to develop a robust and scalable medical report segmentation system requiring minimum user input for efficient retrieval and extraction of information from free-text clinical narratives. Hand-crafted rules were used to automatically identify a high-confidence training set. This automatically created training dataset was later used to develop metrics and an algorithm that determines the semantic structure of the medical reports. A word-vector cosine similarity metric combined with several heuristics was used to classify each report sentence into one of several pre-defined semantic sections. This baseline algorithm achieved 79% accuracy. A Support Vector Machine (SVM) classifier trained on additional formatting and contextual features was able to achieve 90% accuracy. Plans for future work include developing a configurable system that could accommodate various medical report formatting and content standards. C1 [Apostolova, Emilia; Furst, Jacob; Lytinen, Steven; Raicu, Daniela] Depaul Univ, Coll Comp & Digital Media, Chicago, IL 60604 USA. [Channin, David S.] Northwestern Univ, Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Demner-Fushman, Dina] Natl Lib Med, Commun Engn Branch, Bethesda, MD 20894 USA. RP Apostolova, E (reprint author), Depaul Univ, Coll Comp & Digital Media, Chicago, IL 60604 USA. EM emilia.aposto@gmail.com; dchannin@nmh.org; ddemner@mail.nih.gov; jfurst@cdm.depaul.edu; lytinen@cs.depaul.edu; dstan@cs.depaul.edu NR 15 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5905 EP + DI 10.1109/IEMBS.2009.5334831 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543604202 ER PT S AU Zhuge, Y Cao, Y Miller, RW AF Zhuge, Ying Cao, Yong Miller, Robert W. GP IEEE TI GPU Accelerated Fuzzy Connected Image Segmentation by using CUDA SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID OBJECT DEFINITION; ALGORITHMS; QUANTIFICATION; PRINCIPLES; SYSTEM AB Image segmentation techniques using fuzzy connectedness principles have shown their effectiveness in segmenting a variety of objects in several large applications in recent years. However, one problem of these algorithms has been their excessive computational requirements when processing large image datasets. Nowadays commodity graphics hardware provides high parallel computing power. In this paper, we present a parallel fuzzy connected image segmentation algorithm on Nvidia's Compute Unified Device Architecture (CUDA) platform for segmenting large medical image data sets. Our experiments based on three data sets with small, medium, and large data size demonstrate the efficiency of the parallel algorithm, which achieves a speed-up factor of 7.2x, 7.3x, and 14.4x, correspondingly, for the three data sets over the sequential implementation of fuzzy connected image segmentation algorithm on CPU. C1 [Zhuge, Ying; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Cao, Yong] Virginia Polytecn Inst & State Univ, Comp Sci Dept, Blacksburg, VA 24060 USA. RP Zhuge, Y (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhugey@mail.nih.gov; rwmiller@mail.nih.gov NR 20 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6341 EP + DI 10.1109/IEMBS.2009.5333158 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605041 ER PT S AU Linguraru, MG Wang, SJ Shah, F Gautam, R Peterson, J Linehan, WM Summers, RM AF Linguraru, Marius George Wang, Shijun Shah, Furhawn Gautam, Rabindra Peterson, James Linehan, W. Marston Summers, Ronald M. GP IEEE TI Computer-Aided Renal Cancer Quantification and Classification from Contrast-enhanced CT via Histograms of Curvature-Related Features SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID COLONIC POLYPS; SEGMENTATION; RECOGNITION; TUMOR; MODEL AB In clinical practice, renal cancer diagnosis is performed by manual quantifications of tumor size and enhancement, which are time consuming and show high variability. We propose a computer-assisted clinical tool to assess and classify renal tumors in contrast-enhanced CT for the management and classification of kidney tumors. The quantification of lesions used level-sets and a statistical refinement step to adapt to the shape of the lesions. Intra-patient and inter-phase registration facilitated the study of lesion enhancement From the segmented lesions, the histograms of curvature-related features were used to classify the lesion types via random sampling. The clinical tool allows the accurate quantification and classification of cysts and cancer from clinical data. Cancer types are further classified into four categories. Computer-assisted image analysis shows great potential for tumor diagnosis and monitoring. C1 [Linguraru, Marius George; Wang, Shijun; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Shah, Furhawn] Univ Rochester, Sch Med & Dent, Bethesda, MD 14620 USA. [Shah, Furhawn] Natl Inst Hlth, Clin Ctr, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Gautam, Rabindra; Peterson, James; Linehan, W. Marston] Natl Inst Hlth, Urolog Oncol Branch, Natl Canc Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov FU National Institutes of Health; Clinical Center and National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center and National Cancer Institute NR 23 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6679 EP + DI 10.1109/IEMBS.2009.5334012 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605127 ER PT S AU Nandy, K Gudla, PR Meaburn, KJ Misteli, T Lockett, SJ AF Nandy, Kaustav Gudla, Prabhakar R. Meaburn, Karen J. Misteli, Tom Lockett, Stephen J. GP IEEE TI Automatic Nuclei Segmentation And Spatial FISH Analysis For Cancer Detection SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB Spatial analysis of gene localization using fluorescent in-situ hybridization (FISH) labeling is potentially a new method for early cancer detection. Current methodology relies heavily upon accurate segmentation of cell nuclei and FISH signals in tissue sections. While automatic FISH signal detection is a relatively simpler task, accurate nuclei segmentation is still a manual process which is fairly time consuming and subjective. Hence to use the methodology as a clinical application, it is necessary to automate all the steps involved in the process of spatial FISH signal analysis using fast, robust and accurate image processing techniques. In this work, we describe an intelligent framework for analyzing the FISH signals by coupling hybrid nuclei segmentation algorithm with pattern recognition algorithms to automatically identify well segmented nuclei. Automatic spatial statistical analysis of the FISH spots was carried out on the output from the image processing and pattern recognition unit. Results are encouraging and show that the method could evolve into a full fledged clinical application for cancer detection. C1 [Nandy, Kaustav; Gudla, Prabhakar R.; Lockett, Stephen J.] NCI, Opt Microscopy & Anal Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Meaburn, Karen J.; Misteli, Tom] Natl Inst Hlth, Natl Canc Inst, Bethesda, MD 20892 USA. RP Nandy, K (reprint author), NCI, Opt Microscopy & Anal Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM nandyk@ncifcrf.gov; reddyg@ncifcrf.gov; meaburnk@mail.nih.gov; mistelit@mail.nih.gov; slockett@ncifcrf.gov OI Meaburn, Karen/0000-0002-1327-5957 FU National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. 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 13 TC 2 Z9 2 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6718 EP + DI 10.1109/IEMBS.2009.5332922 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605138 ER PT S AU Brychta, RJ Rothney, MP Skarulis, MC Chen, KY AF Brychta, Robert J. Rothney, Megan P. Skarulis, Monica C. Chen, Kong Y. GP IEEE TI Optimizing Energy Expenditure Detection in Human Metabolic Chambers SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID INDIRECT CALORIMETRY AB Whole-room indirect calorimeters are capable of measuring human metabolic rate in conditions representative of quasi-free-living state through measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). However, the relatively large room size required for patient comfort creates low signal-to-noise ratio for the VO2 and VCO2 signals. We proposed a wavelet-based approach to efficiently remove noise while retaining important dynamic changes in the VO2 and VCO2. We used correlated noise modeled from gas-infusion experiments superimposed on theoretical VO2 sequences to test the accuracy of a wavelet based processing method. The wavelet filtering is demonstrated to improve the accuracy and sensitivity of minute-to-minute changes in VO2, while maintaining stability during steady-state periods. The wavelet method is shown to have a lower mean absolute error and reduced total error when compared to standard methods of processing calorimeter signals. C1 [Brychta, Robert J.; Skarulis, Monica C.; Chen, Kong Y.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Rothney, Megan P.] GE Global Res, New York, NY 12309 USA. RP Brychta, RJ (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM brychtar@niddk.nih.gov OI Chen, Kong/0000-0002-0306-1904 FU National Institutes of Health [Z01- DK071044] FX Manuscript received April 23, 2009. This work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (Z01- DK071044) and the Clinical Center, both from the National Institutes of Health. NR 12 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6864 EP + DI 10.1109/IEMBS.2009.5333121 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605174 ER PT B AU Chen, XD Bai, O AF Chen, Xuedong Bai, Ou GP IEEE TI Towards Multi-Dimensional Robotic Control via Noninvasive Brain-Computer Interface SO 2009 ICME INTERNATIONAL CONFERENCE ON COMPLEX MEDICAL ENGINEERING LA English DT Proceedings Paper CT ICME International Conference on Complex Medical Engineering CY APR 09-11, 2009 CL Tempe, AZ SP ICME ID EVENT-RELATED DESYNCHRONIZATION; CORTICAL POTENTIALS; FINGER MOVEMENTS; EEG; COMMUNICATION; SIGNALS; HAND AB Brain-computer interface (BCI) provides a new communication pathway for patients with neurological disorders who may not make voluntary muscle contraction. A potential BCI application is that patients may control a neuro-prosthetic robot directly from their brain so that they can achieve virtual interaction with environment. Therefore, a BCI supports multi-dimensional control is highly demanded for a multi-dimensional robot. We hypothesized that human intentions to move his right, left hand, leg and tongue can be detected by the somatotopic spatial activation patterns from single-trial MEG signal. Under reliable detection, human can intentionally control a two-dimensional robotic motion; right, left, up and down. The hypothesis was tested offline; the classification was performed on beta band activation (15-30Hz) of SAM virtual channels. Cross-validation results using linear discrimination provided high detection accuracy (70-90%) when considering a random level of 25%. We demonstrated that noninvasive BCI methods may support reliable multi-dimensional control of neuro-prosthetic robotics. C1 [Chen, Xuedong] Huazhong Univ, Sch Mech Sci & Engn, Wuhan, Peoples R China. [Bai, Ou] Natl Inst Hlth, Natl Inst Neurol Disorders, Bethesda, MD 20878 USA. [Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, Richmond, VA 23284 USA. RP Chen, XD (reprint author), Huazhong Univ, Sch Mech Sci & Engn, Wuhan, Peoples R China. EM chenxd@mail.hust.edu.cn; obai@vcu.edu FU Intramural Research Program of the NIH; National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. The authors would like to thank P. Lin, K. Sharma, T. Holroyd, M. Hallett, H. Battapady, D. Fei for their assistance in data collection, analysis and comments on the experimental design. NR 16 TC 0 Z9 0 U1 0 U2 6 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3315-5 PY 2009 BP 21 EP + PG 2 WC Engineering, Biomedical; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BMF84 UT WOS:000272211300005 ER PT B AU Bai, O Lin, P Wu, JL Chen, XD Fei, DY Hallett, M AF Bai, Ou Lin, Peter Wu, Jinglong Chen, Xuedong Fei, DingYu Hallett, Mark GP IEEE TI Event-Related Coherence and Correlogram for Analysis of Corticomuscular Connectivity SO 2009 ICME INTERNATIONAL CONFERENCE ON COMPLEX MEDICAL ENGINEERING LA English DT Proceedings Paper CT ICME International Conference on Complex Medical Engineering CY APR 09-11, 2009 CL Tempe, AZ SP ICME ID MUSCLE; DESYNCHRONIZATION; SYNCHRONIZATION; OSCILLATIONS; MOVEMENT; PATTERNS AB Corticomuscular coupling estimated by EEG-EMG coherence may reveal functional cortical driving of peripheral muscular activity. EEG-EMG coherence in the beta band (15-30Hz) has been extensively studied under isometric muscle contraction tasks. We attempted to study the time-course of corticomuscular connectivity under a dynamic target tracking task. A new device was developed for the real-time measurement of dynamic force created by pinching the thumb and index finger. Healthy subjects were asked to track visual targets with the feedback forces. Spectral parameters were explored for reliable estimation of event-related coherence and correlogram for representing corticomuscular connectivity. C1 [Bai, Ou; Fei, DingYu] Virginia Commonwealth Univ, Dept Biomed Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA. [Bai, Ou; Lin, Peter; Hallett, Mark] NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Wu, Jinglong] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama, Japan. [Chen, Xuedong] Tsinghua Univ, Sch Mech Sci & Engn, Wuhan, Peoples R China. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM obai@vcu.edu; linpe@ninds.nih.gov; wu@mech..okayama-u.ac.jp; chenxd@mail.hust.edu.cn; fei@vcu.edu; hallettm@ninds.nih.gov FU NIH; National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 16 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3315-5 PY 2009 BP 304 EP + PG 2 WC Engineering, Biomedical; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BMF84 UT WOS:000272211300060 ER PT S AU Carroll, H Clement, M Snell, Q McClellan, D AF Carroll, Hyrum Clement, Mark Snell, Quinn McClellan, David GP IEEE TI ChemAlign: Biologically Relevant Multiple Sequence Alignment Using Physicochemical Properties SO 2009 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine (BIBMW 2009) CY NOV 01-04, 2009 CL Washington, DC SP IEEE, IEEE Comp Soc, Natl Sci Fdn DE multiple sequence alignment; physicochemical properties; Physicochemical Properties Difference score ID SECONDARY STRUCTURE; PROTEIN; BENCHMARK; ACCURACY AB We present a new algorithm, Chem Align, that uses physicochemical properties and secondary structure elements to create biologically relevant multiple sequence alignments (MSAs). Additionally, we introduce the Physicochemical Property Difference (PPD) score for the evaluation of MSAs. This score is the normalized difference of physicochemical property values between a calculated and a reference alignment. It takes a step beyond sequence similarity and measures characteristics of the amino acids to provide a more biologically relevant metric. Chem Align is able to produce more biologically correct alignments and can help to identify potential drug docking sites. C1 [Carroll, Hyrum] NIH, Bldg 10, Bethesda, MD 20892 USA. [Carroll, Hyrum; Clement, Mark; Snell, Quinn] Brigham Young Univ, Dept CS, Provo, UT USA. [McClellan, David] Bigelow Lab Ocean Sci, West Boothbay Harbor, ME USA. RP Carroll, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM HyrumCarroll@gmail.com; clement@cs.byu.edu; snell@cs.byu.edu; dmcclellan@bigelow.org NR 20 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2156-1125 BN 978-0-7695-3885-3 J9 IEEE INT C BIOINFORM PY 2009 BP 70 EP + DI 10.1109/BIBM.2009.75 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Engineering GA BNY71 UT WOS:000275900200013 ER PT S AU Nelson, SJ Zeng, K Kilbourne, J AF Nelson, Stuart J. Zeng, Kelly Kilbourne, John GP IEEE TI Building a Standards-Based and Collaborative E-Prescribing Tool-MyRxPad SO 2009 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine (BIBMW 2009) CY NOV 01-04, 2009 CL Washington, DC SP IEEE, IEEE Comp Soc, Natl Sci Fdn DE RxNorm; e-prescribing; Continuity of Care Document (CCD); Personal Health Record (PHR) AB MyRxPad is a prototype application developed at the National Library of Medicine that helps prescribers lower some of the e-prescribing adoption barriers and encourages an early positive experience of e-prescribing. We envision a practitioner-patient collaborative approach towards e-prescribing: patients play an active role in their healthcare by maintaining up-to-date and accurate medication lists. Prescribers make well-informed and safe prescribing decisions based on personal medication records contributed by patients. In the paper, we discuss the development of MyRxPad, a vehicle for collaborations with patients using MyMedicationList. Integration with personal medication records in the context of e-prescribing is thus enabled. An early version of MyRxPad is available at http://rxp.nlm.nih.gov. C1 [Nelson, Stuart J.; Zeng, Kelly; Kilbourne, John] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Nelson, SJ (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM nelson@nlm.nih.gov; zeng@nlm.nih.gov; kilbourj@nlm.nih.gov NR 11 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2156-1125 BN 978-0-7695-3885-3 J9 IEEE INT C BIOINFORM PY 2009 BP 210 EP 215 DI 10.1109/BIBM.2009.30 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Engineering GA BNY71 UT WOS:000275900200038 ER PT S AU Chen, ZL Zhang, JX Yang, R Kellman, P Johnston, LA Egan, GF AF Chen, Zhaolin Zhang, Jingxin Yang, Ran Kellman, Peter Johnston, Leigh A. Egan, Gary F. GP IEEE TI 2D IIR Filter For Parallel Magnetic Resonance Image Reconstruction SO 2009 IEEE INTERNATIONAL CONFERENCE ON CONTROL AND AUTOMATION, VOLS 1-3 SE IEEE International Conference on Control and Automation ICCA LA English DT Proceedings Paper CT IEEE International Conference on Control and Automation CY DEC 09-11, 2009 CL Christchurch, NEW ZEALAND SP IEEE DE parallel MRI; GRAPPA; 2D GRAPPA; IIR GRAPPA ID GRAPPA; MRI AB Accelerated parallel MRI has been widely used in medical research and clinical diagnoses. This paper presents a two dimensional (2D) infinite impulse response (IIR) model of inverse filter to replace the finite impulse response model currently used in GRAPPA class image reconstruction methods. The IIR model better characterizes the correlation of k-space data points and better approximates the inversion of parallel imaging process. The experiments on in vivo accelerated cardiac imaging show that the proposed method significantly reduces reconstruction errors compared with conventional 2D GRAPPA method, particularly at the high acceleration rates. C1 [Chen, Zhaolin; Johnston, Leigh A.; Egan, Gary F.] Howard Florey Inst, Melbourne, Vic, Australia. [Chen, Zhaolin; Zhang, Jingxin] Monash Univ, Dept Elect & Comp Syst Engn, Clayton, Vic 3800, Australia. [Yang, Ran] Sun Yat Sen Univ, Sch Informat Sci & Technol, Guangzhou, Guangdong, Peoples R China. [Kellman, Peter] NHLB, NIH, Lab Cardiac Energet, Bethesda, MD USA. [Chen, Zhaolin; Johnston, Leigh A.] Univ Melbourne, Dept Elect & Elect Engn, Melbourne, Vic 3010, Australia. [Egan, Gary F.] Univ Melbourne, Ctr Neurosci, Melbourne, Vic 3010, Australia. RP Chen, ZL (reprint author), Howard Florey Inst, Melbourne, Vic, Australia. RI Egan, Gary/A-1381-2013; Johnston, Leigh/D-7102-2014 OI Johnston, Leigh/0000-0002-5032-4674 NR 10 TC 1 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3449 BN 978-1-4244-4706-0 J9 IEEE INT CONF CON AU PY 2009 BP 1792 EP + DI 10.1109/ICCA.2009.5410221 PG 2 WC Automation & Control Systems SC Automation & Control Systems GA BQB01 UT WOS:000280542300312 ER PT B AU Yao, JH Han, W Summers, RM AF Yao, Jianhua Han, Wei Summers, Ronald M. GP IEEE TI COMPUTER AIDED EVALUATION OF PLEURAL EFFUSION USING CHEST CT IMAGES SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE Internaional Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Pleural Effusion; CAD; Segmentation AB A pleural effusion is a condition where there is a buildup of abnormal fluid within the pleural space. This paper presents an automated method to evaluate the severity of pleural effusion using regular chest CT images. First the lungs are segmented using region growing, mathematical morphology and anatomical knowledge. Then the visceral and parietal layers of the pleura are extracted based on anatomical landmarks, curve fitting and active contour models. Finally, the pleural space is segmented and the pleural effusion is quantified. Our method was tested on 15 chest CT studies. The automated segmentation is validated against manual tracing and radiologist's qualitative grading. The Pearson correlation between computer evaluation and radiologist's grading is 0.956 (p= 10(-7)). The Dice coefficient between the automated and manual segmentation is 0.74+/-0.07, which is comparable to the variation between two different manual tracings. C1 [Yao, Jianhua; Han, Wei; Summers, Ronald M.] NIH, Radiol & Image Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Radiol & Image Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 241 EP 244 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400060 ER PT B AU Wang, W Zhu, YY Huang, XL Lopresti, D Xue, ZY Long, R Antani, S Thoma, G AF Wang, Wei Zhu, Yaoyao Huang, Xiaolei Lopresti, Daniel Xue, Zhiyun Long, Rodney Antani, Sameer Thoma, George GP IEEE TI A CLASSIFIER ENSEMBLE BASED ON PERFORMANCE LEVEL ESTIMATION SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE classifier ensemble; segmentation; cervigram; multiple classifier system; sensitivity; specificity AB In this paper, we introduce a new classifier ensemble approach, applied to tissue segmentation in optical images of the uterine cervix. Ensemble methods combine the predictions of a set of diverse classifiers. The main contribution of our approach is an effective way of combination based on each classifier's performance level-namely, the sensitivity p and specificity q, which also produces an optimal estimate of the true segmentation. In comparison with previous work [1] that utilizes the STAPLE algorithm [2] for performance level based combination, this work achieves multiple-observer segmentation in a Bayesian decision framework using the maximum a posterior (MAP) principle, considering each classifier as an observer. In our experiments, we applied our method and several other popular ensemble methods to the problem of detecting Acetowhite regions in cervical images. On 100 images, the overall performance of the proposed method is better than: (i) an overall classifier learned using the entire training set, (ii) average voting ensemble, (iii) ensemble based on the STAPLE algorithm; it is comparable to that of majority voting and that of the (manually picked) best-performing individual classifier in the ensemble set. C1 [Wang, Wei; Zhu, Yaoyao; Huang, Xiaolei; Lopresti, Daniel] Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. [Xue, Zhiyun; Long, Rodney; Antani, Sameer; Thoma, George] Natl Lib Med, Commun Engn Branch, Bethesda, MD 20894 USA. RP Wang, W (reprint author), Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. OI Antani, Sameer/0000-0002-0040-1387 FU Communications Engineering Branch; National Library of MedicineNIH; Hormonal and Reproductive Epidemiology Branch; National Cancer InstituteNIH FX We would like to thank the Communications Engineering Branch, National Library of MedicineNIH, and the Hormonal and Reproductive Epidemiology Branch, National Cancer InstituteNIH, for providing the data and support of this work. NR 11 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 342 EP + DI 10.1109/ISBI.2009.5193054 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400086 ER PT B AU Guan, HY Antani, S Long, LR Thoma, GR AF Guan, Haiying Antani, Sameer Long, L. Rodney Thoma, George R. GP IEEE TI BRIDGING THE SEMANTIC GAP USING RANKING SVM FOR IMAGE RETRIEVAL SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Content-Based Image Retrieval; NHANES II database; Ranking SVM; digital radiography AB One of the main challenges for Content-Based Image Retrieval (CBIR) is to achieve meaningful mappings between the high-level semantic concepts and the low-level visual features in images. This paper presents an approach for bridging this semantic gap to improve retrieval quality using the Ranking Support Vector Machine (Ranking SVM) algorithm. Ranking SVM is a supervised learning algorithm which models the relationship between semantic concepts and image features, and performs retrieval at the semantic level. We apply it to the problem of vertebra shape retrieval on a digitized spine x-ray image collection from the second National Health and Nutrition Examination Survey (NHANES II). The experimental results show that the retrieval precision is improved 2.45 - 15.16% using the proposed approach. C1 [Guan, Haiying; Antani, Sameer; Long, L. Rodney; Thoma, George R.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Guan, HY (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. EM guanh@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 17 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 354 EP 357 DI 10.1109/ISBI.2009.5193057 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400089 ER PT B AU Reyes, M Ballester, MAG Li, ZX Kozic, N Chin, S Summers, RM Linguraru, MG AF Reyes, Mauricio Ballester, Miguel A. Gonzalez Li, Zhixi Kozic, Nina Chin, See Summers, Ronald M. Linguraru, Marius George GP IEEE TI ANATOMICAL VARIABILITY OF ORGANS VIA PRINCIPAL FACTOR ANALYSIS FROM THE CONSTRUCTION OF AN ABDOMINAL PROBABILISTIC ATLAS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE probabilistic atlas; principal factor analysis; registration; clusterization; anatomical variability ID MR-IMAGES; SEGMENTATION AB Extensive recent work has taken place on the construction of probabilistic atlases of anatomical organ. We propose a probabilistic atlas of ten major abdominal organs which retains structural variability by using a size-preserving affine registration, and normalizes the physical organ locations to an anatomical landmark. Restricting the degrees of freedom in the transformation, the bias from the reference data is minimized, in terms of organ shape, size and position. Additionally, we present a scheme for the study, of anatomical variability within the abdomen, including the clusterization of the modes of variation. The analysis of deformation fields showed a strong correlation with anatomical landmarks and known mechanical deformations in the abdomen. The atlas and its dependencies represent a potentially important research tool for abdominal diagnosis, modeling and soft tissue interventions. C1 [Reyes, Mauricio; Kozic, Nina] Univ Bern, ARTORG Ctr Biomed Engn Res, CH-3012 Bern, Switzerland. [Ballester, Miguel A. Gonzalez] Alma IT Syst, Barcelona, Spain. [Li, Zhixi; Chin, See; Summers, Ronald M.; Linguraru, Marius George] NIH, Clin Cntr, Radiol & Imaging Sci, Bethesda, MD USA. RP Reyes, M (reprint author), Univ Bern, ARTORG Ctr Biomed Engn Res, CH-3012 Bern, Switzerland. EM lingurarum@mail.nih.gov RI Gonzalez Ballester, Miguel Angel/D-1349-2013 OI Gonzalez Ballester, Miguel Angel/0000-0002-9227-6826 FU Intramural Research Program of the National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 9 TC 5 Z9 5 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 682 EP + DI 10.1109/ISBI.2009.5193139 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400171 ER PT B AU Harouni, AA Bluemke, DA Osman, NF AF Harouni, Ahmed A. Bluemke, David A. Osman, Nael F. GP IEEE TI FULLY AUTOMATED SEGMENTATION OF LONG-AXIS MRI STRAIN-ENCODED (SENC) IMAGES USING ACTIVE SHAPE MODEL (ASM) SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE image segmentation; active shape model; strain encoded MRI; right ventricle strain AB Myocardial strain is an important measure used for assessing regional function, which could help in detecting myocardial infarction as well as following up with patients with heart diseases. MRI Strain-Encoding technique (SENC) produces strain values throughout the cardiac cycle. SENC has proved to be one of the few techniques that can quantify right ventricle (RV) regional function. However, SENC images suffer from low signal-to-noise ratio (SNR). In this paper we present a fully automatic method to detect, segment, and track the myocardium throughout the cardiac cycle using prior knowledge of the shape of the 4-champers long-axis (LA) view. Our detection algorithm has a success rate of 91% (33/36 cases). The dice similarity coefficient was 0.81 +/- 0.07 and 0.71 +/- 0.15 for the left ventricle-septum (LV-SEP) and RV respectively, yielding a high correlation R >= 0.91 between strain values measured from automatic and manual segmentation. C1 [Harouni, Ahmed A.; Osman, Nael F.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Osman, Nael F.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. [Bluemke, David A.] Natl Inst Hlth, Bethesda, MD USA. RP Harouni, AA (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. OI Bluemke, David/0000-0002-8323-8086 FU NHLBI [R01 HL072704]; NIH [1P50HL08946] FX This work was supported by grants NHLBI R01 HL072704 and NIH 1P50HL08946 NR 10 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 827 EP + DI 10.1109/ISBI.2009.5193180 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400212 ER PT B AU George, AK Arai, AE McVeigh, ER AF George, A. K. Arai, A. E. McVeigh, E. R. GP IEEE TI TIME-RESOLVED CARDIAC CT RECONSTRUCTION USING A NONLINEAR KALMAN-FILTER BASED ALGORITHM SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Cardiac; Dynamic Tomography; Time-resolved; Computed Tomography; Kalman filter; Nonlinear Kalman filter; Extended Kalman filter AB We propose an algorithm to solve the problem of Time-Resolved Cardiac Computed Tomography (CT). The goal of the algorithm is to reconstruct a snapshot of the moving heart at any time instant from CT projection data acquired over a single heart-cycle. The object is modeled by a spatio-temporal state-space model which requires a nonlinear version of the Kalman Filter to assimilate the sequentially acquired projection data. Simulation results show that the nonlinear model overcomes shortcomings of the previously used linear model. C1 [George, A. K.; Arai, A. E.] NHLBI, NIH, Bethesda, MD 20892 USA. [McVeigh, E. R.] Johns Hopkins Univ Sch Med, Dept Biomed Engn, Baltimore, MD USA. RP George, AK (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 859 EP + DI 10.1109/ISBI.2009.5193188 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400220 ER PT B AU Kozic, N Ballester, MAG Buchler, P Reimers, N Nolte, LP Linguraru, MG Reyes, M AF Kozic, Nina Gonzalez Ballester, Miguel A. Buechler, Philippe Reimers, Nils Nolte, Lutz P. Linguraru, Marius G. Reyes, Mauricio GP IEEE TI POPULATION-SPECIFIC EVALUATION OF IMPLANT BONE FITTING USING PCA SHAPE SPACE AND LEVEL SETS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE statistical shape models; image registration; principal component analysis; level sets; implant fitting ID MODELS AB Currently in orthopedic research, bone shape variability within a specific population has been seldom investigated and used to optimise implant design, which is commonly performed by evaluating implant bone fitting on a limited dataset. In this paper, we extend our method for optimisation in statistical shape space, to global assessment of population-specific implant bone fitting. The method is based on a level set segmentation approach, used on the parametric space of the statistical shape model of the target population. The method highlights which patterns of bone variability are more important for implant fitting, allowing and easing implant design improvements. Results are presented for proximal human tibia. C1 [Kozic, Nina; Buechler, Philippe; Nolte, Lutz P.; Reyes, Mauricio] Univ Bern, ARTORG Ctr Biomed Engn Res, CH-3012 Bern, Switzerland. [Gonzalez Ballester, Miguel A.] Alma IT Syst, Barcelona, Spain. [Reimers, Nils] Stryker Trauma GmbH, Kiel, Germany. [Linguraru, Marius G.] Natl Inst Hlth, Radiol & Imaging Sci, Bethesda, MD USA. RP Kozic, N (reprint author), Univ Bern, ARTORG Ctr Biomed Engn Res, CH-3012 Bern, Switzerland. RI Gonzalez Ballester, Miguel Angel/D-1349-2013 OI Gonzalez Ballester, Miguel Angel/0000-0002-9227-6826 FU Swiss National Science Foundation FX This research was funded by the Swiss National Science Foundation through its National Center of Competence in Research (NCCR) on Computer Aided and Image Guided Medical Interventions (http://co-me.ch). NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 883 EP + DI 10.1109/ISBI.2009.5193194 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400226 ER PT B AU Aman, J Yao, JH Summers, RM AF Aman, Javed Yao, Jianhua Summers, Ronald M. GP IEEE TI REDUCING THE FALSE POSITIVE RATE OF COMPUTER AIDED DETECTION FOR CT COLONOGRAPHY USING CONTENT BASED IMAGE RETRIEVAL SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE Internaional Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Content Based Image Retrieval; CT Colonography; Computer Aided Detection ID POLYP DETECTION; POPULATION AB We present a method to reduce the false positive rate of our computed tomographic colonography computer aided detection (CTC-CAD) system based on the paradigm of Content Based Image Retrieval (CBIR). Using the feature vectors generated from our CTC-CAD system in conjunction with the distance metric of our CBIR system we rank detections based on their likelihood of being true positive. By eliminating detections with low rank, we prune approximately half of the false-positive detections from our CAD system. C1 [Aman, Javed; Yao, Jianhua; Summers, Ronald M.] NIH, Radiol & Image Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Aman, J (reprint author), NIH, Radiol & Image Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 915 EP 918 DI 10.1109/ISBI.2009.5193202 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400234 ER PT B AU Li, HS Shen, T Smith, MB Fujiwara, I Vavylonis, D Huang, XL AF Li, Hongsheng Shen, Tian Smith, Matthew B. Fujiwara, Ikuko Vavylonis, Dimitrios Huang, Xiaolei GP IEEE TI AUTOMATED ACTIN FILAMENT SEGMENTATION, TRACKING AND TIP ELONGATION MEASUREMENTS BASED ON OPEN ACTIVE CONTOUR MODELS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Actin Filament; Tracking; Elongation Measurement; Active Contour Models ID FLUORESCENCE MICROSCOPY; POLYMERIZATION AB This paper presents an automated method for actin filament segmentation and tracking for measuring tip elongation rates in Total Internal Reflection Fluorescence Microscopy (TIRFM) images. The main contributions of the paper are: (i) we use a novel open active contour model for filament segmentation and tracking, which is fast and robust against noise; and (ii) different strategies are proposed to solve the filament intersection problem, which is shown to be the main difficulty in filament tracking. Application to experimental results demonstrated the robustness and effectiveness of this method. C1 [Li, Hongsheng; Shen, Tian; Huang, Xiaolei] Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. [Smith, Matthew B.; Vavylonis, Dimitrios] Lehigh Univ, Dept Phys, Bethlehem, PA 18015 USA. [Fujiwara, Ikuko] NIH, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. RP Li, HS (reprint author), Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. RI Fujiwara, Ikuko/H-5717-2016 OI Fujiwara, Ikuko/0000-0002-9361-636X FU NIH [R21GM083928] FX This work was supported by NIH grant R21GM083928 NR 10 TC 10 Z9 10 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 1302 EP + PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400333 ER PT B AU Linguraru, MG Gautam, R Peterson, J Yao, JH Linehan, WM Summers, RM AF Linguraru, Marius George Gautam, Rabindra Peterson, James Yao, Jianhua Linehan, W. Marston Summers, Ronald M. GP IEEE TI RENAL TUMOR QUANTIFICATION AND CLASSIFICATION IN TRIPLE-PHASE CONTRAST-ENHANCED ABDOMINAL CT SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE contrast-enhanced CT; kidney cancer; quantification; classification; computer-assisted radiology ID SEGMENTATION; REGISTRATION; MODEL AB It is estimated that a quarter of a million people in the USA are living with kidney cancer. In clinical practice, the response to treatment is monitored by manual measurements of tumor size, which are time consuming and show high intra- and inter-operator variability. We propose a computer-assisted radiology tool to assess renal tumors in contrast-enhanced CT for the management of tumor diagnoses and treatments. The algorithm employs anisotropic diffusion, a combination of fast-marching and geodesic level-sets, and a novel statistical refinement step to adapt to the shape of the lesions. It also quantifies the 3D size, volume and enhancement of the lesion and allows serial management of tumors. The comparison between manual and semi-automated quantifications shows disparity within the limits of inter-observer variability. The automated tumor classification shows great separation between cysts, von Hippel-Lindau syndrome (VHL) lesions and hereditary papillary renal carcinomas (HPRC) (p < 0.004). C1 [Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Gautam, Rabindra; Peterson, James; Linehan, W. Marston] NIH, Natl Canc Inst, Urol Oncol, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov FU Intramural Research Program at National Institutes of Health; Clinical Center and National Cancer Institute; Center for Cancer Research FX This work was supported by the Intramural Research Program at National Institutes of Health, Clinical Center and National Cancer Institute, Center for Cancer Research. NR 15 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 1310 EP + DI 10.1109/ISBI.2009.5193305 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400335 ER PT B AU Shamir, L Eckley, DM Delaney, J Orlov, N Goldberg, IG AF Shamir, Lior Eckley, D. Mark Delaney, John Orlov, Nikita Goldberg, Ilya G. GP IEEE TI An Image Informatics Method for Automated Quantitative Analysis of Phenotype Visual Similarities SO 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP LA English DT Proceedings Paper CT IEEE/NIH Life Science Systems and Applications Workshop CY APR 09-10, 2009 CL Bethesda, MD SP IEEE, NIH ID HEIGHT; CELLS AB The post genomic era introduced the need to define single gene functions within biological pathways. A systems biology approach can be realized by automating image acquisition and phenotype classification. While machinery for automated data acquisition have been developing rapidly in the past years, the main bottleneck remains the effectiveness of the computer vision algorithms. Here we describe a fully automated process for finding phenotype similarities within a dataset acquired from an RNAi screen. The source code for the algorithms is available for free download. C1 [Shamir, Lior; Eckley, D. Mark; Delaney, John; Orlov, Nikita; Goldberg, Ilya G.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Shamir, L (reprint author), NIA, Genet Lab, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov RI Eckley, Mark/M-3526-2014 OI Eckley, Mark/0000-0003-2296-5164 NR 16 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4292-8 PY 2009 BP 96 EP 99 DI 10.1109/LISSA.2009.4906718 PG 4 WC Engineering, Biomedical SC Engineering GA BKH13 UT WOS:000268062300025 ER PT B AU Orlov, NV Delaney, J Eckley, DM Shamir, L Goldberg, IG AF Orlov, Nikita V. Delaney, John Eckley, D. Mark Shamir, Lior Goldberg, Ilya G. GP IEEE TI Pattern Recognition for Biomedical Imaging and Image-Guided Diagnosis SO 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP LA English DT Proceedings Paper CT IEEE/NIH Life Science Systems and Applications Workshop CY APR 09-10, 2009 CL Bethesda, MD SP IEEE, NIH AB Pattern recognition techniques can potentially be used to quantitatively analyze a wide variety of biomedical images. A challenge in applying this methodology is that biomedical imaging uses many imaging modalities and subjects. Pattern recognition relies on numerical image descriptors (features) to describe image content. Thus, the application of pattern recognition to biomedical imaging requires the development of a wide variety of image features. In this study we compared the efficacy of different techniques for constructing large feature spaces. A two-stage method was employed where several types of derived images were used as inputs for a bank of feature extraction algorithms. Image pyramids, subband filters, and image transforms were used in the first-stage. The feature bank consisted of polynomial coefficients, textures, histograms and statistics as previously described [1]. The basis for comparing the performance of these feature sets was the biological imaging benchmark described in [2]. Our results show that a set of image transforms (Fourier, Wavelet, Chebyshev) performed significantly better than a set of image filters (image pyramids, sub-band filters, and spectral decompositions). The transform technique was used to analyze images of H&E-stained tissue biopsies from two cancers: lymphoma (three types of malignancies) and melanoma (benign, primary, and five secondary tumor sites). The overall classification accuracy for these cancer data sets was 97%. C1 [Orlov, Nikita V.; Delaney, John; Eckley, D. Mark; Shamir, Lior; Goldberg, Ilya G.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Orlov, NV (reprint author), NIA, Genet Lab, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM norlov@nih.gov; delaneyjd@nih.gov; dme@nih.gov; shamirli@nih.gov; igg@nih.gov RI Eckley, Mark/M-3526-2014 OI Eckley, Mark/0000-0003-2296-5164 NR 8 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4292-8 PY 2009 BP 120 EP 123 DI 10.1109/LISSA.2009.4906724 PG 4 WC Engineering, Biomedical SC Engineering GA BKH13 UT WOS:000268062300031 ER PT B AU Yuan, SA Roney, CA Li, Q Lai, M Jiang, J Xu, BY Ma, HZ Cable, A Summers, RM Chen, Y AF Yuan, Shuai Roney, Celeste A. Li, Qian Lai, Michael Jiang, James Xu, Biying Ma, Hongzhou Cable, Alex Summers, Ronald M. Chen, Yu GP IEEE TI Simultaneous Morphology and Molecular Imaging of Colon Cancer SO 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP LA English DT Proceedings Paper CT IEEE/NIH Life Science Systems and Applications Workshop CY APR 09-10, 2009 CL Bethesda, MD SP IEEE, NIH ID OPTICAL COHERENCE TOMOGRAPHY; INDUCED FLUORESCENCE SPECTROSCOPY; MODEL AB The objective of this study is to investigate the feasibility of imaging colon cancers using multi-modal optical imaging system combining optical coherence tomography (OCT) and fluorescence molecular imaging (FMI). This system enables simultaneous imaging of tissue morphology and molecular information at high resolution (10-20 mu m) over a 3-5 mm field-of-view. OCT reveals the microstructures of normal colon and colon polyps, and the information is confirmed by the corresponding histology. FMI shows uptake of glycoprotein targeting contrast agents. The locations of high fluorescence intensity correspond with the characteristic morphological features of polyps revealed by the co-registered OCT imaging. Our results suggest that multi-modal optical imaging with OCT and fluorescence imaging holds strong potentials for molecular imaging and in situ characterization of colon cancers. C1 [Yuan, Shuai; Li, Qian; Lai, Michael; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Roney, Celeste A.; Summers, Ronald M.] Natl Inst Hlth, Clin Ctr, Dept Raiol & Imaging Sci, Bethesda, MD 20892 USA. [Jiang, James; Ma, Hongzhou; Cable, Alex] Thorlabs Inc, Newton, NJ 07860 USA. [Xu, Biying] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Yuan, SA (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM yuchen@umd.edu FU Maryland Nano-Biotechnology Award; Minta Martin Foundation; GRB Award of the University of Maryland; Clinical Center, NIH FX This work is supported in part by the Maryland Nano-Biotechnology Award, the Minta Martin Foundation,the GRB Award of the University of Maryland, and the intramural research program of the Clinical Center, NIH. NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4292-8 PY 2009 BP 167 EP + DI 10.1109/LISSA.2009.4906736 PG 2 WC Engineering, Biomedical SC Engineering GA BKH13 UT WOS:000268062300043 ER PT S AU Dieckmann, W Thada, S Barker, WC AF Dieckmann, William Thada, Shanthalaxmi Barker, W. Craig BE Yu, B TI Strategies for Accelerating Forward and Backprojection in List-mode OSEM PET Reconstruction using GPUs SO 2009 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-5 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium Conference 2009 CY OCT 25-31, 2009 CL Orlando, FL SP IEEE, Nucl Plasma Sci Sect, IEEE AB Image reconstruction for the ECAT HRRT PET scanner with MOLAR is computationally demanding and requires a computer cluster for reasonable run times. Parallel computing using GPUs and CUDA offers a means to accelerate MOLAR. However, forward and backprojection operations present unique challenges that must be overcome to achieve acceptable speedup. In this study we implement CPU-accelerated versions of MOLAR's forward projection, backprojection and algorithm update modules and compare their performance to CPU-only versions. During this implementation we optimized the CPU thread configurations for each of these modules separately, along with a hybrid forward-backprojection module that is used for algorithm updates. We also numerically evaluated the reconstruction results to assess the impact of floating-point to integer conversions dictated by the CPU architecture. We found forward projection to be 41 times faster than the CPU-only code, while backprojection was 20 times faster. We found the optimal thread configurations always assigned 64 threads to a thread block, but with different distributions across the nested indexing loops within each module. These results show that MOLAR's forward and backprojection modules can be adequately accelerated to make the MOLAR reconstruction package much more efficient. C1 [Dieckmann, William; Thada, Shanthalaxmi; Barker, W. Craig] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Dieckmann, W (reprint author), NIH, PET Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM wdieckmann@cc.nih.gov; sthada@cc.nih.gov; cbarker@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-3961-4 J9 IEEE NUCL SCI CONF R PY 2009 BP 4110 EP 4113 DI 10.1109/NSSMIC.2009.5402352 PG 4 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA BQA51 UT WOS:000280505102158 ER PT S AU Barker, WC Thada, S Dieckmann, W AF Barker, W. Craig Thada, Shanthalaxmi Dieckmann, William BE Yu, B TI A GPU-Accelerated Implementation of the MOLAR PET Reconstruction Package SO 2009 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-5 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium Conference 2009 CY OCT 25-31, 2009 CL Orlando, FL SP IEEE, Nucl Plasma Sci Sect, IEEE AB MOLAR (Motion-compensation OSEM List-mode Algorithm for Resolution-recovery reconstruction) was written to provide the best possible images from ECAT HRRT PET data. Because of computational demands, MOLAR currently requires a computer cluster for practical use. Here we have applied GPU-acceleration via CUDA to all of the computationally intensive modules of the MOLAR package. Using an NVIDIA Tesla S1070-400 GPU system hosted by an HP xw8400 workstation, we evaluated the CPU-accelerated performance of the modules that perform boundary checking, forward and backprojection, photon scatter modeling and algorithm updates. We compared their performance to CPU-only versions of MOLAR for a range of total counts (500k to 50M). We found boundary checking to be up to 35 times faster using the CPU. Forward and backprojection ran 50 and 20 times faster, respectively, and scatter modeling was 200 times faster. Algorithm updates ran up to 15 times faster. The overall performance of the entire MOLAR package was approximately 40 times faster than the CPU-only code. These results show that MOLAR can be substantially accelerated using GPUs and can thereby be practically extended for use in high count and higher resolution applications, and for 4D parametric reconstructions. C1 [Barker, W. Craig; Thada, Shanthalaxmi; Dieckmann, William] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Barker, WC (reprint author), NIH, PET Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM cbarker@nih.gov; sthada@cc.nih.gov; wdieckmann@cc.nih.gov NR 11 TC 3 Z9 4 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-3961-4 J9 IEEE NUCL SCI CONF R PY 2009 BP 4114 EP 4119 DI 10.1109/NSSMIC.2009.5402353 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA BQA51 UT WOS:000280505102159 ER PT B AU Chen, SY Huang, ML Lu, ZY AF Chen, Shouyuan Huang, Minlie Lu, Zhiyong BE BaezaYates, R Berendt, B Bertino, E Lim, EP Pasi, G TI Summarizing Documents by Measuring the Importance of a Subset of Vertices within a Graph SO 2009 IEEE/WIC/ACM INTERNATIONAL JOINT CONFERENCES ON WEB INTELLIGENCE (WI) AND INTELLIGENT AGENT TECHNOLOGIES (IAT), VOL 1 LA English DT Proceedings Paper CT IEEE/WIC/ACM International Conferences on Web Intelligence (WI)/Intelligent Agent Technologies (IAT), CY SEP 15-18, 2009 CL Milan, ITALY SP IEEE Comp Soc, Web Intelligence Consortium, ACM, Banca Popolare Sondrio, Comune Milano, Yahoo Res, DocFlow Italia SpA, IEEE, Univ Studi Milano Bicocca, Dipartimento Informat, Sistemist & Comunicaz DE document summarization; centrality; graph; diversity AB This paper presents a novel method of generating extractive summaries for multiple documents. Given a cluster of documents, we firstly construct a graph where each vertex represents a sentence and edges are created according to the asymmetric relationship between sentences. Then we develop a method to measure the importance of a subset of vertices by adding a super-vertex into the original graph. The importance of such a super-vertex is quantified as super-centrality, a quantitative measure for the importance of a subset of vertices within the whole graph. Finally, we propose a heuristic algorithm to find the best summary. Our method is evaluated with extensive experiments. The comparative results show that the proposed method outperforms other methods on several datasets. C1 [Chen, Shouyuan] Dept Comp Sci & Technol, Beijing 10084, Peoples R China. [Huang, Minlie] Natl Lab Informat Sci & Technol, Dept Comp Sci & Technol, Beijing 100084, Peoples R China. [Lu, Zhiyong] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Chen, SY (reprint author), Dept Comp Sci & Technol, Beijing 10084, Peoples R China. EM chenshouyuan@gmail.com; aihuang@tsinghua.edu.cn; luzh@ncbi.nlm.nih.gov RI Lu, Zhiyong/H-3622-2016 OI Lu, Zhiyong/0000-0001-9998-916X FU NSFC [60803075]; Chinese 973 Project [2007CB311003]; Intramural Program of the National Institutes of Health FX The work is supported in part by NSFC project No. 60803075, Chinese 973 Project No. 2007CB311003. ZL is supported by the Intramural Program of the National Institutes of Health. We also want to thank Prof. Xiaoyan Zhu for her kind support. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-1-4244-5331-3 PY 2009 BP 269 EP + PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering SC Computer Science GA BPS64 UT WOS:000279800000037 ER PT B AU Chen, SF Zeng, XQ Li, GZ Yang, JY Yang, MQ AF Chen, Su-Fen Zeng, Xue-Qiang Li, Guo-Zheng Yang, Jack Y. Yang, Mary Qu BE Zhang, J Li, GZ Yang, JY TI Redundant Gene Selection based on Particle Swarm Optimization SO 2009 INTERNATIONAL JOINT CONFERENCE ON BIOINFORMATICS, SYSTEMS BIOLOGY AND INTELLIGENT COMPUTING, PROCEEDINGS LA English DT Proceedings Paper CT International Joint Conference on Bioinformatics, Systems Biology and Intelligent Computing CY AUG 03-05, 2009 CL Shanghai, PEOPLES R CHINA SP IEEE Computer Soc, Conf Publish Serv ID EXPRESSION; CANCER; CLASSIFICATION; PREDICTION; RELEVANCE; DESIGN; SYSTEM; TESTS; TUMOR AB Redundant gene selection is an important topic in the field of bioinformatics. This paper proposes a novel algorithm on Redundant Gene Selection by Particle Swarm Optimization (RGS-PSO), which tries to find a compact gene subset with great predictive ability Compared with the previous works, RGS-PSO measures the redundancy of feature set by the maximum feature inter-correlation, which is more reasonable than those by the averaged inter-correlation. The outstanding performance of RGS-PSO has been examined by the experiments on several real world microarray data sets. C1 [Li, Guo-Zheng] Tongji Univ, Dept Control Sci & Engn, Shanghai 201804, Peoples R China. [Chen, Su-Fen] Nanchang Inst Technol, Dept Comp Sci & Technol, Nanchang 330099, Peoples R China. [Zeng, Xue-Qiang] Nanchang Univ, Sch Informat & Engn, Nanchang 330006, Jiangxi, Peoples R China. [Zeng, Xue-Qiang] Shanghai Univ, Sch Comp Engn & Sci, Shanghai 200072, Peoples R China. [Yang, Jack Y.] Harward Univ, Harward Med Sch, Cambridge, MA 02140 USA. [Yang, Mary Qu] Natl Inst Hlth NIH, Natl Human Genome Res Inst, US Dept Hlth & Human Sci, Rockville, MD 20852 USA. RP Li, GZ (reprint author), Tongji Univ, Dept Control Sci & Engn, Shanghai 201804, Peoples R China. EM gzli@tongji.edu.cn FU Natural Science Foundation of China [20503015, 60873129]; STCSM "Innovation Action Plan" Project of China [07DZ19726]; Shanghai Rising-Star Program [08QA1403200] FX This work was supported by the Natural Science Foundation of China under grant no. 20503015 and 60873129, the STCSM Innovation Action Plan Project of China under grant no. 07DZ19726, and the Shanghai Rising-Star Program under grant no. 08QA1403200. NR 22 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3739-9 PY 2009 BP 10 EP + DI 10.1109/IJCBS.2009.72 PG 2 WC Computer Science, Artificial Intelligence; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BRI88 UT WOS:000282797800002 ER PT B AU Xiong, KQ Suh, SC Yang, MQ Yang, JY Arabnia, HR AF Xiong, Kaiqi Suh, Sang C. Yang, Mary Qu Yang, Jack Y. Arabnia, Hamid R. BE Zhang, J Li, GZ Yang, JY TI Next Generation Sequence Analysis Using Genetic Algorithms on Multi-core Technology SO 2009 INTERNATIONAL JOINT CONFERENCE ON BIOINFORMATICS, SYSTEMS BIOLOGY AND INTELLIGENT COMPUTING, PROCEEDINGS LA English DT Proceedings Paper CT International Joint Conference on Bioinformatics, Systems Biology and Intelligent Computing CY AUG 03-05, 2009 CL Shanghai, PEOPLES R CHINA SP IEEE Computer Soc, Conf Publish Serv DE next generation sequence; multi-core computing technolog; genetic alogorithm; high-performance computing AB Advent of recent high-throughput next generation sequencing technologies has fostered the demand of high performance sequence data analysis. Next generation sequence analysis is a very important but very challenging task in bioinformatics due to extremely large-scale datasets. A variety of searching methods have been proposed. Recent emerging multi-core computing technology makes it possible to speed up sequence analysis. In this paper, we discuss the problem of parallelizing next generation sequence analysis queries on multi-core technology. We develop a systematic method to solve this problem by using genetic algorithms. The proposed method provides us a globally optimal solution of this parallelization problem. The resulting efficiency and accuracy is superior to the ones obtained by using those approaches in which this problem is divided into the two parts: location and allocation, respectively. C1 [Xiong, Kaiqi; Suh, Sang C.] Texas A&M Univ, Dept Comp Sci, Commerce, TX 75429 USA. [Yang, Mary Qu] Natl Inst Hlth, Natl Human Genome Res Inst, US Dept Hlth & Human, Bethesda, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Cambridge, MA 02140 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. RP Xiong, KQ (reprint author), Texas A&M Univ, Dept Comp Sci, Commerce, TX 75429 USA. EM Kaiqi_Xiong@tamu-commerce.edu; Sang_Suh@tamu-commerce.edu; yangma@mail.NIH.gov; Dr.Yang@JHU.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3739-9 PY 2009 BP 190 EP + DI 10.1109/IJCBS.2009.104 PG 2 WC Computer Science, Artificial Intelligence; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BRI88 UT WOS:000282797800033 ER PT B AU Xi, D White, JD AF Xi, Dan White, Jeffrey D. BE Zhang, J Li, GZ Yang, JY TI Exploring Systems Biology Approaches to Traditional Chinese Medicine Cancer Research SO 2009 INTERNATIONAL JOINT CONFERENCE ON BIOINFORMATICS, SYSTEMS BIOLOGY AND INTELLIGENT COMPUTING, PROCEEDINGS LA English DT Proceedings Paper CT International Joint Conference on Bioinformatics, Systems Biology and Intelligent Computing CY AUG 03-05, 2009 CL Shanghai, PEOPLES R CHINA SP IEEE Computer Soc, Conf Publish Serv DE component; cancer; sytems biology; Traditional Chinese Medicine AB Cancer is a chronic, complex disease. With advanced high-throughput technologies i.e. various -omics approaches, molecular imaging and computer technologies, conventional medicine and its research of cancer is leading to the emergence of systems biology. Traditional Chinese Medicine (TCM) focuses on the diseased person as a whole to formulate the therapeutic strategies to create a holistic systemic approach to treat the imbalanced systems of a person. TCM practices are usually descriptive, and empirical. To facilitate cross discipline dialog, and potentially research collaboration, it is important to move TCM research toward systems biological approaches. Analysis of FY2006 and 2007 NCI funded TCM research grants portfolio and research approaches will be discussed. C1 [Xi, Dan; White, Jeffrey D.] NCI, Off Canc Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. RP Xi, D (reprint author), NCI, Off Canc Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. EM xida@mail.nih.gov; jeffreyw@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3739-9 PY 2009 BP 367 EP 370 DI 10.1109/IJCBS.2009.125 PG 4 WC Computer Science, Artificial Intelligence; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BRI88 UT WOS:000282797800066 ER PT B AU Lichtenberg, J Alam, M Bitterman, T Drews, F Ecker, K Elnitski, L Evans, S Geisler, M Grotewold, E Gu, DZ Jacox, E Kurz, K Lee, SS Liang, XY Majmudar, PM Morris, P Nelson, C Stockinger, E Welch, JD Wyatt, S Yilmaz, A Welch, LR AF Lichtenberg, Jens Alam, Mohit Bitterman, Thomas Drews, Frank Ecker, Klaus Elnitski, Laura Evans, Susan Geisler, Matt Grotewold, Erich Gu, Dazhang Jacox, Edwin Kurz, Kyle Lee, Stephen S. Liang, Xiaoyu Majmudar, Pooja M. Morris, Paul Nelson, Chase Stockinger, Eric Welch, Joshua D. Wyatt, Sarah Yilmaz, Alper Welch, Lonnie R. GP IEEE COMPUTER SOC TI Construction of Genomic Regulatory Encyclopedias: Strategies and Case Studies SO 2009 OHIO COLLABORATIVE CONFERENCE ON BIOINFORMATICS, PROCEEDINGS LA English DT Proceedings Paper CT 4th Annual Ohio Collaborative Conference on Bioinformatics CY JUN 15-17, 2009 CL Case Western Reserve Univ, Cleveland, OH HO Case Western Reserve Univ DE Motif Discovery; Regulatory Genomics; Transcription Factor Binding Site Discovery; Regulatory Elements; Gene Regulation; cis-regulatory element discovery ID FACTOR-BINDING SITES; ART. NO. 25; TRANSCRIPTION FACTORS; ELEMENTS; GENE; DNA; IDENTIFICATION; ARABIDOPSIS; DISCOVERY; SEQUENCES AB Encyclopedias of regulatory genomic elements provide a foundation for research in areas such as disease diagnosis, disease treatment, and crop enhancement. The construction of complete encyclopedias of organism-specific genomic elements involved in gene regulation remains a significant challenge. To address this problem, the authors present novel bioinformatics strategies for exploring the word landscapes of putative regulatory regions of genomes. The methods are incorporated into the WordSeeker soft-ware tool, which is available at http://word-seeker.org. The effectiveness of these strategies is demonstrated through several case studies. C1 [Lichtenberg, Jens; Alam, Mohit; Drews, Frank; Ecker, Klaus; Gu, Dazhang; Kurz, Kyle; Liang, Xiaoyu; Welch, Joshua D.; Welch, Lonnie R.] Ohio Univ, Sch Elect Engn & Comp Sci, Athens, OH 45701 USA. [Bitterman, Thomas] Ohio Supercomp Ctr, Cyberinfrastructure Grp, Columbus, OH USA. [Elnitski, Laura; Jacox, Edwin] NIH, Natl Human Genome Res Inst, Genom Funct Anal Sect, Rockville, MD USA. [Elnitski, Laura; Evans, Susan; Majmudar, Pooja M.] Ohio Univ, Edison Biotechnol Inst, Athens, Greece. [Geisler, Matt] Southern Illinois Univ, Dept Plant Biol, Carbondale, IL USA. [Grotewold, Erich; Yilmaz, Alper] Ohio Univ, Plant Cellular & Mol Biol, Columbus, OH USA. [Lee, Stephen S.] Univ Idaho, Dept Stat, Moscow, ID USA. [Morris, Paul] Bowling Green State Univ, Dept Biol Sci, Bowling Green, OH USA. [Nelson, Chase] Oberlin Coll, Dept Biol, Oberlin, OH USA. [Stockinger, Eric] Ohio Univ, OARDC, Dept Horticulture & Crop Sci, Wooster, OH USA. [Wyatt, Sarah] Ohio Univ, Dept Environm & Plant Biol, Athens, OH USA. [Majmudar, Pooja M.; Welch, Lonnie R.] Ohio Univ, Biomed Engn Program, Athens, OH USA. [Evans, Susan; Majmudar, Pooja M.; Wyatt, Sarah; Welch, Lonnie R.] Ohio Univ, Mol & Cellular Biol Program, Athens, OH USA. RP Lichtenberg, J (reprint author), Ohio Univ, Sch Elect Engn & Comp Sci, Athens, OH 45701 USA. EM lichtenj@ohio.edu; welch@ohio.edu RI Geisler, Matt/A-4156-2008; Yilmaz, Alper/C-7075-2014; OI Geisler, Matt/0000-0003-1888-4652; Yilmaz, Alper/0000-0002-8827-4887; Wyatt, Sarah/0000-0001-7874-0509 FU Ohio Plant Biotechnology Consortium through The Ohio State University; Ohio Agricultural Research and Development Center FX The Ohio University team acknowledges the support of the Stocker Endowment, Ohio University?s Graduate Research and Education Board (GERB), the Ohio Supercomputer Center, the Choose Ohio First Initiative ofthe University System of Ohio . The Ohio University team further acknowledges that salaries and research support are provided by state funds appropriated to the Ohio Plant Biotechnology Consortium through The Ohio State University, Ohio Agricultural Research and Development Center NR 38 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3685-9 PY 2009 BP 65 EP + DI 10.1109/OCCBIO.2009.9 PG 3 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA BMR82 UT WOS:000273427500013 ER PT S AU Kubler-Kielb, J Vinogradov, E Mocca, C Guo, CY Schneerson, R Robbins, JB AF Kubler-Kielb, Joanna Vinogradov, Evgeny Mocca, Chris Guo, Chunyan Schneerson, Rachel Robbins, John B. BE Spier, R TI Shigella sonnei oligosaccharide-protein conjugates SO 2ND GLOBAL CONGRESS ON VACCINES SE Procedia in Vaccinology LA English DT Proceedings Paper CT 2nd Global Congress on Vaccines CY DEC 07-09, 2008 CL Boston, MA DE shigell; sonnei; LPS; conjugate; vaccine AB Synthetic oligosaccharides composed of several repeats of Shigella dysenteriae type 1 O-specific polysaccharide (O-SP), bound by their reducing ends to a carrier protein ("sun" type configuration), induced in mice significantly higher antibody levels than conjugates of the native O-SP ("lattice" type configuration). Here we present isolation and characterization of low molecular mass oligosaccharides of Shigella sonnei lipopolysaccharides and their conjugation to several carrier proteins. Conjugates were formed by oxime linkages between the terminal Kdo residues of the reducing ends of the saccharides and aminooxy linkers bound to the protein. IgG antibody levels induced in young outbread mice by these conjugates were significantly higher than those prepared with the full length native O-SP. We propose clinical evaluation of the new S. sonnei conjugates. (C) 2009 Elsevier B. V. All rights reserved C1 [Kubler-Kielb, Joanna; Mocca, Chris; Guo, Chunyan; Schneerson, Rachel; Robbins, John B.] NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Vinogradov, Evgeny] CNR, Inst Biol Sci, Ottawa K1A 0R6, ON, Canada. RP Kubler-Kielb, J (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov FU NIH; NICHD FX This research was supported by the Intramural Research Program of the NIH, NICHD. NR 4 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2009 VL 1 IS 1 BP 63 EP 66 DI 10.1016/j.provac.2009.07.011 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BOF33 UT WOS:000276449200010 ER PT S AU Klinman, DM Tross, D AF Klinman, Dennis M. Tross, Debra BE Spier, R TI Improvements in the Prevention and Treatment of Anthrax Infection SO 2ND GLOBAL CONGRESS ON VACCINES SE Procedia in Vaccinology LA English DT Proceedings Paper CT 2nd Global Congress on Vaccines CY DEC 07-09, 2008 CL Boston, MA DE anthrax; vaccine; adjuvant ID CPG OLIGONUCLEOTIDES IMPROVE; BACTERIAL-DNA; BACILLUS-ANTHRACIS; INHALATIONAL ANTHRAX; DENDRITIC CELLS; POSTEXPOSURE PROPHYLAXIS; INTERFERON-GAMMA; RHESUS MACAQUES; ADVERSE EVENTS; CUTTING EDGE AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN are finding use as vaccine adjuvants based on their ability to increase the speed, magnitude and duration of vaccine-specific immune responses. We conducted studies examining the capacity of CpG ODN to accelerate and prolong the protection induced by AVA (Anthrax Vaccine Adsorbed). Co-administering CpG-adjuvanted AVA with Dalbavancin, a long-activity antibiotic, protected naive mice from both the immediate and long-term threat posed by exposure to anthrax spores. A majority of animals immunized only once with CpG-adjuvanted AVA maintained resistance to anthrax infection for more than one year, even after their Ab titers declined to sub-protective levels. This survival was mediated by the de novo production of protective Abs by high affinity long-lived memory B cells that were generated by vaccination with CpG-adjuvanted AVA. Abbreviations: Ab; antibody, Ag; antigen, APC; antigen presenting cell, AVA; Anthrax Vaccine Adsorbed, AVP; Anthrax Vaccine precipitated, LD 50; 50% lethal dose, ODN; oligodeoxynucleotide, rPA; recombinant protective antigen (C) 2009 Elsevier B. V. All rights reserved C1 [Klinman, Dennis M.; Tross, Debra] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 54 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL PY 2009 VL 1 IS 1 BP 89 EP 96 DI 10.1016/j.provac.2009.07.016 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BOF33 UT WOS:000276449200015 ER PT B AU Sauna, ZE Ambudkar, SV AF Sauna, Zuben E. Ambudkar, Suresh V. BE PonteSucre, A TI Evolution and Function of the Multi-drug Resistance-linked ABC Transporters in Bacteria and Cancer Cells SO ABC TRANSPORTERS IN MICROORGANISMS: RESEARCH, INNOVATION AND VALUE AS TARGETS AGAINST DRUG RESISTANCE LA English DT Article; Book Chapter ID ATP-BINDING CASSETTE; P-GLYCOPROTEIN ABCB1; OCCLUDED NUCLEOTIDE CONFORMATION; MEMBRANE-PROTEINS; ESCHERICHIA-COLI; CATALYTIC CYCLE; GENE ABCR; HYDROLYSIS; MECHANISM; SYSTEMS AB The ATP-binding cassette (ABC) genes constitute one of the largest super-families in living organisms. The majority of ABC proteins encode membrane proteins that utilize the energy of ATP binding and hydrolysis to transport a diverse set of compounds. ABC systems are critical to the cellular physiology of prokaryotes, facilitating the import of nutrients, the extrusion of toxins and for DNA repair. In eukaryotes, ABC proteins function primarily as efflux pumps (or as import pumps in intracellular organelles) playing important roles in protecting organisms from xenobiotics, antigen presentation, cholesterol and lipid transport. As ABC transporters extrude an unusually large set of chemically diverse compounds, they impede the treatment of microbial infections and human cancers and are implicated in multidrug resistance (MDR). Among prokaryotes, ABC proteins segregate into 29 families belonging to three main classes approximating the functional divisions of the ABC system (importers, exporters and 'other'). However, the vertebrate ABC proteins do not have the functional or organizational diversity of the prokaryotic proteins. The primary focus of this review is to discuss the evolution and structure-function relationship of microbial and mammalian ABC transporters responsible for MDR and the current status of substrate specificity and mechanistic aspects of mammalian ABC drug transporters. C1 [Sauna, Zuben E.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Sauna, ZE (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM saunaz@mail.nih.gov; ambudkar@mail.nih.gov NR 73 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-49-3 PY 2009 BP 35 EP 50 PG 16 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA BKX07 UT WOS:000269516200002 ER PT B AU Pacher, P Kunos, G AF Pacher, Pal Kunos, George BE Despres, JP DiMarzo, V TI The Endocannabinoid System and Cardiovascular Disease SO ABDOMINAL OBESITY AND THE ENDOCANNABINOID SYSTEM: FROM BASIC ASPECTS TO CLINICAL MANAGEMENT OF RELATED CARDIOMETABOLIC RISK LA English DT Article; Book Chapter ID CANNABINOID-1 RECEPTOR BLOCKER; RISK-FACTORS; OVERWEIGHT PATIENTS; RIMONABANT; ACTIVATION; OBESITY; WEIGHT; INJURY C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Kunos, George] NIAAA, Sect Neuroendocrinol, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND BN 978-1-4200-6085-0; 978-1-4200-6084-3 PY 2009 BP 179 EP 183 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA BC3SB UT WOS:000351879100026 ER PT J AU Summers, RM Frentz, SM Liu, JM Yao, JH Brown, L Louie, A Barlow, DS Jensen, DW Dwyer, AJ Pickhardt, PJ Petrick, N AF Summers, Ronald M. Frentz, Suzanne M. Liu, Jiamin Yao, Jianhua Brown, Linda Louie, Adeline Barlow, Duncan S. Jensen, Donald W. Dwyer, Andrew J. Pickhardt, Perry J. Petrick, Nicholas TI Conspicuity of Colorectal Polyps at CT Colonography: Visual Assessment, CAD Performance, and the Important Role of Polyp Height SO ACADEMIC RADIOLOGY LA English DT Article DE CT; colon; colon cancer; conspicuity ID COMPUTED-TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; STRUCTURED NOISE; AIDED DETECTION; MISSED LESIONS; FLAT; FEATURES; NODULES; SEARCH AB Rationale and Objectives. The factors that influence the conspicuity of polyps on computed tomographic (CT) colonography (CTC) are poorly understood. The aim of this study is to compare radiologists' visual assessment of polyp conspicuity to quantitative image features and show the relationship between Visual conspicuity and the detection of colonic polyps by computer-aided detection (CAD) on CTC. Methods. One polyp (size range 6-10 mm) was selected from the CTC examination of each of 29 patients from a larger cohort. All patients underwent oral contrast-enhanced CTC with same-day optical colonoscopy with segmental unblinding. The polyps were analyzed by a previously validated CAD system and placed into one of two groups (detected [n = 12] or not detected [n = 171 by CAD). The study population was intentionally enriched with polyps that were not detected by the CAD system. Four board-certified radiologists, blinded to the CAD results, reviewed two- and three-dimensional CTC images of the polyps and scored the conspicuity of the polyps using a 4-point scale (0 = least conspicuous, 3 = most conspicuous). Polyp height and width were measured by a trained observer. A t-test (two-tailed, unpaired equal variance) was done to determine statistical significance. Intra- and interobserver variabilities of the conspicuity scores were assessed using the weighted kappa test. Regression analysis was used to investigate the relationship of conspicuity to polyp height and width. Results. A statistically significant difference was found between the average conspicuity scores for polyps that were detected by CAD compared to those that were not (2.3 +/- 0.6 vs. 1.4 +/- 0.8) (P = .004). There was moderate intraobserver agreement of the conspicuity scores (weighted kappa 0.57 +/- 0.09). Interobserver agreement was fair (average weighted kappa for six pair-wise comparisons, 0.38 +/- 0.15). Conspicuity was correlated with manual measurement of polyp height (r(2) = 0.38-0.56 P < .001). Conclusions. This CAD system tends to detect 6-10 mm polyps that are more visually conspicuous. Polyp height is a major determinant of visual conspicuity. The generalizability of these findings to other CAD systems is currently unknown. Nevertheless, CAD developers may need to specifically target flatter and less conspicuous polyps for CAD to better assist the radiologist to find polyps in this clinically important size category. C1 [Summers, Ronald M.; Frentz, Suzanne M.; Liu, Jiamin; Yao, Jianhua; Brown, Linda; Louie, Adeline; Dwyer, Andrew J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Barlow, Duncan S.; Jensen, Donald W.] Natl Naval Med Ctr, Colon Hlth Initiat, Bethesda, MD USA. [Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. [Petrick, Nicholas] FDA CDRH OSEL, LAMIS Image Anal Lab, Silver Spring, MD USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural Research Programs of the NIH Clinical Center; National Institute of Biomedical Imaging and Bioengineering FX This research was supported in part by the Intramural Research Programs of the NIH Clinical Center and the National Institute of Biomedical Imaging and Bioengineering. NR 25 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2009 VL 16 IS 1 BP 4 EP 14 DI 10.1016/j.acra.2008.06.007 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 388LP UT WOS:000262021600002 PM 19064206 ER PT J AU Armato, SG Roberts, RY Kocherginsky, M Aberle, DR Kazerooni, EA MacMahon, H van Beek, EJR Yankelevitz, D McLennan, G McNitt-Gray, MF Meyer, CR Reeves, AP Caligiuri, P Quint, LE Sundaram, B Croft, BY Clarke, LP AF Armato, Samuel G., III Roberts, Rachael Y. Kocherginsky, Masha Aberle, Denise R. Kazerooni, Ella A. MacMahon, Heber van Beek, Edwin J. R. Yankelevitz, David McLennan, Geoffrey McNitt-Gray, Michael F. Meyer, Charles R. Reeves, Anthony P. Caligiuri, Philip Quint, Leslie E. Sundaram, Baskaran Croft, Barbara Y. Clarke, Laurence P. TI Assessment of Radiologist Performance in the Detection of Lung Nodules: Dependence on the Definition of "Truth" SO ACADEMIC RADIOLOGY LA English DT Article DE Lung nodule; computed tomography (CT); thoracic imaging; interobserver variability; computer-aided diagnosis (CAD) ID IMAGE-DATABASE-CONSORTIUM; LIDC; CT; ANNOTATION; RESOURCE; SIZE AB Rationale and Objectives. Studies that evaluate the lung nodule detection performance of radiologists or computerized methods depend on an initial inventory of the nodules within the thoracic images (the "truth"). The purpose of this study was to analyze (1) variability in the "truth" defined by different combinations of experienced thoracic radiologists and (2) variability in the performance of other experienced thoracic radiologists based on these definitions of "truth" in the context of lung nodule detection in Computed tomographic (CT) scans. Materials and Methods. Twenty-five thoracic CT scans were reviewed by four thoracic radiologists, who independently marked lesions they considered to be nodules >= 3 mm in maximum diameter. Panel "truth" sets of nodules were then derived from the nodules marked by different combinations of two and three of these four radiologists. The nodule detection performance of the other radiologists was evaluated based on these panel "truth" sets. Results. The number of "true" nodules in the different panel "truth" sets ranged from 15 to 89 (mean 49.8 +/- 25.6). The mean radiologist nodule detection sensitivities across radiologists and panel "truth" sets for different panel "truth" conditions ranged from 51.0 to 83.2%: mean false-positive rates ranged from 0.33 to 1.39 per case. Conclusions. Substantial variability exists across radiologists in the task Of hung nodule identification in CT scans. The definition of "truth" on which lung nodule detection studies are based must be carefully considered, because even experienced thoracic radiologists may not perform well when measured against the "truth" established by other experienced thoracic radiologists. C1 [Armato, Samuel G., III; Roberts, Rachael Y.; MacMahon, Heber; Caligiuri, Philip] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Kocherginsky, Masha] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Aberle, Denise R.; McNitt-Gray, Michael F.] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Kazerooni, Ella A.; Meyer, Charles R.; Quint, Leslie E.; Sundaram, Baskaran] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [van Beek, Edwin J. R.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [McLennan, Geoffrey] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [McLennan, Geoffrey] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [McLennan, Geoffrey] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. [Reeves, Anthony P.] Cornell Univ, Dept Elect & Comp Engn, Ithaca, NY USA. [Yankelevitz, David] Cornell Univ, Weill Med Coll, Ithaca, NY USA. [Croft, Barbara Y.; Clarke, Laurence P.] NCI, Canc Imaging Program, Rockville, MD USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA. EM s-armato@uchicago.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU USPHS [U01CA091085, U01CA091090, U01CA091099, U01CA091100, U01CA091103] FX Supported in part by USPHS Grants U01CA091085, U01CA091090, U01CA091099, U01CA091100, and U01CA091103. NR 20 TC 30 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2009 VL 16 IS 1 BP 28 EP 38 DI 10.1016/j.acra.2008.05.022 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 388LP UT WOS:000262021600005 PM 19064209 ER PT J AU Resnik, DB AF Resnik, David B. TI INTERNATIONAL STANDARDS FOR RESEARCH INTEGRITY: AN IDEA WHOSE TIME HAS COME? SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Article DE conflict of interest; ethics; integrity; international research; misconduct ID CONFLICTS-OF-INTEREST AB A movement to promulgate international ethics standards covering areas of conduct other than research with human subjects has now begun to gain momentum. This commentary explains why it is important to develop international research integrity standards and some of the problems that must be overcome to bring them to fruition. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,MD CU-03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) FX This research was sponsored by the intramural program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). It does not represent the views of the NIEHS, NIH, or U. S. government. NR 32 TC 13 Z9 13 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 J9 ACCOUNT RES JI Account. Res. PY 2009 VL 16 IS 4 BP 218 EP 228 DI 10.1080/08989620903065350 PG 11 WC Medical Ethics SC Medical Ethics GA 599SD UT WOS:000277932500003 PM 20183162 ER PT J AU Resnik, DB Peddada, S Brunson, W AF Resnik, David B. Peddada, Shyamal Brunson, Winnon, Jr. TI RESEARCH MISCONDUCT POLICIES OF SCIENTIFIC JOURNALS SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Article DE definitions; ethics; misconduct; policies; procedures; scientific journals AB The purpose of this study was to gather information on the misconduct policies of scientific journals. We contacted editors from a random sample of 399 journals drawn from the ISI Web of Knowledge database. We received 197 responses (49.4% response rate): 54.8% had a policy, and 47.7% had a formal (written) policy; 28.9% had a policy that only outlined procedures for handling misconduct, 15.7% had a policy that only defined misconduct, 10.2% had a policy that included both a definition and procedures; 26.9% of journals had a policy that was generated by the publisher, 13.2% had a policy that was generated by the journal, and 14.7% had a policy that was generated by another source, such as a professional association. We analyzed the relationship between having a policy and impact factor, field of science, publishing house, and nationality. Impact factor was the only variable with a statistically significant association with having a policy. Impact factor was slightly positively associated with whether or not the publisher had a policy, with an odds ratio of 1.49 (P<.0004) per 10 units increase in the impact factor, with a 95% confidence interval (1.20, 1.88). Our research indicates that more than half of scientific journals have developed misconduct policies, but that most of these policies do not define research misconduct and most of these policies were not generated by the journal. C1 [Resnik, David B.; Peddada, Shyamal] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Brunson, Winnon, Jr.] Grinnell Coll, Grinnell, IA 50112 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) FX This research was supported by the intramural program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). It does not represent the views of the NIEHS or NIH. NR 12 TC 19 Z9 20 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 J9 ACCOUNT RES JI Account. Res. PY 2009 VL 16 IS 5 BP 254 EP 267 DI 10.1080/08989620903190299 PG 14 WC Medical Ethics SC Medical Ethics GA 599SE UT WOS:000277932600002 PM 19757231 ER PT J AU Gladwin, MT Grubina, R Doyle, MP AF Gladwin, Mark T. Grubina, Rozalina Doyle, Michael P. TI The New Chemical Biology of Nitrite Reactions with Hemoglobin: R-State Catalysis, Oxidative Denitrosylation, and Nitrite Reductase/Anhydrase SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID RED-BLOOD-CELLS; S-NITROSOHEMOGLOBIN; AUTOCATALYTIC OXIDATION; REDUCTIVE NITROSYLATION; HYPOXIC VASODILATION; FLOW REGULATION; LIGAND-BINDING; BOUND DIOXYGEN; HEME PROTEINS; IN-VIVO AB Because of their critical biological roles, hemoglobin and myoglobin are among the most extensively studied proteins in human history, while nitrite tops the list of most-studied small molecules. And although the reactions between them have been examined for more than 140 years, a series of unusual and critical allosterically modulated reactions have only recently been characterized. In this Account, we review three novel metal- and nitrite-catalyzed reaction pathways in the context of historical studies of nitrite and hemoglobin chemistry and attempt to place them in the biological framework of hypoxic signaling. Haldane first described the reaction between nitrite and deoxymyoglobin, forming iron-nitrosylated myoglobin, in his analysis of the meat-curing process more than a century ago. The reaction of nitrous acid with deoxyhemoglobin to form nitric oxide (NO) and methemoglobin was more fully characterized by Brooks in 1937, while the mechanism and unusual behavior of this reaction were further detailed by Doyle and colleagues in 1981. During the past decade, multiple physiological studies have surprisingly revealed that nitrite represents a biological reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. Importantly, chemical analysis of this new biology suggests a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction in these processes. The use of UV-vis deconvolution and electron paramagnetic resonance (EPR) spectroscopy, in addition to refined gas-phase chemiluminescent NO detection, has led to the discovery of three novel and unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. First, R-state, or allosteric, autocatalysis of nitrite reduction increases the rate of NO generation by deoxyhemoglobin and results in maximal NO production at approximately 50% hemoglobin oxygen saturation, which is physiologically associated with greatest NO-dependent vasodilation. Second, oxidative denitrosylation of the iron-nitrosyl product formed in the deoxyhemoglobin-nitrite reaction allows for NO formation and release in a partially oxygenated environment. Finally, the deoxyhemoglobin-nitrite reaction participates in a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of two molecules of nitrite into dinitrogen trioxide (N(2)O(3))center dot N(2)O(3) may then nitrosate proteins, diffuse across hydrophobic erythrocyte membrane channels such as aquaphorin or Rh, or reconstitute NO via homolysis to NO and NO(2)(center dot). Importantly, the nitrite reductase/anhydrase redox pathway also represents a novel mechanism of both anaerobic and metal-catalyzed N(2)O(3) formation and S-nitrosation and may thus play a vital role in NO-dependent signaling in a hypoxic and heme-rich environment. We consider how these reactions may contribute to physiological and pathological hypoxic signaling. C1 [Gladwin, Mark T.; Grubina, Rozalina] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark T.] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. [Grubina, Rozalina] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20814 USA. [Doyle, Michael P.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Gladwin, MT (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. EM gladwinmt@upmc.edu RI Doyle, Michael/C-3367-2009 OI Doyle, Michael/0000-0003-1386-3780 NR 55 TC 102 Z9 104 U1 5 U2 46 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD JAN PY 2009 VL 42 IS 1 BP 157 EP 167 DI 10.1021/ar800089j PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 396UM UT WOS:000262616700016 PM 18783254 ER PT J AU Huter, EN Lee, CCR Sherry, RM Udey, MC AF Hueter, Eva N. Lee, Chyi-Chia R. Sherry, Richard M. Udey, Mark C. TI Spontaneous Regression and Recurrence in a Case of Nodular Fasciitis SO ACTA DERMATO-VENEREOLOGICA LA English DT Letter ID LESIONS C1 [Hueter, Eva N.] NCI, Immunol Lab, NIAID, NIH, Bethesda, MD 20892 USA. [Lee, Chyi-Chia R.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Udey, Mark C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Sherry, Richard M.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Huter, EN (reprint author), NCI, Immunol Lab, NIAID, NIH, Bethesda, MD 20892 USA. EM udey@helix.nih.gov NR 10 TC 3 Z9 3 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2009 VL 89 IS 4 BP 438 EP 439 DI 10.2340/00015555-0664 PG 2 WC Dermatology SC Dermatology GA 484CW UT WOS:000269021900028 PM 19688171 ER PT J AU Blair, A AF Blair, Aaron TI Occupation and cancer in the Nordic countries SO ACTA ONCOLOGICA LA English DT Editorial Material ID MORTALITY C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, EPS Room 8003, Bethesda, MD 20892 USA. EM blaira@exchange.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 2009 VL 48 IS 5 BP 644 EP 645 DI 10.1080/02841860902988696 PG 2 WC Oncology SC Oncology GA 478EH UT WOS:000268570100001 PM 19925374 ER PT J AU Mohapatra, S Park, SJ Boyapalle, S Pastey, MK Graham, BS Blanck, G AF Mohapatra, S. Park, S. J. Boyapalle, S. Pastey, M. K. Graham, B. S. Blanck, G. TI Human respiratory syncytial virus reduces the number of cells in S-phase and increases GADD153 expression in HEp-2 cells SO ACTA VIROLOGICA LA English DT Article DE Human respiratory syncytial virus; cell cycle; S-phase; G1-phase; GADD153 ID US CHILDREN; DISEASE; RSV; INHIBITION; MECHANISMS; ASTHMA AB Human respiratory syncytial virus (HRSV) associated with bronchiolitis and asthma is known to replicate actively in ciliated epithelial cells. However, little is known about the influence of HRSV replication on the cell cycle. We found that HRSV infection of HEp-2 cells led to a reduction of the number ofcells in S-phase, to an increase in the number ofcells in G1-phase, together with an increase of GADD 153 mRNA levels and GADD153 protein expression. These results implied that a shorter S-phase supported HRSV replication suggesting possible strategies for interfering with productive HRSV infection. C1 [Mohapatra, S.; Blanck, G.] Univ S Florida, Coll Med, Joy McCann Culverhouse Airway Dis Ctr, Dept Mol Med,VA Hosp, Tampa, FL 33620 USA. [Mohapatra, S.; Park, S. J.; Boyapalle, S.] Univ S Florida, Coll Med, Joy McCann Culverhouse Airway Dis Ctr, Dept Internal Med,VA Hosp, Tampa, FL USA. [Pastey, M. K.] Oregon State Univ, Coll Vet Med, Dept Biomed Sci, Corvallis, OR 97331 USA. [Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Blanck, G (reprint author), Univ S Florida, Coll Med, Joy McCann Culverhouse Airway Dis Ctr, Dept Mol Med,VA Hosp, Tampa, FL 33620 USA. EM gblanck@health.usf.edu RI Mohapatra, Shyam/C-2500-2012; Blanck, George/A-5365-2012 FU American Cancer Society [RPG-98-184-01-CIM]; National Institutes of Health [RO1 CA81497-01]; VA Merit Review Award; VA Senior Career Scientist Award FX We thank the Moffitt Cancer Center and Research Institute Molecular Biology Core Facility and Dr. Mary Beth Colter for the assistance with real-time PCR. This work was supported by the grants RPG-98-184-01-CIM from the American Cancer Society, RO1 CA81497-01 from the National Institutes of Health, VA Merit Review Award, and VA Senior Career Scientist Award. NR 15 TC 4 Z9 4 U1 0 U2 1 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PY 2009 VL 53 IS 3 BP 207 EP 211 DI 10.4149/av_2009_03_207 PG 5 WC Virology SC Virology GA 501KB UT WOS:000270379400010 PM 19953728 ER PT J AU Jaszyna-Gasior, M Schroeder, JR Thorner, ED Heishman, SJ Collins, CC Lo, S Moolchan, ET AF Jaszyna-Gasior, Maria Schroeder, Jennifer R. Thorner, Elissa D. Heishman, Stephen J. Collins, Charles C. Lo, Suzanne Moolchan, Eric T. TI Age at menarche and weight concerns in relation to smoking trajectory and dependence among adolescent girls enrolled in a smoking cessation trial SO ADDICTIVE BEHAVIORS LA English DT Article DE Adolescents; Smoking; Menarche; Weight; Tobacco cessation ID NICOTINE DEPENDENCE; GENDER AB Many girls adopt dieting and other practices (i.e. cigarette smoking) to control weight during puberty. This analysis explored the relationship between age at menarche and onset of daily smoking, and whether this relationship was influenced by weight concerns among treatment seeking female adolescents. The sample consisted of 71 participants enrolled in a smoking cessation trial (age 15.2 +/- 1.3 years; 74.7% European American, baseline BMI 24.7 +/- 5.4, age at menarche 11.7 +/- 1.3 years, Fagerstrom Test for Nicotine Dependence score 7.0 +/- 1.2). Over 60% of participants reported weight concerns at baseline. based on responses to the Eating Disorders module from the Diagnostic Interview for Children and Adolescents. Linear regression analyses revealed a significant association between age at menarche and age of onset of daily smoking (beta = 0.18 +/- 0.09, p = 0.038). Having weight concerns did not modify the relationships between age at menarche and smoking trajectory/severity or abstinence. Findings support previous research showing that early maturation represents a risk factor for substance use. Further study in larger samples that include non-treatment-seeking adolescent female smokers is warranted. Published by Elsevier Ltd. C1 [Jaszyna-Gasior, Maria; Schroeder, Jennifer R.; Thorner, Elissa D.; Heishman, Stephen J.; Collins, Charles C.; Lo, Suzanne; Moolchan, Eric T.] NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, NIH,Dept Hlth & Human Serv,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, NIH,Dept Hlth & Human Serv,Biomed Res Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM etmoolcha@intra.nida.nih.gov FU NIH, National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 16 TC 3 Z9 3 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN PY 2009 VL 34 IS 1 BP 92 EP 95 DI 10.1016/j.addbeh.2008.08.001 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 380SQ UT WOS:000261485900013 PM 18940275 ER PT J AU Proctor, EK Landsverk, J Aarons, G Chambers, D Glisson, C Mittman, B AF Proctor, Enola K. Landsverk, John Aarons, Gregory Chambers, David Glisson, Charles Mittman, Brian TI Implementation Research in Mental Health Services: an Emerging Science with Conceptual, Methodological, and Training challenges SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT 19th National Conference on Mental Health Services Research CY JUL 23, 2007 CL Washington, DC SP NIMH DE Implementation; Evidence-based practice; Mental health services; Translation two research ID INTERVENTION RESEARCH; UNITED-STATES; CARE; QUALITY; TECHNOLOGY; STRATEGIES; ILLNESS; ORGANIZATIONS; PERSPECTIVES; PREVENTION AB One of the most critical issues in mental health services research is the gap between what is known about effective treatment and what is provided to consumers in routine care. Concerted efforts are required to advance implementation science and produce skilled implementation researchers. This paper seeks to advance implementation science in mental health services by over viewing the emergence of implementation as an issue for research, by addressing key issues of language and conceptualization, by presenting a heuristic skeleton model for the study of implementation processes, and by identifying the implications for research and training in this emerging field. C1 [Proctor, Enola K.; Landsverk, John] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Landsverk, John] San Diego Childrens Hosp Work, Child & Adolescent Serv Res Ctr, San Diego, CA USA. [Aarons, Gregory] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Chambers, David] NIMH, Disseminat & Implementat Res Program, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Glisson, Charles] Univ Tennessee, Childrens Mental Hlth Serv Res Ctr, Knoxville, TN USA. [Mittman, Brian] Greater Angeles Healthcare Syst, VA Ctr Implementat Res & Improvement Sci, Dept Vet Affairs, Los Angeles, CA USA. RP Proctor, EK (reprint author), Washington Univ, George Warren Brown Sch Social Work, 1 Brookings Dr,Campus Box 1196, St Louis, MO 63130 USA. EM ekp@wustl.edu OI Mittman, Brian/0000-0003-3589-9178 FU NIMH NIH HHS [5P30 MH 068579, P30 MH068579, R21 MH082731, R25 MH080916] NR 82 TC 319 Z9 319 U1 4 U2 49 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 2009 VL 36 IS 1 BP 24 EP 34 DI 10.1007/s10488-008-0197-4 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 403CD UT WOS:000263058500004 PM 19104929 ER PT B AU Winters, KC Botzet, AM Fahnhorst, T Stinchfield, R Koskey, R AF Winters, Ken C. Botzet, Andria M. Fahnhorst, Tamara Stinchfield, Randy Koskey, Rachel BE Leukefeld, CG Gullotta, TP StatonTindall, M TI Adolescent Substance Abuse Treatment: A Review of Evidence-Based Research SO ADOLESCENT SUBSTANCE ABUSE: EVIDENCE-BASED APPROACHES TO PREVENTION AND TREATMENT SE Issues in Childrens and Families Lives LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; MULTIDIMENSIONAL FAMILY-THERAPY; ALCOHOL-USE DISORDERS; DRUG-ABUSE; OUTPATIENT TREATMENT; TREATMENT OUTCOMES; TREATMENT PROGRAMS; BRIEF INTERVENTION; CONDUCT DISORDER; MINNESOTA MODEL C1 [Winters, Ken C.; Stinchfield, Randy] Univ Minnesota, Dept Psychiat, Ctr Adolescent Subst Abuse Res, Minneapolis, MN 55455 USA. [Winters, Ken C.] Treatment Res Inst, Philadelphia, PA USA. [Winters, Ken C.] NIDA, Bethesda, MD USA. [Winters, Ken C.] WHO, New York, NY USA. RP Winters, KC (reprint author), Univ Minnesota, Dept Psychiat, Ctr Adolescent Subst Abuse Res, Minneapolis, MN 55455 USA. NR 92 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-09730-5 J9 ISSUES CHILD FAM LIV PY 2009 BP 73 EP 96 DI 10.1007/978-0-387-09732-9_4 D2 10.1007/978-0-387-09732-9 PG 24 WC Substance Abuse; Psychology, Developmental; Social Work SC Substance Abuse; Psychology; Social Work GA BJW71 UT WOS:000267322800004 ER PT B AU Sloboda, Z AF Sloboda, Zili BE Leukefeld, CG Gullotta, TP StatonTindall, M TI School Prevention SO ADOLESCENT SUBSTANCE ABUSE: EVIDENCE-BASED APPROACHES TO PREVENTION AND TREATMENT SE Issues in Childrens and Families Lives LA English DT Article; Book Chapter ID ABUSE RESISTANCE EDUCATION; DRUG-ABUSE; FOLLOW-UP; SUBSTANCE-ABUSE; YOUTH SMOKING; PROJECT DARE; RANDOM NOTIFICATION; DISEASE PREVENTION; ALCOHOL-PROBLEMS; META-ANALYSIS C1 [Sloboda, Zili] Univ Akron, Inst Hlth & Social Policy, Akron, OH 44325 USA. [Sloboda, Zili] NIDA, Div Epidemiol & Prevent Res, Bethesda, MD USA. RP Sloboda, Z (reprint author), Univ Akron, Inst Hlth & Social Policy, Akron, OH 44325 USA. NR 83 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-09730-5 J9 ISSUES CHILD FAM LIV PY 2009 BP 191 EP 212 DI 10.1007/978-0-387-09732-9_10 D2 10.1007/978-0-387-09732-9 PG 22 WC Substance Abuse; Psychology, Developmental; Social Work SC Substance Abuse; Psychology; Social Work GA BJW71 UT WOS:000267322800010 ER PT B AU Staton-Tindall, M Gullotta, TP Stoops, WW Leukefeld, CG AF Staton-Tindall, Michele Gullotta, Thomas P. Stoops, William Walton Leukefeld, Carl G. BE Leukefeld, CG Gullotta, TP StatonTindall, M TI Epilogue: The Status of Knowledge Development and the Unknown SO ADOLESCENT SUBSTANCE ABUSE: EVIDENCE-BASED APPROACHES TO PREVENTION AND TREATMENT SE Issues in Childrens and Families Lives LA English DT Article; Book Chapter C1 [Staton-Tindall, Michele] Ctr Drug & Alcohol Res, Lexington, KY USA. [Leukefeld, Carl G.] NIH, Community Level Hlth Promot Study Sect, Bethesda, MD USA. [Leukefeld, Carl G.] NIDA, NIH, Hlth Serv Initial Review Grp, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-09730-5 J9 ISSUES CHILD FAM LIV PY 2009 BP 251 EP 256 D2 10.1007/978-0-387-09732-9 PG 6 WC Substance Abuse; Psychology, Developmental; Social Work SC Substance Abuse; Psychology; Social Work GA BJW71 UT WOS:000267322800012 ER PT S AU Elmore, SA Nyska, A Tischler, AS AF Elmore, Susan A. Nyska, Abraham Tischler, Arthur S. BE Harvey, PW Everett, DJ Springall, CJ TI The Adrenal Medulla as a Target Organ in Toxicologic Studies of Rats and Mice SO Adrenal Toxicology SE Target Organ Toxicology Series LA English DT Article; Book Chapter ID CHROMAFFIN CELL-PROLIFERATION; NERVE GROWTH-FACTOR; NEUROFIBROMATOSIS KNOCKOUT MICE; ENDOCRINE NEOPLASIA SYNDROME; MALE F344 RAT; PHEOCHROMOCYTOMA CELLS; PROGRAM EXPERIENCE; ANTIGEN RETRIEVAL; NEUROPEPTIDE-Y; GLAND C1 [Elmore, Susan A.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel. [Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA USA. RP Elmore, SA (reprint author), NIEHS, Cellular & Mol Pathol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 1073-0842 BN 978-1-4200-6130-7; 978-1-4200-6129-1 J9 TARG ORG T PY 2009 VL 26 BP 111 EP 138 PG 28 WC Endocrinology & Metabolism; Toxicology SC Endocrinology & Metabolism; Toxicology GA BC5QW UT WOS:000353499200005 ER PT S AU Gorbach, AM Wang, H Wiedenbeck, B Liu, W Smith, PD Elster, E AF Gorbach, A. M. Wang, H. Wiedenbeck, B. Liu, W. Smith, P. D. Elster, E. BE MahadevanJansen, A VoDinh, T Grundfest, WS TI Functional Assessment of Hand Vasculature Using Infrared and Laser Speckle Imaging SO ADVANCED BIOMEDICAL AND CLINICAL DIAGNOSTIC SYSTEMS VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Advanced Biomedical and Clinical Diagnostic Systems VII CY JAN 25-26, 2009 CL San Jose, CA SP SPIE DE Infrared imaging; laser speckle imaging; vasomotion; temperature regulation; human hand; arterio-venous anastomosis ID ARTERIOVENOUS ANASTOMOSES; HUMAN SKIN; REAL-TIME; BRAIN; OSCILLATIONS; DOPPLER AB To assess vascular responses of the human hand to inspiratory gasps and hand cooling, two imaging "remote sensing" instruments were utilized: 1) a high-resolution infrared (IR) imaging camera and 2) a full-field laser perfusion imager (FLPI). Data analysis was performed on the data sets collected simultaneously from both instruments. A non-localized drop of both FLPI and IR signals was observed at similar to 0.5-2.0 min after gasp onset. Spontaneous oscillations, much below the human cardiac and respiratory frequencies, were observed with both imagers. The dominant oscillations for both imaging modalities centered around 0.01Hz. Spectral frequencies, their power, and the duration of temperature oscillations (bursts) for different hand areas changed in time and were spatially heterogeneous. The highest spatial correlation between the two data sets was found between the mean IR derivative image and the mean original FLPI image for the baseline conditions. Heterogeneous images of the human hand were consistently detected non-invasively by both instruments. After cooling, a temperature elevation of similar to 0.5 degrees C was seen as a spotted pattern mainly in the thenar and hypothenar areas. A generalized increase in perfusion over the same areas was observed in FLPI images. Both IR and FLPI imagers sensitively identify vasoconstrictor responses induced by inspiratory gasp and hand cooling maneuvers. The specificity to physiological changes and high imaging rate for both instruments, coupled with the current ease of use of optical cameras in clinical settings, make the described combination of two instruments an ideal imaging approach to studying the dynamics of thermal and perfusion heterogeneity in human skin. C1 [Gorbach, A. M.; Wang, H.; Wiedenbeck, B.; Smith, P. D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Gorbach, AM (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. EM gorbach@helix.nih.gov NR 14 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7415-5 J9 PROC SPIE PY 2009 VL 7169 AR 716919 DI 10.1117/12.809589 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BSH07 UT WOS:000284395100029 ER PT S AU Rahman, M Pumphrey, JG Lipkowitz, S AF Rahman, Monzur Pumphrey, Janet G. Lipkowitz, Stanley BE VandeWoude, GF Klein, G TI The TRAIL to Targeted Therapy of Breast Cancer SO ADVANCES IN CANCER RESEARCH, VOL 103 SE Advances in Cancer Research LA English DT Review; Book Chapter ID APOPTOSIS-INDUCING LIGAND; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; RECEPTOR-ENHANCED CHEMOSENSITIVITY; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN MONOCLONAL-ANTIBODY; FADD-DEPENDENT APOPTOSIS; FAS-INDUCED APOPTOSIS; CELL-LINES; MEDIATED APOPTOSIS AB Breast cancers can be classified into those which express the estrogen (ER) and progesterone (PR) receptors, those with HER-2 amplification, and those without expression of ER, PR, or amplified HER-2 (referred to as triple-negative or basal-like breast cancer). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates apoptosis upon binding to its receptors in many tumor types and the ligand and agonist antibodies are currently being studied in patients in clinical phases I and II trials. Cell line studies suggest that many breast cancer cell lines are very resistant to TRAIL-induced apoptosis. However, recent data suggest that a subset of triple-negative/basal-like breast cancer cells is sensitive to TRAIL as a single agent. In addition, many studies have demonstrated that resistance to TRAIL-mediated apoptosis in breast cancer cells can be overcome by combinations of TRAIL with chemotherapy, radiation, and various targeted agents. This chapter will discuss the Current understanding of the mechanisms, which control TRAIL-mediated apoptosis in breast cancer cells. The prechnical data supporting the use of TRAIL ligands and agonistic antibodies alone and in combination in breast cancer will also be discussed. (C) 2009 Elsevier Inc. C1 [Rahman, Monzur] Johns Hopkins Med Inst, Dept Pediat Cardiol, Baltimore, MD 21205 USA. [Pumphrey, Janet G.; Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rahman, M (reprint author), Johns Hopkins Med Inst, Dept Pediat Cardiol, Baltimore, MD 21205 USA. FU Intramural NIH HHS [ZIA SC007263-17] NR 153 TC 38 Z9 43 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-374773-0 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2009 VL 103 BP 43 EP + DI 10.1016/S0065-230X(09)03003-6 PG 32 WC Oncology SC Oncology GA BME43 UT WOS:000272011900003 PM 19854352 ER PT S AU Coxon, B AF Coxon, Bruce BE Horton, D TI DEVELOPMENTS IN THE KARPLUS EQUATION AS THEY RELATE TO THE NMR COUPLING CONSTANTS OF CARBOHYDRATES SO ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL 62 SE Advances in Carbohydrate Chemistry and Biochemistry LA English DT Review; Book Chapter ID VICINAL PROTON-PROTON; NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS SIMULATIONS; AMINO SUGAR-DERIVATIVES; CONFORMATIONAL-ANALYSIS; ANGULAR-DEPENDENCE; C-13 NMR; ONE-BOND; C-C; SUBSTITUENT ELECTRONEGATIVITIES C1 NIH, Bethesda, MD 20892 USA. RP Coxon, B (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HD999999] NR 176 TC 27 Z9 27 U1 4 U2 31 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2318 BN 978-0-12-374743-3 J9 ADV CARBOHYD CHEM BI JI Adv. Carbohydr .Chem. Biochem. PY 2009 VL 62 BP 17 EP + DI 10.1016/S0065-2318(09)00003-1 PG 69 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA BJZ56 UT WOS:000267537500001 PM 19501704 ER PT S AU Shears, SB AF Shears, Stephen B. BE Weber, G Forrest Weber, CE Cocco, L TI Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1 SO ADVANCES IN ENZYME REGULATION, VOL 49 SE ADVANCES IN ENZYME REGULATION LA English DT Proceedings Paper CT 49th International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY SEP 22-23, 2008 CL Univ Bologna, Bologna, ITALY HO Univ Bologna ID ACTIVATED CHLORIDE CHANNELS; DEPENDENT PROTEIN-KINASE; PHOSPHOLIPASE-C ACTIVITY; MAMMARY-TUMOR CELLS; 1,3,4-TRISPHOSPHATE 5/6-KINASE; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; 1,3,4,6-TETRAKISPHOSPHATE 5-KINASE; COP9 SIGNALOSOME; EPITHELIAL-CELLS; CYSTIC-FIBROSIS C1 Natl Inst Environm Hlth Sci, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), Natl Inst Environm Hlth Sci, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU Intramural NIH HHS [Z01 ES080046-19] NR 79 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0065-2571 J9 ADV ENZYME REGUL PY 2009 VL 49 BP 87 EP 96 DI 10.1016/j.advenzreg.2008.12.008 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BKL62 UT WOS:000268442700008 PM 19200440 ER PT S AU Munford, R Lu, MF Varley, A AF Munford, Robert Lu, Mingfang Varley, Alan BE Alt, FW TI Kill the Bacteria ... and Also Their Messengers? SO ADVANCES IN IMMUNOLOGY, VOL 103 SE Advances in Immunology LA English DT Review; Book Chapter ID HUMAN ACYLOXYACYL HYDROLASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PERITONEAL INFLAMMATORY EXUDATE; FATTY ACYL AMIDASES; DEACYLATED LIPOPOLYSACCHARIDE; DICTYOSTELIUM-DISCOIDEUM; LIPID-A; EXTRACELLULAR COMPONENTS; SALMONELLA-TYPHIMURIUM; IMMUNE ACTIVATION AB We consider here a previously neglected aspect of recovery from infectious diseases: how animals dispose of the dead microbes in their tissues. For one of the most important disease-causing microorganisms, Gram-negative bacteria, there is now evidence that the host catabolism of a key microbial molecule is essential for full recovery. As might be expected, it is the same bacterial molecule that animals sense to detect the presence of Gram-negative bacteria in their tissues, the cell wall lipopolysaccharide (LPS). Here, we discuss current knowledge about LPS sensing with emphasis on the host enzyme that inactivates this microbial "messenger" molecule. We also consider the possibility that the rate at which stimulatory microbial molecules undergo inactivation may influence the duration and severity of diseases caused by other infectious agents. C1 [Munford, Robert; Lu, Mingfang; Varley, Alan] UT SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. [Munford, Robert; Lu, Mingfang; Varley, Alan] UT SW Med Ctr, Dept Microbiol, Dallas, TX USA. [Munford, Robert; Lu, Mingfang] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Munford, R (reprint author), UT SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. FU NIAID NIH HHS [R01 AI018188, R56 AI018188, R37 AI018188, AI18188, R01 AI018188-28] NR 64 TC 9 Z9 11 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-374832-4 J9 ADV IMMUNOL JI Adv.Immunol. PY 2009 VL 103 BP 29 EP 48 DI 10.1016/S0065-2776(09)03002-8 PG 20 WC Immunology SC Immunology GA BLU02 UT WOS:000271012100002 PM 19755182 ER PT S AU Ribeiro, JMC Arca, B AF Ribeiro, Jose M. C. Arca, Bruno BE Simpson, SJ Casas, J TI From Sialomes to the Sialoverse: An Insight into Salivary Potion of Blood-Feeding Insects SO ADVANCES IN INSECT PHYSIOLOGY, VOL 37: PHYSIOLOGY OF HUMAN AND ANIMAL DISEASE VECTORS SE Advances in Insect Physiology LA English DT Review; Book Chapter ID ADULT FEMALE MOSQUITO; FLY LUTZOMYIA-LONGIPALPIS; BUG RHODNIUS-PROLIXUS; PLATELET-AGGREGATION INHIBITOR; GLOSSINA-MORSITANS-MORSITANS; VECTOR ANOPHELES-GAMBIAE; HORIZONTAL GENE-TRANSFER; RICH SECRETORY PROTEINS; PHLEBOTOMINE SAND FLIES; YELLOW-FEVER MOSQUITO C1 [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Arca, Bruno] Univ Naples Federico II, Dept Struct & Funct Biol, Naples, Italy. [Arca, Bruno] Univ Roma La Sapienza, Dept Publ Hlth, Parasitol Sect, Rome, Italy. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Rm 2E-32D, Rockville, MD 20852 USA. OI Arca, Bruno/0000-0002-4029-0984; Ribeiro, Jose/0000-0002-9107-0818 NR 317 TC 49 Z9 49 U1 2 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2806 BN 978-0-12-374829-4 J9 ADV INSECT PHYSIOL JI Adv. Insect Physiol. PY 2009 VL 37 BP 59 EP + DI 10.1016/S0065-2806(09)37002-2 PG 61 WC Entomology SC Entomology GA BMN60 UT WOS:000272973600003 ER PT J AU Finkel, T AF Finkel, Toren TI Breathing lessons: Tor tackles the mitochondria SO AGING-US LA English DT Article ID CHRONOLOGICAL LIFE-SPAN; NITRIC-OXIDE; PATHWAY; SUPERCOMPLEXES; BIOGENESIS; EXPRESSION; RAPAMYCIN; YEAST C1 NIH, Translat Med Branch, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Translat Med Branch, Bldg 10 CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 14 TC 3 Z9 3 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2009 VL 1 IS 1 BP 9 EP 11 PG 3 WC Cell Biology SC Cell Biology GA 579DK UT WOS:000276347200003 PM 20157592 ER PT J AU McCord, RA Michishita, E Hong, T Berber, E Boxer, LD Kusumoto, R Guan, SH Shi, XB Gozani, O Burlingame, AL Bohr, VA Chua, KF AF McCord, Ronald A. Michishita, Eriko Hong, Tao Berber, Elisabeth Boxer, Lisa D. Kusumoto, Rika Guan, Shenheng Shi, Xiaobing Gozani, Or Burlingame, Alma L. Bohr, Vilhelm A. Chua, Katrin F. TI SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair SO AGING-US LA English DT Article DE Sir2; SIRT6; genomic stability; DNA repair; DNA damage; aging ID SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; CALORIE RESTRICTION; SIR2-LIKE PROTEINS; GENE-EXPRESSION; LIFE-SPAN; DEACETYLASE; SIRTUINS; POLYMERASE; LONGEVITY AB The Sir2 chromatin regulatory factor links maintenance of genomic stability to life span extension in yeast. The mammalian Sir2 family member SIRT6 has been proposed to have analogous functions, because SIRT6-deficiency leads to shortened life span and an aging-like degenerative phenotype in mice, and SIRT6 knockout cells exhibit genomic instability and DNA damage hypersensitivity. However, the molecular mechanisms underlying these defects are not fully understood. Here, we show that SIRT6 forms a macromolecular complex with the DNA double-strand break (DSB) repair factor DNA-PK (DNA-dependent protein kinase) and promotes DNA DSB repair. In response to DSBs, SIRT6 associates dynamically with chromatin and is necessary for an acute decrease in global cellular acetylation levels on histone H3 Lysine 9. Moreover, SIRT6 is required for mobilization of the DNA-PK catalytic subunit (DNA-PKcs) to chromatin in response to DNA damage and stabilizes DNA-PKcs at chromatin adjacent to an induced site-specific DSB. Abrogation of these SIRT6 activities leads to impaired resolution of DSBs. Together, these findings elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair factor with chromatin impacts on the efficiency of repair, and establish a link between chromatin regulation, DNA repair, and a mammalian Sir2 factor. C1 [McCord, Ronald A.; Michishita, Eriko; Hong, Tao; Berber, Elisabeth; Boxer, Lisa D.; Chua, Katrin F.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [McCord, Ronald A.; Michishita, Eriko; Hong, Tao; Berber, Elisabeth; Boxer, Lisa D.; Chua, Katrin F.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA 94304 USA. [Kusumoto, Rika; Bohr, Vilhelm A.] NIA, Dept Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Guan, Shenheng; Burlingame, Alma L.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Guan, Shenheng; Burlingame, Alma L.] Univ Calif San Francisco, Mass Spectrometry Facil, San Francisco, CA 94143 USA. [Shi, Xiaobing; Gozani, Or] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. RP Chua, KF (reprint author), Stanford Med Sch, Dept Med, 300 Pasteur Dr, Palo Alto, CA 94305 USA. EM kfchua@stanford.edu FU NIH; Department of Veterans Affairs Merit Review; Ellison Medical Foundation/American Federation for Aging Research; National Institute on Aging/NIH intramural program; Searle Scholars Program FX R. A. M., T. H., E. M., and E. B. contributed independently to this work. We thank K. Meek for Flag-DNA-PKcs cDNA, and J.C. Barrett, Brian North, and Eric Verdin for SIRT reagents, and Michael Kastan for I-PpoI reagents. This work was supported by grants from the NIH (to K. F. C., R. A. M., T. H., O.G., and A. L. B), Department of Veterans Affairs Merit Review (K. F. C.), the Ellison Medical Foundation/American Federation for Aging Research (K. F. C. and E. M.), and funds from the National Institute on Aging/NIH intramural program (R. K. and V. A. B.). K. F. C. is a Paul Beeson Scholar and an Ellison Medical Foundation New Scholar in Aging. O.G. is a recipient of awards from the Searle Scholars Program. NR 38 TC 141 Z9 152 U1 1 U2 12 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2009 VL 1 IS 1 BP 109 EP 121 PG 13 WC Cell Biology SC Cell Biology GA 579DK UT WOS:000276347200013 PM 20157594 ER PT J AU Chander, G Himelhoch, S Fleishman, JA Hellinger, J Gaist, P Moore, RD Gebo, KA AF Chander, Geetanjali Himelhoch, Seth Fleishman, John A. Hellinger, James Gaist, Paul Moore, Richard D. Gebo, Kelly A. TI HAART receipt and viral suppression among HIV-infected patients with co-occurring mental illness and illicit drug use SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; mental health; illicit drug use; viral suppression ID ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE USE DISORDERS; VIROLOGICAL RESPONSE; ABUSE; ADHERENCE; SCHIZOPHRENIA; DEPRESSION; ASSOCIATION; COMORBIDITY; MANAGEMENT AB Mental illness (MI) and illicit drug use (DU) frequently co-occur. We sought to determine the individual and combined effects of MI and DU on highly active antiretroviral therapy (HAART) receipt and HIV-RNA suppression among individuals engaged in HIV care. Using 2004 data from the HIV Research Network (HIVRN), we performed a cross-sectional study of HIV-infected patients followed at seven primary care sites. Outcomes of interest were HAART receipt and virological suppression, defined as an HIV-RNA 400 copies/ml. Independent variables of interest were: (1) MI/DU; (2) DU only; (3) MI only; and (4) Neither. We used chi-squared analysis for comparison of categorical variables, and logistic regression to adjust for age, race, sex, frequency of outpatient visits, years in clinical care, CD4 nadir, and study site. During 2004, 10,284 individuals in the HIVRN were either on HAART or HAART eligible defined as a CD4 cell count 350. Nearly half had neither MI nor DU (41%), 22% MI only, 15% DU only, and 22% both MI and DU. In multivariate analysis, co-occurring MI/DU was associated with the lowest odds of HAART receipt (Adjusted Odds Ratio: 0.63 (95% CI: (0.55-0.72]), followed by those with DU only (0.75(0.63-0.87)), compared to those with neither. Among those on HAART, concurrent MI/DU (0.66 (0.58-0.75)), DU only (0.77 (0.67-0.88)), were also associated with a decreased odds of HIV-RNA suppression compared to those with neither. MI only was not associated with a statistically significant decrease in HAART receipt (0.93(0.81-1.07)) or viral suppression (0.93 (0.82-1.05)) compared to those with neither. Post-estimation testing revealed a significant difference between those with MI/DU and DU only, and MI/DU and MI only. Co-occurring MI and DU is associated with lower HAART receipt and viral suppression compared to individuals with either MI or DU or neither. Integrating HIV, substance abuse, and mental healthcare may improve outcomes in this population. C1 [Chander, Geetanjali; Moore, Richard D.; Gebo, Kelly A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Himelhoch, Seth] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Fleishman, John A.] Agcy Healthcare Res & Qual, Rockville, MD USA. [Hellinger, James] Community Med Alliance, Boston, MA USA. [Gaist, Paul] NIH, Bethesda, MD 20892 USA. [Hellinger, James] Tufts Univ New England Med Ctr, Boston, MA USA. RP Chander, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. EM GChande1@jhmi.edu FU NIAAA NIH HHS [K23 AA 015313, K23 AA015313, K23 AA015313-05]; NIAID NIH HHS [U01 AI069918]; NIDA NIH HHS [K23-DA 019820, K23 DA000523, K23 DA019820, K23-DA 00523, K24 DA 00432, K24 DA000432] NR 32 TC 20 Z9 20 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 EI 1360-0451 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2009 VL 21 IS 5 BP 655 EP 663 AR PII 911200181 DI 10.1080/09540120802459762 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 445WB UT WOS:000266081100015 PM 19444675 ER PT J AU Imamichi, H Koita, O Dabitao, D Dao, S Ibrah, M Sogoba, D Dewar, RL Berg, SC Jiang, MK Parta, M Washington, JA Polis, MA Lane, HC Tounkara, A AF Imamichi, Hiromi Koita, Ousmane Dabitao, Djeneba Dao, Sounkalo Ibrah, Mahamadou Sogoba, Dramane Dewar, Robin L. Berg, Steve C. Jiang, Min-Kang Parta, Mark Washington, Janice A. Polis, Michael A. Lane, H. Clifford Tounkara, Anatole CA Project Serefo TI Identification and Characterization of CRF02_AG, CRF06_cpx, and CRF09_cpx Recombinant Subtypes in Mali, West Africa SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV TYPE-1 STRAINS; GENETIC DIVERSITY; CAMEROON; FORM; PREDOMINANCE; INFECTIONS; LINEAGES; COMPLEX; NIGERIA; SPREAD AB Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to cocirculate in Africa. In West Africa, the high prevalence of CRF02_AG, and cocirculation of subtype A, CRF01_AE, CRF06_cpx, and other complex intersubtype recombinants has been well documented. Mali, situated in the heart of West Africa, is likely to be affected by the spread of recombinant subtypes. However, the dynamics of the spread of HIV-1 recombinant subtypes as well as nonrecombinant HIV-1 group M subtypes in this area have not been systematically assessed. Herein, we undertook genetic analyses on full-length env sequences derived from HIV-1-infected individuals living in the capital city of Mali, Bamako. Of 23 samples we examined, 16 were classified as CRF02_AG and three had a subsubtype A3. Among the remaining HIV-1 strains, CRF06_cpx and CRF09_cpx were each found in two patients. Comparison of phylogenies for six matched pol and full-length env sequences revealed that two strains had discordant subtype/CRF designations between the pol and env regions: one had A3 pol CRF02_AG env and the other had CRF02_AG pol A3 env. Taken together, our study demonstrated the high prevalence of CRF02_AG and complexity of circulating HIV-1 strains in Mali. It also provided evidence of ongoing virus evolution of CRF02_AG, as illustrated by the emergence of more complex CRF02_AG/A3 intersubtype recombinants in this area. C1 [Imamichi, Hiromi] NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. [Koita, Ousmane; Dabitao, Djeneba; Dao, Sounkalo; Ibrah, Mahamadou; Sogoba, Dramane; Tounkara, Anatole] Univ Bamako, Fac Med Pharm & Odontostomatol, Ctr Res & Training HIV & TB, Bamako, Mali. [Washington, Janice A.; Polis, Michael A.; Lane, H. Clifford] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. RP Imamichi, H (reprint author), NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, POB B,Bldg 550,Room 201-A, Ft Detrick, MD 21702 USA. EM himamichi@nih.gov OI Polis, Michael/0000-0002-9151-2268 FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; National Institute of Allergy and Infectious Disease FX The authors thank Julia A. Metcalf, Jeanne Warfield, and Jennifer L. Imes for arrangement of blood specimens. This project has been funded in whole or in part with federal funds from the National Cancer Institute, 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. This project was supported in part by the National Institute of Allergy and Infectious Disease, National Institutes of Health, under contract N01-CO-12400. NR 32 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2009 VL 25 IS 1 BP 45 EP 55 DI 10.1089/aid.2008.0111 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 402GZ UT WOS:000263003500006 PM 19182920 ER PT J AU Li, Q Okada, Y Marczak, E Wilson, WA Lazarus, LH Swartzwelder, HS AF Li, Qiang Okada, Yoshio Marczak, Ewa Wilson, Wilkie A. Lazarus, Lawrence H. Swartzwelder, H. S. TI The Novel mu-Opioid Receptor Antagonist, [N-Allyl-Dmt(1)]Endomorphin-2, Attenuates the Enhancement of GABAergic Neurotransmission by Ethanol SO ALCOHOL AND ALCOHOLISM LA English DT Article ID NUCLEUS-ACCUMBENS; DEVELOPMENTAL DIFFERENCES; SYNAPTIC-TRANSMISSION; ALCOHOL-DRINKING; OPIATE RECEPTOR; HIPPOCAMPAL CA1; BETA-ENDORPHIN; MEDIATED IPSCS; KNOCKOUT MICE; IN-VITRO AB Aims: We investigated the effects of [N-allyl-Dmt(1)]endomorphin-2 (TL-319), a novel and highly potent mu-opioid receptor antagonist, on ethanol (EtOH)-induced enhancement of GABA(A) receptor-mediated synaptic activity in the hippocampus. Methods: Evoked and spontaneous inhibitory postsynaptic currents (eIPSCs and sIPSCs) were isolated from CA1 pyramidal cells from brain slices of male rats using whole-cell patch-clamp techniques. Results: TL-319 had no effect on the baseline amplitude of eIPSCs or the frequency of sIPSCs. However, it induced a dose-dependent suppression of an ethanol-induced increase of sIPSC frequency with full reversal at concentrations of 500 nM and higher. The non-specific competitive opioid receptor antagonist naltrexone also suppressed EtOH-induced increases in sIPSC frequency but only at a concentration of 60 mu M. Conclusion: These data indicate that blockade of mu-opioid receptors by low concentrations of [N-allyl-Dmt(1)]endomorphin-2 can reverse ethanol-induced increases in GABAergic neurotransmission and possibly alter its anxiolytic or sedative effects. This suggests the possibility that high potency opioid antagonists may emerge as possible candidate compounds for the treatment of ethanol addiction. C1 [Swartzwelder, H. S.] Duke Univ, Med Ctr, VA Med Ctr, Dept Psychiat, Durham, NC 27705 USA. [Li, Qiang; Wilson, Wilkie A.; Swartzwelder, H. S.] Vet Adm Med Ctr, Neurobiol Res Lab, Durham, NC 27705 USA. [Okada, Yoshio] Kobe Gakuin Univ, Fac Pharmaceut Sci, Dept Med Chem, Nishi Ku, Kobe, Hyogo 6512180, Japan. [Okada, Yoshio] Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. [Marczak, Ewa; Lazarus, Lawrence H.] NIEHS, Med Chem Grp, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Wilson, Wilkie A.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RP Swartzwelder, HS (reprint author), Duke Univ, Med Ctr, VA Med Ctr, Dept Psychiat, Room 24,Bldg 16,508 Fulton St, Durham, NC 27705 USA. EM HSS@duke.edu FU IMR; NIAAA [01489]; NIH; NIEHS FX This work was supported by IMR grant to Q. L. and NIAAA grant AA-01489 to H. S. S., by VA senior Research Career Scientist Awards to H. S. S. and W. A. W., and in part by the Intramural Research Program of the NIH and NIEHS. NR 46 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2009 VL 44 IS 1 BP 13 EP 19 DI 10.1093/alcalc/agn085 PG 7 WC Substance Abuse SC Substance Abuse GA 386ON UT WOS:000261892600003 PM 18971291 ER PT J AU Dawson, DA Li, TK Chou, SP Grant, BF AF Dawson, Deborah A. Li, Ting-Kai Chou, S. Patricia Grant, Bridget F. TI Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval dagger SO ALCOHOL AND ALCOHOLISM LA English DT Article ID PRIMARY-CARE PATIENTS; GENERAL-POPULATION SAMPLE; DSM-IV ALCOHOL; HEALTH-STATUS; PSYCHIATRIC COMORBIDITY; SCHEDULE AUDADIS; RELIABILITY; DEPENDENCE; VALIDITY; CRITERIA AB Aims: The aim of this study was to investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general US population sample. Methods: The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n = 22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders. Results: Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL. Conclusions: These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior. C1 [Dawson, Deborah A.; Chou, S. Patricia; Grant, Bridget F.] NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Li, Ting-Kai] NIAAA, Off Director, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3071,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov FU Intramural NIH HHS NR 50 TC 33 Z9 35 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2009 VL 44 IS 1 BP 84 EP 92 DI 10.1093/alcalc/agn094 PG 9 WC Substance Abuse SC Substance Abuse GA 386ON UT WOS:000261892600013 PM 19042925 ER PT J AU Masten, AS Faden, VB Zucker, RA Spear, LP AF Masten, Ann S. Faden, Vivian B. Zucker, Robert A. Spear, Linda P. TI A Developmental Perspective on Underage Alcohol Use SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Underage drinking; child; adolescent; alcohol and other drug (AOD) use, abuse, and dependence; AOD use initiation; age of AOD use onset; growth and development; biological development; psychological development; developmental psychopathology; risk and protective factors; genetic factors; environmental factors; AOD effects and consequences ID USE DISORDERS; ADULT RATS; ETHANOL-CONSUMPTION; HIPPOCAMPAL VOLUME; ADOLESCENT BRAIN; UNITED-STATES; SUBSTANCE USE; FEMALE RATS; DRINKING; MODEL AB Underage alcohol use can be viewed as a developmental phenomenon because many kinds of developmental changes and expectations appear to influence this behavior and also because it has consequences for development. Data on alcohol use, abuse, and dependence show clear age-related patterns. Moreover, many of the effects that alcohol use has on the drinker, in both the short and long term, depend on the developmental timing of alcohol use or exposure. Finally, many developmental connections have been observed in the risk and protective factors that predict the likelihood of problem alcohol use in young people. Therefore, efforts to understand and address underage drinking would benefit from a developmental perspective, and the general principles of developmental psychopathology offer a useful conceptual framework for research and prevention concerned with underage drinking. C1 [Masten, Ann S.] Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. [Faden, Vivian B.] NIAAA, Off Sci Policy & Commun, Bethesda, MD USA. [Zucker, Robert A.] Univ Michigan, Dept Psychiat & Psychol, Ann Arbor, MI 48109 USA. [Zucker, Robert A.] Univ Michigan, Addict Res Ctr, Ann Arbor, MI 48109 USA. [Spear, Linda P.] SUNY Binghamton, Dept Psychol, Binghamton, NY USA. RP Masten, AS (reprint author), Univ Minnesota, Inst Child Dev, 51 E River Rd, Minneapolis, MN 55455 USA. RI Masten, Ann/E-7091-2011; OI Masten, Ann/0000-0003-2871-7508 NR 63 TC 36 Z9 37 U1 8 U2 24 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2009 VL 32 IS 1 BP 3 EP 15 PG 13 WC Substance Abuse SC Substance Abuse GA 499AI UT WOS:000270188200001 PM 23104443 ER PT J AU Zucker, RA Donovan, JE Masten, AS Mattson, ME Moss, HB AF Zucker, Robert A. Donovan, John E. Masten, Ann S. Mattson, Margaret E. Moss, Howard B. TI Developmental Processes and Mechanisms Ages 0-10 SO ALCOHOL RESEARCH & HEALTH LA English DT Review DE Children; youth; growth and development; psychological development; underage drinking; alcohol and other drug (AOD) use initiation; AOD use behavior; risk factors; protective factors; environmental factors; social-environmental factors; predictive factors; early AOD use onset; AOD expectancies ID PRENATAL ALCOHOL EXPOSURE; ILLICIT DRUG-USE; ADOLESCENT SUBSTANCE USE; AGE-OF-ONSET; YOUNG ADULTHOOD; RISK-FACTORS; PROBLEM DRINKING; USE DISORDERS; FOLLOW-UP; DEPRESSIVE SYMPTOMS AB Little information is available on alcohol use in children up to age 10, although rates appear to be low. This age-group is not without risk, however. In fact, numerous nonspecific and specific risk factors for subsequent alcohol use are prevalent in childhood. Alcohol-nonspecific risk factors include externalizing and internalizing behaviors, as well as environmental and social factors (e.g., stress, physical abuse, or other aspects of social interaction). Nonspecific childhood factors (i.e., predictors) are being identified to target specific population subgroups for preventive interventions. These efforts have identified a variety of predictors of drinking onset during childhood or early adolescence that predict adolescent and young-adult problem drinking, as well as adult alcohol use and alcohol use disorders. Alcohol-specific risk factors also are being identified, including children's beliefs and expectancies about alcohol, as well as childhood social contexts (e.g., modeling of alcohol use by parents, portrayal of alcohol use in the mass media, and growing up in a family with an alcoholic family member). Together, these specific and nonspecific influences play a heavy role in determining a child risk of or resilience to later alcohol use and related problems. C1 [Zucker, Robert A.] Univ Michigan, Dept Psychiat & Psychol, Ann Arbor, MI 48109 USA. [Zucker, Robert A.] Univ Michigan, Addict Res Ctr, Ann Arbor, MI 48109 USA. [Donovan, John E.] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Masten, Ann S.] Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. [Mattson, Margaret E.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA. RP Zucker, RA (reprint author), Univ Michigan, Dept Psychiat & Psychol, Ann Arbor, MI 48109 USA. OI Masten, Ann/0000-0003-2871-7508 FU NIAAA NIH HHS [R01 AA012342] NR 102 TC 11 Z9 11 U1 8 U2 24 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2009 VL 32 IS 1 BP 16 EP 29 PG 14 WC Substance Abuse SC Substance Abuse GA 499AI UT WOS:000270188200002 PM 23104444 ER PT J AU Windle, M Spear, LP Fuligni, AJ Angold, A Brown, JD Pine, D Smith, GT Giedd, J Dahl, RE AF Windle, Michael Spear, Linda P. Fuligni, Andrew J. Angold, Adrian Brown, Jane D. Pine, Daniel Smith, Greg T. Giedd, Jay Dahl, Ronald E. TI Transitions Into Underage and Problem Drinking Summary of Developmental Processes and Mechanisms: Ages 10-15 SO ALCOHOL RESEARCH & HEALTH LA English DT Review DE Preadolescent; adolescent; puberty; underage drinking; problematic drinking; risk factors; protective factors; alcohol and other drug (AOD) use initiation; AOD use behavior; growth and development; biological development; psychological development ID ELEMENTARY-SCHOOL-CHILDREN; EARLY ALCOHOL-USE; ADULT RATS; EARLY ADOLESCENCE; ETHANOL-CONSUMPTION; SOCIAL FACILITATION; SEXUAL-MATURATION; BRAIN-DEVELOPMENT; SUBSTANCE-ABUSE; FEMALE RATS AB Adolescents ages 10-15 experience dramatic changes in their biological cognitive, emotional, and social development as well as in their physical and social environments. These include the physiological and psychological changes associated with puberty; further development of the brain; changes in family, peer, and romantic relationships; and exposure to new societal and cultural influences. During this period, many adolescents also begin to use alcohol. Alcohol use during adolescence has adverse effects on the body and increases the risk of alcohol dependence later in life. To better understand why some children drink whereas others do not, researchers are examining nonspecific and alcohol-specific factors that put adolescents at risk for, or which protect them from, early alcohol use and its associated problems. Nonspecific risk factors include certain temperamental and personality traits, family factors, and nonnormative development. Examples of nonspecific protective factors include certain temperamental characteristics, religiosity, and parenting factors (e.g., parental nurturance and monitoring). Among the most influential alcohol-specific risk and protective factors are a family history of alcoholism and the influences of siblings and peers, all of which shape all adolescents expectancies about the effects of alcohol, which in turn help determine alcohol use behaviors. C1 [Windle, Michael] Emory Univ, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. [Spear, Linda P.] SUNY Binghamton, Dept Psychol, Binghamton, NY USA. [Fuligni, Andrew J.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Angold, Adrian] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Brown, Jane D.] Univ N Carolina, Sch Journalism & Mass Commun, Chapel Hill, NC USA. [Pine, Daniel] NIMH, Sect Dev & Affect Neurosci, Child Psychiat Branch, Bethesda, MD 20892 USA. [Smith, Greg T.] Univ Kentucky, Dept Psychol, Lexington, KY 40506 USA. [Giedd, Jay] NIMH, Unit Brain Imaging, Child Psychiat Branch, Bethesda, MD 20892 USA. [Dahl, Ronald E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Dahl, Ronald E.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA USA. RP Windle, M (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. RI Giedd, Jay/A-3080-2008; Price, Katie/H-1931-2012; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 107 TC 21 Z9 22 U1 14 U2 34 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2009 VL 32 IS 1 BP 30 EP 40 PG 11 WC Substance Abuse SC Substance Abuse GA 499AI UT WOS:000270188200003 PM 23104445 ER PT J AU Brown, SA Mcgue, M Maggs, J Schulenberg, J Hingson, R Swartzwelder, S Martin, C Chung, T Tapert, SF Sher, K Winters, KC Lowman, C Murphy, S AF Brown, Sandra A. McGue, Matthew Maggs, Jennifer Schulenberg, John Hingson, Ralph Swartzwelder, Scott Martin, Christopher Chung, Tammy Tapert, Susan F. Sher, Kenneth Winters, Ken C. Lowman, Cherry Murphy, Stacia TI Underage Alcohol Use Summary of Developmental Processes and Mechanisms: Ages 16-20 SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Adolescence; underage drinking; adolescent drinking; drinking behavior; binge drinking; heavy drinking; alcohol and other drug effects and consequences; risk and protective factors; brain; biological development; cognitive development; emotional development; socialization; decisionmaking ID SUBSTANCE-USE DISORDERS; VISUOSPATIAL WORKING-MEMORY; BINGE DRINKING TRAJECTORIES; ADOLESCENT ALCOHOL; DECISION-MAKING; PSYCHIATRIC COMORBIDITY; RISK-TAKING; ETHANOL EXPOSURE; EARLY ADULTHOOD; CHILDHOOD AB Late adolescence (i.e., the age-group between 16 and 20 years) is characterized by significant changes in neurological and cognitive processes, behavioral and social functioning, and relational and physical contexts as the individual moves toward adulthood. In this age-group, major role transitions affect almost every aspect of life. Moreover, brain development continues-and with it the development of cognitive functions, working memory, emotional and behavioral self-regulation, and decisionmaking. The adolescents social and emotional development also continues to evolve, affecting interactions with parents, siblings, peers, and first romantic relationships. All of these changes impact drinking behavior during late adolescence, and, in fact, alcohol use, binge drinking, and heavy drinking are particularly prevalent in youth ages 16-20. Determining the common trajectories of drinking behavior in this age-group is important for understanding bow adolescent alcohol rise helps shape adult outcomes and for identifying risk and protective factors. It also is important to study the short- and long-term consequences of adolescent alcohol use and abuse, including alcohol effects oil the developing adolescent brain and accomplishment of important developmental tasks of this age. C1 [Brown, Sandra A.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92103 USA. [Brown, Sandra A.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Brown, Sandra A.] San Diego Vet Affairs Hlth Care Syst, San Diego, CA USA. [McGue, Matthew] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Maggs, Jennifer] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. [Schulenberg, John] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Hingson, Ralph] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. [Swartzwelder, Scott] Duke Univ, Dept Psychol, Durham, NC 27706 USA. [Martin, Christopher; Chung, Tammy] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Tapert, Susan F.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Sher, Kenneth] Univ Missouri, Dept Psychol Studies, Columbia, MO USA. [Winters, Ken C.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Lowman, Cherry] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA. [Murphy, Stacia] NIAAA, St Louis, MO USA. RP Brown, SA (reprint author), Univ Calif San Diego, Dept Psychol, San Diego, CA 92103 USA. RI Schulenberg, John/A-2212-2008; Chung, Tammy/B-9712-2017 OI Schulenberg, John/0000-0003-2129-8486; Chung, Tammy/0000-0002-1527-2792 NR 83 TC 19 Z9 19 U1 11 U2 30 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2009 VL 32 IS 1 BP 41 EP 52 PG 12 WC Substance Abuse SC Substance Abuse GA 499AI UT WOS:000270188200004 PM 23104446 ER PT J AU Sjostrand, M Bossios, A Radinger, M Lotvall, J AF Sjostrand, M. Bossios, A. Radinger, M. Lotvall, J. TI Interleukin-33 expression in a mouse model of allergic airway inflammation SO ALLERGY LA English DT Meeting Abstract CT 28th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2009 CL Warsaw, POLAND SP European Acad Allergy & Clin Immunol C1 [Sjostrand, M.; Bossios, A.; Lotvall, J.] Univ Gothenburg, Dept Internal Med, Lung Pharmacol Grp, Gothenburg, Sweden. [Radinger, M.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 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 0105-4538 J9 ALLERGY JI Allergy PY 2009 VL 64 MA 315 BP 139 EP 139 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 447DJ UT WOS:000266171500305 ER PT J AU Ni, H Coady, S Rosamond, W Folsom, AR Chambless, L Russell, SD Sorlie, PD AF Ni, Hanyu Coady, Sean Rosamond, Wayne Folsom, Aaron R. Chambless, Lloyd Russell, Stuart D. Sorlie, Paul D. TI Trends from 1987 to 2004 in sadden death due to coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study SO AMERICAN HEART JOURNAL LA English DT Article ID SUDDEN CARDIAC DEATH; UNITED-STATES; SURVEILLANCE; MORTALITY AB Background Few data are available on the secular changes in sudden coronary heart disease (CHID) death in US communities. Methods We examined trends in sudden CHID death from 1987 to 2004, using data from the Atherosclerosis Risk in Communities (ARIC) study. Sudden CHID deaths in residents of 4 communities aged 35 to 74 years were ascertained using multiple sources such as death certificates, informant and coroner interviews, and physician adjudications. Poisson regression was used to assess the trends for the 6 periods: 1987 to 1989, 1990 to 1992, 1993 to 1995, 1996 to 1998, 1999 to 2001, 2002 to 2004, after adjusting for demographic factors. Results Overall, 32.6% of CHID deaths were sudden, occurring within an hour after the onset of symptoms, 63.5% of which had no prior diagnosis of CHID. For women, the rate declined by 40% (P = .059) for sudden deaths with CHID history, 27% (P = .067) for those without CHID history, and 39% (P < .001) for nonsudden CHID deaths. The trends did not differ by community. For men, the trends differed by community for sudden deaths with and without CHID history (Ps for the interaction = .019 and .009, respectively) but not for nonsudden CHID death (P for the interaction = .10). For all communities combined, the decline in men was greatest for sudden deaths with CHID history (by 58%, P < .001), followed by nonsudden CHID deaths (by 39%, P < .001) and sudden deaths without CHID history (by 31%, P = .002). However, the proportion of CHID deaths that were sudden had remained stable over time. Conclusion Although the rate of sudden CHID deaths, with and without CHD history, declined overtime, the trend pattern may differ by community and gender. (Am Heart J 2009;157:46-52.) C1 [Ni, Hanyu; Coady, Sean; Sorlie, Paul D.] NHLBI, NIH, Bethesda, MD 20892 USA. [Rosamond, Wayne; Chambless, Lloyd] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Russell, Stuart D.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. RP Ni, H (reprint author), Rockledge 2,Room 10186,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM nihanyu@mail.nih.gov 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] FX The ARIC study is carried out as 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. The authors thank the staff and participants of the ARIC study for their important contributions. NR 14 TC 41 Z9 43 U1 0 U2 2 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 JAN PY 2009 VL 157 IS 1 BP 46 EP 52 DI 10.1016/j.ahj.2008.08.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 385ZI UT WOS:000261851700006 PM 19081395 ER PT J AU Wendler, D AF Wendler, David TI Must Research Participants Understand Randomization? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE randomization; informed consent; research; understanding; interests; clinical judgment ID INFORMED-CONSENT; CLINICAL-TRIALS; RANDOM ALLOCATION; CANCER; COMMUNICATION; PERSPECTIVES; SENSE AB In standard medical care, physicians select treatments for patients based on clinical judgment, considering which treatment is best for the individual patient, given the patient's history and circumstances. In contrast, investigators conducting randomized clinical trials select treatments for participants based on a random selection process. Because this process represents a significant departure from the norms of standard medical care, it is widely assumed that potential research participants must understand randomization to give valid informed consent. This assumption, together with data that many research participants do not understand randomization, implies that randomized clinical trials often fail to obtain adequately informed consent. Before accepting this conclusion, and before initiating extensive efforts to improve research participants' understanding of randomization, we should assess the plausible, but rarely analyzed assumption that participants need to understand randomization to give valid informed consent for randomized clinical trials. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 21 TC 9 Z9 9 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 2 BP 3 EP 8 AR PII 908348759 DI 10.1080/15265160802654145 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 400ZG UT WOS:000262907300002 PM 19180378 ER PT J AU Danis, M Hurst, SA AF Danis, Marion Hurst, Samia A. TI Developing the Capacity of Ethics Consultants to Promote Just Resource Allocation SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID HEALTH-CARE C1 [Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Hurst, Samia A.] Univ Geneva, Sch Med, CH-1211 Geneva 4, Switzerland. RP Danis, M (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM mdanis@nih.gov RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 FU Intramural NIH HHS [Z01 CL010518-07] NR 13 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 4 BP 37 EP 39 DI 10.1080/15265160802716803 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 425MM UT WOS:000264641800011 PM 19326310 ER PT J AU Miller, FG Colloca, L AF Miller, Franklin G. Colloca, Luana TI The Legitimacy of Placebo Treatments in Clinical Practice: Evidence and Ethics SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE Placebo treatments; Clinical practice; Healing; Bioethics; Informed consent; Deception ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; IRRITABLE-BOWEL-SYNDROME; OPEN-LABEL USE; ALTERNATIVE MEDICINE; QUESTIONNAIRE SURVEY; COMPARING PLACEBO; NO TREATMENT; ACUPUNCTURE; MIGRAINE AB Physicians commonly recommend 'placebo treatments', which are not believed to have specific efficacy for the patient's condition. Motivations for placebo treatments include complying with patient expectations and promoting a placebo effect. In this article, we focus on two key empirical questions that must be addressed in order to assess the ethical legitimacy of placebo treatments in clinical practice: 1) do placebo treatments have the potential to produce clinically significant benefit? and 2) can placebo treatments be effective in promoting a therapeutic placebo response without the use of deception? We examine evidence from clinical trials and laboratory experiments bearing on these two questions. The conclusion is reached that based on currently available evidence, it is premature to judge whether placebo treatments are ethically justifiable, with the possible exception of acupuncture for pain relief. C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Colloca, Luana] Univ Turin, Sch Med, I-10124 Turin, Italy. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov OI Colloca, Luana/0000-0002-6503-4709 NR 49 TC 67 Z9 68 U1 3 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 12 BP 39 EP 47 DI 10.1080/15265160903316263 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 538QE UT WOS:000273198200016 PM 20013499 ER PT J AU Resnik, DB AF Resnik, David B. TI Direct-to-Consumer Genomics, Social Networking, and Confidentiality SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 7 TC 4 Z9 4 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 6-7 BP 45 EP 46 DI 10.1080/15265160902893924 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 464GJ UT WOS:000267493100014 PM 19998113 ER PT J AU Miller, FG AF Miller, Franklin G. TI The Rationale for Placebo-Controlled Trials: Methodology and Policy Considerations SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 3 TC 3 Z9 3 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 9 BP 49 EP 50 DI 10.1080/15265160903098408 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 494FP UT WOS:000269797400016 PM 19998193 ER PT J AU Lepora, C Danis, M Wertheimer, A AF Lepora, Chiara Danis, Marion Wertheimer, Alan TI No Exceptionalism Needed to Treat Terrorists SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Lepora, Chiara] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Lepora, C (reprint author), NIH, Dept Bioeth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM leporac@cc.nih.gov NR 5 TC 3 Z9 3 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 10 BP 53 EP 54 DI 10.1080/15265160902998814 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 508EB UT WOS:000270909700018 PM 19998090 ER PT J AU Lynch, HF Dawson, L AF Lynch, Holly Fernandez Dawson, Liza TI Adding Insult to Injury: Reluctance to Engage in Clinical Research with At-Risk Groups Further Disenfranchises These Populations SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Lynch, Holly Fernandez] NIAID, Human Subjects Protect Branch, HJF DAIDS, Bethesda, MD 20892 USA. [Dawson, Liza] NIAID, Human Subjects Protect Branch, DAIDS, Bethesda, MD 20892 USA. RP Lynch, HF (reprint author), 6700B Rockledge Dr,Room 4229, Bethesda, MD 20817 USA. EM lynchhf@niaid.nih.gov FU PHS HHS [HHSN272200800014C] NR 3 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 11 BP 62 EP 64 DI 10.1080/15265160903197655 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 523NS UT WOS:000272081600023 PM 19882465 ER PT J AU Wendler, D AF Wendler, David TI Response to Open Peer Commentaries on "Must Research Participants Understand Randomization?'' SO AMERICAN JOURNAL OF BIOETHICS LA English DT Letter C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 6 TC 0 Z9 0 U1 2 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 2 BP W1 EP W2 DI 10.1080/15265160802715656 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 400ZG UT WOS:000262907300025 PM 19180377 ER PT J AU Fernandez, AB Keyes, MJ Pencina, M D'Agostino, R O'Donnell, CJ Thompson, PD AF Fernandez, Antonio B. Keyes, Michelle J. Pencina, Michael D'Agostino, Ralph O'Donnell, Christopher J. Thompson, Paul D. TI Relation of Corneal Arcus to Cardiovascular Disease (from the Framingham Heart Study Data Set) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; RISK-FACTORS; SERUM-LIPIDS; FOLLOW-UP; ASSOCIATION; SENILIS AB Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD. A prospective analysis was performed using Cox proportional-hazards regression models in the Framingham Heart Study Original Cohort and Offspring Cohort database. This cohort included 23,376 patient-examinations, during 3,890 (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD, and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus was no longer predictive of either CVD or CAD, however, after adjustment for age and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and 1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus predicted CVD and CAD in the community-based Framingham Heart Study cohort because of the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CAD. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:64-66) C1 [Fernandez, Antonio B.; Thompson, Paul D.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Keyes, Michelle J.; Pencina, Michael; D'Agostino, Ralph] Boston Univ, Dept Math, Boston, MA 02215 USA. [Keyes, Michelle J.; Pencina, Michael; D'Agostino, Ralph] Boston Univ, Dept Stat, Boston, MA 02215 USA. [Keyes, Michelle J.; D'Agostino, Ralph; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Thompson, Paul D.] Hartford Hosp, Henry Low Heart Ctr, Div Cardiol, Hartford, CT 06115 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Thompson, PD (reprint author), Univ Connecticut, Ctr Hlth, Farmington, CT USA. EM pthomps@harthosp.org FU National Heart, Lung and Blood Institute, Bethesda, Maryland [N01-HC-25195]; Framingham Heart Study FX This work was supported by Contract No. N01-HC-25195 from the the National Heart, Lung and Blood Institute, Bethesda, Maryland, Framingham Heart Study. NR 25 TC 12 Z9 12 U1 0 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 JAN 1 PY 2009 VL 103 IS 1 BP 64 EP 66 DI 10.1016/j.amjcard.2008.08.030 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 394CB UT WOS:000262421700012 PM 19101231 ER PT J AU Luke, A Dugas, LR Ebersole, K Durazo-Arvizu, RA Cao, GC Schoeller, DA Adeyemo, A Brieger, WR Cooper, RS AF Luke, Amy Dugas, Lara R. Ebersole, Kara Durazo-Arvizu, Ramon A. Cao, Guichan Schoeller, Dale A. Adeyemo, Adebowale Brieger, William R. Cooper, Richard S. TI Energy expenditure does not predict weight change in either Nigerian or African American women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID DOUBLY LABELED WATER; PHYSICAL-ACTIVITY; CARDIORESPIRATORY FITNESS; UNITED-STATES; PIMA-INDIANS; BODY-WEIGHT; OBESITY; PREVALENCE; POPULATIONS; ADIPOSITY AB Background: The relation between variation in interindividual levels of energy expenditure and weight gain remains controversial. Objective: To determine whether or not components of the energy budget predict weight change, we conducted an international comparative study in 2 cohorts of women from sociocultural environments that give rise to the extremes of obesity prevalence. Design: This was a prospective study with energy expenditure measured at baseline and weight measured annually for 3 y. Participants included 149 women from rural Nigeria and 172 African American women. The energy budget was determined by using respiratory gas exchange and doubly labeled water. Main outcomes included total, resting, and activity energy expenditure and physical activity level (ie, total energy expenditure/resting energy expenditure); baseline anthropometric measures; and annual weight change. Results: Mean body mass index (in kg/m(2)) was 23 among the Nigerians and 31 among the African Americans; the prevalences of obesity were 7% and 50%, respectively. After adjustment for body size, no differences in mean activity energy expenditure or physical activity level were observed between the 2 cohorts. In addition, in a mixed-effects, random-coefficient model, interindividual variation in activity energy expenditure at baseline was unrelated to the subsequent pattern of weight change. Conclusions: These data suggest that interindividual levels of energy expended during activity do not have a large influence on age-related trends in adiposity. In addition, contrary to expectations, these data suggest that mean activity energy expenditure does not vary substantially between contemporary social groups with low and high prevalences of obesity. Am J Clin Nutr 2009; 89: 169-76. C1 [Luke, Amy; Dugas, Lara R.; Ebersole, Kara; Durazo-Arvizu, Ramon A.; Cao, Guichan; Cooper, Richard S.] Loyola Univ Chicago, Dept Epidemiol & Prevent Med, Stritch Sch Med, Maywood, IL 60153 USA. [Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Adeyemo, Adebowale] Univ Ibadan, Univ Coll Hosp, Dept Paediat, Ibadan, Nigeria. [Brieger, William R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Brieger, William R.] Univ Ibadan, Univ Coll Hosp, Dept Prevent & Social Med, Ibadan, Nigeria. RP Luke, A (reprint author), Loyola Univ Chicago, Dept Epidemiol & Prevent Med, Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM aluke@lumc.edu OI Brieger, William/0000-0001-9863-8296; Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [DK56781, HL45508, GK30031] FX Supported in part by grants from the National Institutes of Health (DK56781, HL45508, and GK30031). NR 45 TC 36 Z9 36 U1 1 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 JAN 1 PY 2009 VL 89 IS 1 BP 169 EP 176 DI 10.3945/ajcn.2008.26630 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 391VM UT WOS:000262262300023 PM 19056567 ER PT J AU Wen, WQ Shu, XO Li, HL Yang, G Ji, BT Cai, H Gao, YT Zheng, W AF Wen, Wanqing Shu, Xiao Ou Li, Honglan Yang, Gong Ji, Bu-Tian Cai, Hui Gao, Yu-Tang Zheng, Wei TI Dietary carbohydrates, fiber, and breast cancer risk in Chinese women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GROWTH-FACTOR-I; GLYCEMIC LOAD; SWEET FOODS; INSULIN; INDEX; SHANGHAI; HEALTH; COHORT; CONSUMPTION AB Background: Few studies have investigated the association of dietary carbohydrate and fiber intake with breast cancer risk in women in China, where carbohydrate intake is traditionally high. Objective: The objective was to prospectively evaluate the association of dietary carbohydrates, glycemic index, glycemic load, and dietary fiber with breast cancer risk and to determine whether the effect of these dietary intakes is modified by age and selected insulin- or estrogen-related risk factors. Design: A total of 74,942 women aged 40-70 y were recruited into the Shanghai Women's Health Study, a population-based cohort study. Dietary intake was assessed by in-person interviews. A Cox proportional hazards regression model was used to evaluate associations. Results: During an average of 7.35 y of follow-up, 616 incident breast cancer cases were documented. A higher carbohydrate intake was associated with a higher risk of premenopausal breast cancer (P for trend = 0.002). Compared with the lowest quintile, the hazard ratios (and 95% CIs) were 1.47 (1.00, 2.32) and 2.01 (1.26, 3.19) for the fourth and fifth quintiles, respectively. A similar pattern was found for glycemic load. The association between carbohydrate intake and breast cancer was significantly modified by age; the increased breast cancer risk associated with carbohydrate intake was restricted to women who were younger than 50 y. No significant association of breast cancer risk with glycemic index or dietary fiber intake was found. Conclusion: Our data suggest that a high carbohydrate intake and a diet with a high glycemic load may be associated with breast cancer risk in premenopausal women or women,50 y. Am J Clin Nutr 2009; 89: 283-9. C1 [Wen, Wanqing] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Med Ctr, Nashville, TN 37203 USA. [Li, Honglan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Wen, WQ (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Med Ctr, 6th Floor,Suite 600,2525 W End Ave, Nashville, TN 37203 USA. EM wanqing.wen@vanderbilt.edu FU US Public Health Service [R01 CA070867] FX Supported by US Public Health Service grant number R01 CA070867. NR 50 TC 39 Z9 40 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN 1 PY 2009 VL 89 IS 1 BP 283 EP 289 DI 10.3945/ajcn.2008.26356 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 391VM UT WOS:000262262300037 PM 19056583 ER PT J AU George, SM Park, Y Leitzmann, MF Freedman, ND Dowling, EC Reedy, J Schatzkin, A Hollenbeck, A Subar, AF AF George, Stephanie M. Park, Yikyung Leitzmann, Michael F. Freedman, Neal D. Dowling, Emily C. Reedy, Jill Schatzkin, Arthur Hollenbeck, Albert Subar, Amy F. TI Fruit and vegetable intake and risk of cancer: a prospective cohort study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; NIH-AARP DIET; NATIONAL-INSTITUTES; COLORECTAL-CANCER; PREVENTION; CONSUMPTION; QUESTIONS; NUTRITION; PATTERNS AB Background: There is probable evidence that some types of fruit and vegetables provide protection against many cancers. Objective: We hypothesized that fruit and vegetable intakes are inversely related to the incidence of total cancers among women and men aged >50 y. Design: We performed a prospective study among the cohort of the National Institutes of Health-AARP Diet and Health Study. We merged the MyPyramid Equivalents Database (version 1.0) with food-frequency-questionnaire data to calculate cup equivalents for fruit and vegetables. From 1995 to 2003, we identified 15,792 and 35,071 cancer cases in 195,229 women and 288,109 men, respectively. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% CIs associated with the highest compared with the lowest quintile (Q) of fruit and vegetable intakes. Results: Fruit intake was not associated with the risk of total cancer among women (RR(Q5) (vs) (Q1) = 0.99; 95% CI: 0.94, 1.05; P trend = 0.059) or men (RR(Q5) (vs) (Q1) = 0.98; 95% CI: 0.95, 1.02; P for trend = 0.17). Vegetable intake was not associated with risk of total cancer among women (RR(Q5) (vs) (Q1) = 1.04; 95% CI: 0.98, 1.09; P for trend = 0.084), but was associated with a significant decrease in risk in men (RR(Q5) (vs) (Q1) = 0.94; 95% CI: 0.91, 0.97; P trend = 0.004). This significant finding among men was no longer evident when we limited the analysis to men who never smoked (RRQ5 vs Q1 0.97; 95% CI: 0.91, 1.04; P for trend = 0.474). Conclusions: Intake of fruit and vegetables was generally unrelated to total cancer incidence in this cohort. Residual confounding by smoking is a likely explanation for the observed inverse association with vegetable intake among men. Am J Clin Nutr 2009; 89: 347-53. C1 [George, Stephanie M.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Park, Yikyung; Freedman, Neal D.; Schatzkin, Arthur] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Leitzmann, Michael F.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany. [Dowling, Emily C.; Reedy, Jill; Subar, Amy F.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Subar, AF (reprint author), 6130 Executive Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. EM subara@mail.nih.gov RI Freedman, Neal/B-9741-2015; OI Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X FU National Cancer Institute, National Institutes of Health, Bethesda, MD FX Supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 27 TC 61 Z9 62 U1 1 U2 12 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 JAN 1 PY 2009 VL 89 IS 1 BP 347 EP 353 DI 10.3945/ajcn.2008.26722 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 391VM UT WOS:000262262300044 PM 19056579 ER PT J AU Bao, YP Liu, ZM Epstein, DH Du, C Shi, J Lu, L AF Bao, Yan-ping Liu, Zhi-min Epstein, David H. Du, Cun Shi, Jie Lu, Lin TI A Meta-Analysis of Retention in Methadone Maintenance by Dose and Dosing Strategy SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Dosing strategy; meta-analysis; methadone; opioid dependence; retention ID OPIOID DEPENDENCE; DOUBLE-BLIND; RANDOMIZED-TRIAL; HEROIN-ADDICTS; DRUG-USERS; BUPRENORPHINE; ACETATE; MANAGEMENT; RISK AB Objective: To estimate, via meta-analysis, the influence of different methadone dose ranges and dosing strategies on retention rates in methadone maintenance treatment (MMT). Methods: A systematic literature search identified 18 randomized controlled trials (RCTs) evaluating methadone dose and retention. Retention was defined as the percentage of patients remaining in treatment at a specified time point. After initial univariate analyses of retention by Pearson chi-squares, we used multilevel logistic regression to calculate summary odds ratios (ORs) and 95% confidence intervals for the effects of methadone dose (above or below 60 mg/day), flexible vs. fixed dosing strategy, and duration of follow-up. Results: The total number of opioid-dependent participants in the 18 studies was 2831, with 1797 in MMT and 1034 receiving alternative mediations or placebo. Each variable significantly predicted retention with the other variables controlled for. Retention was greater with methadone doses 60 than with doses 60 (OR: 1.74, 95% CI: 1.43-2.11). Similarly, retention was greater with flexible-dose strategies than with fixed-dose strategies (OR: 1.72, 95% CI: 1.41-2.11). Conclusions: Higher doses of methadone and individualization of doses are each independently associated with better retention in MMT. C1 [Bao, Yan-ping; Liu, Zhi-min; Du, Cun; Shi, Jie; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Epstein, David H.] NIDA, Intramural Res Program, Natl Inst Hlth, Baltimore, MD USA. RP Liu, ZM (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn FU Intramural NIH HHS [Z99 DA999999] NR 42 TC 46 Z9 48 U1 0 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2009 VL 35 IS 1 BP 28 EP 33 AR PII 907874089 DI 10.1080/00952990802342899 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 395FB UT WOS:000262508900005 PM 19152203 ER PT J AU Al-Ghananeem, AM Herman, BH Abbassi, M Yu, E Miotto, K O'Brien, CP Ling, W Montgomery, A Walsh, R AF Al-Ghananeem, Abeer M. Herman, Barbara H. Abbassi, Maggie Yu, Elmer Miotto, Karen O'Brien, Charles P. Ling, Walter Montgomery, Ann Walsh, Robert TI Urine and Plasma Pharmacokinetics of Lofexidine after Oral Delivery in Opiate-Dependent Patients SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Clinical trial; lofexidine; oral delivery; pharmacokinetics; urine AB Objectives: The objective of this study was to investigate lofexidine urine and plasma pharmacokinetics using three different dosing regimens in opioid dependent subjects. To date, there have been no published studies on lofexidine appearance and excretion in urine of opioid dependent subjects. Methods: Subjects were stabilized with 100 mg morphine sulphate on days 3-8 of the study. The dosing regimens of lofexidine hydrochloride were .8 mg twice a day (BID), 1.2 mg BID, or .8 mg three times a day (TID) on days 9 through 16 of the study. Plasma and urine samples were collected at appropriate time points. Area under the concentration-time curve (AUC), maximum concentration in plasma (C(max)), time when maximum concentration was reached (T(max)) and fraction excreted unchanged in urine (Fe) were calculated. Results: The average half-life obtained from all profiles was 12.1 +/- 6.3 hr. Steady-state (SS) was reached by study day 15. The plasma pharmacokinetic parameters for 1.2 mg BID and .8 mg TID dosing regimens did not seem to be different at steady state (day 15). T(max) was not statistically significantly different across dosing regimens. Fe values ranged between .01% and 34% with high variability within the same dosing regimen. For the total dose of 2.4 mg/day the two dosing regimens that were evaluated, namely 1.2 mg BID and .8 mg TID, did not show a significant statistical difference in plasma and urine pharmacokinetic parameters. Conclusion: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine urine pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis. C1 [Al-Ghananeem, Abeer M.; Abbassi, Maggie] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. [Herman, Barbara H.; Montgomery, Ann; Walsh, Robert] Natl Inst Drug Abuse, DPMCDA, NIH, Bethesda, MD USA. [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Elmer; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Miotto, Karen; Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, Long Beach Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. RP Al-Ghananeem, AM (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 927 Rose St, Lexington, KY 40536 USA. EM amalg0@email.uky.edu NR 17 TC 0 Z9 0 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2009 VL 35 IS 5 BP 311 EP 315 DI 10.1080/00952990903060135 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 562EG UT WOS:000275031700009 PM 19637105 ER PT J AU Mills, JL Carter, TC AF Mills, James L. Carter, Tonia C. TI Invited Commentary: Preventing Neural Tube Defects and More via Food Fortification? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID FOLIC-ACID FORTIFICATION; DIETARY-FOLATE; CARDIOVASCULAR EVENTS; COGNITIVE FUNCTION; CONTROLLED-TRIAL; UNITED-STATES; HIGH-RISK; HOMOCYSTEINE; DECLINE; CANCER AB Many neural tube defects can be prevented if women take folic acid around the time of conception. However, the majority of women do not take folic acid at the critical time, so the US government required that food be fortified with folic acid effective January 1, 1998. Whether the amount being added was sufficient to prevent all folate-related neural tube defects has been hotly debated. Mosley et al. (Am J Epidemiol. 2008;169(1):9-17) found no evidence that folic acid supplement use or dietary folate intake was related to neural tube defects, indicating that fortified food is probably providing sufficient folic acid to prevent folate-related defects. Because data on the effectiveness of fortification in the United States are scarce, this is an important contribution. There is great interest in the other effects of fortification. Folic acid reduces homocysteine levels, and homocysteine has been linked to cardiovascular disease and cancer. On the basis of current evidence, however, it seems unlikely that fortification will reduce cardiovascular disease rates. Its effect on cancer remains unclear. Folic acid may be useful in primary prevention but may also stimulate the growth of existing malignancies or premalignant lesions. Although these issues remain unresolved, Mosley et al. have provided important data to address the primary question: Does fortification prevent folate-related neural tube defects?. C1 [Mills, James L.; Carter, Tonia C.] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Epidemiol Branch, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Epidemiol Branch, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 43 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2009 VL 169 IS 1 BP 18 EP 21 DI 10.1093/aje/kwn329 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 390GL UT WOS:000262152200003 PM 18953060 ER PT J AU Chang, MH Lindegren, ML Butler, MA Chanock, SJ Dowling, NF Gallagher, M Moonesinghe, R Moore, CA Ned, RM Reichler, MR Sanders, CL Welch, R Yesupriya, A Khoury, MJ AF Chang, Man-huei Lindegren, Mary Lou Butler, Mary A. Chanock, Stephen J. Dowling, Nicole F. Gallagher, Margaret Moonesinghe, Ramal Moore, Cynthia A. Ned, Renee M. Reichler, Mary R. Sanders, Christopher L. Welch, Robert Yesupriya, Ajay Khoury, Muin J. CA CDC NCI NHANES III Genomics Workin TI Prevalence in the United States of Selected Candidate Gene Variants SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; POPULATION STRATIFICATION; BREAST-CANCER; DISEASE ASSOCIATIONS; STRUCTURAL VARIATION; COLORECTAL-CANCER; MEXICAN-AMERICANS; HUMAN LONGEVITY; HAPLOTYPE MAP; FTO GENE AB Population-based allele frequencies and genotype prevalence are important for measuring the contribution of genetic variation to human disease susceptibility, progression, and outcomes. Population-based prevalence estimates also provide the basis for epidemiologic studies of gene-disease associations, for estimating population attributable risk, and for informing health policy and clinical and public health practice. However, such prevalence estimates for genotypes important to public health remain undetermined for the major racial and ethnic groups in the US population. DNA was collected from 7,159 participants aged 12 years or older in Phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III). Certain age and minority groups were oversampled in this weighted, population-based US survey. Estimates of allele frequency and genotype prevalence for 90 variants in 50 genes chosen for their potential public health significance were calculated by age, sex, and race/ethnicity among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. These nationally representative data on allele frequency and genotype prevalence provide a valuable resource for future epidemiologic studies in public health in the United States. C1 [Chang, Man-huei; Dowling, Nicole F.; Moonesinghe, Ramal; Ned, Renee M.; Yesupriya, Ajay; Khoury, Muin J.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA 30341 USA. [Lindegren, Mary Lou; Reichler, Mary R.] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30341 USA. [Butler, Mary A.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Chanock, Stephen J.] NCI, NIH, Rockville, MD USA. [Gallagher, Margaret] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Moore, Cynthia A.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30341 USA. [Sanders, Christopher L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Welch, Robert] NCI Frederick, Core Genotyping Facil, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD USA. RP Chang, MH (reprint author), Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, 4770 Buford Highway,Mail Stop K89, Atlanta, GA 30341 USA. EM mdc9@cdc.gov RI Ned, Renee/D-3746-2009 FU Centers for Disease Control and Prevention, Atlanta, Georgia FX This work was supported by the Centers for Disease Control and Prevention, Atlanta, Georgia. NR 76 TC 57 Z9 57 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2009 VL 169 IS 1 BP 54 EP 66 DI 10.1093/aje/kwn286 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 390GL UT WOS:000262152200008 PM 18936436 ER PT J AU Howards, PP Schisterman, EF Wactawski-Wende, J Reschke, JE Frazer, AA Hovey, KM AF Howards, Penelope P. Schisterman, Enrique F. Wactawski-Wende, Jean Reschke, Jennifer E. Frazer, Andrea A. Hovey, Kathleen M. TI Timing Clinic Visits to Phases of the Menstrual Cycle by Using a Fertility Monitor: The BioCycle Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID BREAST-CANCER; PREMENOPAUSAL WOMEN; STEROID-HORMONES; RISK; LENGTH AB Planning study visits during specific menstrual cycle phases is important if the exposure or outcome is influenced by hormonal variation. However, hormone profiles differ across cycles and across women. The value of using fertility monitors to time clinic visits was evaluated in the BioCycle Study (2005-2007). Women aged 18-44 years (mean, 27.4) with self-reported menstrual cycle lengths of 21-35 days were recruited in Buffalo, New York, for 2 cycles (n = 250). Participants were provided with home fertility monitors that measured urinary estrone-3-glucuronide and luteinizing hormone (LH). The women were instructed to visit the clinic for a blood draw when the monitor indicated an LH surge. The monitor recorded a surge during 76% of the first cycles and 78% of the second cycles. Scheduling visits by using set cycle days or algorithms based on cycle length, such as a midcycle window or a window determined by assuming a fixed luteal phase length, would be simpler. However, even with perfect attendance in a 3-day window, these methods would have performed poorly, capturing the monitor-detected LH surge only 37%-57% of the time. Fertility monitors appear to be useful in timing clinic visits in a compliant population with flexible schedules. C1 [Howards, Penelope P.; Schisterman, Enrique F.] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Wactawski-Wende, Jean; Reschke, Jennifer E.; Frazer, Andrea A.; Hovey, Kathleen M.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Sch Med & Biomed Sci, Dept Obstet Gynecol, Buffalo, NY 14260 USA. RP Howards, PP (reprint author), Emory Univ, 1518 Clifton Rd NE,Room 450, Atlanta, GA 30322 USA. EM penelope.howards@emory.edu OI Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 14 TC 65 Z9 65 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2009 VL 169 IS 1 BP 105 EP 112 DI 10.1093/aje/kwn287 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 390GL UT WOS:000262152200013 PM 18974081 ER PT J AU Meissner, HI Yabroff, KR Dodd, KW Leader, AE Ballard-Barbash, R Berrigan, D AF Meissner, Helen I. Yabroff, K. Robin Dodd, Kevin W. Leader, Amy E. Ballard-Barbash, Rachel Berrigan, David TI Are Patterns of Health Behavior Associated With Cancer Screening? SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Health Behavior; Pattern; Cancer; Screening; Colon; Breast; Lifestyle; Prevention Research ID RECREATIONAL PHYSICAL-ACTIVITY; DISEASE RISK-FACTORS; COLORECTAL-CANCER; INTERVIEW SURVEY; BREAST-CANCER; CARDIOVASCULAR-DISEASE; CERVICAL-CANCER; UNITED-STATES; US ADULTS; WOMEN AB Purpose. This study investigates the relationship between patterns of health behaviors and the use of cancer-screening tests while controlling for sociodemographic and health system factors. Design. Cross-sectional analysis of the 2000 National Health Interview (NHIS). Setting. Nationally representative samples. Subjects. Adults 50 years and older. Measures. Use of cancer-screening tests, health behaviors, sociodemographic factors, and health system factors from self-reported responses form the NHIS. Sixteen health behavior patterns were identified based on lifestyle recommendations for physical activity, tobacco use, alcohol consumption, and fruit and vegetable consumption. Results. Health behavior patterns, age, educational attainment, usual source of care, and health insurance were significantly associated with the use of breast, cervical, and colorectal cancer screening (p<.05). Approximate R(2) for the four models ranged from .067 for colorectal cancer screening in women to .122 for cervical cancer screening. having a usual source of care was the strongest correlate of screening; the magnitude of associations for health behavior patterns and demographic variables and screening was similar and much smaller than those for usual source of care. Conclusion. These findings demonstrate relationships between patterns of multiple health behaviors and use of recommended cancer-screening tests, even when accounting for factors known to influence test use. This suggests potential for addressing cancer screening in the context of multiple behavior change interventions once barriers to health care access are removed. (Am J Health Promot 209; 23[3]: 168-175.) C1 [Meissner, Helen I.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Leader, Amy E.] George Washington Univ, Washington, DC USA. RP Meissner, HI (reprint author), NCI, Div Canc Control & Populat Sci, Execut Plaza N,Suite 4102,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM hm36d@nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572; Leader, Amy/0000-0002-9514-3631 NR 43 TC 18 Z9 18 U1 1 U2 4 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2009 VL 23 IS 3 BP 168 EP 175 DI 10.4278/ajhp.07082085 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 395BX UT WOS:000262498400003 PM 19149421 ER PT J AU Semba, RD Najjar, SS Sun, K Lakatta, EG Ferrucci, L AF Semba, Richard D. Najjar, Samer S. Sun, Kai Lakatta, Edward G. Ferrucci, Luigi TI Serum Carboxymethyl-Lysine, an Advanced Glycation End Product, Is Associated With Increased Aortic Pulse Wave Velocity in Adults SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID CROSS-LINK BREAKER; DENSITY-LIPOPROTEIN CHOLESTEROL; ARTERIAL STIFFNESS; RISK-FACTOR; DIETARY GLYCOTOXINS; GLYCOSYLATION; DISEASE; ATHEROSCLEROSIS; HYPERTENSION; ENDPRODUCTS AB BACKGROUND The relationship between advanced glycation end products and arterial stiffness has previously been examined in highly selected groups of patients with diabetes or hypertension. Our aim was to determine whether elevated serum advanced glycation end products are associated with increased arterial stiffness in relatively healthy, community-dwelling adults. METHODS Aortic pulse wave velocity (PWV), an index of aortic stiffness, and serum advanced glycation end products (AGEs), as represented by the specific AGE, serum carboxymethyl-lysine (CIVIL), were measured in 493 adults, aged 26-93 years, who participated in the Baltimore Longitudinal Study of Aging (BLSA). RESULTS Mean (s.d.) PWV (m/s) was 6.6 (1.8) m/s. Mean CIVIL was 0.47 (0.13) mu g/ml. Serum CML (per 1 s.d.) was associated with PWV (beta = 0.16, s.e.=0.07, P=0.02), adjusting forage, sex, body mass index, mean arterial pressure, fasting plasma glucose, high-density lipoprotein cholesterol, smoking, and other covariates. After excluding all diabetic patients, serum CML (per 1 s.d.) was associated with PWV (beta = 0.18, s.e. = 0.07, P = 0.009), adjusting for the same covariates. CONCLUSIONS Elevated AGEs are associated with increased arterial stiffness, a known predictor of adverse cardiovascular outcomes, among relatively healthy community-dwelling adults. Interventions to lower levels of AGES, such as altering the pattern of dietary intake, warrant examination as putative novel strategies to lower arterial stiffness in adults. C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM rdsemba@jhmi.edu FU National Institute on Aging, NIH [R01 AG027012] FX This work was supported by National Institute on Aging Grant R01 AG027012 and the Intramural Research Program, National Institute on Aging, NIH. NR 40 TC 68 Z9 77 U1 0 U2 8 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 JAN PY 2009 VL 22 IS 1 BP 74 EP 79 DI 10.1038/ajh.2008.320 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 387GM UT WOS:000261939700016 PM 19023277 ER PT J AU Semba, RD Ferrucci, L Fink, JC Sun, K Beck, J Dalal, M Guralnik, JM Fried, LP AF Semba, Richard D. Ferrucci, Luigi Fink, Jeffrey C. Sun, Kai Beck, Justine Dalal, Mansi Guralnik, Jack M. Fried, Linda P. TI Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Advanced glycation end products; reduced glomerular filtration rate ID GLOMERULAR-FILTRATION-RATE; RENAL-FAILURE PATIENTS; CROSS-LINK BREAKER; SOLUBLE RECEPTOR; DIABETIC-NEPHROPATHY; DIETARY GLYCOTOXINS; RISK-FACTOR; SERUM CREATININE; CELL-SURFACE; DISEASE AB Background: Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of kidney disease; however, their relation with level of kidney function has not been well characterized. Study Design: Cross-sectional and prospective. Setting & Participants: 548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, MD. Predictor: Serum carboxymethyl-lysine (CML), a dominant AGE; total soluble RAGE (sRAGE); and endogenous secretory RAGE (esRAGE). Outcomes & Measurements: Glomerular filtration rate (GFR), prevalent and incident decreased GFR (GFR < 60 mUmin/1.73 m(2)). Serum CML, sRAGE, and esRAGE. Results: Of 548 women, 283 (51.6%) had decreased GFR at baseline. Serum CML level was associated with decreased GFR (OR [all expressed per 1 SDI, 1.98; 95% CI, 1.41 to 2.76; P < 0.001) in a multivariate logistic regression model adjusting for age, race, hemoglobin A(1c) level, and chronic diseases. Serum sRAGE and esRAGE levels (both in nanograms per milliliter) were associated with decreased GFR (OR, 1.42; 95% CI, 1.12 to 1.79; P = 0.003; OR, 1.42; 95% CI, 1.14 to 1.77; P = 0.001, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Of 230 women without decreased GFR at baseline, 32 (13.9%) developed decreased GFR by the follow-up visit 12 months later. Serum CML (in micrograms per milliliter), sRAGE, and esRAGE levels at baseline were associated with the prevalence of decreased GFR 12 months later (OR, 1.80; 95% CI, 1.19 to 2.71; P = 0.005; OR, 1.32; 95% CI, 1.01 to 1.74; P = 0.05; and OR, 1.33; 95% CI, 1.01 to 1.77; P = 0.05, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Limitations: Small number of incident cases, limited follow-up, creatinine values not standardized. Conclusions: AGE and circulating RAGE levels are independently associated with decreased GFR and seem to predict decreased GFR. AGEs are amenable to interventions because serum AGE levels can be decreased by change in dietary pattern and pharmacological treatment. Am J Kidney Dis 53:51-58. 0 2008 by the National Kidney Foundation, Inc. C1 [Semba, Richard D.; Sun, Kai; Beck, Justine; Dalal, Mansi; Fried, Linda P.] Johns Hopkins Med Inst, Bethesda, MD USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Bethesda, MD 20892 USA. [Fink, Jeffrey C.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Bethesda, MD USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Epidemiol & Demog Sect, Bethesda, MD 20892 USA. RP Semba, RD (reprint author), 550 N Broadway,Ste 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu OI Fink, Jeffrey/0000-0002-5622-5052 FU National Institutes of Health (NIH) National Institute on Aging [R01 AG027012, AG 11703-01A1, N01-AG12112]; Intramural Research Program; NIH National Center for Research Resources and Out Patient Department-General Clinical Research Center [RR00722] FX Support: This work was supported by the National Institutes of Health (NIH) National Institute on Aging through Grants R01 AG027012 and AG 11703-01A1, Contract N01-AG12112, and the Intramural Research Program. Additional support was received in the form of Grant RR00722 from the NIH National Center for Research Resources and Out Patient Department-General Clinical Research Center. NR 54 TC 33 Z9 34 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2009 VL 53 IS 1 BP 51 EP 58 DI 10.1053/j.ajkd.2008.06.018 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 390NY UT WOS:000262172200009 PM 18789567 ER PT J AU Bostom, AG Carpenter, MA Hunsicker, L Jacques, PF Kusek, JW Levey, AS McKenney, JL Mercier, RY Pfeffer, MA Selhub, J AF Bostom, Andrew G. Carpenter, Myra A. Hunsicker, Lawrence Jacques, Paul F. Kusek, John W. Levey, Andrew S. McKenney, Joyce L. Mercier, Renee Y. Pfeffer, Marc A. Selhub, Jacob CA FAVORIT Study Investigators TI Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Chronic kidney disease; renal transplantation; hyperhomocysteinemia; creatinine clearance; estimated glomerular filtration rate (GFR); arteriosclerosis; diabetes ID CHRONIC KIDNEY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; CHRONIC RENAL-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; TOTAL HOMOCYSTEINE; SERUM CREATININE; B-VITAMINS; HYPERHOMOCYSTEINEMIA; RECIPIENTS AB Background: Hyperhomocysteinemia maybe a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. Objectives: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins 136 and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). Study Design: Cross-sectional survey within a randomized controlled trial cohort. Setting & Participants: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (>= 12.0 mu mol/L in men and >= 1.0 mu mol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. Results: Of 4,1110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) mu mol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (ie, 30 to 89 mL/min). Limitations: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. Conclusions: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial. Am J Kidney Dis 53:121-128. (C) 2008 by the National Kidney Foundation, Inc. C1 [Bostom, Andrew G.; McKenney, Joyce L.] Rhode Isl Hosp, Providence, RI 02903 USA. [Carpenter, Myra A.] Univ N Carolina, Chapel Hill, NC USA. [Hunsicker, Lawrence] Univ Iowa, Iowa City, IA USA. [Jacques, Paul F.; Selhub, Jacob] Jean Mayer USDA HNRCA, Boston, MA USA. [Kusek, John W.] NIDDKD, Bethesda, MD 20892 USA. [Levey, Andrew S.] Tufts Med Ctr, Boston, MA USA. [Mercier, Renee Y.; Pfeffer, Marc A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bostom, AG (reprint author), Rhode Isl Hosp, Phys Off Bldg,Rm 242,593 Eddy St, Providence, RI 02903 USA. EM abostom@lifespan.org FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK61700]; National Institutes of Health FX Support: Supported by cooperative agreement U01 DK61700 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Support also provided by the Office of Dietary Supplements, NIH. PamLab LLC of Covington, LA, provided the high-and low-dose multivitamins. NR 28 TC 26 Z9 26 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 JAN PY 2009 VL 53 IS 1 BP 121 EP 128 DI 10.1053/j.ajkd.2008.08.010 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 390NY UT WOS:000262172200017 PM 19022547 ER PT J AU Allanson, JE Biesecker, LG Carey, JC Hennekam, RCM AF Allanson, Judith E. Biesecker, Leslie G. Carey, John C. Hennekam, Raoul C. M. TI Elements of Morphology: Introduction SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE nomenclature; definitions; morphology; dysmorphology; birth defects; malformations; minor anomalies; common variants AB An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we describe the general background of the project and the various issues we have tried to take into account in defining the terms. Published 2009 Wiley-Liss, Inc. C1 [Allanson, Judith E.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Carey, John C.] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT USA. [Hennekam, Raoul C. M.] UCL, Great Ormond St Hosp Children, Inst Child Hlth, Clin & Mol Genet Unit, London, England. [Hennekam, Raoul C. M.] UVA, Acad Med Ctr, Dept Paediat, Amsterdam, Netherlands. RP Hennekam, RCM (reprint author), Inst Child Hlth, Clin & Mol Genet Unit, 30 Guilford St, London WC1N 1EH, England. EM r.hennekam@ich.ucl.ac.uk FU Birth Defects Foundation, Newlife (UK); Institute of Child Health (UK); National Foundation of the March of Dimes (USA); National Human Genome Research Institute (USA); Catholic University of Rome (Italy); John Wiley and Sons publishing FX We are grateful for financial support from the Birth Defects Foundation, Newlife (UK), Institute of Child Health (UK), National Foundation of the March of Dimes (USA), National Human Genome Research Institute (USA), Catholic University of Rome (Italy), and John Wiley and Sons publishing. In the initial phase of the project Dr. Heval Ozgen and Dr. Jan Maarten Cobben (Amsterdam) provided invaluable input. NR 6 TC 54 Z9 54 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2009 VL 149A IS 1 BP 2 EP 5 DI 10.1002/ajmg.a.32601 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 401EI UT WOS:000262921800002 PM 19127575 ER PT J AU Allanson, JE Cunniff, C Hoyme, HE McGaughran, J Muenke, M Neri, G AF Allanson, Judith E. Cunniff, Christopher Hoyme, H. Eugene McGaughran, Julie Muenke, Max Neri, Giovanni TI Elements of Morphology: Standard Terminology for the Head and Face SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE nomenclature; definitions; anatomy; anthropometry; head; cranium; face; neck; chin; maxilla; mandible AB An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the craniofacies and define and illustrate the terms that describe the major characteristics of the cranium and face. Published 2009 Wiley-Liss, Inc. C1 [Allanson, Judith E.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. [Cunniff, Christopher] Univ Arizona, Dept Pediat, Sect Med & Mol Genet, Tucson, AZ 85721 USA. [Hoyme, H. Eugene] Univ S Dakota, Dept Pediat, Sioux Falls, SD USA. [McGaughran, Julie] Royal Childrens Hosp, Brisbane, Qld, Australia. [Muenke, Max] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Neri, Giovanni] Univ Cattolica Sacro Cuore, Ist Genet Med, Rome, Italy. RP Allanson, JE (reprint author), Childrens Hosp Eastern Ontario, Dept Genet, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. EM allanson@cheo.on.ca RI McGaughran, Julie/A-2563-2012; OI Hoyme, Harold/0000-0002-1979-693X FU Intramural NIH HHS [Z99 HG999999] NR 8 TC 51 Z9 53 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2009 VL 149A IS 1 BP 6 EP 28 DI 10.1002/ajmg.a.32612 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA 401EI UT WOS:000262921800003 PM 19125436 ER PT J AU Biesecker, LG Aase, JM Clercuzio, C Gurrieri, M Temple, IK Toriello, H AF Biesecker, Leslie G. Aase, Jon M. Clercuzio, Carol Gurrieri, Fiorella Temple, I. Karen Toriello, Helga TI Elements of Morphology: Standard Terminology for the Hands and Feet SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital abnormalities; terminology; anatomy; anthropometry; hands; feet; congenital limb deformities; nails; malformed nails; dermatoglyphics ID FOOT AB An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human Phenotype and facilitate reliable comparisons of findings among Patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the hands and feet and define and illustrate the terms that describe the major characteristics of the hands and feet. Published 2009 Wiley-Liss, Inc. C1 [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Aase, Jon M.; Clercuzio, Carol] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. [Gurrieri, Fiorella] Univ Cattolica Sacro Cuore, Inst Med Genet, Rome, Italy. [Temple, I. Karen] Univ Southampton, Wessex Clin Genet Acad Grp, Southampton, Hants, England. [Toriello, Helga] Spectrum Hlth, Grand Rapids, MI USA. RP Biesecker, LG (reprint author), NHGRI, NIH, 49 Convent Dr 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov RI temple, isabel/K-2391-2015; Gurrieri, Fiorella/K-3214-2016 OI Gurrieri, Fiorella/0000-0002-6775-5972 FU National Institutes of Health FX This paper was reviewed and edited by the co-Chairs of the International Dysmorphologic Terminology working group (Judith Allanson, Leslie G. Biesecker, John Carey, and Raoul C.M. Hennekam). This review and editing was necessary to increase the consistency of formatting and content among the six manuscripts [Carey et al., 2009; Hall et al., 2009; Hennekam et al., 2009; Hunter et al., 2009; Allanson et al., 2009b] and this paper. While the authors of the papers are responsible for the original definitions and drafting of the papers, final responsibility for the content of each paper is shared by the authors and the four co-Chairs. Images were provided by several of the authors, Raoul C.M. Hennekam, Helen Hughes, and Julia Fekecs. The efforts of LGB were supported by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health. NR 23 TC 42 Z9 43 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2009 VL 149A IS 1 SI SI BP 93 EP 127 DI 10.1002/ajmg.a.32596 PG 35 WC Genetics & Heredity SC Genetics & Heredity GA 401EI UT WOS:000262921800008 PM 19125433 ER PT J AU Hurst, FP Abbott, KC Neff, RT Elster, EA Falta, EM Lentine, KL Agodoa, LY Jindal, RM AF Hurst, Frank P. Abbott, Kevin C. Neff, Robert T. Elster, Eric A. Falta, Edward M. Lentine, Krista L. Agodoa, Lawrence Y. Jindal, Rahul M. TI Incidence, Predictors and Outcomes of Transplant Renal Artery Stenosis after Kidney Transplantation: Analysis of USRDS SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Transplant renal artery stenosis; Kidney transplantation; Immunosuppression; Graft survival; Ischemic heart disease ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; RECIPIENTS AB Objective: We analyzed the United States Renal Data System registry to study the risks, predictors, and outcomes of transplant renal artery stenosis (TRAS) in contemporary practice. Methods: The study sampled comprised adults with Medicare primary insurance who received kidney transplants in 2000-2005. We examined associations of recipient, donor and transplant factors with time-to-TRAS by the Kaplan-Meier method and multivariate Cox regression. Survival analysis methods were employed to estimate graft survival after TRAS, and to model TRAS as a time-dependent outcome predictor. Kaplan-Meier analysis was used to estimate time to allograft loss in patients who did or did not have an angioplasty procedure for TRAS. Results: There were 823 cases of TRAS among 41,867 transplant patients, with an incidence rate of 8.3 (95% CI 7.8-8.9) cases per 1,000 patient-years. Mean time to diagnosis of TRAS was 0.83 +/- 0.81 years after transplant. Factors associated with TRAS were older recipient and donor age, extended criteria donors, induction immunosuppression, delayed graft function, and ischemic heart disease. There was no association of TRAS with deceased donors, prolonged cold ischemia time, acute rejection or cytomegalovirus status. TRAS was associated with increased risk of graft loss (including death; adjusted hazard ratio 2.84, 95% CI 1.70-4.72). Among the 823 patients with TRAS, 145 (17.6%) underwent angioplasty. Graft survival after TRAS was not significantly different in patients treated with angioplasty compared to those without angioplasty. Conclusions: TRAS is an important complication that predicts adverse patient and graft outcomes. Treatment strategies for TRAS warrant prospective investigation in clinical trials. Copyright (C) 2009 S. Karger AG, Basel C1 [Hurst, Frank P.; Abbott, Kevin C.; Neff, Robert T.] Walter Reed Army Med Ctr, Dept Nephrol, Washington, DC 20307 USA. [Elster, Eric A.; Falta, Edward M.; Jindal, Rahul M.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Lentine, Krista L.] St Louis Univ, Sch Med, Ctr Outcomes Res, St Louis, MO USA. [Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Jindal, RM (reprint author), Walter Reed Army Med Ctr, Dept Organ Transplant, 6630 Georgia Ave, Washington, DC 20307 USA. EM jindalr@msn.com OI Abbott, Kevin/0000-0003-2111-7112 NR 16 TC 29 Z9 36 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 30 IS 5 BP 459 EP 467 DI 10.1159/000242431 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 501EC UT WOS:000270361300009 PM 19776559 ER PT J AU Kajiyama, H Titus, S Austin, CP Chiotos, K Matsumoto, T Sakairi, T Kopp, JB AF Kajiyama, Hiroshi Titus, Steve Austin, Christopher P. Chiotos, Kathleen Matsumoto, Takayuki Sakairi, Toru Kopp, Jeffrey B. TI Tetracycline-Inducible Gene Expression in Conditionally Immortalized Mouse Podocytes SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Tetracycline-inducible system; Conditional immortalization; Transcription; Gene of interest ID CELL-LINES; NEPHRIN AB Background: Conditionally immortalized podocytes are valuable research tools but are difficult to efficiently transfect and do not provide graded transgene expression. Methods: Conditionally immortalized mouse podocyte cell lines were established employing a tetracycline-inducible system. Glomerular cells, isolated from transgenic mice bearing two transgenes, NPHS2-reverse tetracycline-controlled transactivator, rtTA (A transgene) and H2-Kb-thermosensitive SV40 T, ts58A (I transgene), were cloned. One clone (AI podocytes) expressing WT1 and synaptopodin was transfected with pBI-EGFP (enhanced green fluorescent protein, G transgene) and separately with ptTS-Neo (transcriptional suppressor, T transgene) to produce stable transformants, AIG podocytes and AIT podocytes. Results: AIG podocytes expressed EGFP at 33 and 37 C after doxycycline treatment, and retained podocin and rtTA mRNA expression and temperature-sensitive growth regulation. AIT podocytes, transiently transfected with luciferase-BI-EGFP (LG transgene), showed reduced background expression of EGFP and luciferase in the absence of doxycycline. In AITLG podocytes, generated by stable transfection of AIT podocytes with the LG transgene, luciferase expression was tightly regulated by doxycycline in a time- and concentration-dependent manner both at 33 and 37 degrees C, although background expression was not entirely eliminated. These podocytes retained temperature-sensitive growth regulation and expression of podocyte differentiation markers. Conclusion: Mouse podocytes expressed tetracycline-induced transgenes efficiently while retaining differentiation markers. Copyright (c) 2008 S. Karger AG, Basel C1 [Titus, Steve; Austin, Christopher P.; Kopp, Jeffrey B.] NHGRI, NIH, Chem Genom Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kajiyama, Hiroshi; Chiotos, Kathleen; Matsumoto, Takayuki; Sakairi, Toru; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Kidney Dis Branch, Bethesda, MD USA. RP Kopp, JB (reprint author), NHGRI, NIH, Chem Genom Ctr, Dept Hlth & Human Serv, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS [Z01 DK043411-01] NR 10 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 3 BP 153 EP 163 DI 10.1159/000151770 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 375RW UT WOS:000261132000002 PM 18753740 ER PT J AU Freedman, BI Kopp, JB Winkler, CA Nelson, GW Rao, DC Eckfeldt, JH Leppert, MF Hicks, PJ Divers, J Langefeld, CD Hunt, SC AF Freedman, Barry I. Kopp, Jeffrey B. Winkler, Cheryl A. Nelson, George W. Rao, D. C. Eckfeldt, John H. Leppert, Mark F. Hicks, Pamela J. Divers, Jasmin Langefeld, Carl D. Hunt, Steven C. TI Polymorphisms in the Nonmuscle Myosin Heavy Chain 9 Gene (MYH9) Are Associated with Albuminuria in Hypertensive African Americans: The HyperGEN Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE African Americans; Albuminuria; Chronic kidney disease; Essential hypertension; HyperGEN study; MYH9 gene ID STAGE RENAL-DISEASE; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; KIDNEY-DISEASE; BLOOD-PRESSURE; NEPHROSCLEROSIS; TRIAL; RISK; MUTATIONS AB Background: MYH9 is a podocyte-expressed gene encoding nonmuscle myosin IIA that is associated with idiopathic and human immunodeficiency virus-associated focal segmental glomerulosclerosis (FSGS) and hypertensive end-stage renal disease in African Americans. Methods: Four single nucleotide polymorphisms comprising the major MYH9 E1 risk haplotype were tested for association with estimated glomerular filtration rate (eGFR) and urine albumin: creatinine ratio (ACR) in 2,903 HyperGEN participants (1,458 African Americans (AA) in 895 families and 1,445 European Americans (EA) in 859 families) to determine the role of MYH9 in subclinical nephropathy. Association analyses employed general linear models in unrelated probands and generalized estimating equations in families. Adjustment was performed for age, sex, diabetes, BMI, medications, and mean arterial pressure separately in each race. Results: Mean (SD) eGFR and ACR were 74.3 (16.0) ml/min/1.73 m(2) and 20.3 (119.9) mg/g in EA, and 88.6 (20.9) ml/min/1.73 m(2) and 76.8 (394.5) mg/g in AA (both p < 0.0001 across ethnicities). Urine ACR was associated with rs3752462 (p = 0.01) and rs4821481 (p = 0.05) in unrelated AA and with rs4821481 (p = 0.03), rs2032487 (p = 0.04) and the E1 3224 haplotype (p = 0.013) in AA families. Single nucleotide polymorphisms and the haplotype were not associated with ACR in EA or with eGFR in either ethnic group. Conclusions: MYH9 variants are associated with albuminuria in hypertensive AA. The strength of the association was weaker than that in FSGS and hypertensive end-stage renal disease. MYH9 risk variants appear to be associated with primary FSGS with secondary hypertension, although nephrosclerosis may develop in response to hypertension in subjects homozygous for the MYH9 E1 risk haplotype. Copyright (c) 2009 S. Karger AG, Basel C1 [Freedman, Barry I.] Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Bethesda, MD USA. [Winkler, Cheryl A.; Nelson, George W.] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21701 USA. [Rao, D. C.] Washington Univ, Sch Med, St Louis, MO USA. [Eckfeldt, John H.] Univ Minnesota, Minneapolis, MN USA. [Leppert, Mark F.; Hunt, Steven C.] Univ Utah, Sch Med, Salt Lake City, UT USA. RP Freedman, BI (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM bfreedma@wfubmc.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU National Heart, Lung, and Blood Institute [R01 HL55673]; NIH [RO1 DK 070942, N01-CO-12400, HHSN261200800001E]; National Cancer Institute FX The HyperGEN network is funded by National Heart, Lung, and Blood Institute R01 HL55673 and cooperative agreements (U10) with National Heart, Lung, and Blood Institute: HL54471 (Utah FC), HL54472 (Minn. Lab), HL54473 (DCC), HL54495 (Ala. FC), HL54496 (Minn. FC), HL54509 (N. C.), HL54515 (Utah DNA Lab). This work was also supported in part by NIH grant RO1 DK 070942 (B. I. F.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400 and HHSN261200800001E. 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 Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 28 TC 55 Z9 57 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 6 BP 626 EP 632 DI 10.1159/000194791 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 442SP UT WOS:000265861200017 PM 19153477 ER PT J AU Jolly, SE Li, S Chen, SC Narva, AS Jurkovitz, CT Norris, KC Shlipak, MG AF Jolly, Stacey E. Li, Suying Chen, Shu-Cheng Narva, Andrew S. Jurkovitz, Claudine T. Norris, Keith C. Shlipak, Michael G. TI Risk Factors for Chronic Kidney Disease among American Indians and Alaska Natives - Findings from the Kidney Early Evaluation Program SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Risk factors; American Indians; Alaska Natives ID GLOMERULAR-FILTRATION-RATE; TYPE-2 DIABETES-MELLITUS; SERUM CREATININE VALUES; STAGE RENAL-DISEASE; UNITED-STATES; COLLABORATIVE APPROACH; NATIONAL-HEALTH; HEART-FAILURE; PIMA-INDIANS; FOLLOW-UP AB Background: American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR. Methods: Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, < 60 ml/min/1.73 m(2), or albuminuria, a urine albumin/creatinine ratio >= 30 mg/g. Results: The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% Cl 5.92-11.98), followed by hypertension (OR 2.38, 95% Cl 1.74-3.26). In contrast, diabetes (OR 2.04, 95% Cl 1.57-2.64) and hypertension (OR 2.63, 95% Cl 1.93-3.59) were the only predictors of albuminuria among persons with a normal eGFR. Conclusion: The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN. Copyright (c) 2008 S. Karger AG, Basel C1 [Jolly, Stacey E.; Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Li, Suying; Chen, Shu-Cheng] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Narva, Andrew S.] NIDDK, Bethesda, MD USA. [Jurkovitz, Claudine T.] Christiana Care Hlth Syst, Ctr Outcomes Res, Newark, DE USA. [Norris, Keith C.] Charles R Drew Univ, Dept Internal Med, Los Angeles, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Jolly, SE (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Campus Mailbox 1364, San Francisco, CA 94143 USA. EM stacey.jolly@ucsf.edu FU Health Resources and Services Administration Faculty Development [D55HP05165]; American Heart Association's Established Investigator; [R01-DK066488]; [R01-AG027002] FX Dr. Jolly was supported by Health Resources and Services Administration Faculty Development in Primary Care Grant D55HP05165 for this study. Dr. Shlipak's effort on this paper was supported by R01-DK066488, R01-AG027002, and the American Heart Association's Established Investigator Award. NR 32 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 5 DI 10.1159/000174857 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 428SO UT WOS:000264870200014 PM 19011277 ER PT J AU Gray, RH Kigozi, G Serwadda, D Makumbi, F Nalugoda, F Watya, S Moulton, L Chen, MZ Sewankambo, NK Kiwanuka, N Sempijja, V Lutalo, T Kagayii, J Wabwire-Mangen, F Ridzon, R Bacon, M Wawer, MJ AF Gray, Ronald H. Kigozi, Godfrey Serwadda, David Makumbi, Frederick Nalugoda, Fred Watya, Stephen Moulton, Laurence Chen, Michael Z. Sewankambo, Nelson K. Kiwanuka, Noah Sempijja, Victor Lutalo, Tom Kagayii, Joseph Wabwire-Mangen, Fred Ridzon, Renee Bacon, Melanie Wawer, Maria J. TI The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 15th Conference on Retroviruses and Opportunistic Infections CY FEB 03-06, 2008 CL Boston, MA DE bacterial vaginosis; female genital ulceration; male circumcision; trichomonas; vaginal infections ID SEXUALLY-TRANSMITTED-DISEASES; BACTERIAL VAGINOSIS; HIV PREVENTION; RISK-FACTORS; ACQUISITION; KENYA; FLORA; WOMEN; MEN; ASSOCIATION AB OBJECTIVE: The objective of the study was to assess effects of male circumcision on female genital symptoms and vaginal infections. STUDY DESIGN: Human immunodeficiency virus (HIV)-negative men enrolled in a trial were randomized to immediate or delayed circumcision (control arm). Genital symptoms, bacterial vaginosis (BV), and trichomonas were assessed in HIV-negative wives of married participants. Adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (CIs) were assessed by multivariable log-binomial regression, intent-to-treat analyses. RESULTS: A total of 783 wives of control and 825 wives of intervention arm men were comparable at enrollment. BV at enrollment was higher in control (38.3%) than intervention arm spouses (30.5%, P = .001). At 1 year follow-up, intervention arm wives reported lower rates of genital ulceration (adjPRR, 0.78; 95% CI, 0.63-0.97), but there were no differences in vaginal discharge or dysuria. The risk of trichomonas was reduced in intervention arm wives (adjPRR, 0.52; 95% CI, 0.05-0.98), as were the risks of any BV (adjPRR, 0.60; 95% CI, 0.38-0.94) and severe BV (prevalence risk ratios, 0.39; 95% CI, 0.24-0.64). CONCLUSION: Male circumcision reduces the risk of ulceration, trichomonas, and BV in female partners. C1 [Gray, Ronald H.; Chen, Michael Z.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA. [Moulton, Laurence] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. [Kigozi, Godfrey; Serwadda, David; Makumbi, Frederick; Nalugoda, Fred; Sewankambo, Nelson K.; Kiwanuka, Noah; Sempijja, Victor; Lutalo, Tom; Kagayii, Joseph; Wabwire-Mangen, Fred] Makerere Univ, Rakai Hlth Sci Program, Kampala, Uganda. [Serwadda, David; Kiwanuka, Noah; Wabwire-Mangen, Fred] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Watya, Stephen] Makerere Univ, Dept Urol, Mulago Hosp, Kampala, Uganda. [Kiwanuka, Noah] Makerere Univ, Fac Med, Kampala, Uganda. [Ridzon, Renee] Bill & Melinda Gates Fdn, Seattle, WA USA. [Bacon, Melanie] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, E4132,615 N Wolfe St, Baltimore, MD 21205 USA. EM rgray@jhsph.edu OI Sewankambo, Nelson/0000-0001-9362-053X; Moulton, Lawrence/0000-0001-7041-7387 FU FIC NIH HHS [2 D 43 TW000010-19-AITRP, 5D43TW001508, D43 TW001508]; Intramural NIH HHS; NIAID NIH HHS [U01 AI051171-02, U01 AI051171, U01 AI11171-01-02] NR 22 TC 14 Z9 16 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 JAN PY 2009 VL 200 IS 1 AR 42.e1 DI 10.1016/j.ajog.2008.07.069 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 393VB UT WOS:000262400600007 PM 18976733 ER PT J AU Grobman, WA Lai, Y Landon, MB Spong, CY Leveno, KJ Rouse, DJ Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Grobman, William A. Lai, Yinglei Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Rouse, Dwight J. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Eunice Kennedy Shriver Natl Inst I TI Can a prediction model for vaginal birth after cesarean also predict the probability of morbidity related to a trial of labor? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE morbidity; prediction; vaginal birth after cesarean ID PERINATAL OUTCOMES; DELIVERY AB OBJECTIVE: The objective of the study was to determine whether a model for predicting vaginal birth after cesarean (VBAC) can also predict the probabilty of morbidity associated with a trial of labor (TOL). STUDY DESIGN: Using a previously published prediction model, we categorized women with 1 prior cesarean by chance of VBAC. Prevalence of maternal and neonatal morbidity was stratfied by probability of VBAC success and delivery approach. RESULTS: Morbidity became less frequent as the predicted chance of VBAC increased among women who underwent TOL (P < .001) but not elective repeat cesarean section (ERCS) (P > .05). When the predicted chance of VBAC was less than 70%, women undergoing a TOL were more likely to have maternal morbidity (relative risk [RR], 2.2; 95% confidence interval [CI], 1.5-3.1) than those who underwent an ERCS; when the predicted chance of VBAC was at least 70%, total maternal morbidity was not different between the 2 groups (RR, 0.8; 95% CI, 0.5-1.2). The results were similar for neonatal morbidity. CONCLUSION: A prediction model for VBAC provides information regarding the chance of TOL-related morbidity and suggests that maternal morbidity is not greater for those women who undergo TOL than those who undergo ERCS if the chance of VBAC is at least 70%. C1 [Grobman, William A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. [Grobman, William A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Moawad, Atef H.] Univ Chicago, Chicago, IL 60637 USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Harper, Margaret] Wake Forest Univ, Winston Salem, NC 27109 USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [Miodovnik, Menachem] Columbia Univ, New York, NY USA. [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Langer, Oded] Univ Texas San Antonio, San Antonio, TX USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Houston, Houston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Grobman, WA (reprint author), Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801] FX This study was supported by Grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, and HD36801). NR 11 TC 12 Z9 15 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 JAN PY 2009 VL 200 IS 1 AR 56.e1 DI 10.1016/j.ajog.2008.06.039 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 393VB UT WOS:000262400600013 PM 18822401 ER PT J AU Ferris, FL AF Ferris, Frederick L. TI Clinical Trials - More Than an Assessment of Treatment Effect: LXV Edward Jackson Memorial Lecture SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NEURITIS TREATMENT TRIAL; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; TREATMENT DIABETIC-RETINOPATHY; OCULAR HYPERTENSION TREATMENT; CARE TECHNOLOGY FORUM; OPEN-ANGLE GLAUCOMA; OPTIC NEURITIS; MACULAR DEGENERATION; VISUAL-ACUITY; FOLLOW-UP AB PURPOSE: To review the development of clinical trials and demonstrate their value beyond the assessment of the treatment effect. " DESIGN: Retrospective literature review. METHODS: Retrospective literature review. RESULTS: There has been a rapid increase in the number of clinical trials in ophthalmology as assessed by the number of ophthalmic publications and the number of ongoing National Eye Institute-(NEI) sponsored clinical trials over the last four decades. The public health significance of the results of these NEI clinical trials goes beyond the demonstration of treatment effects and side effects. From these trials, we learn about the clinical course and risk factors of disease, allowing us to better determine who and when to treat. Furthermore, the collaboration of investigators, as they develop and carry out protocols, facilitates incorporation of new ideas into the practice of medicine. CONCLUSIONS: The practice of medicine is increasingly dependent on the results of carefully designed clinical trials. The determination as to whether a new treatment is safe and effective is important, but the additional information we can obtain regarding natural history, risk factors, and patient satisfaction adds immeasurably to our ability to care for our patients. (Am J Ophthalmol 2009;147:22-32. Published by Elsevier Inc.) C1 [Ferris, Frederick L.] NEI, Bethesda, MD 20892 USA. RP Ferris, FL (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 3-2531, Bethesda, MD USA. EM RickFerris@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 62 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2009 VL 147 IS 1 BP 22 EP 32 DI 10.1016/j.ajo.2008.09.013 PG 11 WC Ophthalmology SC Ophthalmology GA 387PK UT WOS:000261963900006 PM 19100353 ER PT J AU Jampel, HD Friedman, D Quigley, H Vitale, S Miller, R Knezevich, F Ding, YL AF Jampel, Henry D. Friedman, David Quigley, Harry Vitale, Susan Miller, Rhonda Knezevich, Frederick Ding, Yulan TI Agreement Among Glaucoma Specialists in Assessing Progressive Disc Changes From Photographs in Open-Angle Glaucoma Patients SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTIC DISC; INTRAOCULAR-PRESSURE; STEREOPHOTOGRAPHS; REPRODUCIBILITY AB PURPOSE: To determine the agreement among glaucoma specialists in assessing progressive disc changes from photographs in a cohort of patients with glaucomatous visual field loss. DESIGN: Retrospective cohort study. METHODS: Three glaucoma specialists, masked to chronological sequence, examined pairs of optic disc stereophotographs to determine whether the appearance of the optic disc had changed. Eyes for which the observers disagreed were adjudicated to reach a consensus about which discs had changed over time. RESULTS: Sequential stereophotographs, separated in time by a median of 26 months (range, five to 50), from 164 eyes of 111 patients were analyzed. Among the three observers, the number of interpretable discs judged to have changed was 11 of 155 (7%) for Observer 1, 17 of 155 (11%) for Observer 2, and 44 of 155 (28%) for Observer 3 (K = 0.20). Sixty-six eyes (43%) required adjudication. After adjudication, the consensus was that 10 discs had changed, six eyes in which the disc was worse in the later photograph and four eyes in which the disc was judged to appear more glaucomatous in the earlier photograph. CONCLUSION: Interobserver agreement among glaucoma specialists in judging progressive optic disc change from stereophotographs was slight to fair. After masked adjudication, in 40% of the cases in which the optic disc appeared to have progressed in glaucoma severity, the photograph of the "worse" optic disc was in fact taken at the start of the study. Caution must be exercised when using disc change on photographs as the "gold standard" for diagnosing open-angle glaucoma or determining its progression. (Am J Ophthalmol 2009;147:39-44. (c) 2009 by Elsevier Inc. All rights reserved.) C1 [Vitale, Susan] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Jampel, Henry D.; Friedman, David; Quigley, Harry; Vitale, Susan; Miller, Rhonda; Knezevich, Frederick; Ding, Yulan] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21218 USA. RP Jampel, HD (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Woods 377, Baltimore, MD 21287 USA. EM hjampel@jhmi.edu FU NEI NIH HHS [R01 EY012295-04, R01 EY012295-05, R01 EY012295, R01 EY 12295] NR 16 TC 61 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2009 VL 147 IS 1 BP 39 EP 44 DI 10.1016/j.ajo.2008.07.023 PG 6 WC Ophthalmology SC Ophthalmology GA 387PK UT WOS:000261963900008 PM 18790472 ER PT J AU Liu, Q Cheng, LI Yi, L Zhu, N Wood, A Changpriroa, CM Ward, JM Jackson, SH AF Liu, Qi Cheng, Lily I. Yi, Liang Zhu, Nannan Wood, Adam Changpriroa, Cattlena May Ward, Jerrold M. Jackson, Sharon H. TI p47(phox) Deficiency Induces Macrophage Dysfunction Resulting in Progressive Crystalline Macrophage Pneumonia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; NADPH OXIDASE; MICE; EXPRESSION; PROTEIN; MOUSE; YM1; 129S4/SVJAE; ACTIVATION; PATHOLOGY AB Nicotinamide dinucleotide phosphate oxidase-deficient (p47(phox-/-)) mice are a model of human chronic granulomatous disease; these mice are prone to develop systemic infections and inflammatory diseases. The use of antibiotic (Bactrim) prophylaxis in a specific pathogen-free environment, however, impedes infection in the majority of p47(phox-/-) mice. We examined infection-free P47(phox-/-) mice between I and 14 months of age and found that they developed proliferative macrophage lesions containing Ym1/Ym2 protein and crystals in lung, bone marrow, lymph nodes, and spleen. Here, we show that the lung lesions progressed from single macrophages with intracellular Ym1/Ym2 protein crystals to severe diffuse crystalline macrophage pneumonia without histological evidence of either granulation tissue or pulmonary fibrosis. Yml/Ym2 is a chitinase-like secretory protein that is transiently induced in alternatively activated macrophages during T-helper (Th)2-biased pathogenesis and during chemical and traumatic inflammation. Bronchoalveolar lavage from p47(phox-/-) mice contained significantly higher levels of Th-1 (hiterferon-gamma), Th-2 (interleukin-4), and Th-17 (interleukin-17)-associated cytokines than wildtype mice, as well as copious amounts of interleukin-12, indicating that Yml-secreting p47(phox-/-) macrophages are also integrated into classically activated macrophage responses. These results suggest that p47(phox-/-) macrophages are extremely pliable, due in part to an intrinsic dysfunction of macrophage activation pathways that allows for distinct classical or alternative activation phenotypes. (Ani J Pathol 2009, 174:153-163; DOI: 10.2353/ajpath.2009.080555) C1 [Liu, Qi; Yi, Liang; Zhu, Nannan; Wood, Adam; Changpriroa, Cattlena May; Jackson, Sharon H.] NIAID, Host Def Lab, NIH, Monocyte Trafficking Unit, Bethesda, MD 20892 USA. [Cheng, Lily I.; Ward, Jerrold M.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Jackson, SH (reprint author), NIAID, Host Def Lab, NIH, Monocyte Trafficking Unit, CRC Bldg 5 W Labs,Room 5-3942,10 Ctr Dr MSC 1456, Bethesda, MD 20892 USA. EM siackson@niaid.nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Center on Minority Health and Health Disparities FX Supported by the Division of Intramural Research of the National Institutes of Health/National Institute of Allergy and Infectious Diseases. This work was also partially supported by the National Center on Minority Health and Health Disparities/National Institutes of Health. NR 23 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2009 VL 174 IS 1 BP 153 EP 163 DI 10.2353/ajpath.2009.080555 PG 11 WC Pathology SC Pathology GA 391FO UT WOS:000262219400016 PM 19095958 ER PT J AU Leaner, VD Chick, JF Donninger, H Linniola, I Mendoza, A Khanna, C Birrer, MJ AF Leaner, Virna D. Chick, Jeffrey F. Donninger, Howard Linniola, Ilona Mendoza, Arnulfo Khanna, Chand Birrer, Michael J. TI Inhibition of AP-1 Transcriptional Activity Blocks the Migration, Invasion, and Experimental Metastasis of Murine Osteosarcoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID N-TERMINAL PHOSPHORYLATION; BREAST-CANCER CELLS; C-JUN; IN-VITRO; TRANSGENIC MICE; UP-REGULATION; FOS; TRANSFORMATION; ACTIVATION; KINASE AB A well-characterized murine osteosarcoma model for metastasis and invasion was used in this study to determine the role of AP-1 in the progression of this disease. We analyzed K12 and K7M2 cells, two clonally related murine osteosarcoma cell lines that have been characterized as low metastatic or high metastatic, respectively, for AP-1 components and activity. AP-1 DNA binding was similar between the two cell fines; however AP-1 transcriptional activity was enhanced by 3- to 5-fold in K7M2 cells relative to that in K12 cells. The AP-1 complexes in K12 and K7M2 cells was composed primarily of cJun, JunD, FosB, Fra1, and Fra2, with the contribution of individual components in the complex varying between the two cell lines. In addition, an increase in phosphorylated cJun, JNK activity, and phosphorylated ERK1/2 was associated with the more metastatic osteosarcoma phenotype. The significance of AP-1 activation was confirmed by conditional expression of TAM67, a dominant negative mutant of cJun. Under conditions where TAM67 inhibited AP-1 activity in K7M2 cells, migration and invasion potential was significantly blocked. Tam67 expression in aggressive osteosarcoma cells decreased long-term in vivo experimental metastasis and increased survival of mice. This study shows that differences in metastatic activity can be due to AP-1 activation. The inhibition of AP-1 activity may serve as a therapeutic tool in the management of osteosarcoma. (Am J Pathol 2009, 174:265-275; DOI: 10.2353/ajpath.2009.071006) C1 [Leaner, Virna D.; Chick, Jeffrey F.; Donninger, Howard; Linniola, Ilona; Birrer, Michael J.] Natl Canc Ctr, Cell & Canc Biol Dept, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mendoza, Arnulfo] Natl Canc Ctr, Cell & Canc Biol Dept, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Leaner, Virna D.; Khanna, Chand] Univ Cape Town, Div Med Biochem, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. RP Birrer, MJ (reprint author), Natl Canc Ctr, Cell & Canc Biol Dept, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM birrerm@mail.nih.gov NR 36 TC 19 Z9 21 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2009 VL 174 IS 1 BP 265 EP 275 DI 10.2353/ajpath.2009.071006 PG 11 WC Pathology SC Pathology GA 391FO UT WOS:000262219400027 PM 19074613 ER PT J AU Fischer, A Prufer, K Mullikin, JC Good, JM Turcotte, C Butarbutar, NB Szekeres, E Egholm, M Hober, B Hoffner, B Weihmann, A Kelsol, J Paabo, S Ptak, SF AF Fischer, A. Pruefer, K. Mullikin, J. C. Good, J. M. Turcotte, C. Butarbutar, N. B. Szekeres, E., Jr. Egholm, M. Hoeber, B. Hoeffner, B. Weihmann, A. Kelsol, J. Paeaebo, S. Ptak, S. F. TI Bonobo genome sequencing. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 78th Annual Meeting of the American-Association-of-Physical-Anthropologists CY MAR 31-APR 03, 2009 CL Chicago, IL SP Amer Assoc Phys Anthropol C1 [Mullikin, J. C.] Natl Human Genome Res Inst, Bethesda, MD USA. [Fischer, A.; Pruefer, K.; Good, J. M.; Hoeber, B.; Hoeffner, B.; Weihmann, A.; Kelsol, J.; Paeaebo, S.; Ptak, S. F.] Max Planck Inst Evolutionary Anthropol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2009 BP 127 EP 128 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408NW UT WOS:000263442700251 ER PT J AU Krause, J Green, RE Briggs, AW Stenzel, U Pruefer, K Maricic, T Kichner, M Kelso, J Reich, D Mullikin, JC Egholm, M Paabo, S AF Krause, J. Green, R. E. Briggs, A. W. Stenzel, U. Pruefer, K. Maricic, T. Kichner, M. Kelso, J. Reich, D. Mullikin, J. C. Egholm, M. Paeaebo, S. TI Insights from sequencing the Neandertal genome. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 78th Annual Meeting of the American-Association-of-Physical-Anthropologists CY MAR 31-APR 03, 2009 CL Chicago, IL SP Amer Assoc Phys Anthropol C1 [Krause, J.; Green, R. E.; Briggs, A. W.; Stenzel, U.; Pruefer, K.; Maricic, T.; Kichner, M.; Kelso, J.; Paeaebo, S.] Max Planck Inst Evolutionary Anthropol, Leipzig, 02138, Germany. [Reich, D.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Reich, D.] Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. [Reich, D.] MIT, Cambridge, MA USA. [Mullikin, J. C.] Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. RI Krause, Johannes/E-6640-2015 OI Krause, Johannes/0000-0001-5475-4690 NR 0 TC 0 Z9 0 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2009 SU 48 BP 170 EP 170 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408NW UT WOS:000263442700450 ER PT J AU Schwandt, ML Lindell, SG Higley, JD Suomi, SJ Heilig, M Barr, CS AF Schwandt, M. L. Lindell, S. G. Higley, J. D. Suomi, S. J. Heilig, M. Barr, C. S. TI OPRMI gene variation influences neuroendocrine function but not behavior in rhesus macaque (Macaca mulatta) mothers. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 78th Annual Meeting of the American-Association-of-Physical-Anthropologists CY MAR 31-APR 03, 2009 CL Chicago, IL SP Amer Assoc Phys Anthropol C1 [Schwandt, M. L.; Lindell, S. G.; Heilig, M.; Barr, C. S.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. [Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2009 BP 232 EP 233 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408NW UT WOS:000263442701261 ER PT J AU Wasserman, DH AF Wasserman, David H. TI Four grams of glucose SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE insulin; mice; rat; dog; glycogen; epinephrine; hexokinase; glucose transport; glucose delivery ID HUMAN SKELETAL-MUSCLE; NONHEPATIC SPLANCHNIC TISSUE; UPTAKE IN-VIVO; HEXOKINASE-II; INSULIN-RESISTANCE; INTENSE EXERCISE; BLOOD-FLOW; INTERSTITIAL GLUCOSE; C57BL/6J MICE; MUSCULAR WORK AB Wasserman DH. Four grams of glucose. Am J Physiol Endocrinol Metab 295: E11-E21, 2008. First published October 7, 2008; doi: 10.1152/ajpendo.90563.2008.-Four grams of glucose circulates in the blood of a person weighing 70 kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4 g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated. The body has a remarkable capacity to satisfy the nutritional need for glucose, while still maintaining blood glucose homeostasis. The essential role of glucagon and insulin and the importance of distributed control of glucose fluxes are highlighted in this review. With regard to the latter, studies are presented that show how regulation of muscle glucose uptake is regulated by glucose delivery to muscle, glucose transport into muscle, and glucose phosphorylation within muscle. C1 [Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Wasserman, David H.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. RP Wasserman, DH (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Light Hall Rm 702, Nashville, TN 37232 USA. EM david.wasserman@vanderbilt.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-50277, R01-DK-54902, U24-DK-59637, P60-DK-20593] FX The research was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK-50277,R01-DK-54902,U24-DK-59637, and P60-DK-20593. NR 105 TC 78 Z9 79 U1 1 U2 12 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 JAN PY 2009 VL 296 IS 1 BP E11 EP E21 DI 10.1152/ajpendo.90563.2008 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 388XU UT WOS:000262054400002 PM 18840763 ER PT J AU Bem, RA van Woensel, JBM Bos, AP Koski, A Farnand, AW Domachowske, JB Rosenberg, HF Martin, TR Matute-Bello, G AF Bem, Reinout A. van Woensel, Job B. M. Bos, Albert P. Koski, Amy Farnand, Alex W. Domachowske, Joseph B. Rosenberg, Helene F. Martin, Thomas R. Matute-Bello, Gustavo TI Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE respiratory syncytial virus; acute lung injury ID RESPIRATORY SYNCYTIAL VIRUS; EPITHELIAL-CELL APOPTOSIS; TIDAL VOLUME VENTILATION; DISTRESS-SYNDROME; PNEUMONIA VIRUS; ORGAN DYSFUNCTION; VIRAL BRONCHIOLITIS; CYTOKINE RESPONSE; FAS LIGAND; RAT LUNGS AB Bem RA, van Woensel JB, Bos AP, Koski A, Farnand AW, Domachowske JB, Rosenberg HF, Martin TR, Matute-Bello G. Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection. Am J Physiol Lung Cell Mol Physiol 296: L46-L56, 2009. First published November 7, 2008; doi:10.1152/ajplung.00467.2007.-Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation, the mice were subjected to 4 h of MV (tidal volume, 10 ml/kg) or allowed to breathe spontaneously. When compared with that of mice inoculated with PVM only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid concentrations of the cytokines macrophage inflammatory protein (MIP)-2, MIP-1 alpha (CCL3), and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection. C1 [Bem, Reinout A.; van Woensel, Job B. M.; Bos, Albert P.] Univ Amsterdam, Acad Med Ctr, Pediat Intens Care Unit, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Koski, Amy; Martin, Thomas R.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Farnand, Alex W.; Matute-Bello, Gustavo] Univ Washington, Sch Med, Dept Med, Ctr Lung Biol,Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Syracuse, NY USA. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Matute-Bello, G (reprint author), Univ Washington Med, S Lake Union Campus,815 Mercer St,Box 358052, Seattle, WA 98109 USA. FU National Heart, Lung, and Blood Institute [HL-083044, HL-073996]; American Lung Association FX This work was supported in part by National Heart, Lung, and Blood Institute Grants HL-083044 and HL-073996 and by the American Lung Association. NR 57 TC 21 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2009 VL 296 IS 1 BP L46 EP L56 DI 10.1152/ajplung.00467.2007 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 388YR UT WOS:000262056900007 PM 18996903 ER PT J AU Majka, DS Chang, RW Vu, THT Palmas, W Geffken, DF Ouyang, P Ni, HY Liu, K AF Majka, Darcy S. Chang, Rowland W. Vu, Thanh-Huyen T. Palmas, Walter Geffken, Dominic F. Ouyang, Pamela Ni, Hanyu Liu, Kiang TI Physical Activity and High-Sensitivity C-Reactive Protein The Multi-Ethnic Study of Atherosclerosis SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; CULTURAL ACTIVITY PARTICIPATION; NUTRITION EXAMINATION SURVEY; BODY-MASS INDEX; LEISURE-TIME; INFLAMMATORY MARKERS; GENDER-DIFFERENCES; CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; BLOOD-PRESSURE AB Background: Previous Studies have suggested an inverse relationship between physical activity and markers of inflammation such as high-sensitivity C-reactive protein (hs-CRP). However, these were inconsistent, and few examined whether race and gender influenced the relationship. This study determined a cross-sectional association between physical activity and hs-CRP level in 6142 middle-aged white, Chinese, black, and Hispanic participants enrolled in the Multi-Ethnic Study of Atherosclerosis in 2000-2002. Methods: Combined moderate and vigorous physical activity was measured by self-reported leisure, conditioning, occupational, and household activities. ANCOVA was used to assess the association between moderate/vigorous physical activity and hs-CRP by gender and race. Results: Hs-CRP was higher in women. Blacks had the highest hs-CRP, and Chinese participants had the lowest. Hs-CRP decreased across tertiles of moderate/vigorous physical activity in Hispanic men in models adjusted for age, education, study site, and physical activity questionnaire mode of administration (p=0.005) and further adjusted for smoking, infection, and aspirin use (p=0.020). The trend remained significant after further adjustment for BMI; blood pressure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol; diabetes; and the use of antihypertensive, statin, and diabetes medication (P=0.044). There was a downward trend in hs-CR-P across tertiles of physical activity in black and white men, but the association was weaker. No clear trend was observed in any female racial/ethnic groups. Conclusions: These findings suggest that the association between m ode rate/vigorous physical activity and hs-CRP differs by race and gender. Further studies are needed to confirm this and to examine the mechanisms for these race and gender differences. C1 [Majka, Darcy S.; Chang, Rowland W.] Northwestern Univ, Div Rheumatol, Feinberg Sch Med, Chicago, IL 60611 USA. [Chang, Rowland W.; Vu, Thanh-Huyen T.; Liu, Kiang] Northwestern Univ, Dept Med, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Chang, Rowland W.] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA. [Palmas, Walter] Columbia Univ, New York, NY USA. [Geffken, Dominic F.] Dartmouth Family Med Residency, Concord, NH USA. [Ouyang, Pamela] Johns Hopkins Univ, Baltimore, MD USA. [Ni, Hanyu] NIH, Bethesda, MD 20892 USA. RP Majka, DS (reprint author), Northwestern Univ, Div Rheumatol, Feinberg Sch Med, 240 E Huron,M-200, Chicago, IL 60611 USA. EM d-majka@northwestern.edu FU National Center for Research Resources [K12 RR017707]; National Institute of Arthritis, Musculoskeletal and Skin Diseases [P60 AR48098]; National Heart, Lung, and Blood Institute (NHLBI) [N01-HG-95159, N01-HC-95166]; MESA FX This research was supported by NIH grants K12 RR017707 from the National Center for Research Resources and P60 AR48098 from the National Institute of Arthritis, Musculoskeletal and Skin Diseases, as well as contracts N01-HG-95159 through N01-HC-95166 from the National Heart, Lung, and Blood Institute (NHLBI). NHLBI provided funding for the MESA study and the initial design. The initial design was later modified substantially by investigators. NHLBI participated in the review of this MESA manuscript. NR 39 TC 19 Z9 19 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2009 VL 36 IS 1 BP 56 EP 62 DI 10.1016/j.amepre.2008.09.031 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 389KC UT WOS:000262090300009 PM 19013748 ER PT J AU Byrne, G Suomi, SJ AF Byrne, Gayle Suomi, Stephen J. TI Intimate Social Behavior in Infant Interactions in Cebus apella SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE Cebus apella; capuchin; infant; development; social behavior ID GROUP-BORN INFANTS; CAPUCHIN MONKEYS; TUFTED CAPUCHINS; FACIAL DISPLAYS; CAPTIVITY; PATTERNS; LIFE; FOOD AB The development and individual stability of three intimate social behaviors (Lipsmacking, Carrying Attempts, and Facial Inspection) were examined for 43 group-housed Cebus apella infants from birth to 2 years of age. Occurrence of these behaviors was scored from 10-min videotape samples recorded three times a week over that time. Frequency of Lipsmacking and Carrying Attempts by adult males, adult females, and juveniles were all highest in early months and decreased to low levels by the end of the first year. Facial Inspection of partners by infants, in contrast, first began at 3-4 months and increased over time, at least to adult males and juveniles. Correlational analyses indicated stable individual differences in these interactions with infants and outlined a relationship between these intimate behaviors and more general social patterns reported previously for these animals. Results suggest that adult males may play a special role in affording juveniles opportunities for social learning of foraging and manipulative skills. Am. J. Primatol. 71:77-85, 2009. Published 2008 by Wiley-Liss, Inc. C1 [Byrne, Gayle; Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD USA. RP Byrne, G (reprint author), 13906 Dowlais Dr, Rockville, MD 20853 USA. EM byrneg2@aol.com FU Division of Intramural Research, National Institute of Child Health and Human Development; University of Maryland, College Park FX Contract grant sponsors: Division of Intramural Research, National Institute of Child Health and Human Development; University of Maryland, College Park. NR 24 TC 1 Z9 1 U1 3 U2 9 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 JAN PY 2009 VL 71 IS 1 BP 77 EP 85 DI 10.1002/ajp.20626 PG 9 WC Zoology SC Zoology GA 385NV UT WOS:000261821800009 PM 18925645 ER PT J AU Pine, DS Freedman, R AF Pine, Daniel S. Freedman, Robert TI Child Psychiatry Growin' Up SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID SOCIAL DEFEAT; STRESS C1 [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Bldg 1,Rm B320,9000 Rockville Pike, Bethesda, MD 20892 USA. EM daniel.pine@nih.gov NR 13 TC 6 Z9 6 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2009 VL 166 IS 1 BP 4 EP 7 DI 10.1176/appi.ajp.2008.08101493 PG 4 WC Psychiatry SC Psychiatry GA 390OJ UT WOS:000262173300002 PM 19122010 ER PT J AU Shaw, P Sharp, WS Morrison, M Eckstrand, K Greenstein, DK Clasen, LS Evans, AC Rapoport, JL AF Shaw, Philip Sharp, Wendy S. Morrison, Meaghan Eckstrand, Kristen Greenstein, Deanna K. Clasen, Liv S. Evans, Alan C. Rapoport, Judith L. TI Psychostimulant Treatment and the Developing Cortex in Attention Deficit Hyperactivity Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; DEVELOPMENTAL TRAJECTORIES; CORTICAL THICKNESS; ACTIVITY LEVEL; MOTOR-ACTIVITY; MRI DATA; METHYLPHENIDATE; CHILDREN; ADOLESCENTS; ADHD AB Objective: While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence. Method: Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD. The mean age at the first scan was 12.5 years, and at the second scan, 16.4 years. Nineteen patients not treated with psychostimulants between the scans were compared with an age-matched group of 24 patients who were treated with psychostimulants. Further comparison was made against a template derived from 620 scans of 294 typically developing youths without ADHD. Results: Adolescents taking psychostimulants differed from those not taking psychostimulants in the rate of change of the cortical thickness in the right motor strip, the left middle/inferior frontal gyrus, and the right parieto-occipital region. The group difference was due to more rapid cortical thinning in the group not taking psychostimulants (mean cortical thinning of 0.16 mm/year [SD=0.17], compared with 0.03 mm/year [SD=0.11] in the group taking psychostimulants). Comparison against the typically developing cohort without ADHD showed that cortical thinning in the group not taking psychostimulants was in excess of age-appropriate rates. The treatment groups did not differ in clinical outcome, however. Conclusions: These findings show no evidence that psychostimulants were associated with slowing of overall growth of the cortical mantle. C1 [Shaw, Philip] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Rm 3N202,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov FU NIH Intramural Research Program FX Supported by the NIH Intramural Research Program, which had no role in the design and conduct of the study. The authors thank Xavier Castellanos for initiating the project. NR 28 TC 123 Z9 129 U1 4 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2009 VL 166 IS 1 BP 58 EP 63 DI 10.1176/appi.ajp.2008.08050781 PG 6 WC Psychiatry SC Psychiatry GA 390OJ UT WOS:000262173300013 PM 18794206 ER PT J AU Blum, N Fee, E AF Blum, Nava Fee, Elizabeth TI The St John Eye Hospital: A Bridge for Peace SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Blum, Nava] Univ Haifa, Sch Publ Hlth, Fac Social Welf & Social Sci, IL-31905 Haifa, Israel. [Blum, Nava] Max Stern Acad Coll Emik Yezreel, Dept Hlth Syst Adm, Yezreel Valley, Israel. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Blum, N (reprint author), Univ Haifa, Sch Publ Hlth, Fac Social Welf & Social Sci, IL-31905 Haifa, Israel. EM navablum@hotmail.com NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2009 VL 99 IS 1 BP 32 EP 33 DI 10.2105/AJPH.2008.139154 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 391OA UT WOS:000262241400009 PM 19008500 ER PT J AU Cargill, VA AF Cargill, Victona A. TI Recruiting, Retaining, and Maintaining Racial and Ethnic Minority Investigators: Why We Should Bother, Why We Should Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Cargill, Victona A.] NIH, Off AIDS Res, Bethesda, MD 20892 USA. [Cargill, Victona A.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Cargill, VA (reprint author), NIH, Off AIDS Res, 5635 Fishers Lane,Suite 4000, Bethesda, MD 20892 USA. EM vc52x@nih.gov NR 6 TC 2 Z9 2 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2009 VL 99 BP S5 EP S7 DI 10.2105/AJPH.2008.147645 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423RB UT WOS:000264512300002 PM 19246666 ER PT J AU Forsyth, AD Stoff, DM AF Forsyth, Andrew D. Stoff, David M. TI Key Issues in Mentoring in HIV Prevention and Mental Health for New Investigators From Underrepresented Racial/Ethnic Groups SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MINORITY FACULTY; ACADEMIC MEDICINE; SERVICES RESEARCH; RESEARCHERS; STUDENTS; GENERATION; PROGRAM; MODEL AB We examine the challenges and barriers to quality mentoring for new investigators from underrepresented racial/ethnic groups and propose solutions for establishing a robust pipeline of early-career scientists who are well equipped to conduct research on disparities in HIV and mental health. In addition, we review contributions to this special supplement on mentoring and advocate a multilevel strategy that targets funding agencies, academic and research institutions, mentors, and mentees to enhance the diversity of the nation's scientific workforce and ensure that the public health system benefits from innovations derived from the optimal use of existing human capital. (Am J Public Health. 2009;99:S87-S91. doi:10.2105/AJPH.2008.155085) C1 [Forsyth, Andrew D.; Stoff, David M.] NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. RP Forsyth, AD (reprint author), NIMH, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd,Room 6204,MSC 9619, Bethesda, MD 20892 USA. EM af183p@nih.gov NR 39 TC 10 Z9 10 U1 1 U2 2 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 PY 2009 VL 99 BP S87 EP S91 DI 10.2105/AJPH.2008.155085 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423RB UT WOS:000264512300018 PM 19246661 ER PT J AU Stoff, DM Forsyth, A Marquez, ED McClure, S AF Stoff, David M. Forsyth, Andrew Marquez, Ernest D. McClure, Shelia TI Introduction: The Case for Diversity in Research on Mental Health and HIV/AIDS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material AB This introductory article provides background and sets the stage for the mentoring programs described in this special supplement. The goal of these programs is to develop scientists from racial/ethnic groups underrepresented in the area of HIV/AIDS research on issues related to mental health. We describe recent epidemiological trends associated with HIV infection in diverse populations, the need for mentoring programs to study disparities, and the ongoing mentoring programs supported by the National Institutes of Health targeting investigators underrepresented in the work-force. We also provide a summary of the content of the articles to follow. We conclude with a comment on future needs and actions. (Am J Public Health. 2009;9 9: S8-S15. doi:10.2105/AJPH.2008.153536) C1 [Stoff, David M.; Forsyth, Andrew] NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. [Marquez, Ernest D.] NIMH, Off Special Populat, Bethesda, MD 20892 USA. [McClure, Shelia] NIH, Natl Ctr Res Resources, Div Res Infrastruct, Bethesda, MD 20892 USA. RP Stoff, DM (reprint author), NIMH, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM dstoff@nih.gov NR 34 TC 5 Z9 5 U1 2 U2 3 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 PY 2009 VL 99 BP S8 EP S15 DI 10.2105/AJPH.2008.153536 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423RB UT WOS:000264512300003 PM 19246664 ER PT J AU Thiede, H Jenkins, RA Carey, JW Hutcheson, R Thomas, KK Stall, RD White, E Allen, I Mejia, R Golden, MR AF Thiede, Hanne Jenkins, Richard A. Carey, James W. Hutcheson, Rebecca Thomas, Katherine K. Stall, Ronald D. White, Edward Allen, Iris Mejia, Roberto Golden, Matthew R. TI Determinants of Recent HIV Infection Among Seattle-Area Men Who Have Sex with Men SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; INJECTION-DRUG-USERS; ACTIVE ANTIRETROVIRAL THERAPY; SENSITIVE ENZYME-IMMUNOASSAY; RISK BEHAVIOR; BISEXUAL MEN; HOMOSEXUAL-MEN; SAN-FRANCISCO; UNITED-STATES; METHAMPHETAMINE DEPENDENCE AB Objectives. We sought to identify HIV-infection risk factors related to partner selection and sexual behaviors with those partners among men who have sex with men (MSM) in King County, Washington. Methods. Participants were recruited from HIV testing sites in the Seattle area. Recent HIV infection status was determined by the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) or a self-reported previous HIV-negative test. Data on behaviors with 3 male partners were collected via computer-based self-interviews. Generalized estimating equation models identified partnership factors associated with recent infection. Results. We analyzed data from 32 HIV-positive MSM (58 partners) and 110 HIV-negative MSM (213 partners). In multivariate analysis, recent HIV infection was associated with meeting partners at bathhouses or sex clubs, bars or dance clubs, or online; methamphetamine use during unprotected anal intercourse; and unprotected anal intercourse, except with HIV-negative primary partners. Conclusions. There is a need to improve efforts to promote condom use with casual partners, regardless of their partner's HIV status. New strategies to control methamphetamine use in MSM and to reduce risk behaviors related to meeting partners at high-risk venues are needed. (Am J Public Health. 2009;99: S157-S164. doi:10.2105/AJPH.2006.098582) C1 [Thiede, Hanne; Hutcheson, Rebecca; Golden, Matthew R.] Publ Hlth Seattle & King Cty, Seattle, WA 98104 USA. [Jenkins, Richard A.] Natl Inst Drug Abuse, Bethesda, MD USA. [Carey, James W.] Ctr Dis Control & Prevent, Div HIV AIDS, Atlanta, GA USA. [Thomas, Katherine K.] Univ Washington, Sch Med, Seattle, WA USA. [Stall, Ronald D.] Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA. [White, Edward] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Allen, Iris] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. RP Thiede, H (reprint author), Publ Hlth Seattle & King Cty, 400 Yesler Way,3rd Floor, Seattle, WA 98104 USA. EM hanne.thiede@kingcounty.gov FU Centers for Disease Control and Prevention [U64/CCU019523] FX We would like to thank the Public Health-Seattle & King County Sexually Transmitted Diseases and HIV/AIDS Program chores, jet St. De Lore, Jason Naki, Kim Houk, and Richard Burt for their contributions to this Study, as well as, Erin Picone-DeCaro, Duane Moody. Jamar Barnes, and Karen Andes at the Centers for Disease Control and Prevention. NR 46 TC 41 Z9 41 U1 2 U2 4 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 PY 2009 VL 99 BP S157 EP S164 DI 10.2105/AJPH.2006.098582 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 423RB UT WOS:000264512300029 PM 18445808 ER PT J AU Aaron, CP Tandri, H Barr, RG Johnson, C Bagiella, E Chahal, H Jain, A Kizer, J Lima, JA Bluemke, DA Kawut, SM AF Aaron, C. P. Tandri, H. Barr, R. G. Johnson, C. Bagiella, E. Chahal, H. Jain, A. Kizer, J. Lima, J. A. Bluemke, D. A. Kawut, S. M. TI Physical Activity and Right Ventricular Structure and Function: The MESA-Right Ventricle Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Aaron, C. P.; Barr, R. G.; Bagiella, E.] Columbia Univ, New York, NY 10027 USA. [Tandri, H.; Chahal, H.; Jain, A.; Lima, J. A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Johnson, C.] Univ Washington, Seattle, WA 98195 USA. [Bluemke, D. A.] NIH, Bethesda, MD USA. [Kawut, S. M.] Univ Penn, Philadelphia, PA 19104 USA. EM cp2346@columbia.edu NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A4146 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103499 ER PT J AU Altaweel, L Li, Y Cui, X Su, J Macarthur, H Sherer, K Moayeri, M Leppla, H Fitz, Y Eichacker, PQ AF Altaweel, L. Li, Y. Cui, X. Su, J. Macarthur, H. Sherer, K. Moayeri, M. Leppla, H. Fitz, Y. Eichacker, P. Q. TI A Reduced Catecholamine and Tachycardic Response May Contribute to Early Shock with Anthrax Lethal Toxin (LeTx) in Rats. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Altaweel, L.; Li, Y.; Cui, X.; Su, J.; Sherer, K.; Fitz, Y.; Eichacker, P. Q.] NIH, CCM, Bethesda, MD 20892 USA. [Macarthur, H.; Leppla, H.] NIAID, NIH, Bethesda, MD 20892 USA. [Moayeri, M.] Dept Pharmacol Sci, St Louis, MO USA. EM altaweellr@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4718 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104183 ER PT J AU Arteta, M Campbell, A Minnitti, CP Rana, S Ensing, G Sable, C Darbari, D Nouraie, M Onyenkwere, O Luchtman-Jones, L Kato, GJ Gladwin, M Castro, O Gordeuk, V AF Arteta, M. Campbell, A. Minnitti, C. P. Rana, S. Ensing, G. Sable, C. Darbari, D. Nouraie, M. Onyenkwere, O. Luchtman-Jones, L. Kato, G. J. Gladwin, M. Castro, O. Gordeuk, V. TI Pulmonary Function in Children with Sickle Cell Disease and Its Association with Markers of Inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Arteta, M.; Campbell, A.; Ensing, G.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sable, C.; Darbari, D.; Luchtman-Jones, L.] Childrens Natl Med Ctr, Washington, DC USA. [Rana, S.; Nouraie, M.; Onyenkwere, O.; Castro, O.; Gordeuk, V.] Howard Univ, Washington, DC USA. [Minnitti, C. P.; Kato, G. J.] NHLBI, NIH, Vasc Branch, Bethesda, MD 20892 USA. [Gladwin, M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. EM marteta@umich.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4861 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104325 ER PT J AU Barochia, AV Li, Y Su, J Fitz, Y Solomon, S Eichacker, PQ Cui, X AF Barochia, A. V. Li, Y. Su, J. Fitz, Y. Solomon, S. Eichacker, P. Q. Cui, X. TI E. coli Pneumonia Decreases Left Ventricular Contractility Measures in a Murine Model. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Barochia, A. V.; Li, Y.; Su, J.; Fitz, Y.; Solomon, S.; Eichacker, P. Q.; Cui, X.] NIH, Bethesda, MD 20892 USA. EM barochiaav@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4702 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104167 ER PT J AU Barst, RJ Machado, R Mubarak, K Sood, N Gladwin, M AF Barst, R. J. Machado, R. Mubarak, K. Sood, N. Gladwin, M. CA ASSET Study Grp TI Exercise Capacity and Hemodynamics in Sickle Cell Disease with Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Barst, R. J.] Columbia Univ, New York, NY USA. [Machado, R.] NIH, Bethesda, MD 20892 USA. [Mubarak, K.] Univ Florida, Gainesville, FL USA. [Sood, N.] Ohio State Univ, Columbus, OH 43210 USA. [Gladwin, M.] Univ Pittsburgh, Pittsburgh, PA USA. EM robyn.barst@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4925 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104389 ER PT J AU Bauer, AK Rondini, EE DeGraff, LM Hummel, KA Walker, C Kleeberger, SR AF Bauer, A. K. Rondini, E. E. DeGraff, L. M. Hummel, K. A. Walker, C. Kleeberger, S. R. TI Role of Heat Shock Protein 70 (HSP70) in O3-Induced Lung Inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bauer, A. K.; Rondini, E. E.; Hummel, K. A.] Michigan State Univ, E Lansing, MI 48824 USA. [DeGraff, L. M.; Walker, C.; Kleeberger, S. R.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC USA. EM akbauer@msu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2569 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101688 ER PT J AU Bentley, AR Kritchevsky, S Harris, T Holvoet, P Jensen, R Crapo, R Newman, A Bauer, D Lee, JS Tolley, E Yende, S Cassano, PA AF Bentley, A. R. Kritchevsky, S. Harris, T. Holvoet, P. Jensen, R. Crapo, R. Newman, A. Bauer, D. Lee, J. S. Tolley, E. Yende, S. Cassano, P. A. TI Dietary Antioxidants and FEV1 in the Health Aging and Body Composition (Health ABC) Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bentley, A. R.; Cassano, P. A.] Cornell Univ, Ithaca, NY 14853 USA. [Kritchevsky, S.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Harris, T.] NIA, Bethesda, MD 20892 USA. [Holvoet, P.] Univ Leuven, Louvain, Belgium. [Jensen, R.; Crapo, R.] Univ Utah, Salt Lake City, UT 84112 USA. [Newman, A.; Yende, S.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Bauer, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tolley, E.] Univ Tennessee, Knoxville, TN 37996 USA. [Lee, J. S.] Univ Georgia, Athens, GA 30602 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5524 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105115 ER PT J AU Boon, K Bailey, NW Steele, MP Groshong, S Yang, J Kervitsky, D Brown, KK Schwarz, MI Schwartz, DA AF Boon, K. Bailey, N. W. Steele, M. P. Groshong, S. Yang, J. Kervitsky, D. Brown, K. K. Schwarz, M. I. Schwartz, D. A. TI Molecular Phenotypes Distinguish Rapid and Slow Disease Progression in Idiopathic Pulmonary Fibrosis (IPF) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Boon, K.; Bailey, N. W.; Yang, J.; Schwartz, D. A.] NIEHS NHLBI, Res Triangle Pk, NC USA. [Steele, M. P.] Duke Univ Med Ctr, Durham, NC USA. [Groshong, S.; Kervitsky, D.; Brown, K. K.; Schwartz, D. A.] Natl Jewish Hlth, Denver, CO USA. [Brown, K. K.; Schwarz, M. I.; Schwartz, D. A.] Univ Colorado Hlth Sci Ctr, Denver, CO USA. EM boonc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2172 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101291 ER PT J AU Boon, K Bailey, NW Tomfohr, JK Steele, MP Brown, KK Loyd, JE Schwarz, MI Schwartz, DA AF Boon, K. Bailey, N. W. Tomfohr, J. K. Steele, M. P. Brown, K. K. Loyd, J. E. Schwarz, M. I. Schwartz, D. A. TI Peripheral Blood Genomic Signatures in Familial Interstitial Pneumonia (FIP) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Boon, K.; Bailey, N. W.; Tomfohr, J. K.; Schwartz, D. A.] NIEHS, NHLBI, Res Triangle Pk, NC 27709 USA. [Steele, M. P.] Duke Univ, Med Ctr, Durham, NC USA. [Brown, K. K.; Schwarz, M. I.; Schwartz, D. A.] Natl Jewish Hlth, Denver, CO USA. [Loyd, J. E.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Brown, K. K.; Schwarz, M. I.; Schwartz, D. A.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. EM boonc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2171 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101290 ER PT J AU Brar, SS Martin, WJ AF Brar, S. S. Martin, W. J., II TI Bleomycin Upregulates UCP2 mRNA Expression, Decreases ATP Levels and Induces Apoptosis in Alveolar Epithelial Cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Brar, S. S.; Martin, W. J., II] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. EM brar@niehs.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 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. PY 2009 VL 179 MA A5002 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104466 ER PT J AU Brown, JM Swindle, EJ Metcalfe, DD AF Brown, J. M. Swindle, E. J. Metcalfe, D. D. TI Mast Cell Activation by Silica Is Dependent on Expression of SR-BI/II. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Brown, J. M.] E Carolina Univ, Brody Sch Med, Dept Pharmacol & Toxicol, Greenville, NC USA. [Swindle, E. J.; Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM brownja@ecu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3705 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103058 ER PT J AU Brown, RH Togias, A AF Brown, R. H. Togias, A. TI Phenotyping Bronchodilator-Unresponsive and Responsive Asthma with High Resolution Computerized Tomography (HRCT) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Brown, R. H.] Johns Hopkins Univ, Baltimore, MD USA. [Togias, A.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3917 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103270 ER PT J AU Burch, LH Wise, AL Garantziotis, S Evans, CM Adler, KA Speer, MC Steele, MP Brown, KK Loyd, JE Gudmundsson, G Groshong, SD Dickey, BF Herron, A Kervitsky, D Talbert, JL Markin, C Zhang, L Park, J Auerbach, S Crews, AL Slifer, SH Xu, H Potocky, CF Masinde, T Roy, MG Jancewicz, JM Schwarz, MI Schwartz, DA AF Burch, L. H. Wise, A. L. Garantziotis, S. Evans, C. M. Adler, K. A. Speer, M. C. Steele, M. P. Brown, K. K. Loyd, J. E. Gudmundsson, G. Groshong, S. D. Dickey, B. F. Herron, A. Kervitsky, D. Talbert, J. L. Markin, C. Zhang, L. Park, J. Auerbach, S. Crews, A. L. Slifer, S. H. Xu, H. Potocky, C. F. Masinde, T. Roy, M. G. Jancewicz, J. M. Schwarz, M. I. Schwartz, D. A. TI Variants of MUC5AC Play a Role in the Development of Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Burch, L. H.; Garantziotis, S.; Zhang, L.; Auerbach, S.; Xu, H.; Masinde, T.; Jancewicz, J. M.] NIEHS, Res Triangle Pk, NC 27709 USA. [Wise, A. L.; Brown, K. K.; Groshong, S. D.; Kervitsky, D.; Talbert, J. L.; Schwarz, M. I.; Schwartz, D. A.] Natl Jewsih Hlth, Denver, CO USA. [Wise, A. L.; Brown, K. K.; Groshong, S. D.; Schwarz, M. I.; Schwartz, D. A.] Univ Colorado, Sch Med, Denver, CO USA. [Evans, C. M.; Dickey, B. F.; Roy, M. G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Adler, K. A.; Park, J.; Crews, A. L.] N Carolina State Univ, Raleigh, NC 27695 USA. [Speer, M. C.; Steele, M. P.; Herron, A.; Slifer, S. H.; Potocky, C. F.] Duke Univ Med Ctr, Durham, NC USA. [Loyd, J. E.; Markin, C.] Vanderbilt Univ Sch Med, Nashville, TN USA. [Gudmundsson, G.] Landspitali Univ Hosp, Reykjavik, Iceland. [Slifer, S. H.] Univ Miami, Miami, FL USA. EM schwartzd@njc.org RI Gudmundsson, Gunnar/F-1974-2013; Garantziotis, Stavros/A-6903-2009 OI Gudmundsson, Gunnar/0000-0002-7251-8322; Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2174 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101293 ER PT J AU Cai, X Pacheco-Rodriguez, G Fan, Q Haughey, M El-Chemaly, S Gochuico, B Samsel, L McCoy, JP Darling, TN Moss, J AF Cai, X. Pacheco-Rodriguez, G. Fan, Q. Haughey, M. El-Chemaly, S. Gochuico, B. Samsel, L. McCoy, J. P. Darling, T. N. Moss, J. TI Identification of Disseminated CD44v6(+)/CD9(+) Cells with TSC2 Loss of Heterozygosity in Patients with Lymphangioleiomyomatosis. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cai, X.; Pacheco-Rodriguez, G.; Fan, Q.; Haughey, M.; El-Chemaly, S.; Samsel, L.; McCoy, J. P.; Moss, J.] NHLBI, Bethesda, MD 20892 USA. [Gochuico, B.] NHGRI, Bethesda, MD 20892 USA. [Darling, T. N.] USUHS, Bethesda, MD USA. EM mossj@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A4339 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103692 ER PT J AU Cho, HY Miller-DeGraff, L Perrow, L Gladwell, W Martin, J Yamamoto, M Kleeberger, SR AF Cho, H. Y. Miller-DeGraff, L. Perrow, L. Gladwell, W. Martin, J. Yamamoto, M. Kleeberger, S. R. TI Nrf2 Deficiency Exacerbates Bronchopulmonary Dysplasia Phenotypes Induced by Hyperoxia in Developing Lung. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cho, H. Y.; Miller-DeGraff, L.; Perrow, L.; Gladwell, W.; Martin, J.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC 27709 USA. [Yamamoto, M.] Tohoku Univ, Sendai, Miyagi 980, Japan. EM cho2@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4119 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103472 ER PT J AU Cho, HY DeGraff, LM Perrow, L Yamamoto, M Kleeberger, SR AF Cho, H. Y. DeGraff, L. M. Perrow, L. Yamamoto, M. Kleeberger, S. R. TI Global Gene Expression Analysis in Developing Lungs from Nrf2(+/+) and Nrf2(-/-) Neonates SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cho, H. Y.; DeGraff, L. M.; Perrow, L.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC USA. [Yamamoto, M.] Tohoku Univ, Sendai, Miyagi 980, Japan. EM cho2@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1911 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101030 ER PT J AU Chorley, BN Wang, X Campbell, MR Spira, A Kleeberger, SR Bell, DA AF Chorley, B. N. Wang, X. Campbell, M. R. Spira, A. Kleeberger, S. R. Bell, D. A. CA Lab Mol Genetics Environm Genomics Grp TI Attenuation of MAFG Reduces Oxidative Stress Response in Bronchial Epithelial Cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Chorley, B. N.; Wang, X.; Campbell, M. R.; Kleeberger, S. R.; Bell, D. A.] NIEHS, Res Triangle Pk, NC 27709 USA. [Spira, A.] Boston Univ, Med Ctr, Boston, MA USA. EM chorleyb@niehs.nih.gov NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A4961 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104425 ER PT J AU Ciencewicki, J Imani, F Polack, F Kleeberger, SR AF Ciencewicki, J. Imani, F. Polack, F. Kleeberger, S. R. TI Differential Susceptibility and Response to Respiratory Syncytial Virus Infection in Human Lymphoblast Cell Lines. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ciencewicki, J.; Imani, F.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC 27709 USA. [Polack, F.] Johns Hopkins Univ, Baltimore, MD USA. EM ciencewickij@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3259 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102494 ER PT J AU Clements, D Glasgow, CG Magowan, L Chang, WYC Moss, J Johnson, SR AF Clements, D. Glasgow, C. G. Magowan, L. Chang, W. Y. C. Moss, J. Johnson, S. R. TI Matrilysin/MMP-7 Expression in Lymphangioleiomyomatosis (LAM). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Clements, D.; Magowan, L.; Chang, W. Y. C.; Johnson, S. R.] Univ Nottingham, Queens Med Ctr, Nottingham NG7 2RD, England. [Glasgow, C. G.; Moss, J.] NHLBI, NIH, Bethesda, MD 20892 USA. EM debbie.clements@nottingham.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4346 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103699 ER PT J AU Cui, X Li, Y Su, J Shiloach, J Kaufman, J Fitz, Y Altaweel, L Barochia, A Eiachcker, P AF Cui, X. Li, Y. Su, J. Shiloach, J. Kaufman, J. Fitz, Y. Altaweel, L. Barochia, A. Eiachcker, P. TI Lactobacillus gasseri Cell Wall Produced Mortality, Acidosis, and Inflammatory Changes Similar to or Greater Than S. aureus Cell Wall. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Cui, X.; Li, Y.; Su, J.; Fitz, Y.; Altaweel, L.; Barochia, A.; Eiachcker, P.] NIH, CCMD, CC, Bethesda, MD 20892 USA. [Shiloach, J.; Kaufman, J.] NIDDK, NIH, Bethesda, MD USA. EM cxizhong@mail.cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4709 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104174 ER PT J AU Desai, A Togias, A Schechter, C Fisher, B Skloot, G AF Desai, A. Togias, A. Schechter, C. Fisher, B. Skloot, G. TI Increased Airways Resistance in Obesity Is Not Related to Cholinergic Tone SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Desai, A.; Fisher, B.; Skloot, G.] Mt Sinai Sch Med, New York, NY USA. [Togias, A.] NIAID, NIH, Bethesda, MD 20892 USA. [Schechter, C.] Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3918 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103271 ER PT J AU Desai, A Togias, A Schechter, C Skloot, G AF Desai, A. Togias, A. Schechter, C. Skloot, G. TI Lack of Deep Inspiration-Induced Bronchoprotection in Obesity. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Desai, A.; Skloot, G.] Mt Sinai Sch Med, New York, NY USA. [Togias, A.] NIAID, NIH, Bethesda, MD 20892 USA. [Schechter, C.] Albert Einstein Coll Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2423 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101542 ER PT J AU Ding, Y Gao, ZG Suffredini, AF AF Ding, Y. Gao, Z. -G. Suffredini, A. F. TI Dexamethasone (DEX) Upregulates the Purinergic Receptor P2Y2 and Enhances Adenosine Triphosphate (ATP)-Induced IL-6 Production in Endothelium SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ding, Y.; Suffredini, A. F.] NIH, Dept Crit Care Med, CC, Bethesda, MD 20892 USA. [Gao, Z. -G.] NIDDK, Lab Bioinorgan Chem, NIH, Bethesda, MD 20892 USA. EM dingy@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2344 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101463 ER PT J AU Draper, DW Madenspacher, JH DeGraff, LM Fessler, MB AF Draper, D. W. Madenspacher, J. H. DeGraff, L. M. Fessler, M. B. TI ATP Binding Cassette Transporter G1 Is a Negative Regulator of Pulmonary Innate Immunity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Draper, D. W.; Madenspacher, J. H.; DeGraff, L. M.; Fessler, M. B.] NIEHS, Res Triangle Pk, NC 27709 USA. EM draperd2@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1022 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100023 ER PT J AU El-Chemaly, S Malide, D Zudaire, E Ikeda, Y Weinberg, B Pacheco-Rodriguez, G Rosas, IO MacDonald, SD Wu, HP Cuttitta, F McCoy, JP Gochuico, BR Moss, J AF El-Chemaly, S. Malide, D. Zudaire, E. Ikeda, Y. Weinberg, B. Pacheco-Rodriguez, G. Rosas, I. O. MacDonald, S. D. Wu, H. P. Cuttitta, F. McCoy, J. P. Gochuico, B. R. Moss, J. TI Abnormal Lymphangiogenesis in Idiopathic Pulmonary Fibrosis: Insights into Cellular and Molecular Mechanisms. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [El-Chemaly, S.; Malide, D.; Ikeda, Y.; Weinberg, B.; Pacheco-Rodriguez, G.; Rosas, I. O.; MacDonald, S. D.; Wu, H. P.; McCoy, J. P.; Moss, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Zudaire, E.; Cuttitta, F.] NCI, NIH, Bethsda, MD USA. [Gochuico, B. R.] NHGRI, NIH, Bethesda, MD 20892 USA. EM elchemalys@nhlbi.nih.gov RI Cuttitta, Frank/B-4758-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A6248 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105839 ER PT J AU Fredriksson, K Yao, XL Lam, JK Bhakta, HB Levine, SJ AF Fredriksson, K. Yao, X. -L. Lam, J. K. Bhakta, H. B. Levine, S. J. TI Exosomes Derived from Antigen-Pulsed Immature Dendritic Cells Attenuate Airway Inflammation and Hyperresponsiveness in a Murine Model of Allergic Asthma. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Fredriksson, K.; Yao, X. -L.; Lam, J. K.; Bhakta, H. B.; Levine, S. J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3725 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103078 ER PT J AU Garantziotis, S Adair, JA Stober, V Zhuo, L Roberts, J Kimata, K AF Garantziotis, S. Adair, J. A. Stober, V. Zhuo, L. Roberts, J. Kimata, K. TI Inter-alpha-Trypsin Inhibitor Promotes Epithelial Recovery after Injury through Vitronectin Binding. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Garantziotis, S.; Adair, J. A.; Stober, V.; Roberts, J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Zhuo, L.; Kimata, K.] Aichi Med Univ, Nagakute, Aichi 48011, Japan. EM garantziotis@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A4954 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104418 ER PT J AU Garantziotis, S Stober, V Kornepati, A Siryaporn, E Lim, YP Zhuo, L Kimata, K AF Garantziotis, S. Stober, V. Kornepati, A. Siryaporn, E. Lim, Y. P. Zhuo, L. Kimata, K. TI Inter-alpha-Trypsin Inhibitor Ameliorates Endotoxin-Induced Endothelial Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Garantziotis, S.; Stober, V.; Kornepati, A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Siryaporn, E.; Lim, Y. P.] Brown Univ, East Providence, RI USA. [Siryaporn, E.; Lim, Y. P.] ProThera Biol Inc, East Providence, RI USA. [Zhuo, L.; Kimata, K.] Aichi Med Univ, Nakagute, Aichi, Japan. EM garantziotis@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3059 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102294 ER PT J AU Geyer, A Gochuico, B Kaminski, N Morse, D Rosas, I AF Geyer, A. Gochuico, B. Kaminski, N. Morse, D. Rosas, I. TI Decreased Expression of Cholesterol and Fatty Acid Synthesis Genes in Lungs of Patients with Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Geyer, A.; Morse, D.; Rosas, I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kaminski, N.] Univ Pittsburgh, Pittsburgh, PA USA. [Gochuico, B.] NIH, Bethesda, MD 20892 USA. EM aigeyer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1912 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101031 ER PT J AU Gladwell, W Cho, H Degraff, LM Martin, J Perrow, L Kleeberger, SR AF Gladwell, W., II Cho, H. Degraff, L. Miller Martin, J. Perrow, L. Kleeberger, S. R. TI A Genetic Model of Bronchopulmonary Dysplasia in Neonate Inbred Strains of Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gladwell, W., II; Cho, H.; Degraff, L. Miller; Martin, J.; Perrow, L.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC 27709 USA. EM gladwell@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2762 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101881 ER PT J AU Glasgow, CG Avila, NA Lin, JP Stylianou, MP Moss, J AF Glasgow, C. G. Avila, N. A. Lin, J-P Stylianou, M. P. Moss, J. TI Serum VEGF-D Levels in Patients with Lymphangioleiomyomatosis (LAM) Reflect Lymphatic Involvement. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Glasgow, C. G.; Moss, J.] NHLBI, Translat Med Branch, NIH, Bethesda, MD USA. [Lin, J-P; Stylianou, M. P.] NHLBI, Off Biostat Res, Div Prevent & Publ Serv, NIH, Bethesda, MD USA. [Avila, N. A.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM glasgowc@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4336 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103689 ER PT J AU Graham, BB Zhang, L Mentink-Kane, MM El-Haddad, H Champion, HS Wynn, TA Butrous, G Tuder, RM AF Graham, B. B. Zhang, L. Mentink-Kane, M. M. El-Haddad, H. Champion, H. S. Wynn, T. A. Butrous, G. Tuder, R. M. TI Physiologic and Pathologic Analysis of a Murine Model of Schistosomiasis Pulmonary Vascular Remodeling. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Graham, B. B.; Zhang, L.; Tuder, R. M.] Univ Colorado, Boulder, CO 80309 USA. [Mentink-Kane, M. M.; Wynn, T. A.] Natl Inst Hlth, Bethesda, MD 20892 USA. [Butrous, G.] Univ Kent, Pulm Vasc Res Inst, Canterbury CT2 7NZ, Kent, England. EM brian.graham@uchsc.edu NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A1796 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100796 ER PT J AU Gwinn, WM Kapita, MC Martin, WJ AF Gwinn, W. M. Kapita, M. C. Martin, W. J., II TI Alveolar Macrophages Are Not Required for the Initiation of Bleomycin-Induced Pulmonary Fibrosis. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gwinn, W. M.; Kapita, M. C.; Martin, W. J., II] NIEHS, Res Triangle Pk, NC 27709 USA. EM gwinnwm@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3428 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102663 ER PT J AU Haberg, SE Bentdal, YE London, SJ Stigum, H Kvaerner, KJ Nystad, W Nafstad, P AF Haberg, S. E. Bentdal, Y. E. London, S. J. Stigum, H. Kvaerner, K. J. Nystad, W. Nafstad, P. TI Pre- and Postnatal Parental Smoking and Acute Otitis Media in Early Childhood. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Haberg, S. E.; Stigum, H.; Nystad, W.; Nafstad, P.] Norwegian Inst Publ Hlth, Oslo, Norway. [Bentdal, Y. E.; Kvaerner, K. J.] Akershus Univ Hosp Norway, Lorenskog, Norway. [London, S. J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Kvaerner, K. J.; Nafstad, P.] Univ Oslo, Oslo, Norway. EM siri.haberg@fhi.no NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4804 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104268 ER PT J AU Hancock, DB Romieu, I Sienra-Monge, JJ Chiu, GY Shi, M Wu, H Li, H del Rio-Navarro, BE London, SJ AF Hancock, D. B. Romieu, I. Sienra-Monge, J. J. Chiu, G. Y. Shi, M. Wu, H. Li, H. del Rio-Navarro, B. E. London, S. J. TI Genome-Wide Association Study of Childhood Asthma in Families from Mexico City SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hancock, D. B.; Chiu, G. Y.; Shi, M.; Wu, H.; Li, H.; London, S. J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Romieu, I.] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Sienra-Monge, J. J.; del Rio-Navarro, B. E.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. EM hancockd@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1675 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100675 ER PT J AU Hollingsworth, JW Free, M Li, Z Novack, L Cook, DN AF Hollingsworth, J. W. Free, M. Li, Z. Novack, L. Cook, D. N. TI Ambient Ozone Promotes Sensitization to Inhaled Allergens by a TLR4 and TNF-a Dependent Mechanism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Hollingsworth, J. W.; Li, Z.] Duke Univ, Medicial Ctr, Durham, NC USA. [Free, M.; Novack, L.; Cook, D. N.] NIEHS, Res Triangle Pk, NC 27709 USA. EM holli017@mc.duke.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2245 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101364 ER PT J AU Howden, R Hartzell, KM Gladwell, W Martin, J Clark, J Myers, P Kleeberger, S Mishina, Y AF Howden, R. Hartzell, K. McCann Gladwell, W. Martin, J. Clark, J. Myers, P. Kleeberger, S. Mishina, Y. TI Heart Rate and QT Interval Responses to Hyperoxia in Bmp 2 and Bmp 4 Heterozygous Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Howden, R.] UNC Charlotte, Charlotte, NC USA. [Hartzell, K. McCann; Gladwell, W.; Martin, J.; Clark, J.; Myers, P.; Kleeberger, S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Mishina, Y.] Univ Michcigan, Detroit, MI USA. EM rhowden@uncc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3567 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102801 ER PT J AU Jancewicz, JM Martinez, JC Gonzalez, DR Andaluz, AC Garantziotis, S Schwartz, DA Evans, CM AF Jancewicz, J. M. Martinez, J. C. Gonzalez, D. R. Andaluz, A. C. Garantziotis, S. Schwartz, D. A. Evans, C. M. TI Control of Bleomycin Induced Fibrosis by Muc5ac Production and Mucociliary Clearance. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Jancewicz, J. M.; Evans, C. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Martinez, J. C.; Gonzalez, D. R.; Andaluz, A. C.] Escuela Med, Inst Tecnol Monterrey, Monterrey, Nuevo Leon, Mexico. [Garantziotis, S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Schwartz, D. A.] Natl Jewish Hlth, Denver, CO USA. EM jmfriesk@mdanderson.org RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A6290 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105881 ER PT J AU Kleeberger, SR Fanucchi, MV Fostel, J Ballinger, CA Postlethwait, EM AF Kleeberger, S. R. Fanucchi, M. V. Fostel, J. Ballinger, C. A. Postlethwait, E. M. TI Site-Specific Ozone Exposure Effects on Gene Expression in Developing Primate Lungs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kleeberger, S. R.; Fostel, J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Fanucchi, M. V.; Ballinger, C. A.; Postlethwait, E. M.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2392 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101511 ER PT J AU Kliment, CR Gochuico, BR Kaminski, N Rosas, IO Oury, TD AF Kliment, C. R. Gochuico, B. R. Kaminski, N. Rosas, I. O. Oury, T. D. TI Contrasts between IPF and Mouse Models of Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kliment, C. R.; Kaminski, N.; Oury, T. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Gochuico, B. R.] NHGRI, NIH, Bethesda, MD 20892 USA. [Rosas, I. O.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM crk15@pitt.edu NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A2716 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101835 ER PT J AU Konishi, K Gochuico, BR Herazo, JD Richards, T MacDonald, SD Kaminski, N Rosas, IO AF Konishi, K. Gochuico, B. R. Herazo, J. D. Richards, T. MacDonald, S. D. Kaminski, N. Rosas, I. O. TI Molecular Characterization of Early Interstitial Lung Disease in Familial Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Konishi, K.; Herazo, J. D.; MacDonald, S. D.; Kaminski, N.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Gochuico, B. R.; Richards, T.] NIH, Intramural Div, Bethesda, MD 20892 USA. [Rosas, I. O.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM konishik@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3494 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102729 ER PT J AU Lam, JK Yao, X Fredriksson, K Yu, ZX Bhakta, HC Wagner, S Levine, SJ AF Lam, J. K. Yao, X. Fredriksson, K. Yu, Z. X. Bhakta, H. C. Wagner, S. Levine, S. J. TI Sorafenib, a Multi-Target Receptor Tyrosine Kinase Inhibitor, Attenuates the Induction of Airway Inflammation in a Murine Model of Allergic Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lam, J. K.; Yao, X.; Fredriksson, K.; Yu, Z. X.; Bhakta, H. C.; Wagner, S.; Levine, S. J.] NIH, Bethesda, MD 20892 USA. EM lamjk@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2238 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101357 ER PT J AU Li, H Romieu, I Hancock, DB Wu, H Shi, M Sienra-Monge, JJ Chiu, GY Del-Rio-Navarro, BE London, SJ AF Li, H. Romieu, I. Hancock, D. B. Wu, H. Shi, M. Sienra-Monge, J. J. Chiu, G. Y. Del-Rio-Navarro, B. E. London, S. J. TI Evaluation of Candidate Genes in Relation to Degree of Atopy in a Genome-Wide Association Study among Asthmatic Children in Mexico City. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Li, H.; Hancock, D. B.; Wu, H.; Shi, M.; London, S. J.] NIEHS, Res Triangle Pk, NC 27709 USA. [Romieu, I.] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Sienra-Monge, J. J.; Del-Rio-Navarro, B. E.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Chiu, G. Y.] Westat Corp, Res Triangle Pk, NC USA. EM li12@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5419 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105010 ER PT J AU Li, Y Cui, X Su, J Fitz, Y Barochia, A Altaweel, L Eichacker, PQ AF Li, Y. Cui, X. Su, J. Fitz, Y. Barochia, A. Altaweel, L. Eichacker, P. Q. TI Heparin Increased aPTT but Not Survival in a Mouse E. coli Pneumonia Model. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Li, Y.; Cui, X.; Su, J.; Fitz, Y.; Barochia, A.; Altaweel, L.; Eichacker, P. Q.] NIH, CCMD, CC, Bethesda, MD 20892 USA. EM yli@mail.cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4712 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104177 ER PT J AU Long, RA Palmer, SM Snyder, LR Stober, V Hollingsworth, JW Li, Z Bortner, C Jiang, D Noble, PW Garantziotis, S AF Long, R. A. Palmer, S. M. Snyder, L. R. Stober, V. Hollingsworth, J. W. Li, Z. Bortner, C. Jiang, D. Noble, P. W. Garantziotis, S. TI Bronchial Epithelial Injury in the Context of Alloimmunity Promotes Lymphocytic Bronchiolitis Via Hyaluronan Expression SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Long, R. A.; Stober, V.; Bortner, C.; Garantziotis, S.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Palmer, S. M.; Snyder, L. R.; Hollingsworth, J. W.; Li, Z.; Jiang, D.; Noble, P. W.] Duke Univ, Med Ctr, Durham, NC USA. EM longr2@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A5630 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105221 ER PT J AU Machado, RF Reda, D Tropea, M Gladwin, MT Suffredini, AF AF Machado, R. F. Reda, D. Tropea, M. Gladwin, M. T. Suffredini, A. F. TI The Effects of Inhaled Carbon Monoxide on Endotoxin-Induced Pulmonary Inflammation in Humans. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Machado, R. F.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Machado, R. F.; Reda, D.; Tropea, M.; Suffredini, A. F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Gladwin, M. T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A5673 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105264 ER PT J AU Madenspacher, JH Smoak, KA Draper, DW Fessler, MB AF Madenspacher, J. H. Smoak, K. A. Draper, D. W. Fessler, M. B. TI Dyslipidemia Exerts Opposite Effects on Pulmonary and Extrapulmonary Host Defense. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Madenspacher, J. H.; Smoak, K. A.; Draper, D. W.; Fessler, M. B.] NIEHS, NIH, Res Triangle Pk, NC USA. EM madensp1@niehs.nih.gov NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A3253 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102488 ER PT J AU Martinu, T Kinnier, CV Gowdy, K Smith, RL Kelly, FL Snyder, LD Jiang, D Garantziotis, S Belperio, JA Noble, PW Palmer, SM AF Martinu, T. Kinnier, C. V. Gowdy, K. Smith, R. L. Kelly, F. L. Snyder, L. D. Jiang, D. Garantziotis, S. Belperio, J. A. Noble, P. W. Palmer, S. M. TI CXCR3-Chemokine Pathway in a Model of Murine Alloimmune Lymphocytic Bronchiolitis (AlloLB). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Martinu, T.; Kinnier, C. V.; Gowdy, K.; Smith, R. L.; Kelly, F. L.; Snyder, L. D.; Jiang, D.; Noble, P. W.; Palmer, S. M.] Duke Univ, Durham, NC USA. [Garantziotis, S.] NIEHS, Res Triangle Pk, NC USA. [Belperio, J. A.] Univ Calif Los Angeles, Los Angeles, CA USA. EM tereza.martinu@duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3742 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103095 ER PT J AU Matthay, MA Brower, R Thompson, BT Schoenfeld, D Eisner, MD Carson, S Moss, M Douglas, I Hite, D MacIntyre, N Liu, KD AF Matthay, M. A. Brower, R. Thompson, B. T. Schoenfeld, D. Eisner, M. D. Carson, S. Moss, M. Douglas, I. Hite, D. MacIntyre, N. Liu, K. D. CA NHLBI ARDS Network TI Randomized, Placebo-Controlled Trial of an Aerosolized Beta-2 Adrenergic Agonist (Albuterol) for the Treatment of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Matthay, M. A.; Brower, R.; Thompson, B. T.; Schoenfeld, D.; Eisner, M. D.; Carson, S.; Moss, M.; Douglas, I.; Hite, D.; MacIntyre, N.; Liu, K. D.] NHLBI ARDS Network, Bethesda, MD 20892 USA. EM michael.matthay@ucsf.edu NR 0 TC 16 Z9 16 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. PY 2009 VL 179 MA A2166 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101285 ER PT J AU McAllister, DA MacNee, W Duprez, D Hoffman, E Vogel-Claussen, J Jiang, R Bleumke, D Barr, RG AF McAllister, D. A. MacNee, W. Duprez, D. Hoffman, E. Vogel-Claussen, J. Jiang, R. Bleumke, D. Barr, R. G. TI Aortic Distensibility Is Not Associated with Lung Function or CT Percent Low Attenuation Area in Participants without Clinical Cardiovascular Disease. The MESA-Lung Study. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [McAllister, D. A.; MacNee, W.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Duprez, D.] Univ Minnesota, Minneapolis, MN 55455 USA. [Hoffman, E.] Univ Iowa, Iowa City, IA 52242 USA. [Vogel-Claussen, J.; Bleumke, D.] NIH, Bethesda, MD USA. [Jiang, R.; Barr, R. G.] Columbia Univ, New York, NY 10027 USA. EM david.mcallister@ed.ac.uk NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A4026 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103379 ER PT J AU Meoli, DF Haight, D Franciscetti, I Awad, H White, RJ AF Meoli, D. F. Haight, D. Franciscetti, I. Awad, H. White, R. J. TI Ixolaris, a Tissue Factor Inhibitor, Preserves Vascular Perfusion as Assessed by Quantitative Micro CT Scan in Rats with Established Pulmonary Arterial Hypertension (PAH) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Meoli, D. F.; Haight, D.; White, R. J.] Univ Rochester, Aab CVRI, Rochester, NY USA. [Meoli, D. F.; Haight, D.; White, R. J.] Pulm CCM, Rochester, NY USA. [Franciscetti, I.] NIAID, NIH, Bethesda, MD 20892 USA. [Awad, H.] Univ Rochester, Ctr Musculoskel, Rochester, NY USA. EM David_Meoli@urmc.rochester.edu RI Awad, Hani/G-6976-2014 OI Awad, Hani/0000-0003-2197-2610 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1837 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100836 ER PT J AU Merrick, BA Madenspacher, JH DeGraff, LM Fessler, MF AF Merrick, B. A. Madenspacher, J. H. DeGraff, L. M. Fessler, M. F. TI p53 Is a Negative Regulator of Pulmonary Innate Immunity. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Merrick, B. A.; Madenspacher, J. H.; DeGraff, L. M.; Fessler, M. F.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. EM merrick@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2846 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102081 ER PT J AU Munson, JC Kreider, ME Chen, Z Christie, JD Kimmel, SE AF Munson, J. C. Kreider, M. E. Chen, Z. Christie, J. D. Kimmel, S. E. TI Factors Associated with Corticosteroid Therapy in Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Munson, J. C.; Kreider, M. E.; Christie, J. D.; Kimmel, S. E.] Univ Penn, Philadelphia, PA 19104 USA. [Chen, Z.] NIH, Bethesda, MD 20892 USA. EM jeffrey.munson@uphs.upenn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4050 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103403 ER PT J AU Nakhleh, N Swisher, M Francis, R Giese, R Chatterjee, B Connelly, P Sami, I Kuehl, K Olivier, K Jonas, R Tian, X Zariwala, M Omran, H Leigh, M Knowles, M Leatherbury, L Lo, CW AF Nakhleh, N. Swisher, M. Francis, R. Giese, R. Chatterjee, B. Connelly, P. Sami, I. Kuehl, K. Olivier, K. Jonas, R. Tian, X. Zariwala, M. Omran, H. Leigh, M. Knowles, M. Leatherbury, L. Lo, C. W. TI Low Nasal Nitric Oxide and Ciliary Dysmotility in Patients with Congenital Heart Disease and Heterotaxy: The Challenge of Defining a Ciliopathy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nakhleh, N.; Swisher, M.; Francis, R.; Giese, R.; Chatterjee, B.; Connelly, P.; Olivier, K.; Tian, X.; Leatherbury, L.; Lo, C. W.] NIH, Bethesda, MD 20892 USA. [Nakhleh, N.; Sami, I.; Kuehl, K.; Jonas, R.; Leatherbury, L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Omran, H.] Univ Childrens Hosp, Freiburg, Germany. [Zariwala, M.; Leigh, M.; Knowles, M.] Univ N Carolina, Chapel Hill, NC USA. EM nnakhleh@cnmc.org NR 0 TC 0 Z9 0 U1 1 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. PY 2009 VL 179 MA A2213 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101332 ER PT J AU OBrien, CM Cao, YX Gochuico, BR Ramirez, MI AF OBrien, C. M. Cao, Y. X. Gochuico, B. R. Ramirez, M. I. TI Chromatin Remodeling in the Regulation of Gene Expression in Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [OBrien, C. M.; Cao, Y. X.; Ramirez, M. I.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gochuico, B. R.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1886 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101005 ER PT J AU Prevots, DR Strickland, D Jackson, L Shaw, P Shea, YR de Oca, RM Olivier, KN AF Prevots, D. R. Strickland, D. Jackson, L. Shaw, P. Shea, Y. R. de Oca, R. Montes Olivier, K. N. TI Prevalence of Nontuberculous Mycobacterial Disease, Kaiser Permanente Southern California, and Group Health Cooperative, Seattle, Washington, 1991-2006. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Prevots, D. R.; Shaw, P.; Shea, Y. R.; de Oca, R. Montes; Olivier, K. N.] NIH, Bethesda, MD 20892 USA. [Strickland, D.] Kaiser Permanente So Calif, Pasadena, CA 91101 USA. [Jackson, L.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. EM rprevots@niaid.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A5266 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104730 ER PT J AU Quagliarello, B Hoffman, E Jacobs, D Klein, R Klein, B Wong, T Cotch, MF Jerosch-Herold, M Barr, RG AF Quagliarello, B. Hoffman, E. Jacobs, D. Klein, R. Klein, B. Wong, T. Cotch, M. F. Jerosch-Herold, M. Barr, R. G. TI Systemic Microvascular Changes and Lung Function: The MESA Lung Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Quagliarello, B.; Barr, R. G.] Columbia Univ, New York, NY USA. [Hoffman, E.] Univ Iowa, Iowa City, IA USA. [Jacobs, D.; Jerosch-Herold, M.] Univ Minnesota, Minneapolis, MN USA. [Klein, R.; Klein, B.] Univ Wisconsin, Madison, WI USA. [Wong, T.] Univ Melbourne, Melbourne, Vic, Australia. [Cotch, M. F.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4521 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103874 ER PT J AU Rump, AP Holland, SM Olivier, KN AF Rump, A. P. Holland, S. M. Olivier, K. N. TI Use of Posaconazole for Airway Fungi in Pulmonary Nontuberculous Mycobacteria (PNTM) Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Rump, A. P.] NCI, LCID, SAIC Frederick Inc, Frederick, MD 21701 USA. [Holland, S. M.; Olivier, K. N.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A1689 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100689 ER PT J AU Sapru, A Liu, KD Wiemels, J Pawlikowska, L Hansen, H Sen, S Aouizerat, B Witte, J Calfee, CS Ware, LB Matthay, MA AF Sapru, A. Liu, K. D. Wiemels, J. Pawlikowska, L. Hansen, H. Sen, S. Aouizerat, B. Witte, J. Calfee, C. S. Ware, L. B. Matthay, M. A. CA NHLBI ARDS Network TI Common Genetic Variants in the Protein C, Endothelial Protein C Receptor and Thrombomodulin Genes Are Associated with Outcomes in Acute Lung Injury. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sapru, A.; Liu, K. D.; Wiemels, J.; Pawlikowska, L.; Hansen, H.; Sen, S.; Aouizerat, B.; Witte, J.; Calfee, C. S.; Ware, L. B.; Matthay, M. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [NHLBI ARDS Network] NIH, Bethesda, MD 20892 USA. EM aniil.sapru@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103229 ER PT J AU Schlenz, H Wess, J Kummer, W Krasteva, G AF Schlenz, H. Wess, J. Kummer, W. Krasteva, G. TI Muscarinic Receptor-2-Mediated Constriction of Murine Bronchi Is Caveolae-Dependent SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Schlenz, H.; Kummer, W.; Krasteva, G.] Univ Giessen, UGLC, ECCPS, Inst Anat & Cell Biol, Giessen, Germany. [Wess, J.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. EM Heike.Schlenz@anatomie.med.uni-giessen.de NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2061 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101180 ER PT J AU Seitz, A Oliver, K Steiner, C de Oca, RM Prevots, DR AF Seitz, A. Oliver, K. Steiner, C. de Oca, R. Montes Prevots, D. R. TI Prevalence of Bronchiectasis-Associated Hospitalizations: USA, 1993-2006. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Seitz, A.; Oliver, K.; de Oca, R. Montes; Prevots, D. R.] NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3222 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102457 ER PT J AU Shah, NG Tulapurkar, ME Almutairy, EA Hasday, JD AF Shah, N. G. Tulapurkar, M. E. Almutairy, E. A. Hasday, J. D. TI Febrile-Range Hyperthermia Augments TNF-alpha Induced Permeability in Human Microvascular Endothelial Cells in the Lung (hMVEC-L). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Shah, N. G.; Tulapurkar, M. E.; Almutairy, E. A.; Hasday, J. D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Shah, N. G.] NIH, Bethesda, MD 20892 USA. EM shahn2@mail.nih.gov RI tulapurkar, mohan/F-1926-2015 OI tulapurkar, mohan/0000-0002-2476-5417 NR 0 TC 1 Z9 1 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. PY 2009 VL 179 MA A4014 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103367 ER PT J AU Shehata, ML Singh, S Mathai, SC Lima, JA Bluemke, DA Hassoun, P Vogel-Claussen, J AF Shehata, M. L. Singh, S. Mathai, S. C. Lima, J. A. Bluemke, D. A. Hassoun, P. Vogel-Claussen, J. TI Flow Dynamics and Pulmonary Distensibility in Systemic Sclerosis Using Velocity Encoded MRI. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Shehata, M. L.; Singh, S.; Mathai, S. C.; Lima, J. A.; Hassoun, P.; Vogel-Claussen, J.] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, D. A.] NIH, Bethesda, MD 20892 USA. EM mshehat1@jhmi.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3393 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102628 ER PT J AU Silva, PMRE Ferreira, TPT Arantes, ACS Rocco, PRM Puri, R Hogaboam, C Martins, MA AF Silva, P. M. R. E. Ferreira, T. P. T. Arantes, A. C. S. Rocco, P. R. M. Puri, R. Hogaboam, C. Martins, M. A. TI Therapeutic Attenuation of Silica-Induced Pulmonary Fibrosis by Immunotoxin Chimeric Molecule IL-13PE. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Silva, P. M. R. E.; Ferreira, T. P. T.; Arantes, A. C. S.; Martins, M. A.] Fundacao Oswaldo Cruz, Rio De Janeiro, Brazil. [Rocco, P. R. M.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Puri, R.] NIH, Bethesda, MD 20892 USA. [Hogaboam, C.] Univ Michigan, Ann Arbor, MI 48109 USA. EM patmar@ioc.fiocruz.br RI hogaboam, cory /M-3578-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4001 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103354 ER PT J AU Swisher, MW Jonas, R Tian, X Lo, CW Leatherbury, L AF Swisher, M. W. Jonas, R. Tian, X. Lo, C. W. Leatherbury, L. TI Increased Postoperative Respiratory Complications in Patients with Congenital Heart Disease and Heterotaxy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Swisher, M. W.; Tian, X.; Lo, C. W.; Leatherbury, L.] NIH, Bethesda, MD 20892 USA. [Jonas, R.; Leatherbury, L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. EM mws17@duke.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1223 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100224 ER PT J AU Takaro, TK Arbes, SJ Calatroni, A Zeldin, DC AF Takaro, T. K. Arbes, S. J. Calatroni, A. Zeldin, D. C. TI The Association between Systemic Inflammation and Asthma Is Greater in the Non-Atopic Phenotype: A Comparison of NHANES III and NHANES 2005-2006. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Takaro, T. K.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Arbes, S. J.; Calatroni, A.] Rho Inc, Chapel Hill, NC USA. [Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA. EM ttakaro@sfu.ca NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4756 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104220 ER PT J AU Takaro, TK Arbes, SJ Calatroni, A Zeldin, DC AF Takaro, T. K. Arbes, S. J. Calatroni, A. Zeldin, D. C. TI The Association between Systemic Inflammation and Decreased FEV1 Is Greater in the Non-Atopic Phenotype in NHANES III. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Takaro, T. K.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Arbes, S. J.; Calatroni, A.] Rho Inc, Chapel Hill, NC USA. [Zeldin, D. C.] NIEHS, Res Triangle Pk, NC USA. EM ttakaro@sfu.ca NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4757 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104221 ER PT J AU Tauseef, M Knezevic, N Kini, V Vogel, S Dietrich, A Malik, AB Birnbaumer, L Mehta, D AF Tauseef, M. Knezevic, N. Kini, V. Vogel, S. Dietrich, A. Malik, A. B. Birnbaumer, L. Mehta, D. TI TRPC6 Channel Mediated Calcium Entry Requires RhoA and Myosin Light Chain Kinase To Increase Lung Vascular Permeability SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Tauseef, M.; Knezevic, N.; Kini, V.; Vogel, S.; Malik, A. B.; Mehta, D.] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA. [Dietrich, A.; Birnbaumer, L.] NIH, Div Intramural Res, Bethesda, NC USA. EM mtauseef@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2333 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101452 ER PT J AU Taveira-DaSilva, AM Steagall, WK Rabel, A Hathaway, OM Harari, S Cassandro, R Stylianou, M Moss, J AF Taveira-DaSilva, A. M. Steagall, W. K. Rabel, A. Hathaway, O. M. Harari, S. Cassandro, R. Stylianou, M. Moss, J. TI Reversible Airflow Obstruction in Lymphangioleiomyomatosis. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Taveira-DaSilva, A. M.; Steagall, W. K.; Rabel, A.; Hathaway, O. M.; Stylianou, M.; Moss, J.] NIH, Bethesda, MD 20892 USA. [Harari, S.; Cassandro, R.] Osped San Giuseppe, Milan, Italy. EM dasilvaa@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4345 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103698 ER PT J AU Thorne, PS Cohn, RD Mav, D Arbes, SJ Zeldin, DC AF Thorne, P. S. Cohn, R. D. Mav, D. Arbes, S. J., Jr. Zeldin, D. C. TI Predictors of Endotoxin Concentration and Load in US Housing. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Thorne, P. S.] Univ Iowa, Iowa City, IA USA. [Cohn, R. D.; Mav, D.] Constella Grp LLC, Durham, NC USA. [Arbes, S. J., Jr.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA. EM peter-thorne@uiowa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4747 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104211 ER PT J AU Trivedi, S Ciencewicki, J Cho, HY Horvath, K Jaspers, I Kleeberger, SR AF Trivedi, S. Ciencewicki, J. Cho, H. Y. Horvath, K. Jaspers, I. Kleeberger, S. R. TI Expression of Notch and Its Ligands in Mice Exposed to Ozone SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Trivedi, S.; Ciencewicki, J.; Cho, H. Y.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC 27709 USA. [Horvath, K.; Jaspers, I.] Univ N Carolina, Chapel Hill, NC USA. EM trivedis@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2572 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101691 ER PT J AU Ventetuolo, CE Ouyang, P Bluemke, DA Tandri, H Barr, RG Bagiella, E Bristow, M Johnson, C Kizer, J Lima, JA Kawut, SM AF Ventetuolo, C. E. Ouyang, P. Bluemke, D. A. Tandri, H. Barr, R. G. Bagiella, E. Bristow, M. Johnson, C. Kizer, J. Lima, J. A. Kawut, S. M. TI Sex Hormones and the Right Ventricle: The MESA-Right Ventricle Study. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ventetuolo, C. E.; Barr, R. G.; Bagiella, E.] Columbia Univ, New York, NY USA. [Ouyang, P.; Tandri, H.; Lima, J. A.] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, D. A.] NIH, Bethesda, MD 20892 USA. [Bristow, M.] Univ Colorado, Denver, CO 80202 USA. [Johnson, C.] Univ Washington, Seattle, WA 98195 USA. [Kizer, J.] Cornell Univ, New York, NY 10021 USA. [Kawut, S. M.] Univ Penn, Philadelphia, PA 19104 USA. EM cev2105@columbia.edu NR 0 TC 1 Z9 1 U1 1 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. PY 2009 VL 179 MA A4150 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103503 ER PT J AU Walters, DM Martin, JR Gladwell, W Wiltshire, T Kleeberger, SR AF Walters, D. M. Martin, J. R. Gladwell, W. Wiltshire, T. Kleeberger, S. R. TI Genetic Susceptibility to Vanadium-Induced Lung Phenotypes in Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Walters, D. M.; Martin, J. R.; Gladwell, W.; Kleeberger, S. R.] NIEHS, Res Triangle Pk, NC USA. [Walters, D. M.] ECU, BSOM, Dept Physiol, Greenville, NC USA. [Wiltshire, T.] UNC CH, Sch Pharm, Chapel Hill, NC USA. EM waltersd@ecu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1663 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100663 ER PT J AU Wang, PM Martin, WJ AF Wang, P. M. Martin, W. J., II CA Lab Lung Injury Repair Lab Resp Biol TI Alveolar Tissuegenesis and Repair by Airway Delivery of Donor Type II Epithelial Cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, P. M.; Martin, W. J., II] NIEHS, Res Triangle Pk, NC 27709 USA. EM wangp3@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5383 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104847 ER PT J AU Wang, PM Martin, WJ AF Wang, P. M. Martin, W. J., II CA Lab Lung Injury Repair Lab Resp Biol TI Transmigration of Inflammatory Cells through Pulmonary Arterioles in Murine Lungs after Bleomycin SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, P. M.] NIEHS, Res Triangle Pk, NC 27709 USA. EM wangp3@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2725 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101844 ER PT J AU Wohlford-Lenane, CL Giomarelli, B McMahon, JB O'Keefe, BR Meyerholz, D McCray, PB AF Wohlford-Lenane, C. L. Giomarelli, B. McMahon, J. B. O'Keefe, B. R. Meyerholz, D. McCray, P. B. TI Protective Role of Griffithsin in Severe Acute Respiratory Syndrome Pulmonary Infection. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wohlford-Lenane, C. L.; McCray, P. B.] Univ Iowa, Iowa City, IA USA. [Giomarelli, B.; McMahon, J. B.; O'Keefe, B. R.] NCI, Frederick, MD 21701 USA. [Meyerholz, D.] Roy J & Lucille A Carver Coll Med, Iowa City, IA USA. EM c-wohlford-lenane@uiowa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5954 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105545 ER PT J AU Wood, RA Visness, C Gergen, P Bloomberg, GR Kattan, M Sandel, M Conroy, K Dresen, A Gern, JE AF Wood, R. A. Visness, C. Gergen, P. Bloomberg, G. R. Kattan, M. Sandel, M. Conroy, K. Dresen, A. Gern, J. E. CA Inner City Asthma Consortium TI Effect of Immune Development and Clinical Predictors on Atopic Outcomes at Age 12 Months in an Urban Birth Cohort Study. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wood, R. A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Gergen, P.] NIAID, NIH, Bethesda, MD 20892 USA. [Bloomberg, G. R.] Washington Univ, St Louis, MO 63130 USA. [Kattan, M.] Columbia Univ, New York, NY 10027 USA. [Sandel, M.; Conroy, K.] Boston Univ, Boston, MA 02215 USA. [Dresen, A.; Gern, J. E.] Univ Wisconsin Madison, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 2009 VL 179 MA A6223 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105814 ER PT J AU Woszczek, G Chen, LY Nagineni, S Shelhamer, JH AF Woszczek, G. Chen, L. Y. Nagineni, S. Shelhamer, J. H. TI Concentration Dependent Non-Cysteinyl Leukotriene Type 1 Receptor (CysLT1) Mediated Inhibitory Activity of Leukotriene Receptor Antagonists (LTRAs). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Woszczek, G.; Chen, L. Y.; Nagineni, S.; Shelhamer, J. H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Woszczek, G.] Kings Coll London, Dept Asthma Allergy & Resp Sci, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2856 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102091 ER PT J AU Wu, H Romieu, I Hancock, DB Li, H Shi, M Sienra-Monge, JJ Chiu, GY del Rio-Navarro, BE London, SJ AF Wu, H. Romieu, I. Hancock, D. B. Li, H. Shi, M. Sienra-Monge, J. J. Chiu, G. Y. del Rio-Navarro, B. E. London, S. J. TI Evaluation of Asthma Candidate Genes in a Genome-Wide Association Study of Childhood Asthma in a Mexican Population. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wu, H.; Hancock, D. B.; Li, H.; Shi, M.; London, S. J.] NIEHS, DIR, NIH, DHHS, Res Triangle Pk, NC USA. [Romieu, I.] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Sienra-Monge, J. J.; del Rio-Navarro, B. E.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Chiu, G. Y.] Westat Corp, Res Triangle Pk, NC USA. EM wuh2@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5416 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105007 ER PT J AU Yu, G Konishi, K Herazo, JD Hanley, D Pacheco, G Richards, T Kaminski, N Rosas, IO AF Yu, G. Konishi, K. Herazo, J. D. Hanley, D. Pacheco, G. Richards, T. Kaminski, N. Rosas, I. O. TI Positive Feedback Loop Regulates Transcription of Syndecan-2 and Multiple TGF-beta Target Genes in HL-60 Cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yu, G.; Konishi, K.; Herazo, J. D.; Hanley, D.; Richards, T.; Kaminski, N.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Pacheco, G.] Intramural NHLBI, Bethesda, MD 20892 USA. [Rosas, I. O.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM yug@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1876 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100875 ER PT J AU Morovic, A Jaffe, ES Raffeld, M Schrager, JA AF Morovic, Anamarija Jaffe, Elaine S. Raffeld, Mark Schrager, Jeffrey A. TI Metachronous EBV-associated B-cell and T-cell Posttransplant Lymphoproliferative Disorders in a Heart Transplant Recipient SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE posttransplant lymphoproliferative disorders; bilineal; Epstein-Barr virus; case report ID EPSTEIN-BARR-VIRUS; LIVER-TRANSPLANTATION; LYMPHOMA; IMMUNOGLOBULIN; EXPRESSION; REARRANGEMENT; NEOPLASMS; RISK; PTLD AB Postransplant lymphoproliferative disorders (PTLDs) may occur as it complication of immunosuppression in patients who have received solid organ or bone marrow allografts. Most PTLDs are of B-cell lineage, whereas T-cell proliferations are rare. The majority of B-cell lesions are associated with Epstein-Barr virus infection. The occurrence of both B-cell and T-cell PTLDs in the same patient is extremely rare and only 6 cases have been previously published. We report it case of a 63-year-old man who developed 2 metachronous Epstein-Barr virus-related PTLDs beginning 10 years after heart transplantation. A polymorphic B-cell PTLD developed first that completely regressed after immunosuppressive therapy was partially withdrawn. Then, it monomorphic T-cell PTLD developed 31 months litter. The patient died 17 months later owing to disease progression. We highlight the diagnostic challenge of this case that required numerous ancillary studies for lineage assessment and classification. Such studies are often needed in patients with it history of immunosuppression. C1 [Morovic, Anamarija; Schrager, Jeffrey A.] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA. [Jaffe, Elaine S.; Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Schrager, JA (reprint author), Genzyme Genet, 521 W 57th St,6th Floor, New York, NY 10019 USA. EM jeffrey.schrager@genzyme.com NR 25 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2009 VL 33 IS 1 BP 149 EP 154 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 392CO UT WOS:000262280700019 PM 18941401 ER PT J AU Dhanireddy, KK Bruno, DA Weaver, TA Xu, H Zhang, X Leopardi, FV Hale, DA Kirk, AD AF Dhanireddy, K. K. Bruno, D. A. Weaver, T. A. Xu, H. Zhang, X. Leopardi, F. V. Hale, D. A. Kirk, A. D. TI Portal Venous Donor-Specific Transfusion in Conjunction with Sirolimus Prolongs Renal Allograft Survival in Nonhuman Primates SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Donor-specific transfusion; rhesus monkey; tolerance ID SINUSOIDAL ENDOTHELIAL-CELLS; ANTI-CD4 MONOCLONAL-ANTIBODY; T-CELLS; TRANSPLANTATION TOLERANCE; ISLET TRANSPLANTATION; BLOOD-TRANSFUSIONS; CARDIAC ALLOGRAFTS; LIVER; RECIPIENTS; CHIMERISM AB Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immunosuppression. Rodent studies have shown in some strain combinations that portal venous (PV) DST alone can induce tolerance, and uncontrolled clinical use of PVDST has been reported. In order to determine if pretransplant PVDST has a clinically relevant salutary effect, we studied it and the influence of concomitant immunosuppression in rhesus monkeys undergoing renal allotransplantation. Animals received PVDST with unfractionated bone marrow and/or tacrolimus or sirolimus 1 week prior to transplantation. Graft survival was assessed without any posttransplant immunosuppression. PVDST alone or in combination with tacrolimus was ineffective. However, PVDST in combination with sirolimus significantly prolonged renal allograft survival to a mean of 24 days. Preoperative sirolimus alone had no effect, and peripheral DST with sirolimus prolonged graft survival in 2/4 animals, but resulted in accelerated rejection in 2/4 animals. These data demonstrate that PVDST in combination with sirolimus delays rejection in a modest but measurable way in a rigorous model. It may thus be a preferable method for donor antigen administration. C1 [Dhanireddy, K. K.; Bruno, D. A.; Weaver, T. A.; Xu, H.; Zhang, X.; Leopardi, F. V.; Hale, D. A.; Kirk, A. D.] NIDDK, Transplantat Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dhanireddy, K. K.; Bruno, D. A.] Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. [Weaver, T. A.; Leopardi, F. V.; Kirk, A. D.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. RP Kirk, AD (reprint author), NIDDK, Transplantat Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM ADKirk@emory.edu RI Kirk, Allan/B-6905-2012 FU Division of Intramural Research; National Institute of Diabetes; Digestive and Kidney Disease; National Institutes of Health; Department of Surgery; Georgetown University Hospital; ASTS-NKF Folkert Belzer Research Award; Howard Hughes Medical Institute; Georgia Research Alliance; McKelvey Foundation FX This study was funded in part by the Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health. Salary support for KKD was provided by the Department of Surgery, Georgetown University Hospital. Salary support for DAB was provided by the ASTS-NKF Folkert Belzer Research Award. TAW was supported by the Howard Hughes Medical Institute. ADK is supported by the Georgia Research Alliance and by the McKelvey Foundation. The authors have no conflicting financial interests. NR 40 TC 5 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2009 VL 9 IS 1 BP 124 EP 131 DI 10.1111/j.1600-6143.2008.02448.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 386LT UT WOS:000261885400019 PM 18976300 ER PT J AU Olthoff, KM Emond, JC Trotter, JF Tong, L Merion, RM Baker, TB Berg, CL Fisher, RA Freise, CE Hayashi, PH Hong, J Everhart, JE AF Olthoff, K. M. Emond, J. C. Trotter, J. F. Tong, L. Merion, R. M. Baker, T. B. Berg, C. L. Fisher, R. A. Freise, C. E. Hayashi, P. H. Hong, J. Everhart, J. E. CA A2ALL Study Grp TI Liver Regeneration in Donors and Recipients in the Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Olthoff, K. M.; Emond, J. C.; Trotter, J. F.; Tong, L.; Merion, R. M.; Baker, T. B.; Berg, C. L.; Fisher, R. A.; Freise, C. E.; Hayashi, P. H.; Hong, J.; Everhart, J. E.; A2ALL Study Grp] NIDDK, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 232 EP 232 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800142 ER PT J AU Graham, LJ Hurst, FP Jindal, RM Falta, EM Agodoa, LY Neff, RT Abbott, KC AF Graham, Lindsey J. Hurst, Frank P. Jindal, Rahul M. Falta, Edward M. Agodoa, Lawrence Y. Neff, Robert T. Abbott, Kevin C. TI Incidence and Predictors of De Novo Renal Cell Carcinoma after Kidney Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Graham, Lindsey J.; Hurst, Frank P.; Jindal, Rahul M.; Falta, Edward M.; Neff, Robert T.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Agodoa, Lawrence Y.] NIDDK, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 238 EP 238 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800166 ER PT J AU Cohee, BM Hartzell, JD Hurst, FP Jindal, RM Agodoa, LY Abbott, KC Neff, RT AF Cohee, Brian M. Hartzell, Joshua D. Hurst, Frank P. Jindal, Rahul M. Agodoa, Lawrence Y. Abbott, Kevin C. Neff, Robert T. TI Incidence and Prognosis of West Nile Virus Following Kidney Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Cohee, Brian M.; Hartzell, Joshua D.; Hurst, Frank P.; Jindal, Rahul M.; Abbott, Kevin C.; Neff, Robert T.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA. 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 301 EP 301 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800383 ER PT J AU Breidenbach, W Herzig, R Kaufman, C Slone, S Blair, B Wilson, W Buell, J Ravindra, K AF Breidenbach, Warren Herzig, Roger Kaufman, Christina Slone, Stephen Blair, Brenda Wilson, Wyndom Buell, Joesph Ravindra, Kadiyala TI An Unusual PTLD-Like Syndrome in Hand Transplant Recipient 2 Years Post Transplant. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Herzig, Roger] Univ Louisville, Bone Marrow Transplant JGBCC, Louisville, KY 40292 USA. [Blair, Brenda; Buell, Joesph; Ravindra, Kadiyala] Jewish Hosptial & St Marys Healthcare, Transplant Ctr, Louisville, KY USA. NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 316 EP 316 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800433 ER PT J AU Andakyan, A Shen, XD Baibakov, B Ghobrial, MR Semiletova, NV AF Andakyan, Arthur Shen, Xiu-Da Baibakov, Boris Ghobrial, M. R. Semiletova, Natalya V. TI Severity of Chronic Rejection Might Be Modulated by Infiltrating Cells with Regulatory Phenotype SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Andakyan, Arthur; Shen, Xiu-Da; Semiletova, Natalya V.] Univ Calif Los Angeles, Los Angeles, CA USA. [Baibakov, Boris] NIDDK, NIH, Bethesda, MD USA. [Ghobrial, M. R.] Methodist Hosp, Houston, TX 77030 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 391 EP 391 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800692 ER PT J AU Kinnier, C Martinu, T Snyder, L Smith, R Kelly, F Lin, KF Garantziotis, S Palmer, S AF Kinnier, Christine Martinu, Tereza Snyder, Laurie Smith, Renata Kelly, Francine Lin, Kaifeng Garantziotis, Stavros Palmer, Scott TI Pulmonary Innate Immunity Differentially Regulates the Development of Allogeneic or Syngeneic Lung Disease in a Novel Adoptive Transfer Model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kinnier, Christine; Martinu, Tereza; Snyder, Laurie; Smith, Renata; Kelly, Francine; Lin, Kaifeng; Palmer, Scott] Duke Univ, Durham, NC 27706 USA. [Garantziotis, Stavros] NIEHS, Res Triangle Pk, NC USA. RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 401 EP 401 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800727 ER PT J AU Bostom, AG Carpenter, MA Hunsicker, L Jacques, PF Kusek, JW Levey, AS McKenney, JL Mercier, RY Pfeffer, MA Selhub, J AF Bostom, Andrew G. Carpenter, Myra A. Hunsicker, Lawrence Jacques, Paul F. Kusek, John W. Levey, Andrew S. McKenney, Joyce L. Mercier, Renee Y. Pfeffer, Marc A. Selhub, Jacob TI Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Rhode Isl Hosp, Providence, RI 02903 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Iowa, Iowa City, IA 52242 USA. NIDDK, Bethesda, MD 20892 USA. Tufts Med Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 429 EP 429 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800834 ER PT J AU Savin, VJ Sharma, M McCarthy, ET Sharma, R Reddy, S Dong, J Hess, S Kopp, J AF Savin, Virginia J. Sharma, Mukut McCarthy, Ellen T. Sharma, Ram Reddy, Sreenivas Dong, JunWu Hess, Sonja Kopp, Jeffrey TI Cardiotrophin-Like cytokine-1: Candidate for FSGS Permeability Factor, Potential Predictor of Recurrence. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Savin, Virginia J.; Sharma, Mukut; Reddy, Sreenivas] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [McCarthy, Ellen T.] Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66103 USA. [Sharma, Ram] VA Med Ctr, Renal Res Lab, Kansas City, MO USA. [Dong, JunWu] Wuhan 1 Hosp, Wuhan, Hubei, Peoples R China. [Hess, Sonja] CALTECH, Pasadena, CA 91125 USA. [Kopp, Jeffrey] NIDDK, 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 569 EP 569 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801364 ER PT J AU Sansanwal, P Li, L Ying, L Gahl, W Sarwal, M AF Sansanwal, P. Li, L. Ying, L. Gahl, W. Sarwal, Minnie TI Novel Mechanisms for Tissue Injury in Nephropathic Cystinosis and Extended Graft Survival in Cystinosis Transplant Patients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Sansanwal, P.; Li, L.; Ying, L.; Sarwal, Minnie] Stanford Univ, Stanford, CA 94305 USA. [Gahl, W.] 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 576 EP 576 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801390 ER PT J AU Buydens-Branchey, L Branchey, M Hibbeln, J AF Buydens-Branchey, Laure Branchey, Marc Hibbeln, Joseph R. TI Low Plasma Levels of Docosahexaenoic Acid Are Associated with an Increased Relapse Vulnerability in Substance Abusers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; RAT FRONTAL-CORTEX; SEROTONINERGIC NEUROTRANSMISSION; N-3; OMEGA-3-FATTY-ACIDS; DOPAMINE; ADDICTION; ANXIETY AB Low levels of some polyunsaturated fatty acids (PUFAs) could influence behaviors leading to the abuse of substances through their actions on serotonergic and dopaminergic mechanisms. Because substance abusers tend to have poor dietary habits, the possibility that a deficient intake of n-3 PUFAs, available from dietary sources only, and subsequent low n-3 plasma levels would predict their relapse rates was explored. Thirty-five patients admitted to substance abuse clinics were enrolled and followed for one year. Dietary questionnaires and blood samples were collected at baseline and on a quarterly basis, and relapse rates monitored on a monthly basis. Six patients dropped out shortly after study entry, 11 relapsed in the course of the study and dropped out, 7 relapsed but completed the study, and 11 did not relapse and completed the study. Non-relapsers were found to have significantly higher levels of docosahexaenoic acid (DHA) calculated as g/ml and % TFA, when compared to relapsers (p = .031 and p = .010, respectively) and to relapsers and non-completers combined (p = .014 and p = .009, respectively). These pilot data suggest, but do not prove, the existence of a relationship between low levels of DHA and relapse vulnerability in some individuals who abuse substances. The study of the efficacy of n-3 supplements or of dietary modifications on relapse appears warranted. C1 [Buydens-Branchey, Laure; Branchey, Marc] DVA New York Harbor Healthcare Syst, Psychiat Serv, Brooklyn, NY USA. [Hibbeln, Joseph R.] NIAAA, Bethesda, MD USA. RP Buydens-Branchey, L (reprint author), Narrows Inst Biomed Res, 800 Poly Pl, Brooklyn, NY 11209 USA. EM lbuydens@worldnet.att.net FU NIDA NIH HHS [R01-DA15360] NR 27 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 1 BP 73 EP 80 AR PII 908705327 DI 10.1080/10550490802544003 PG 8 WC Substance Abuse SC Substance Abuse GA 407LV UT WOS:000263366600010 PM 19219668 ER PT J AU Mannelli, P Patkar, AA Peindl, K Gottheil, E Wu, LT Gorelick, DA AF Mannelli, Paolo Patkar, Ashwin A. Peindl, Kathleen Gottheil, Edward Wu, Li-Tzy Gorelick, David A. TI Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT 161st Annual Meeting of the American-Psychiatric-Association CY MAY 03-08, 2008 CL Washington, DC SP Amer Psychiat Assoc ID RANDOMIZED CONTROLLED-TRIAL; OPIATE ADDICTS; HEROIN DETOXIFICATION; ABUSE TREATMENT; DEPENDENCE; MAINTENANCE; METHADONE; NALOXONE; ALCOHOL; RELAPSE AB Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence. C1 [Mannelli, Paolo; Patkar, Ashwin A.; Peindl, Kathleen; Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Gottheil, Edward] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. RP Mannelli, P (reprint author), Duke Univ, Med Ctr, Dept Psychiat, 2218 Elder St,Suite 123, Durham, NC 27705 USA. EM paolo.mannelli@duke.edu FU Intramural NIH HHS; NIDA NIH HHS [R21 DA015469, DA15469] NR 47 TC 5 Z9 5 U1 4 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 2 BP 109 EP 116 AR PII 909498181 DI 10.1080/10550490902772785 PG 8 WC Substance Abuse SC Substance Abuse GA 418GX UT WOS:000264137800002 PM 19283561 ER PT J AU Wu, LT Blazer, DG Patkar, AA Stitzer, ML Wakim, PG Brooner, RK AF Wu, Li-Tzy Blazer, Dan G. Patkar, Ashwin A. Stitzer, Maxine L. Wakim, Paul G. Brooner, Robert K. TI Heterogeneity of Stimulant Dependence: A National Drug Abuse Treatment Clinical Trials Network Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID LATENT CLASS ANALYSIS; COCAINE WITHDRAWAL SYMPTOMS; DSM-IV; ALCOHOL DEPENDENCE; TREATMENT PROGRAMS; UNITED-STATES; USE DISORDERS; METHAMPHETAMINE; USERS; COMMUNITY AB We investigated the presence of DSM-IV subtyping for dependence on cocaine and amphetamines (with versus without physical dependence) among outpatient stimulant users enrolled in a multisite study of the Clinical Trials Network (CTN). Three mutually exclusive groups were identified: primary cocaine users (n = 287), primary amphetamine users (n = 99), and dual users (cocaine and amphetamines; n = 29). Distinct subtypes were examined with latent class and logistic regression procedures. Cocaine users were distinct from amphetamine users in age and race/ethnicity. There were four distinct classes of primary cocaine users: non-dependence (15%), compulsive use (14%), tolerance and compulsive use (15%), and physiological dependence (tolerance, withdrawal, and compulsive use; 56%). Three distinct classes of primary amphetamine users were identified: non-dependence (11%), intermediate physiological dependence (31%), and physiological dependence (58%). Regardless of stimulants used, most female users were in the most severe or the physiological dependence group. These results lend support for subtyping dependence in the emerging DSM-V. C1 [Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med,Duke Clin Res Inst, Durham, NC 27710 USA. [Stitzer, Maxine L.; Brooner, Robert K.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Wakim, Paul G.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Wu, LT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med,Duke Clin Res Inst, Box 3419, Durham, NC 27710 USA. EM litzy.wu@duke.edu FU NIDA NIH HHS [HHSN271200522071C]; PHS HHS [HHSN271200522071C] NR 38 TC 12 Z9 12 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 3 BP 206 EP 218 AR PII 910143855 DI 10.1080/10550490902787031 PG 13 WC Substance Abuse SC Substance Abuse GA 427QM UT WOS:000264793800004 PM 19340639 ER PT J AU Jason, LA Pokorny, SB Adams, M Topliff, A Harris, C Hunt, Y AF Jason, Leonard A. Pokorny, Steven B. Adams, Monica Topliff, Annie Harris, Courtney Hunt, Yvonne TI Youth Tobacco Access and Possession Policy Interventions: Effects on Observed and Perceived Tobacco Use SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SMOKING; LAWS; ADOLESCENTS; PROGRAMS; PURCHASE; MINORS; PEER AB This study evaluated the effects of tobacco Purchase, Use and Possession (PUP) laws on student perceptions of adolescent tobacco use within towns and schools. Twenty-four towns were randomly assigned into two conditions, the experimental condition (E PUP) involved efforts to increase both PUP law enforcement and reduce minors' access to commercial sources of tobacco, whereas the control condition (C) focused only on efforts to reduce minors' access to commercial sources of tobacco. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The present study found that over time, youth in the experimental PUP condition observed less youth tobacco usage at school and in their town, and perceived lower rates of tobacco among their peers at school and among friends than youth in the control condition. The findings suggest that PUP law enforcement might be used to strengthen community norms against youth tobacco use. (Am J Addict 2009; 18: 367-374) C1 [Jason, Leonard A.; Adams, Monica; Topliff, Annie; Harris, Courtney] Depaul Univ, Chicago, IL 60604 USA. [Pokorny, Steven B.] Univ Florida, Gainesville, FL USA. [Hunt, Yvonne] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Jason, LA (reprint author), Ctr Community Res, 990 Fullerton Ave,Suite 3100, Chicago, IL 60614 USA. EM LJASON@depaul.edu FU NCI NIH HHS [R01 CA080288-01A2, CA80288, R01 CA080288] NR 24 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 5 BP 367 EP 374 DI 10.1080/10550490903077788 PG 8 WC Substance Abuse SC Substance Abuse GA 539QX UT WOS:000273273500005 PM 19874155 ER PT J AU Szabo, ST Gould, TD Manji, HK AF Szabo, Steven T. Gould, Todd D. Manji, Husseini K. BE Schatzberg, AF Nemeroff, CB TI Neurotransmitters, Receptors, Signal Transduction, and Second Messengers in Psychiatric Disorders SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID PROTEIN-KINASE-C; LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE RECEPTORS; GLYCOGEN-SYNTHASE KINASE-3; CHRONIC ANTIDEPRESSANT TREATMENT; CELLULAR PLASTICITY CASCADES; BDNF VAL66MET POLYMORPHISM; BETA-ADRENERGIC-RECEPTORS; MANIC-DEPRESSIVE ILLNESS; FAMILY-BASED ASSOCIATION C1 [Szabo, Steven T.] NIMH, Mood & Anxiety Disorders Program, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, CNS & Pain, Titusville, NJ USA. [Gould, Todd D.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Szabo, ST (reprint author), NIMH, Mood & Anxiety Disorders Program, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 273 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 3 EP 58 PG 56 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700002 ER PT J AU Pine, DS AF Pine, Daniel S. BE Schatzberg, AF Nemeroff, CB TI Neurobiology of Childhood Disorders SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC BIPOLAR DISORDER; MAJOR DEPRESSIVE DISORDER; ANTISOCIAL-BEHAVIOR; ANXIETY DISORDERS; CHILDREN; BRAIN; NEUROSCIENCE; ADOLESCENTS; AUTISM C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Pine, DS (reprint author), NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 1061 EP 1077 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700053 ER PT J AU Kasarskis, EJ Lindquist, JH Coffman, CJ Grambow, SC Feussner, JR Allen, KD Oddone, EZ Kamins, KA Horner, RD AF Kasarskis, Edward J. Lindquist, Jennifer H. Coffman, Cynthia J. Grambow, Steven C. Feussner, John R. Allen, Kelli D. Oddone, Eugene Z. Kamins, Kimberly A. Horner, Ronnie D. CA ALS Gulf War Clinical Review Team TI Clinical aspects of ALS in Gulf War Veterans SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE ALS; epidemiology; cohort studies; risk factors ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; 2 DANISH COUNTIES; ENVIRONMENTAL EXPOSURE; NATURAL-HISTORY; EPIDEMIOLOGY; PROVINCE; SURVIVAL; PROGNOSIS; PROGRESSION AB The increased incidence of ALS in military veterans of the first Persian Gulf War raised speculation that they may have a 'Persian Gulf' variant of ALS with atypical clinical features. Medical records of military veterans with ALS, previously identified in our epidemiological study, were evaluated for clinical features (age and site of onset, race, unexplained atypical findings) and ventilator-free survival. Comparisons between deployed versus non-deployed cohorts were made with deployment status based on designation by the Department of Defense Manpower Data Center (DMDC) or by self-report. Other than the young age of onset in both cohorts (40.8 years overall mean; 40.1 years for DMDC deployed, 41.2 years for DMDC non-deployed), review of the medical records failed to document any atypical features. After adjusting for bulbar onset, median survival from symptom onset in those 40 years of age was 35.5 months (2.96 years) compared to 64.7 months (5.39 years) in the group 40 years of age (hazard ratio (HR)=0.47, 95% CI 0.30-0.73, p=0.0006). After adjusting for age, median survival was 45.4 months (3.78 years) and 54.8 months (4.57 years) in bulbar- versus non-bulbar onset groups, respectively (HR=1.41, 95% CI 0.83-2.39, p=0.20). After adjusting for age and site of onset, deployed veterans had significantly shorter survival than non-deployed (40.2 vs. 57.0 months, HR=0.62, 95% CI 0.40-0.96, p=0.03) using DMDC data. In conclusion, although veterans developing ALS after deployment to the Persian Gulf in 1990-1991 exhibited otherwise typical clinical features, they experienced shorter ventilator-free survival than non-deployed veterans. C1 [Kasarskis, Edward J.] Lexington VA Med Ctr, Div Neurol, Lexington, KY USA. [Kasarskis, Edward J.] Univ Kentucky, Dept Neurol, Lexington, KY USA. [Kasarskis, Edward J.] Univ Kentucky, Dept Toxicol, Lexington, KY USA. [Kasarskis, Edward J.] Univ Kentucky, Dept Nutr, Lexington, KY USA. [Lindquist, Jennifer H.] Durham VA Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. [Coffman, Cynthia J.; Grambow, Steven C.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Feussner, John R.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Allen, Kelli D.; Oddone, Eugene Z.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Kamins, Kimberly A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Horner, Ronnie D.] Univ Cincinnati, Med Ctr, Dept Publ Hlth Sci, Cincinnati, OH 45267 USA. RP Kasarskis, EJ (reprint author), Neurol Serv 127, 1101 Vet Dr, Lexington, KY 40511 USA. EM ejkas@uky.edu RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 FU VA Cooperative Studies Program 500; Cynthia Shaw Crispen ALS Endowment FX The authors thank the individuals who contributed to the study at various stages including: M. Lyon (formerly with the ALS Association), D. Howard, D. Barrett (Center for Disease Control), M. Dove (DMDC), M. A. K. Ryan, P. Spencer (University of Oregon), V. Palmer, T. Elza Mims, L. Dempsey-Hall, and H. Rowe. The study was supported by VA Cooperative Studies Program 500 and the Cynthia Shaw Crispen ALS Endowment. NR 40 TC 14 Z9 14 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 1 BP 35 EP 41 AR PII 902483959 DI 10.1080/17482960802351029 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 399FW UT WOS:000262786800004 PM 18792848 ER PT J AU Peters, T Floeter, MK AF Peters, Tracy L. Floeter, Mary Kay TI Usage of support services in primary lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Amyotrophic lateral sclerosis; internet support groups; primary lateral sclerosis; wheelchair; survival ID QUALITY-OF-LIFE AB Patients with amyotrophic lateral sclerosis (ALS) rely on a variety of support services during the course of their illness. Patients with primary lateral sclerosis (PLS) have a slower progression of disease and different clinical spectrum. Their needs for allied health services and social support have not been well characterized. To investigate these needs, 25 patients with PLS and caregivers were surveyed on the use of assistive devices and support services. Needs for assistance changed as the disease progressed. Their greatest need was for gait-assistive devices and home help for activities requiring mobility. As in other chronic diseases, there was a striking use of the internet to gather information and for patient support groups. C1 [Peters, Tracy L.; Floeter, Mary Kay] NINDS, Human Spinal Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Floeter, MK (reprint author), 10 Ctr Dr MSC-1404,Bld 10 CRC 7-5680, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov FU Intramural Research Program of the NIH; National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. We thank Michelle Bernal for help in mailing questionnaires and correspondence. NR 7 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 3 BP 187 EP 191 AR PII 909789892 DI 10.1080/17482960902818224 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 447QC UT WOS:000266205200009 PM 19308765 ER PT J AU Chio, A Logroscino, G Hardiman, O Swingler, R Mitchell, D Beghi, E Traynor, BG AF Chio, Adriano Logroscino, Giancarlo Hardiman, Orla Swingler, Robert Mitchell, Douglas Beghi, Ettore Traynor, Bryan G. CA Eurals Consortium TI Prognostic factors in ALS: A critical review SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Review DE Amyotrophic lateral sclerosis; survival; prognostic factors; trials ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; PREDICTS SURVIVAL-TIME; GROWTH-FACTOR-I; NATURAL-HISTORY; PROLONGED SURVIVAL; CLINICAL-TRIALS; NONINVASIVE VENTILATION; SUPEROXIDE-DISMUTASE AB We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10-20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are consistently reported to have a worse outcome. There are conflicting data on gender, diagnostic delay and El Escorial criteria. The rate of symptom progression was revealed to be an independent prognostic factor. Psychosocial factors, FTD, nutritional status, and respiratory function are also related to ALS outcome. The effect of enteral nutrition on survival is still unclear, while NIPPV has been found to improve survival. There are no well established biological markers of progression, although some are likely to emerge in the near future. These findings have relevant implications for the design of future trials. Randomization, besides the type of onset, should take into account age, respiratory status at entry, and a measure of disease progression pre-entry. Alternative trial designs can include the use of natural history controls, the so-called minimization method for treatment allocation, and the futility approach. C1 [Chio, Adriano] Univ Turin, Dept Neurosci, I-10126 Turin, Italy. [Chio, Adriano] San Giovanni Battista Hosp, Turin, Italy. [Logroscino, Giancarlo] Harvard Univ, Dept Epidemiol, HSPH, Boston, MA 02115 USA. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, Orla] Trinity Coll Dublin, Inst Neurosci, Dublin, Ireland. [Swingler, Robert] Univ Dundee, Ninewells Hosp & Med Sch, Dept Neurol, Dundee DD1 9SY, Scotland. [Mitchell, Douglas] Royal Preston Hosp, Preston MND Care & Res Ctr, Preston, Lancs, England. [Beghi, Ettore] Ist Ric Farmacol Mario Negri, Milan, Italy. [Traynor, Bryan G.] NIMH, Sect Dev Genet Epidemiol, NIH, Bethesda, MD 20892 USA. RP Chio, A (reprint author), Univ Turin, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI LOGROSCINO, GIANCARLO/K-5148-2016; Al-Chalabi, Ammar/E-5361-2010; Traynor, Bryan/G-5690-2010 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291; Al-Chalabi, Ammar/0000-0002-4924-7712; FU Intramural NIH HHS [ZIA AG000933-05] NR 107 TC 202 Z9 208 U1 4 U2 20 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 5-6 BP 310 EP 323 DI 10.3109/17482960802566824 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 526MN UT WOS:000272294000008 PM 19922118 ER PT J AU Floeter, MK Mills, R AF Floeter, Mary Kay Mills, Reversa TI Progression in primary lateral sclerosis: A prospective analysis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE Primary lateral sclerosis; motor neuron disorders; spasticity; upper motor neuron syndrome ID HEREDITARY SPASTIC PARAPLEGIA; MOTOR-NEURON SYNDROMES; NATURAL-HISTORY; CLINICAL-FEATURES; ALS2 GENE; ONSET; SCALE; DIFFERENTIATION; DEGENERATION; RELIABILITY AB Objective: To determine whether rates and patterns of progression differ among primary lateral sclerosis (PLS) patients. Methods: Fifty patients fulfilling clinical criteria for PLS were classified on initial presentation into three subtypes: ascending, multifocal, and sporadic paraparesis (PLS-A, PLS-M or PLS-SP). Patients were surveyed annually. Measures of movement speed, clinical rating scales, and transcranial magnetic stimulation were re-assessed at 1-5 year intervals for spread to additional body regions and progression of severity within affected regions. Results: Forty-seven patients continued to fulfill criteria for PLS over a mean follow-up of 6.6 years, with a mean disease duration >14 years. PLS-A patients had more predictable progression to additional body regions. Severity progressed faster in newly affected regions followed by stabilization in PLS-A or PLS-M subtypes. Conclusion: Clinical progression in PLS does not occur steadily, but has periods of faster decline upon spreading to a newly affected region. Classification of PLS patients by subtype is more relevant to predicting the spread of disease, but not progression of severity. C1 [Floeter, Mary Kay; Mills, Reversa] NINDS, Electromyog Sect, Bethesda, MD 20892 USA. RP Floeter, MK (reprint author), 10 Ctr Dr,Bld 10 CRC,Room 7-5680, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov FU Intramural Research Program of the National Institutes of Health, NINDS FX The study was supported by the Intramural Research Program of the National Institutes of Health, NINDS. We thank the patients who participated in this study and the medical students and fellows who assisted in patient evaluations during rotations in the laboratory. We are grateful to Laura Danielian for technical assistance and Michelle Bernal for coordinating patient visits. NR 40 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2009 VL 10 IS 5-6 BP 339 EP 346 DI 10.3109/17482960903171136 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 526MN UT WOS:000272294000011 PM 19922121 ER PT J AU Temporini, C Ceruti, S Calleri, E Ferrario, S Moaddel, R Abbracchio, MP Massolini, G AF Temporini, Caterina Ceruti, Stefania Calleri, Enrica Ferrario, Silvia Moaddel, Ruin Abbracchio, Maria P. Massolini, Gabriella TI Development of an immobilized GPR17 receptor stationary phase for binding determination using frontal affinity chromatography coupled to mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE FAC-MS; GPR17 receptor; Binding assay; Immobilized artificial membranes (IAM) ID CONFORMATIONAL MOBILITY; FAC-MS; DISCOVERY; COLUMNS; PATHOPHYSIOLOGY; PROTEINS AB A liquid chromatographic stationary phase containing immobilized membranes from cells expressing the P2Y-like receptor GPR17 is described. Cellular membranes from 1321N1 cells transiently transfected with GPR17 vector [GPR17(+)] and from the same cell line transfected with the corresponding empty vector [GPR17(-)] were entrapped on immobilized artificial membrane (IAM) support and packed into 6.6-mm-i.d. glass columns to create GPR17(+)-IAM and GPR17(-)-IAM stationary phases. Frontal chromatography experiments on both GPR17(+)-IAM and GPR17(-)-IAM demonstrated the presence of a specific interaction with GPR17 only in the former that was maximized by increasing the membrane/IAM ratio. GPR17(+)-IAM was used in frontal affinity chromatography experiments to calculate the dissociation constants (Kt) of three ligands-the antagonist cangrelor (formerly AR-C69931MX, a P2Y(12)/P2Y(13) antagonist), MRS2179 (a P2Y(1) receptor antagonist), and the agonist UDP-all of which have been reported to also interact with GPR17. Immobilized GPR17 retained its ability to specifically bind the three analytes, as demonstrated by the agreement of the calculated K(d) values with previously reported data. Preliminary ranking experiments suggest the application of GPR17(+)-IAM in ranking affinity studies for the selection of new potential candidates. (C) 2008 Elsevier Inc. All rights reserved. C1 [Temporini, Caterina; Calleri, Enrica; Massolini, Gabriella] Univ Pavia, Dept Pharmaceut Chem, I-27100 Pavia, Italy. [Ceruti, Stefania; Ferrario, Silvia; Abbracchio, Maria P.] Univ Milan, Dept Pharmaceut Sci, Lab Mol & Cellular Pharmacol Purinerg Transmiss, I-20133 Milan, Italy. [Moaddel, Ruin] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Massolini, G (reprint author), Univ Pavia, Dept Pharmaceut Chem, Via Palestro 3, I-27100 Pavia, Italy. EM g.massolini@unipv.it RI Abbracchio, Maria Pia/B-9342-2014; OI Abbracchio, Maria Pia/0000-0002-7833-3388; CALLERI, ENRICA/0000-0002-4246-460X; Temporini, Caterina/0000-0003-1925-7845; Ceruti, Stefania/0000-0003-1663-4211 FU Italian Ministry of Education [RBNE03YA3L_009, RBNE03YA3L_006]; Intramural Research Program of the NIH, National Institute on Aging FX The authors are grateful to F. Corana (Centro Grandi Strumenti, University of Pavia) for advice on the LTQ instrument. Cangrelor was a kind gift of The Medicines Company (Parsippany, NJ, USA). This work was supported by the Italian Ministry of Education (FIRB project RBNE03YA3L_009 to M.P.A. and RBNE03YA3L_006, to G.M.) and partially by the Intramural Research Program of the NIH, National Institute on Aging. NR 25 TC 28 Z9 30 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2009 VL 384 IS 1 BP 123 EP 129 DI 10.1016/j.ab.2008.09.010 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 404AV UT WOS:000263124000017 PM 18835238 ER PT J AU Wang, G Wu, WW Zhang, Z Masilamani, S Shen, RF AF Wang, Guanghui Wu, Wells W. Zhang, Zheng Masilamani, Shyama Shen, Rong-Fong TI Decoy Methods for Assessing False Positives and False Discovery Rates in Shotgun Proteomics SO ANALYTICAL CHEMISTRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; PROTEIN IDENTIFICATION; SEQUENCE DATABASES; PEPTIDE IDENTIFICATION; SEARCH STRATEGY; YEAST PROTEOME; SPECTRAL DATA; CONFIDENCE; ALGORITHM; MODEL AB The potential of getting a significant number of false positives (FPs) in peptide-spectrum matches (PSMs) obtained by proteomic database search has been well-recognized. Among the attempts to assess FPs, the concomitant use of target and decoy databases is widely practiced. By adjusting filtering criteria, FPs and false discovery rate (FDR) can be controlled at a desired level. Although the target-decoy approach is gaining in popularity, subtle differences in decoy construction (e.g., reversing vs stochastic methods), rate calculation (e.g., total vs unique PSMs), or searching (separate vs composite) do exist among various implementations. In the present study, we evaluated the effects of these differences on FP and FDR estimations using a rat kidney protein sample and the SEQUEST search engine as an example. On the effects of decoy construction, we found that, when a single scoring filter (XCorr) was used, stochastic methods generated a higher estimation of FPs and FDR than sequence reversing methods, likely due to an increase in unique peptides. This higher estimation could largely be attenuated by creating decoy databases similar in effective size but not by a simple normalization with a unique-peptide coefficient. When multiple filters were applied, the differences seen between reversing and stochastic methods significantly diminished, suggesting multiple filterings reduce the dependency on how a decoy is constructed. For a fixed set of filtering criteria, FDR and FPs estimated by using unique PSMs were almost twice those using total PSMs. The higher estimation seemed to be dependent on data acquisition setup. As to the differences between performing separate or composite searches, in general, FDR estimated from the separate search was about three times that from the composite search. The degree of difference gradually decreased as the filtering criteria became more stringent. Paradoxically, the estimated true positives in separate search were higher when multiple filters were used. By analyzing a standard protein mixture, we demonstrated that the higher estimation of FDR and FPs in the separate search likely reflected an overestimation, which could be corrected with a simple merging procedure. Our study illustrates the relative merits of different implementations of the target-decoy strategy, which should be worth contemplating when large-scale proteomic biomarker discovery is to be attempted. C1 [Shen, Rong-Fong] NIA, Prote & Analyt Biochem Unit, Res Resources Branch, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Wang, Guanghui; Wu, Wells W.] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Zhang, Zheng; Masilamani, Shyama] Virginia Commonwealth Univ, Dept Internal Med, Div Nephrol, Richmond, VA 23298 USA. RP Shen, RF (reprint author), NIA, Prote & Analyt Biochem Unit, Res Resources Branch, NIH,Biomed Res Ctr, Rm 8B121,251 Bayview Blvd, Baltimore, MD 21224 USA. EM shenr2@mail.nih.gov FU NHLBI; National Institutes of Health FX This research was supported by Intramural Research Programs of NHLBI, the National Institutes of Health. NR 24 TC 44 Z9 46 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2009 VL 81 IS 1 BP 146 EP 159 DI 10.1021/ac801664q PG 14 WC Chemistry, Analytical SC Chemistry GA 389RY UT WOS:000262113400024 PM 19061407 ER PT J AU Masood, MA Xu, X Acharya, JK Veenstra, TD Blonder, J AF Masood, M. Athar Xu, Xia Acharya, Jairaj K. Veenstra, Timothy D. Blonder, Josip TI Enhanced Detection of Sphingoid Bases via Divalent Ruthenium Bipyridine Complex Derivatization and Electrospray Ionization Tandem Mass Spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID CERAMIDE; CHROMATOGRAPHY; SPHINGOLIPIDS; 1-PHOSPHATE; SPHINGOMYELIN; METABOLISM; MEDIATORS; SIGNAL; RAFTS AB Sphingoid bases, such as unsaturated sphingosine (So) and its corresponding dihydro-saturated species sphinganine (Sa), are present in cell samples in low abundance. This fact combined with their low-to-moderate electrospray ionization (ESI) potential, compared to other sphingolipids such as sphingomyelins, limits their detection and quantitation by liquid chromatography-tandem mass spectrometry (LC-MS(2)). To enhance the ESI efficiency of sphingoid bases, a novel procedure to generate stably derivatized analytes that enhance the LC-MS(2) detection of sphingoid bases when analyzed using LC-MS(2) was developed. In this method, a ruthenium complex, [4-(N-succimidyloxycarbonyl propyl)-4'-methyl-2,2'-bipyridine] bis(2,2'-bipyridine) Ru(II) dihexafluorophosphate, is added directly to a cell extract. This complex reacts with and covalently binds to an amino group within the sphingoid bases. The dicationic nature of the ruthenium ion enhances the compound's ionization efficiency resulting in increased LC-MS(2) signals for the derivatized sphingoid bases. Consequently, the detection and quantitation of sphingoid bases are greatly improved. C1 [Masood, M. Athar; Xu, Xia; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Masood, MA (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM masoodaa@mail.nih.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, 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. NR 25 TC 4 Z9 4 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2009 VL 81 IS 1 BP 495 EP 502 DI 10.1021/ac8019043 PG 8 WC Chemistry, Analytical SC Chemistry GA 389RY UT WOS:000262113400069 PM 19055420 ER PT J AU Levine, KE Stout, MD Ross, GT Essader, AS Perlmutter, JM Grohse, PM Fernando, RA Lang, M Collins, BJ AF Levine, Keith E. Stout, Matthew D. Ross, Glenn T. Essader, Amal S. Perlmutter, Jason M. Grohse, Peter M. Fernando, Reshan A. Lang, Michelle Collins, Bradley J. TI Validation of a Method for the Determination of Total Chromium in Rat Feces by Inductively Coupled Plasma Optical Emission Spectrometry SO ANALYTICAL LETTERS LA English DT Article DE Chromium; feces; inductively coupled plasma optical emission spectrometry ID TOXICITY; CARCINOGENICITY; HUMANS AB The validation of a method for the determination of total chromium in Fischer-344 rat feces by inductively coupled plasma optical emission spectrometry following a rapid, atmospheric-pressure microwave digestion is described. The performance of the method was evaluated over the concentration range of 5.00 to 200 mu g Cr/g feces. Data for method linearity, accuracy, precision, digest stability, and storage stability are presented along with limit of detection and limit of quantitation data. Data from a cross-validation method for B6C3F1 mouse feces are also presented. Following validation, the method was applied to analyze samples collected in support of two chronic toxicological investigations. C1 [Levine, Keith E.; Ross, Glenn T.; Essader, Amal S.; Perlmutter, Jason M.; Grohse, Peter M.; Fernando, Reshan A.; Lang, Michelle] RTI Int, Res Triangle Pk, NC 27709 USA. [Stout, Matthew D.; Collins, Bradley J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Levine, KE (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM levine@rti.org FU National Institute of Environmental Health Sciences, National Institute of Health [N01-ES-05455, N01-ES-65554] FX The analytical work was funded in full by the National Institute of Environmental Health Sciences, National Institute of Health, Contract Numbers N01-ES-05455 and N01-ES-65554. NR 21 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0003-2719 J9 ANAL LETT JI Anal. Lett. PY 2009 VL 42 IS 17 BP 2729 EP 2746 AR PII 916481324 DI 10.1080/00032710902721931 PG 18 WC Chemistry, Analytical SC Chemistry GA 515XZ UT WOS:000271507500001 ER PT J AU Luo, ZC Yu, M Smith, SD Kritzer, M Du, CW Ma, Y Volkow, ND Glass, PS Benveniste, H AF Luo, Zhongchi Yu, Mei Smith, S. David Kritzer, Mary Du, Congwu Ma, Yu Volkow, Nora D. Glass, Peter S. Benveniste, Helene TI The Effect of Intravenous Lidocaine on Brain Activation During Non-Noxious and Acute Noxious Stimulation of the Forepaw: A Functional Magnetic Resonance Imaging Study in the Rat SO ANESTHESIA AND ANALGESIA LA English DT Article ID SYSTEMICALLY ADMINISTERED COCAINE; AXOTOMIZED SENSORY NEURONS; PERIPHERAL-NERVE INJURY; NEUROPATHIC PAIN; SODIUM-CHANNELS; LOCAL-ANESTHETICS; VIBRISSAE STIMULATION; HEMODYNAMIC-RESPONSES; POSTOPERATIVE PAIN; SCIATIC-NERVE AB BACKGROUND: Lidocaine can alleviate acute as well as chronic neuropathic pain at very low plasma concentrations in humans and laboratory animals. The mechanism(s) underlying lidocaine's analgesic effect when administered systemically is poorly understood but clearly not related to interruption of peripheral nerve conduction. Other targets for lidocaine's analgesic action(s) have been suggested, including sodium channels and other receptor sites in the central rather than peripheral nervous system. To our knowledge, the effect of lidocaine on the brain's functional response to pain has never been investigated. Here, we therefore characterized the effect of systemic lidocaine on the brain's response to innocuous and acute noxious Stimulation in the rat using functional magnetic resonance imaging (fMRI). METHODS: Alpha-chloralose anesthetized rats underwent fMRI to quantify brain activation patterns in response to innocuous and noxious forepaw Stimulation before and after IV administration of lidocaine RESULTS: Innocuous forepaw stimulation elicited brain activation only in the contralateral primary somatosensory (S1) cortex. Acute noxious forepaw stimulation induced activation in additional brain areas associated with pain perception, including the secondary somatosensory cortex (S2), thalamus, insula and limbic regions. Lidocaine administered at IV doses of either 1 mg/kg, 4 mg/kg or 10 mg/kg did not abolish or diminish brain activation in response to innocuous or noxious stimulation. In fact, IV doses of 4 mg/kg and 10 mg/kg lidocaine enhanced S1 and S2 responses to acute nociceptive stimulation, increasing the activated cortical volume by 50%-60%. CONCLUSION: The analgesic action of systemic lidocaine in acute pain is not reflected in a straightforward interruption of pain-induced fMRI brain activation as has been observed with opioids. The enhancement of cortical fMRI responses to acute pain by lidocaine observed here has also been reported for cocaine. We recently showed that both lidocaine and cocaine increased intracellular calcium concentrations in cortex, suggesting that this pharmacological effect Could account for the enhanced sensitivity to somatosensory stimulation. As our model only measured physiological acute pain, it will be important to also test the response of these same pathways to lidocaine in a model of neuropathic pain to further investigate lidocaine's analgesic mechanism of action. C1 [Smith, S. David; Du, Congwu; Benveniste, Helene] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Luo, Zhongchi] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Yu, Mei; Du, Congwu; Ma, Yu; Glass, Peter S.] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA. [Kritzer, Mary] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. [Volkow, Nora D.] NIAAA, NIH, Bethesda, MD USA. RP Benveniste, H (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. EM benveniste@bnl.gov FU Energy Office of Science and Biological Reseach [DE-AC02-98CHI-886]; New York State Office of Science, Technology, and Academic Research FX Supported by Department of Energy Office of Science and Biological Reseach (Contract No. DE-AC02-98CHI-886), and New York State Office of Science, Technology, and Academic Research. NR 65 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2009 VL 108 IS 1 BP 334 EP 344 DI 10.1213/ane.0b013e31818e0d34 PG 11 WC Anesthesiology SC Anesthesiology GA 387PB UT WOS:000261963000049 PM 19095870 ER PT J AU Dong, SW Hamel, E Bai, RL Covell, DG Beutler, JA Porco, JA AF Dong, Suwei Hamel, Ernest Bai, Ruoli Covell, David G. Beutler, John A. Porco, John A., Jr. TI Enantioselective Synthesis of (+)-Chamaecypanone C: A Novel Microtubule Inhibitor SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cycloaddition; cyclopentadienone; microtubule inhibitor; natural product; total synthesis ID OBTUSA VAR.-FORMOSANA; ONE-STEP SYNTHESIS; ANTIMITOTIC AGENTS; ALDER REACTION; CYCLOPENTADIENONE; SKELETON; TUBULIN; HEARTWOOD C1 [Dong, Suwei; Porco, John A., Jr.] Boston Univ, Ctr Chem Methodol & Lib Dev CMLD BU, Dept Chem, Boston, MA 02215 USA. [Beutler, John A.] NCI, Mol Targets Dev Program, Frederick, MD 21701 USA. [Hamel, Ernest; Bai, Ruoli] NCI, Toxicol & Pharmacol Branch, Frederick, MD 21701 USA. [Covell, David G.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. RP Porco, JA (reprint author), Boston Univ, Ctr Chem Methodol & Lib Dev CMLD BU, Dept Chem, 590 Commonwealth Ave, Boston, MA 02215 USA. EM porco@bu.edu RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Institutes of Health [GM-073855, P50 GM067041]; Wyeth Pharmaceuticals; Merck Research Laboratories; NCI intramural research program FX Financial support from the National Institutes of Health (GM-073855 and P50 GM067041), Wyeth Pharmaceuticals, Merck Research Laboratories, and the NCI intramural research program is gratefully acknowledged. We thank the Developmental Therapeutics Program at the NCI for the 60-cell assay, ThalesNano, Inc. (Budapest, Hungary) for assistance with the continuous-flow hydrogenation reactor, and Prof Dr. Corey Stephenson (Boston University) for helpful discussions. NR 35 TC 38 Z9 39 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2009 VL 48 IS 8 BP 1494 EP 1497 DI 10.1002/anie.200805486 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 410JB UT WOS:000263572200029 PM 19140149 ER PT J AU Wall, R Powell, A Sohn, E Foster-Frey, J Bannerman, D Paape, M AF Wall, R. Powell, A. Sohn, E. Foster-Frey, J. Bannerman, D. Paape, M. TI Enhanced Host Immune Recognition of Mastitis Causing Escherchia Coli in CD-14 Transgenic Mice SO ANIMAL BIOTECHNOLOGY LA English DT Article DE CD-14; Mammary gland; Mastitis; Transgenic mice ID CD14 REDUCES SEVERITY; SOLUBLE CD14; MAMMARY-GLAND; ESCHERICHIA-COLI; MILK; EXPRESSION; LIPOPOLYSACCHARIDE; INFECTION; LYSOSTAPHIN; PROTEIN AB Escherchia coli causes mastitis, an economically significant disease in dairy animals. E. coli endotoxin (lipopolysaccharide, LPS) when bound by host membrane proteins such as CD-14, causes release of proinflammatory cytokines recruiting neutrophils as an early, innate immune response. Excessive proinflammatory cytokines causes tissue damage, compromising mammary function. If present, soluble CD-14 (sCD-14) might out compete membrane bound CD-14, lessening the severity of the inflammatory response. To test this hypothesis transgenic mice, expressing sCD-14 in their milk (31 to 316g/ml), were evaluated. A cell culture study demonstrated, in the presence of LPS, milk from transgenic mice increased secretion of cytokine IL-8 compared to milk from nontransgenic littermates (183 vs. 352ng/mL, p0.001). To assess protection afforded by the transgene, glands were infused with E. coli. Recovery of bacteria showed no clear relationship between sCD14 concentration and the number of organisms recovered; however, there was a strong relationship between sCD14 concentration and edema (r2=0.999, p0.001), as measured by weight of fluid in harvested glands. Highest expressing lines had the least edema, suggesting the presence of sCD14 had an effect on reducing the inflammatory response to E. coli, thus, possibly protecting against gland tissue damage. C1 [Wall, R.; Powell, A.; Foster-Frey, J.] Agr Res Serv, Anim Biosci & Biotechnol Lab, Beltsville, MD USA. [Sohn, E.] NIDDK, Genet Dis Resistance Sect, NIH, Bethesda, MD USA. [Bannerman, D.; Paape, M.] Agr Res Serv, Bovine Funct Genom Lab, Beltsville, MD USA. RP Wall, R (reprint author), Bldg 230,Rm 101,Barc E, Beltsville, MD 20705 USA. EM Bob.Wall@ARS.USDA.GOV NR 24 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2009 VL 20 IS 1 BP 1 EP 14 AR PII 908031438 DI 10.1080/10495390802594206 PG 14 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 397CA UT WOS:000262638300001 PM 19160083 ER PT J AU Qiao, JW Su, XO Li, YX Yang, JM Wang, YQ Kouadir, M Zhou, XM Yang, LF Yin, XM Zhao, DM AF Qiao, Jun-Wen Su, Xiao-Ou Li, Yu-Xing Yang, Jian-Min Wang, Yi-Qin Kouadir, Mohammed Zhou, Xiang-Mei Yang, Li-Feng Yin, Xiao-Min Zhao, De-Ming TI Variable Levels of 37-kDa/67-kDa Laminin Receptor (RPSA) mRNA in Ovine Tissues: Potential Contribution to the Regulatory Processes of PrPSc Propagation? SO ANIMAL BIOTECHNOLOGY LA English DT Article DE Laminin receptor; mRNA expression; PrPC; PrPSc propagation; Real-time quantitative RT-PCR ID BOVINE SPONGIFORM ENCEPHALOPATHY; PRION DISEASES; SCRAPIE; PATHOGENESIS; PROTEIN; CELLS; GENE; ACTS AB The 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR, also known as ribosomal protein SA, RPSA) has been reported to be involved in cancer development and prion internalization. Previous studies have shown that the LRP/LR is expressed in a wide variety of tissues. In particular, expression of LRP/LR mRNA may be closely related to the degree of PrPSc propagation. This study presents a detailed investigation of the LRP/LR mRNA expression levels in eleven normal ovine tissues. Using real-time quantitative PCR, the highest LRP/LR expression was found in neocortex (p0.05). Slightly lower levels were found in the heart and obex. Intermediate levels were seen in hippocampus, cerebellum, spleen, thalamus, mesenteric lymph node, and the lowest levels were present in liver, kidney, and lung. In general, the LRP/LR mRNA levels were much higher in neuronal tissues than in peripheral tissues. The observation that differences in LRP/LR mRNA expression levels are consistent with the corresponding variation in PrPSc accumulation suggests that the 37-kDa/67-kDa laminin receptor may be involved in the regulation of PrPSc propagation. C1 [Qiao, Jun-Wen; Su, Xiao-Ou; Yang, Jian-Min; Wang, Yi-Qin; Kouadir, Mohammed; Zhou, Xiang-Mei; Yang, Li-Feng; Yin, Xiao-Min; Zhao, De-Ming] China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Beijing 100193, Peoples R China. [Li, Yu-Xing] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Zhao, DM (reprint author), China Agr Univ, Coll Vet Med, Natl Anim TSE Lab, Beijing 100193, Peoples R China. EM zhaodm@cau.edu.cn FU Natural Science Foundation of China [30571399]; 973 Project [2005CB523000]; Key Projects of National Science & Technology Pillar Program [2006BAD06A13] FX This work was supported by the Natural Science Foundation of China (Project No. 30571399), the 973 Project (No. 2005CB523000), and the Key Projects of National Science & Technology Pillar Program in the 11th 5 Years of China (Program No. 2006BAD06A13). The authors would like to thank Dr. Wilfred. Goldmann (The Roslin Institute, R (D) SVS, University of Edinburgh) for help with the manuscript. NR 15 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2009 VL 20 IS 3 BP 151 EP 155 AR PII 912579897 DI 10.1080/10495390902996863 PG 5 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 460PK UT WOS:000267199400007 PM 19544211 ER PT J AU Basile, BM Hampton, RR Suomi, SJ Murray, EA AF Basile, Benjamin M. Hampton, Robert R. Suomi, Stephen J. Murray, Elisabeth A. TI An assessment of memory awareness in tufted capuchin monkeys (Cebus apella) SO ANIMAL COGNITION LA English DT Article DE Metamemory; Metacognition; Explicit memory; Foraging; Visual search ID UNCERTAIN RESPONSE; MACACA-MULATTA; INFORMATION; SEARCHES; PIGEONS; HUMANS AB Humans, apes, and rhesus monkeys demonstrate memory awareness by collecting information when ignorant and acting immediately when informed. In this study, five capuchin monkeys searched for food after either watching the experimenter bait one of four opaque tubes (seen trials), or not watching (unseen trials). Monkeys with memory awareness should look into the tubes before making a selection only on unseen trials because on seen trials they already know the location of the food. In Experiment 1, one of the five capuchins looked significantly more often on unseen trials. In Experiment 2, we ensured that the monkeys attended to the baiting by interleaving training and test sessions. Three of the five monkeys looked more often on unseen trials. Because monkeys looked more often than not on both trial types, potentially creating a ceiling effect, we increased the effort required to look in Experiment 3, and predicted a larger difference in the probability of looking between seen and unseen trials. None of the five monkeys looked more often on unseen trials. These findings provide equivocal evidence for memory awareness in capuchin monkeys using tests that have yielded clear evidence in humans, apes, and rhesus monkeys. C1 [Basile, Benjamin M.; Hampton, Robert R.; Murray, Elisabeth A.] NIMH, Bethesda, MD 20892 USA. [Suomi, Stephen J.] NICHHD, Bethesda, MD 20892 USA. RP Basile, BM (reprint author), Emory Univ, Dept Psychol, 532 Kilgo Circle, Atlanta, GA 30322 USA. EM bbasile@emory.edu OI Murray, Elisabeth/0000-0003-1450-1642 FU NIMH Intramural Research Program; National Institutes of Health [RR-00165]; National Science Foundation [IBN-9876754] FX We thank David Ide of Research Services Branch, NIMH for designing and fabricating the apparatus. We also thank Ruth Woodward of Research Animal Management Branch, NICHD for excellent veterinary care. This research was supported by the NIMH Intramural Research Program. Additional support for preparation of this manuscript was provided by Yerkes Center base grant No. RR-00165 awarded by the Animal Resources Program of the National Institutes of Health, and by the Center for Behavioral Neuroscience under the STC Program of the National Science Foundation under Agreement No. IBN-9876754. These experiments comply with US law. NR 21 TC 43 Z9 43 U1 2 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1435-9448 J9 ANIM COGN JI Anim. Cogn. PD JAN PY 2009 VL 12 IS 1 BP 169 EP 180 DI 10.1007/s10071-008-0180-1 PG 12 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 394XL UT WOS:000262486400016 PM 18712532 ER PT B AU Kalueff, AV Ren-Patterson, RF LaPorte, JL Murphy, DL AF Kalueff, Allan V. Ren-Patterson, Renee F. LaPorte, Justin L. Murphy, Dennis L. BE Rechi, LJ TI DOMAIN-ORIENTED ANALYSIS FOR UNDERSTANDING MOLECULAR INTERACTIONS AND TRANSLATING ANIMAL GENETIC MODELS INTO NEUROPSYCHIATRIC DISORDERS: FOCUS ON SEROTONIN TRANSPORTER AND BDNF SO ANIMAL GENETICS SE Animal Science Issues and Professions LA English DT Article; Book Chapter ID NEUROTROPHIC FACTOR BDNF; NERVE GROWTH-FACTOR; MAJOR DEPRESSIVE DISORDER; STRESS-INDUCED ANHEDONIA; LONG-TERM POTENTIATION; ANXIETY-LIKE BEHAVIOR; EARLY-LIFE BLOCKADE; KNOCK-OUT MICE; DEFICIENT MICE; RAT-BRAIN C1 [Kalueff, Allan V.; Ren-Patterson, Renee F.; LaPorte, Justin L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM avkalueff@inbox.ru NR 183 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-844-3 J9 ANIM SCI ISSUES PROF PY 2009 BP 197 EP 220 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA BPH46 UT WOS:000278854900009 ER PT J AU Maraini, G Williams, SL Sperduto, RD Ferris, FL Milton, RC Clemons, TE Rosmini, F Ferrigno, L AF Maraini, Giovanni Williams, Sally L. Sperduto, Robert D. Ferris, Frederick L. Milton, Roy C. Clemons, Traci E. Rosmini, Francesco Ferrigno, Luigina TI Effects of multivitamin/mineral supplementation on plasma levels of nutrients. Report No. 4 of the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract SO ANNALI DELL ISTITUTO SUPERIORE DI SANITA LA English DT Article DE clinical trial; dietary supplementation; epidemiology; vitamin level AB The use of multivitamin-mineral supplements has become increasingly common, but whether the use of such supplements improves micronutrient status remains still unclear. The objective of this report is to investigate how a long-term vitamin-mineral supplementation following the US Recommended Daily Intake (RDI) affected the plasma levels of selected nutrients in a subset (No. = 407) of participants in the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS). The CTNS was a double-blind, single centre, controlled clinical trial of 1020 participants aged 55-75 years randomized to a daily tablet of Centrum (R) or placebo. A representative sample of 40% of the 1020 subjects, whom plasma level of selected vitamins was determined at the baseline, was retested throughout the treatment period that averaged 9.0 +/- 2.4 years. Participants assigned to Centrum (R) showed a significant increase (p < 0.005) in mean/median plasma levels of vitamin E, beta-carotene, folate, and vitamin B12, and an improved riboflavin status when compared with participants assigned to placebo. Differences concerning vitamin C were statistically less relevant and those concerning vitamin A were at a borderline level. In the treated group the effect of supplementation on plasma levels of vitamins A, E, and C, and on the glutathione reductase activation coefficient was significantly higher in participants with lower nutritional status at baseline. C1 [Rosmini, Francesco; Ferrigno, Luigina] Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, I-00161 Rome, Italy. [Maraini, Giovanni; Williams, Sally L.] Univ Parma, Dipartimento Sci Otorinoodontooftalmol & Cerv Fac, I-43100 Parma, Italy. [Sperduto, Robert D.; Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA. [Milton, Roy C.; Clemons, Traci E.] EMMES Corp, Rockville, MD USA. RP Rosmini, F (reprint author), Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, Viale Regina Elena 299, I-00161 Rome, Italy. EM francesco.rosmini@iss.it NR 32 TC 9 Z9 9 U1 2 U2 4 PU IST POLIGRAFICO ZECCA STATO PI ROMA PA PIAZZA VERDI 10, ROMA, 00198, ITALY SN 0021-2571 J9 ANN I SUPER SANITA JI Ann. Ist. Super. Sanita PY 2009 VL 45 IS 2 BP 119 EP U33 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V15SO UT WOS:000207821900002 PM 19636163 ER PT J AU Strasak, AM Lang, S Kneib, T Brant, LJ Klenk, J Hilbe, W Oberaigner, W Ruttmann, E Kaltenbach, L Concin, H Diem, G Pfeiffer, KP Ulmer, H AF Strasak, Alexander M. Lang, Stefan Kneib, Thomas Brant, Larry J. Klenk, Jochen Hilbe, Wolfgang Oberaigner, Willi Ruttmann, Elfriede Kaltenbach, Lalit Concin, Hans Diem, Guenter Pfeiffer, Karl P. Ulmer, Hanno CA VHM&PP Study Grp TI Use of Penalized Splines in Extended Cox-Type Additive Hazard Regression to Flexibly Estimate the Effect of Time-varying Serum Uric Acid on Risk of Cancer Incidence: A Prospective, Population-Based Study in 78,850 Men SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Cancer incidence; Epidemiology; Extended Cox-type additive hazard regression; Men; Penalized splines; Risk factor; Serum uric acid ID PROSPECTIVE MALE COHORT; DOSE-RESPONSE; CARDIOVASCULAR MORTALITY; INFORMATION CRITERION; TREND ANALYSIS; LONG-TERM; ASSOCIATION; ANTIOXIDANT; DISEASE; MODELS AB PURPOSE: We sough to investigate the effect of sentra uric acid (SUA) levels on risk of cancer incidence in men and to flexibly determine the shape of this association by using a novel analytical approach. METHODS: A population-based cohort of 78,850 Austrian men who received 264,347 serial SUA measurements was prospectively followed-LIP for a median of 1.2.4 years. Data were collected between 1985 and 2003. Penalized splines (P-splines) in extended Cox,type additive hazard regression were used to flexibly model the association between SUA, as a time-dependent covariate, and risk of overall and site-specific cancer incidence and to calculate adjusted hazard ratios with their 95% confidence intervals. RESULTS: During follow-up 5189 incident cancers were observed. Restricted maximum-likelihood optimizing P-spline models revealed a moderately J-shaped effect of SUA on risk of overall cancer incidence, with statistically significantly increased hazard ratios in the upper third of the SUA distribution. Increased SUA (>= 8.00 mg/dL) further significantly increased risk for several site-specific malignancies, with P-spline analyses providing detailed insight about the shape of the association with these outcomes. CONCLUSIONS: Our Study is the first to demonstrate a dose-response association between SUA and cancer incidence in men, simultaneously reporting on the usefulness of a novel methodological framework in epidemiologic research. C1 [Strasak, Alexander M.; Kaltenbach, Lalit; Pfeiffer, Karl P.; Ulmer, Hanno] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria. [Lang, Stefan] Univ Innsbruck, Inst Stat, A-6020 Innsbruck, Austria. [Kneib, Thomas] Univ Munich, Dept Stat, D-80539 Munich, Germany. [Brant, Larry J.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Klenk, Jochen] Univ Ulm, Inst Epidemiol, D-89069 Ulm, Germany. [Hilbe, Wolfgang] Innsbruck Med Univ, Dept Internal Med, A-6020 Innsbruck, Austria. [Oberaigner, Willi] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria. [Ruttmann, Elfriede] Innsbruck Med Univ, Dept Cardiac Surg, A-6020 Innsbruck, Austria. [Concin, Hans; Diem, Guenter; Ulmer, Hanno] Agcy Prevent & Social Med, Bregenz, Austria. RP Strasak, AM (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria. EM alexander.strasak@i-med.ac.at RI Lang, Stefan/E-7500-2010; Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Klenk, Jochen/C-2164-2012; Ulmer, Hanno/C-3488-2011; OI Lang, Stefan/0000-0003-0739-3858; Ulmer, Hanno/0000-0001-5911-1002; Klenk, Jochen/0000-0002-5987-447X FU Intramural NIH HHS [Z01 AG000638-18] NR 49 TC 19 Z9 20 U1 0 U2 2 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 JAN PY 2009 VL 19 IS 1 BP 15 EP 24 DI 10.1016/j.annepidem.2008.08.009 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 387DZ UT WOS:000261933200003 PM 18835524 ER PT J AU Marotta, F Yadav, H Gumaste, U Helmy, A Jain, S Minelli, E AF Marotta, Francesco Yadav, Hariom Gumaste, Upendra Helmy, Amr Jain, Shalini Minelli, Emilio TI Protective effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol-induced liver damage SO ANNALS OF HEPATOLOGY LA English DT Article DE Paracetamol; oxidative stress; DNA fragmentation; DTS ID MITOCHONDRIAL PERMEABILITY TRANSITION; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; CULTURED MOUSE HEPATOCYTES; OXIDANT STRESS; APOPTOSIS; INJURY; MICE; FAILURE; ACTIVATION; TOXICITY AB The hepatoprotective potential DTS (1.5 g/kg bw, Denshici-to-Chiusei, Kyotsu Jigyo, Tokyo, Japan) was evaluated against either toxic (1.5 g/kg bw) and sub-toxic (150 mg/kg bw) dosage of paracetamol-induced liver injury in Sprague-Dawley rat. Paracetamol intoxication caused a reduction of serum total protein and increase levels of serum alkaline phosphatase (ALP), aspartate aminotranferase (AST) and serum alanine aminotranferase (ALT) at higher extent in the toxic group. This phenomenon was paralleled by an impaired liver redox status (reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and increased MDA in both paracetamol-administered groups. Moreover, a marked reduction of ATPase and thiols together with DNA fragmentation occurred in liver tissue. Animals pretreated with DTS showed a marked mitigation of the severity of liver enzyme and of the impaired redox status of the liver. Moreover, DTS partly prevented the DNA fragmentation and the decline of liver tissue ATPase and protein thiol assay as compared with both groups treated with paracetamol alone. Although more detailed studies are awaited to ascertain the detailed mode of action of DTS, it wouls seem to be related to the prevention of formation of the reactive oxygen groups thereby preventing the damage on the hepatocytes and possibly modulating the genes responsible for synthesis of liver antioxidant enzymes thus providing marked DNA protection. C1 [Marotta, Francesco; Minelli, Emilio] Univ Milan, WHO Cntr Biotech & Nat Med, I-20122 Milan, Italy. [Yadav, Hariom] NIDDK, NIH, Bethesda, MD USA. [Gumaste, Upendra] Agharkar Res Inst, Pune, Maharashtra, India. [Helmy, Amr] Menoufia Univ, Liver Inst, Giza, Egypt. [Jain, Shalini] Univ Illinois, Dept Food Sci & Human Nutr, Chicago, IL 60680 USA. RP Marotta, F (reprint author), Via Pisanello 4, I-20146 Milan, Italy. EM fmarchimede@libero.it RI Helmy, Amr/F-2334-2013 NR 36 TC 9 Z9 9 U1 0 U2 0 PU MEXICAN ASSOC HEPATOLOGY PI MEXICO PA PUNTE DE PIEDRA 150, COLONIA TORIELLO GUERRA, MEXICO, DF CP 14040, MEXICO SN 1665-2681 J9 ANN HEPATOL JI Ann. Hepatol. PD JAN-MAR PY 2009 VL 8 IS 1 BP 50 EP 56 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 409AM UT WOS:000263478600010 PM 19221534 ER PT J AU Mohile, NA Iwamoto, FM Beal, K Lymberis, SC Yamada, Y Chang, J Karimi, S Hou, BL Abrey, LE Gutin, PH AF Mohile, N. A. Iwamoto, F. M. Beal, K. Lymberis, S. C. Yamada, Y. Chang, J. Karimi, S. Hou, B. L. Abrey, L. E. Gutin, P. H. TI Safety and Activity of VEGF Inhibition in Combination with Re-irradiation for Recurrent Malignant Gliomas. SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 134th Annual Meeting of the American-Neurological-Association CY OCT 11-14, 2009 CL Baltimore, MD SP Amer Neurol Assoc C1 [Mohile, N. A.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Iwamoto, F. M.] NIH, Neurooncol Branch, Bethesda, MD 20892 USA. [Beal, K.; Lymberis, S. C.; Yamada, Y.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Chang, J.; Karimi, S.; Hou, B. L.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Abrey, L. E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Gutin, P. H.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2009 VL 66 BP S80 EP S80 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 506EW UT WOS:000270757700310 ER PT J AU Sanossian, N Starkman, S Hamilton, S Liebeskind, DS Ali, LK Restrepo, L Sung, G Conwit, R Eckstein, M Pratt, F Stratton, S Saver, JL AF Sanossian, Nerses Starkman, Sidney Hamilton, Scott Liebeskind, David S. Ali, Latisha K. Restrepo, Lucas Sung, Gene Conwit, Robin Eckstein, Marc Pratt, Frank Stratton, Sam Saver, Jeffrey L. CA FAST-MAG Investigators Nurses TI Development and Validation of a Clinical Scale Distinguishing Hemorrhagic and Ischemic Stroke in the First Two Hours after Onset SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 134th Annual Meeting of the American-Neurological-Association CY OCT 11-14, 2009 CL Baltimore, MD SP Amer Neurol Assoc C1 [Sanossian, Nerses; Sung, Gene; Eckstein, Marc] Univ So Calif, Los Angeles, CA 90089 USA. [Starkman, Sidney; Liebeskind, David S.; Ali, Latisha K.; Restrepo, Lucas; Stratton, Sam; Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Hamilton, Scott] Stanford Univ, Stanford, CA 94305 USA. [Conwit, Robin] Torrance Mem Hosp, Torrance, CA USA. [Pratt, Frank] NIH, Bethesda, MD 20892 USA. NR 2 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2009 VL 66 BP S81 EP S81 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 506EW UT WOS:000270757700313 ER PT J AU Paisan-Ruiz, C Bhatia, KP Li, A Hernandez, D Davis, M Wood, NW Hardy, J Houlden, H Singleton, A Schneider, SA AF Paisan-Ruiz, Coro Bhatia, Kailash P. Li, Abi Hernandez, Dena Davis, Mary Wood, Nick W. Hardy, John Houlden, Henry Singleton, Andrew Schneider, Susanne A. TI Characterization of PLA2G6 as a Locus for Dystonia-Parkinsonism SO ANNALS OF NEUROLOGY LA English DT Article ID INFANTILE NEUROAXONAL DYSTROPHY; HALLERVORDEN-SPATZ-SYNDROME; EARLY-ONSET PARKINSONISM; PYRAMIDAL DEGENERATION; MUTATIONS; DEMENTIA AB Background: Although many recessive loci causing parkinsonism dystonia have been identified, these do not explain all cases of the disorder. Methods: We used homozygosity mapping and mutational analysis in three individuals from two unrelated families who presented with adult-onset levodopa-responsive dystonia-parkinsonism, pyramidal signs and cognitive/psychiatric features, and cerebral and cerebellar atrophy on magnetic resonance imaging but absent iron in the basal ganglia. Results: We identified areas of homozygosity on chromosome 22 and, subsequently, PLA2G6 Mutations. Interpretation: PLA2G6 mutations are associated with infantile neuroaxonal dystrophy and have been reported previously to cause early cerebellar signs, and the syndrome was classified as neurodegeneration with brain iron accumulation (type 2). Our cases have neither of these previously pathognomic features. Thus, mutations in PLA2G6 should additionally be considered in patients with adult-onset dystonia-parkinsonism even with absent iron oil brain imaging. C1 [Bhatia, Kailash P.; Schneider, Susanne A.] UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, London WC1N 3BG, England. [Paisan-Ruiz, Coro; Hernandez, Dena; Hardy, John; Singleton, Andrew] Natl Inst Aging Intramural Res Program, Neurogenet Lab, NIH, Bethesda, MD USA. [Paisan-Ruiz, Coro; Li, Abi; Davis, Mary; Wood, Nick W.; Hardy, John; Houlden, Henry] UCL, Dept Mol Neurosci, Inst Neurol, London WC1N 3BG, England. RP Bhatia, KP (reprint author), UCL, Sobell Dept Motor Neurosci & Movement Disorders, Inst Neurol, Box 13,UCL,Queen Sq, London WC1N 3BG, England. EM kbhatia@ion.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Paisan-Ruiz, Coro/C-2912-2009; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Wood, Nicholas/C-2505-2009 OI Houlden, Henry/0000-0002-2866-7777; Wood, Nicholas/0000-0002-9500-3348 FU Supported by the Intramural Research Program of the National Institute on Aging; National Institutes of Health; Department of Health and Human Services [Z01 AG000958-05]; Bachmann Strauss Foundation; Brain Research Trust, United Kingdom FX This work was Supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (Intramural Program Number Z01 AG000958-05), the Bachmann Strauss Foundation (C.P.R., J.H.), and the Brain Research Trust, United Kingdom (JJ Astor prize Studentship, S.A.S.). NR 15 TC 162 Z9 170 U1 0 U2 7 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 JAN PY 2009 VL 65 IS 1 BP 19 EP 23 DI 10.1002/ana.21415 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 404BD UT WOS:000263124800006 PM 18570303 ER PT J AU Kaler, SG Tang, JR Donsante, A Kaneski, CR AF Kaler, Stephen G. Tang, Jingrong Donsante, Anthony Kaneski, Christine R. TI Translational Read-through of a Nonsense Mutation in ATP7A Impacts Treatment Outcome in Menkes Disease SO ANNALS OF NEUROLOGY LA English DT Article ID DISEASE/OCCIPITAL HORN SYNDROME; STOP-CODON; GENE; AMINOGLYCOSIDES; READTHROUGH; PROTEIN; REGION; UGA AB Protein translation ends when a stop codon in a gene's messenger RNA transcript enters the ribosomal A site. Mutations that create premature stop codons (nonsense mutations) typically cause premature translation termination. An alternative outcome, read-through translation (or nonsense suppression), is well known in prokaryotic, viral, and yeast genes but has not been clearly documented in humans except in the context of pharmacological manipulations. Here, we identify and characterize native read-through of a nonsense mutation (R201X) in the human copper transport gene, ATP7A. Western blotting, in vitro expression analyses, immunohistochemistry, and yeast complementation assays using cultured fibroblasts from a classic Menkes disease patient all indicated small amounts of native ATP7A(R201X), read-through and were associated with a dramatic clinical response to early copper treatment. C1 [Kaler, Stephen G.; Tang, Jingrong; Donsante, Anthony] NICHHD, Unit Pediat Genet, Program Mol Med, Bethesda, MD 20892 USA. [Kaneski, Christine R.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. RP Kaler, SG (reprint author), Bldg 10,Room 5-2571,10 Ctr Dr MSC 1834, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov OI Kaneski, Christine/0000-0003-1453-2502 FU NIH Intramural Research Program [1201 HD008768] FX This work is Supported by the NIH Intramural Research Program. Project 1201 HD008768 (S.G.K.) NR 24 TC 18 Z9 19 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 JAN PY 2009 VL 65 IS 1 BP 108 EP 113 DI 10.1002/ana.21576 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 404BD UT WOS:000263124800016 PM 19194885 ER PT J AU Milner, JA AF Milner, J. A. TI NUTRITION, LIFESTYLE AND CANCER SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Milner, J. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 2 EP 2 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200007 ER PT J AU Raiten, D AF Raiten, Daniel TI NUTRITION AND HIV - SCIENTIFIC UPDATE AND RESEARCH GAPS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Raiten, Daniel] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 11 EP 11 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200038 ER PT J AU Ross, S AF Ross, Sharon TI IMPLICATION OF DIETARY NATURAL COMPOUNDS IN EPIGENETIC MODIFICATIONS AS A NEW APPROACH TO CANCER CHEMOPREVENTION SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Ross, Sharon] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 13 EP 13 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200045 ER PT J AU Raiten, D AF Raiten, Daniel TI CONSIDERATIONS FOR THE USE OF IRON INTERVENTION IN REGIONS WITH MALARIA SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Raiten, Daniel] NICHD, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 17 EP 17 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200059 ER PT J AU Ross, A AF Ross, A. TI NUTRITION AND EPIGENETICS SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Ross, A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 53 EP 54 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827200198 ER PT J AU Mahabir, S Forman, MR Hajek, RA Dong, YQ Gor, BJ Jones, LA AF Mahabir, Somdat Forman, Michele R. Hajek, Richard A. Dong, Yong Q. Gor, Beverly J. Jones, Lovell A. TI ASSOCIATION BETWEEN OBESITY AND SERUM FOLATES IN PREMENOPAUSAL AFRICAN SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Mahabir, Somdat] NCI, Bethesda, MD 20892 USA. [Forman, Michele R.; Hajek, Richard A.; Dong, Yong Q.; Gor, Beverly J.; Jones, Lovell A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 344 EP 344 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827201353 ER PT J AU Namaste, SM Raiten, D AF Namaste, Sorrel M. Raiten, Daniel TI IRON INTERVENTIONS IN AREAS OF MALARIA BURDEN: CONNECTING SCIENCE TO HEALTH PRACTICE SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Namaste, Sorrel M.; Raiten, Daniel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 428 EP 428 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827201693 ER PT J AU Gordon, RR La Merrill, M Hunter, KW Threadgill, DW Pomp, D AF Gordon, Ryan R. La Merrill, Michele Hunter, Kent W. Threadgill, David W. Pomp, Daniel TI A SYSTEMATIC EVALUATION OF AN F2 MOUSE CROSS PREDISPOSED TO OBESITY AND MAMMARY TUMOR DEVELOPMENT AND FED VARYING LEVELS OF DIETARY FAT SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 [Gordon, Ryan R.] Univ N Carolina, Durham, NC USA. [La Merrill, Michele; Threadgill, David W.; Pomp, Daniel] Univ N Carolina, Chapel Hill, NC USA. [Hunter, Kent W.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2009 VL 55 SU 1 BP 547 EP 547 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 507CF UT WOS:000270827202182 ER PT J AU Sigmond, J Honeywell, RJ Postma, TJ Dirven, CMF de Lange, SM van der Born, K Laan, AC Baayen, JCA Van Groeningen, CJ Bergman, AM Giaccone, G Peters, GJ AF Sigmond, J. Honeywell, R. J. Postma, T. J. Dirven, C. M. F. de Lange, S. M. van der Born, K. Laan, A. C. Baayen, J. C. A. Van Groeningen, C. J. Bergman, A. M. Giaccone, G. Peters, G. J. TI Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer SO ANNALS OF ONCOLOGY LA English DT Article ID TUMOR-CELL LINES; DEOXYCYTIDINE KINASE; PHASE-II; IN-VITRO; 2',2'-DIFLUORODEOXYCYTIDINE; TEMOZOLOMIDE; TISSUE; BRAIN; RADIOTHERAPY; PHARMACOLOGY AB Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood-tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU. Gemcitabine was administered at 500 or 1000 mg/m(2) just before surgery to 10 GBM patients, who were biopsied after 1-4 h. Plasma gemcitabine and dFdU levels varied between 0.9 and 9.2 mu M and 24.9 and 72.6 mu M, respectively. Tumor gemcitabine and dFdU levels varied from 60 to 3580 pmol/g tissue and from 29 to 72 nmol/g tissue, respectively. The gene expression of dCK (beta-actin ratio) varied between 0.44 and 2.56. The dCK and dCDA activities varied from 1.06 to 2.32 nmol/h/mg protein and from 1.51 to 5.50 nmol/h/mg protein, respectively. These enzyme levels were sufficient to enable gemcitabine phosphorylation, leading to 130-3083 pmol gemcitabine nucleotides/g tissue. These data demonstrate for the first time that gemcitabine passes the blood-tumor barrier in GBM patients. In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation. C1 [Sigmond, J.; Honeywell, R. J.; de Lange, S. M.; van der Born, K.; Laan, A. C.; Van Groeningen, C. J.; Peters, G. J.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1007 MB Amsterdam, Netherlands. [Postma, T. J.] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. [Baayen, J. C. A.] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. [Dirven, C. M. F.] Erasmus Univ, Dept Neurosurg, Rotterdam, Netherlands. [Bergman, A. M.] Netherlands Canc Inst, Amsterdam, Netherlands. [Giaccone, G.] NCI, Bethesda, MD 20892 USA. RP Peters, GJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM gj.peters@vumc.nl RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 38 TC 26 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2009 VL 20 IS 1 BP 182 EP 187 DI 10.1093/annonc/mdn543 PG 6 WC Oncology SC Oncology GA 398FM UT WOS:000262718000025 PM 18701427 ER PT S AU Caughey, B Baron, GS Chesebro, B Jeffrey, M AF Caughey, Byron Baron, Gerald S. Chesebro, Bruce Jeffrey, Martin TI Getting a Grip on Prions: Oligomers, Amyloids, and Pathological Membrane Interactions SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE exosomes; glycophosphatidylinositol anchor; protein misfolding diseases; tunneling nanotubes ID BETA-SHEET STRUCTURE; PROTEASE-RESISTANT STATE; CELL-FREE FORMATION; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; SCRAPIE-ASSOCIATED FORM; HET-S PRION; IN-VITRO; INFECTIOUS PRIONS; NEURONAL CELLS; CYCLIC AMPLIFICATION AB The prion (infectious protein) concept has evolved with the discovery of new self-propagating protein states in organisms as diverse as mammals and fungi. The infectious agent of the mammalian transmissible spongiform encephalopathies (TSE) has long been considered the prototypical prion, and recent cell-free propagation and biophysical analyses of TSE infectivity have now firmly established its prion credentials. Other disease-associated protein aggregates, such as some amyloids, can also have prion-like characteristics under certain experimental conditions. However, most amyloids appear to lack the natural transmissibility of TSE prions. One feature that distinguishes the latter from the former is the glycophosphatidylinositol membrane anchor on prion protein, the molecule that is corrupted in TSE diseases. The presence of this anchor profoundly affects TSE pathogenesis, which involves major membrane distortions in the brain, and may be a key reason for the greater neurovirulence of TSE prions relative to many other autocatalytic protein aggregates. C1 [Caughey, Byron; Baron, Gerald S.; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Jeffrey, Martin] Vet Labs Agcy, Penicuik EH26 0PZ, Midlothian, Scotland. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bcaughey@nih.gov; gbaron@nih.gov; bchesebro@nih.gov; m.jeffrey@vla.defra.gsi.gov.uk RI Jeffrey, Martin/D-2251-2009; APHA, Staff publications/E-6082-2010 FU Intramural Research Program of the NIAID; NIH FX We thank Drs. Valerie Sim, Kelly Barton, Winslow Caughey, Leah Christensen, and Kim Hasenkrug for helpful comments oil this manuscript. Gary Hettrick provided excellent graphics assistance. This work was supported by the Intramural Research Program of the NIAID, NIH. NR 161 TC 173 Z9 177 U1 1 U2 44 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0878-0 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2009 VL 78 BP 177 EP 204 DI 10.1146/annurev.biochem.78.082907.145410 PG 28 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 471OZ UT WOS:000268069200009 PM 19231987 ER PT S AU Reyes-Turcu, FE Ventii, KH Wilkinson, KD AF Reyes-Turcu, Francisca E. Ventii, Karen H. Wilkinson, Keith D. TI Regulation and Cellular Roles of Ubiquitin-Specific Deubiquitinating Enzymes SO ANNUAL REVIEW OF BIOCHEMISTRY SE Annual Review of Biochemistry LA English DT Review; Book Chapter DE cell cycle; DNA damage; endocytosis; histone; proteasome; signal transduction ID NF-KAPPA-B; TUMOR-SUPPRESSOR CYLD; RESPIRATORY SYNDROME CORONAVIRUS; POLYGLUTAMINE DISEASE PROTEIN; HISTONE H2B UBIQUITYLATION; FREE POLYUBIQUITIN CHAINS; FANCONI-ANEMIA PATHWAY; C-TERMINAL HYDROLASES; MESSENGER-RNA EXPORT; PAPAIN-LIKE PROTEASE AB Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin or ubiquitin-like gene products, reverse the modification of proteins by a single ubiquitin(-like) protein, and remodel polyubiquitin(-like) chains on target proteins. The human genome encodes nearly 100 DUBs with specificity for ubiquitin in five gene families. Most DUB activity is cryptic, and conformational rearrangements often occur during the binding of ubiquitin and/or scaffold proteins. DUBs with specificity for ubiquitin contain insertions and extensions modulating DUB substrate specificity, protein-protein interactions, and Cellular localization. Binding partners and multiprotein complexes with which DUBs associate Modulate DUB activity and substrate specificity. Quantitative studies of activity and protein-protein interactions, together with genetic studies and the advent of RNAi, have led to new insights into the function of yeast and human DUBs. This review discusses ubiquitin-specific DUBs, some of the generalizations emerging from recent studies of the regulation of DUB activity, and their roles in various cellular processes. C1 [Reyes-Turcu, Francisca E.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Ventii, Karen H.; Wilkinson, Keith D.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. RP Reyes-Turcu, FE (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM genekdw@emory.edu FU NIGMS NIH HHS [R01 GM030308, R01 GM030308-27] NR 220 TC 541 Z9 559 U1 12 U2 89 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 BN 978-0-8243-0878-0 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2009 VL 78 BP 363 EP 397 DI 10.1146/annurev.biochem.78.082307.091526 PG 35 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 471OZ UT WOS:000268069200015 PM 19489724 ER PT S AU Swedlow, JR Goldberg, IG Eliceiri, KW AF Swedlow, Jason R. Goldberg, Ilya G. Eliceiri, Kevin W. CA OME Consortium TI Bioimage Informatics for Experimental Biology SO ANNUAL REVIEW OF BIOPHYSICS SE Annual Review of Biophysics LA English DT Review; Book Chapter DE microscopy; file formats; image management; image analysis; image processing ID FLUORESCENCE MICROSCOPY; QUANTITATIVE-ANALYSIS; SYSTEMS BIOLOGY; OPEN TOOLS; IMAGE DATA; DATABASE; COMMUNITY; PATTERNS; ONTOLOGY AB Over the past twenty years there have been great advances in light microscopy with the result that multidimensional imaging has driven a revolution in modern biology. The development of new approaches of data acquisition is reported frequently, and yet the significant data management and analysis challenges presented by these new complex datasets remain largely unsolved. As in the well-developed field of genome bioinformatics, central repositories are and will be key resources, but there is a critical need for informatics tools in individual laboratories to help manage, share, visualize, and analyze image data. In this article we present the recent efforts by the bioimage informatics community to tackle these challenges, and discuss our own vision for future development of bioimage informatics solutions. C1 [Swedlow, Jason R.] Univ Dundee, Wellcome Trust Ctr Gene Regulat & Express, Coll Life Sci, Dundee DD1 5EH, Scotland. [Goldberg, Ilya G.] NIA, Image Informat & Computat Biol Unit, Genet Lab, IRP,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Eliceiri, Kevin W.] Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI 53706 USA. RP Swedlow, JR (reprint author), Univ Dundee, Wellcome Trust Ctr Gene Regulat & Express, Coll Life Sci, Dundee DD1 5EH, Scotland. EM jason@lifesci.dundee.ac.uk; igg@nih.gov; eliceiri@wisc.edu RI Goldberg, Ilya/H-5307-2011; OI Goldberg, Ilya/0000-0001-8514-6110; Moore, Josh/0000-0003-4028-811X; Eliceiri, Kevin/0000-0001-8678-670X; Swedlow, Jason/0000-0002-2198-1958; Tarkowska, Aleksandra/0000-0002-3392-3691 FU Wellcome Trust; BBSRC [BB/D00151XII]; EPSRC [EP/D050014/1]; NTH [R03EB008516, ROIEB005157] FX JRS is a Wellcome Trust Senior Research Fellow and work in his lab on OME is supported by the Wellcome Trust (Ref 080087 and 085982), BBSRC (BB/D00151XII), and EPSRC (EP/D050014/1). Work in IGGs lab is supported by the National Institutes of Health. The OME work in KAVE's lab is supported by NTH grants R03EB008516 and ROIEB005157. NR 48 TC 59 Z9 59 U1 0 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1936-122X BN 978-0-8243-1838-3 J9 ANNU REV BIOPHYS JI Ann. Rev. Biophys. PY 2009 VL 38 BP 327 EP 346 DI 10.1146/annurev.biophys.050708.133641 PG 20 WC Biophysics SC Biophysics GA 471QB UT WOS:000268072100016 PM 19416072 ER PT S AU Holmes, EC AF Holmes, Edward C. TI The Evolutionary Genetics of Emerging Viruses SO ANNUAL REVIEW OF ECOLOGY EVOLUTION AND SYSTEMATICS SE Annual Review of Ecology Evolution and Systematics LA English DT Review; Book Chapter DE complementation; emergence; epistasis; evolution; fitness; mutation; natural selection; quasispecies; recombination; RNA secondary structure; robustness ID VESICULAR STOMATITIS-VIRUS; HIGH MUTATION-RATES; STRONG PURIFYING SELECTION; RNA SECONDARY STRUCTURES; QUASI-SPECIES THEORY; IN-VIVO; POSITIVE SELECTION; ANTAGONISTIC EPISTASIS; DELETERIOUS MUTATION; REPLICATION FIDELITY AB RNA viruses are the main agents of emerging disease. To understand how RNA viruses are able to jump species boundaries and spread in new hosts it is essential to determine the basic processes of evolutionary change in these infectious agents. RNA virus evolution is largely shaped by very high rates of mutation. This, coupled with potentially enormous intra- and interhost population sizes and continual replication, allows the rapid production of genetic diversity, including those mutations that facilitate host adaptation. However, high mutation rates also act to constrain aspects of RNA virus evolution, as the majority of mutations, including many at synonymous sites, are deleterious, which in turn places an upper limit on genome size. Ironically, although RNA viruses are characterized by their mutation rates, these rates may not be high enough to allow the onset of quasispecies dynamics, in which natural selection acts on the viral population as a whole. C1 [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 119 TC 67 Z9 68 U1 3 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1543-592X BN 978-0-8243-1440-8 J9 ANNU REV ECOL EVOL S JI Annu. Rev. Ecol. Evol. Syst. PY 2009 VL 40 BP 353 EP 372 DI 10.1146/annurev.ecolsys.110308.120248 PG 20 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 528OI UT WOS:000272455700017 ER PT S AU Wang, CX Youle, RJ AF Wang, Chunxin Youle, Richard J. TI The Role of Mitochondria in Apoptosis SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE Bcl-2; bax; cytochrome c; apoptosome; Drosophila; Caenorhabditis elegans ID PROGRAMMED CELL-DEATH; STRESS-INDUCED APOPTOSIS; SERINE-PROTEASE OMI/HTRA2; CYTOCHROME-C RELEASE; X-LINKED INHIBITOR; CASPASE ACTIVATION; ENDONUCLEASE-G; PERMEABILITY TRANSITION; MEMBRANE PERMEABILIZATION; CAENORHABDITIS-ELEGANS AB Mitochondria plan, key roles in activating apoptosis in mammalian cells. Bcl-2 family, members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses. Here we review the extensive literature on proteins released from the intermembrane space and consider genetic evidence for and against their roles in apoptosis activation. We also compare and contrast apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals that indicate major mysteries remaining to be solved. C1 [Wang, Chunxin; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wang, CX (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov RI Wang, Chunxin/B-9312-2016 OI Wang, Chunxin/0000-0001-6015-6806 FU NIH, National Institute of Neurological Disorders and Stroke FX This work was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. We apologize in advance to all the investigators whose research could not be appropriately cited owing to space limitations. NR 158 TC 407 Z9 424 U1 8 U2 67 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1243-5 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2009 VL 43 BP 95 EP 118 DI 10.1146/annurev-genet-102108-134850 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA 543LW UT WOS:000273580300005 PM 19659442 ER PT S AU Swaroop, A Chew, EY Rickman, CB Abecasis, GR AF Swaroop, Anand Chew, Emily Y. Rickman, Catherine Bowes Abecasis, Goncalo R. TI Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE protein homeostasis; gene-environment interaction; genetic variation; neurodegeneration; neovascularization; animal models ID COMPLEMENT-FACTOR-H; RETINAL-PIGMENT EPITHELIUM; GENOME-WIDE ASSOCIATION; BEAVER DAM EYE; CHLAMYDIA-PNEUMONIAE INFECTION; C-REACTIVE PROTEIN; RISK-FACTORS; VISUAL IMPAIRMENT; CHOROIDAL NEOVASCULARIZATION; ALCOHOL-CONSUMPTION AB Aging-associated neurodegenerative diseases significantly influence the quality of life of affected individuals. Genetic approaches, combined with genomic technology, have provided powerful insights into common late-onset diseases, such as age-related macular degeneration (AMD). Here, we discuss current findings on the genetics of AMD to highlight areas of rapid progress and new challenges. We also attempt to integrate available genetic and biochemical data with cellular pathways involved in aging to formulate an integrated model of AMD pathogenesis. C1 [Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Rickman, Catherine Bowes] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Rickman, Catherine Bowes] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. RP Swaroop, A (reprint author), NEI, N NRL, NIH, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825; Swaroop, Anand/0000-0002-1975-1141 FU National Institutes of Health; The Foundation Fighting Blindness; Macula Vision Research Foundation; Research to Prevent Blindness FX We sincerely apologize to our colleagues whose work (particularly on the epidemiology and pathology of AMD, and on CFH and ARM.S2/HTRA1) could not be cited because of page limitations. We are grateful to John Heckenlively, Sheldon Miller, Dwight Stambolian, Robert Fariss, Nicholas Katsanis, Fredrick Ferris, Robert Nussenblatt, AVei Chen, Kari Branham, Atsuhiro Kanda, Rivka Rachel and Mohammad Othinan for discussions, comments, and assistance. NVe are grateful to T iziana Cogliati and Lydia Kibluk for excellent assistance with illustrations. Our research is supported by the intramural program of the National Eye Institute and by grants from the National Institutes of Health, The Foundation Fighting Blindness, Macula Vision Research Foundation, and Research to Prevent Blindness. NR 175 TC 146 Z9 150 U1 2 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3710-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2009 VL 10 BP 19 EP 43 DI 10.1146/annurev.genom.9.081307.164350 PG 25 WC Genetics & Heredity SC Genetics & Heredity GA 500OT UT WOS:000270313200002 PM 19405847 ER PT S AU O'Brien, SJ AF O'Brien, Stephen J. TI Stewardship of Human Biospecimens, DNA, Genotype, and Clinical Data in the GWAS Era SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE biobanks; policy; ethics; GWAS population cohorts ID GENETIC RESEARCH; GENOMIC RESEARCH; PRIVACY; OWNERSHIP; BIOBANKS; AIDS; ASSOCIATION; INFORMATION; ANONYMITY; TISSUE AB An ethical quandary is emerging over custodianship of and access to DNA specimens and attached data, clinical and genetic, held in large disease cohort collections. The balance of patients' rights and science/society's quest for broad open access must be resolved in order to realize the promise of gene association studies of complex human disease. Away forward may be to convene a colloquium of international medical and science organizations charged with developing global consensus guidance and ethical principles for access to and use of genomic biobanks. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@nciferf.gov NR 57 TC 22 Z9 22 U1 1 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3710-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2009 VL 10 BP 193 EP 209 DI 10.1146/annurev-genom-082908-150133 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 500OT UT WOS:000270313200010 PM 19630558 ER PT S AU Ostrander, EA Huson, HJ Ostrander, GK AF Ostrander, Elaine A. Huson, Heather J. Ostrander, Gary K. TI Genetics of Athletic Performance SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE SNP; behavior; endurance; polymorphism; athletics; doping ID ANGIOTENSIN-CONVERTING-ENZYME; ELITE ENDURANCE ATHLETE; HUMAN SKELETAL-MUSCLE; OXIDE SYNTHASE GENE; BETA(2)-ADRENERGIC RECEPTOR POLYMORPHISM; HUMAN PHYSICAL PERFORMANCE; FIBER-TYPE DISTRIBUTION; NITRIC-OXIDE; ALPHA-ACTININ-3 DEFICIENCY; EXERCISE CAPACITY AB Performance enhancing polymorphisms (PEPS) are examples of natural genetic variation that affect the outcome of athletic challenges. Elite athletes, and what separates them from the average competitor, have been the subjects of discussion and debate for decades. While training, diet, and mental fitness are all clearly important contributors to achieving athletic success, the fact that individuals reaching the pinnacle of their chosen sports often share both physical and physiological attributes suggests a role for genetics. That multiple members of a family often participate in highly competitive events, such as the Olympics, further supports this argument. In this review, we discuss what is known regarding the genes and gene families, including the mitochondrial genome, that are believed to play a role in human athletic performance. Where possible, we describe the physiological impact of the critical gene variants and consider predictions about other potentially important genes. Finally, we discuss the implications of these findings on the future for competitive athletics. C1 [Ostrander, Elaine A.; Huson, Heather J.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Huson, Heather J.] Univ Alaska, Coll Nat Sci & Math, Fairbanks, AK 99774 USA. [Ostrander, Gary K.] Univ Hawaii, Pacific Biosci Res Ctr, Honolulu, HI 96821 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU National Human Genome Research Institute FX We thank Drs. Tyrone Spady, Edward Giniger and Adrian Ferre D'Amare for photography, the athletes pictured for permission to print their pictures and Drs. Vence Bonham, Heidi Parker, Cheryl Maslen, Jeff Schoenebeck, Pascale Quignon and Danielle Karyadi for careful reading of this manuscript and thoughtful comments. Finally, we acknowledge Pascale Quignon and Jeff Schoenebeck for assistance with figures. We apologize to the many authors whose work we were unable to cite in the interest of space. We gratefully acknowledge the Intramural Program of the National Human Genome Research Institute for continued support. NR 108 TC 44 Z9 48 U1 4 U2 50 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3710-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2009 VL 10 BP 407 EP 429 DI 10.1146/annurev-genom-082908-150058 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA 500OT UT WOS:000270313200019 PM 19630564 ER PT S AU Belkaid, Y Tarbell, K AF Belkaid, Yasmine Tarbell, Kristin TI Regulatory T Cells in the Control of Host-Microorganism Interactions SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE infection; Foxp3; dendritic cells; Treg ID C VIRUS-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; LEISHMANIA-MAJOR INFECTION; TOLL-LIKE RECEPTORS; CHRONIC HEPATITIS-B; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PLASMODIUM-FALCIPARUM MALARIA; FRIEND RETROVIRUS INFECTION; INTESTINAL DENDRITIC CELLS AB Each microenvironment requires a specific set of regulatory elements that ire finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also hell) limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions. C1 [Belkaid, Yasmine] NIAID, Mucosal Immun Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Tarbell, Kristin] NIDDK, Immune Tolerance Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immun Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov; tarbellk@niddk.nih.gov OI Tarbell, Kristin/0000-0003-3738-379X FU Division of Irtramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Irtramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 327 TC 262 Z9 277 U1 0 U2 26 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3027-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2009 VL 27 BP 551 EP 589 DI 10.1146/annurev.immunol.021908.132723 PG 39 WC Immunology SC Immunology GA 471PW UT WOS:000268071600020 PM 19302048 ER PT S AU Masters, SL Simon, A Aksentijevich, I Kastner, DL AF Masters, Seth L. Simon, Anna Aksentijevich, Ivona Kastner, Daniel L. TI Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE innate immunity; IL-1 beta; inflammasome; type 2 diabetes mellitus; pulmonary fibrosis; Crohn's disease; ankylosing spondylitis; atherosclerosis ID FAMILIAL MEDITERRANEAN FEVER; HEMOLYTIC-UREMIC SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MACROPHAGE ACTIVATION SYNDROME; INFLAMMATORY-BOWEL-DISEASE; UNFOLDED PROTEIN RESPONSE; HYPER-IGD SYNDROME; NF-KAPPA-B; RECURRENT MULTIFOCAL OSTEOMYELITIS AB The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1 beta activation disorders (inflammasomopathies), NF-kappa B activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and it die bedside. C1 [Masters, Seth L.; Aksentijevich, Ivona; Kastner, Daniel L.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Simon, Anna] Radboud Univ Nijmegen, Dept Gen Internal Med, Med Ctr, Nijmegen, Netherlands. RP Masters, SL (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM masterss@mail.nih.gov; a.simon@aig.umcn.nl; aksentii@mail.nih.gov; kastnerd@mail.nih.gov RI Simon, Anna/D-3757-2009; Masters, Seth/N-2886-2013 OI Simon, Anna/0000-0002-6141-7921; Masters, Seth/0000-0003-4763-576X FU National Institute of Arthritis and Musculoskeletal and Skin Diseases FX This work was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 250 TC 449 Z9 471 U1 2 U2 42 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3027-9 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2009 VL 27 BP 621 EP 668 DI 10.1146/annurev.immunol.25.022106.141627 PG 48 WC Immunology SC Immunology GA 471PW UT WOS:000268071600022 PM 19302049 ER PT S AU Kramer, BS Croswell, JM AF Kramer, Barnett S. Croswell, Jennifer Miller TI Cancer Screening: The Clash of Science and Intuition SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE five-year survival; selection bias; lead-time bias; length-biased sampling; overdiagnosis ID MAYO LUNG PROJECT; QUALITY-OF-LIFE; PROSTATE-CANCER; BREAST-CANCER; OVARIAN-CANCER; UNITED-STATES; FOLLOW-UP; SURVIVAL RATES; MORTALITY; JAPAN AB The concept of early detection of cancer holds great promise and intuitive appeal. However, powerful biases can mislead clinicians when evaluating the efficacy of screening tests by clinical observation alone. Selection bias, lead-time bias, length-biased sampling, and overdiagnosis are counterintuitive concepts with critical implications for early detection efforts. This article explains these biases and other common confounders in cancer screening. The most direct and reliable way to avoid being led astray by intuitions is through the use of randomized controlled trials. C1 [Kramer, Barnett S.; Croswell, Jennifer Miller] NIH, Off Director, Off Dis Prevent, Bethesda, MD 20892 USA. RP Kramer, BS (reprint author), NIH, Off Director, Off Dis Prevent, Bethesda, MD 20892 USA. EM bk76p@nih.gov; croswellj@od.nih.gov FU U.S. National Cancer Institute FX Barnett Kramer, as part of his official duties for the U.S. government, serves in leadership positions for two large randomized controlled cancer screening trials funded by the U.S. National Cancer Institute: (a) the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and (b) the National Lung Screening Trial (NLST). Jennifer Miller Croswell is not aware of any factors that might he perceived as affecting the objectivity of this review. NR 53 TC 33 Z9 33 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0560-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 125 EP 137 DI 10.1146/annurev.med.60.101107.134802 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100010 PM 18803476 ER PT S AU Klion, A AF Klion, Amy TI Hypereosinophilic Syndrome: Current Approach to Diagnosis and Treatment SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE chronic eosinophilic leukemia; eosinophil-associated gastrointestinal disorders; Churg-Strauss vasculitis; episodic angioedema and eosinophilia; chronic eosinophilic pneumonia; familial eosinophilia ID CHRONIC EOSINOPHILIC LEUKEMIA; MYELOPROLIFERATIVE VARIANT; LYMPHOCYTIC VARIANT; IMATINIB MESYLATE; MOLECULAR CHARACTERIZATION; IDIOPATHIC EOSINOPHILIA; FAMILIAL EOSINOPHILIA; MEPOLIZUMAB THERAPY; EPISODIC ANGIOEDEMA; PERSISTENT ASTHMA AB Hypereosinophilic syndrome is a heterogeneous group of rare disorders characterized by marked blood or tissue eosinophilia resulting in a wide variety of clinical manifestations. Although the existence of clinical subtypes (or variants) of HES has been appreciated for some time, the recent characterization of some of these variants at the molecular and immunologic levels has demonstrated dramatic differences in disease pathogenesis, response to treatment, and prognosis depending oil the etiology of the eosinophilia. This, together with the availability of novel targeted therapies, including tyrosine kinase inhibitors and monoclonal antibodies, has fundamentally altered the approach to the diagnosis and treatment of HES. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Klion, A (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM aklion@nih.gov OI Klion, Amy/0000-0002-4986-5326 FU National Institutes of Health; NIAID FX Dr. Klion is funded by the Intramural Program of the National Institutes of Health, NIAID. NR 66 TC 46 Z9 53 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0560-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 293 EP 306 DI 10.1146/annurev.med.60.062107.090340 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100022 PM 19630574 ER PT S AU Manolio, TA Collins, FS AF Manolio, Teri A. Collins, Francis S. TI The HapMap and Genome-Wide Association Studies in Diagnosis and Therapy SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE complex diseases; genetic association; genomic variation ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON GENETIC VARIANT; BODY-MASS INDEX; OLIGONUCLEOTIDE ARRAYS; MACULAR DEGENERATION; STRUCTURAL VARIATION; SUSCEPTIBILITY LOCI; PARKINSON-DISEASE; HAPLOTYPE MAP; RISK LOCI AB The International HapMap Project Produced a genome-wide database of genetic Variation for use in genetic association studies of common diseases. The initial output of these studies has been over-whelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations have Suggested previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based oil genetically defined risk. Here we examine the development mid application of the HPAMap to genome-wide association (GWA) studies; present and future technologies for CAVA research; Current major efforts in GWA studies; successes and limitations Of the GWA approach in identifying polymorphisms related to complex diseases; data release and privacy polices; use of these findings by Clinicians, the public, and academic physicians; and sources of ongoing authoritative information on this rapidly evolving field. C1 [Manolio, Teri A.; Collins, Francis S.] NHGRI, Bethesda, MD 20892 USA. RP Manolio, TA (reprint author), NHGRI, Bethesda, MD 20892 USA. EM manolio@nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 60 TC 108 Z9 113 U1 1 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0560-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 443 EP 456 DI 10.1146/annurev.med.60.061907.093117 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100033 PM 19630580 ER PT J AU Sierra, F Hadley, E Suzman, R Hodes, R AF Sierra, Felipe Hadley, Evan Suzman, Richard Hodes, Richard TI Prospects for Life Span Extension SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE aging; longevity ID RANDOMIZED CONTROLLED-TRIAL; CAENORHABDITIS-ELEGANS; CALORIE RESTRICTION; GROWTH-HORMONE; OXIDATIVE STRESS; HUMAN LONGEVITY; RISK-FACTORS; AGE-1 GENE; MICE; INSULIN AB Life expectancy has increased dramatically in the United States and in much of the world in recent years and decades. The factors underlying this increase are incompletely understood and are undoubtedly complex. A question that drives current research is whether life expectancy call he further extended using current knowledge of modifiable risk factors. A still more challenging research focus is on the possibility that life expectancy might he further increased through knowledge gained from studies of the basic biology of aging and its genetic and environmental modifiers. C1 [Sierra, Felipe; Hadley, Evan; Suzman, Richard; Hodes, Richard] NIA, NIH, Bethesda, MD 20892 USA. RP Sierra, F (reprint author), NIA, NIH, Bethesda, MD 20892 USA. EM hodesr@31.nia.nih.gov NR 83 TC 36 Z9 36 U1 1 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 457 EP 469 DI 10.1146/annurev.med.60.061607.220533 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100034 PM 18817460 ER PT J AU Douek, DC Roederer, M Koup, RA AF Douek, Daniel C. Roederer, Mario Koup, Richard A. TI Emerging Concepts in the Immunopathogenesis of AIDS SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE human immunodeficiency virus; T lymphocyte; Th17 cells; cytokines; PD-1 ID CD8(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC HIV-INFECTION; ACQUIRED IMMUNODEFICIENCY SYNDROME; LYMPHATIC TISSUE FIBROSIS; VIRUS TYPE-1 INFECTION; IMMUNE ACTIVATION; SIV INFECTION; VIRAL LOAD; GASTROINTESTINAL-TRACT AB There is an intense interplay between HIV and the immune system, and the literature is replete with studies describing various immunological phenomena associated with HIV infection. Many of these phenomena seem too broad in scope to be attributable either to HIV-infected cells or to the HIV-specific immune response. Recently, a more fundamental understanding of how HIV affects various T cells and T cell compartments has emerged. This review covers the role of immune activation in HIV immunopathogenesis, how that activation could be mediated directly by HIV replicating within and damaging the gut mucosal barrier, how HIV affects multiple T cells functions and phenotypes, and how chronic HIV replication induces immune modulatory pathways to negatively regulate certain functions in HIV-specific T cells. C1 [Douek, Daniel C.] NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. [Roederer, Mario] NIAID, Immunol Technol Sect, NIH, Bethesda, MD 20892 USA. [Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 100 TC 249 Z9 256 U1 5 U2 39 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2009 VL 60 BP 471 EP 484 DI 10.1146/annurev.med.60.041807.123549 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 471PS UT WOS:000268071100035 PM 18947296 ER PT S AU Dupre, DJ Robitaille, M Rebois, RV Hebert, TE AF Dupre, Denis J. Robitaille, Melanie Rebois, R. Victor Hebert, Terence E. TI The Role of G beta gamma Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE signaling specificity; G protein heterotrimers; complex assembly; G protein-coupled receptors; scaffolding proteins ID HETEROTRIMERIC G-PROTEINS; RESONANCE ENERGY-TRANSFER; PHOSDUCIN-LIKE PROTEIN; CYSTEINE-STRING-PROTEIN; RECTIFYING POTASSIUM CHANNELS; GTP-BINDING PROTEINS; CYTOSOLIC CHAPERONIN COMPLEX; NUCLEOTIDE EXCHANGE FACTOR; FORM STABLE COMPLEXES; TRIMERIC G-PROTEINS AB The role of G beta gamma subunits in cellular signaling has become well established in the past 20 years. Not only do they regulate effectors once thought to be the sole targets of G alpha subunits, but it has become clear that they also have a unique set of binding partners and regulate signaling pathways that are not always localized to the plasma membrane. However, this may be only the beginning of the story. G beta gamma subunits interact with G protein-coupled receptors, G alpha subunits, and several different effector molecules during assembly and trafficking of receptor-based signaling complexes and not simply in response to ligand stimulation at sites of receptor cellular activity. G beta gamma assembly itself seems to be tightly regulated via the action of molecular chaperones and in turn may serve a similar role ill the assembly of specific signaling complexes. le propose that specific G beta gamma subunits have a broader role in controlling the architecture, assembly, and activity of cellular signaling pathways. C1 [Dupre, Denis J.] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada. [Robitaille, Melanie; Hebert, Terence E.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. [Rebois, R. Victor] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20824 USA. [Rebois, R. Victor] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA. [Hebert, Terence E.] McGill Univ, Fac Med, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. RP Dupre, DJ (reprint author), Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada. EM denis.dupre@dal.ca RI Dupre, Denis/F-3044-2014 FU Canadian Institutes of Health Research; Heart and Stroke Foundation of Quebec; NIH; National Institute of Deafness and Other Communication Disorders; National Institute of Neurological Disorders and Stroke; Fonds de la Recherche en Santo du Quebec; CIHR New Investigator Award FX This work was supported by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Quebec awarded to T.E.H. and by the Intramural Research Program of the NIH, National Institute of Deafness and Other Communication Disorders, and the National Institute of Neurological Disorders and Stroke, awarded to R.V.R. T.E.H. is a Chercheur National of the Fonds de la Recherche en Sante du Quebec. M.R. holds a doctoral award from the Fonds de la Recherche en Santo du Quebec. D.J.D. is the recipient of a CIHR New Investigator Award. NR 209 TC 126 Z9 129 U1 2 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0448-5 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2009 VL 49 BP 31 EP 56 DI 10.1146/annurev-pharmtox-061008-103038 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 410GQ UT WOS:000263565900002 PM 18834311 ER PT S AU Birnbaumer, L AF Birnbaumer, Lutz TI The TRPC Class of Ion Channels: A Critical Review of Their Roles in Slow, Sustained Increases in Intracellular Ca2+ Concentrations SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE store operated calcium entry (SOCE); capacitative calcium entry (CCE); calcium release activated calcium current (Icrac); G protein-coupled receptor (GPCR); phospholipase C (PLC) ID CAPACITATIVE CALCIUM-ENTRY; CA2+-PERMEABLE CATION CHANNEL; RECEPTOR POTENTIAL CHANNELS; PLASMA MEMBRANE JUNCTIONS; STORE-OPERATED CHANNELS; PANCREATIC ACINAR-CELLS; DEPENDENT K+ CHANNEL; TRANSIENT-RECEPTOR; CRAC CHANNEL; 2-AMINOETHOXYDIPHENYL BORATE AB The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of sequence similarity. T RP channels are nonselective monovalent cation channels, most of which also allow passage of Ca2+. Many members of each of these families, but not all, are involved in sensory signal transduction. The C-type (for canonical or classical) subfamily, differs front the other TRP subfamilies in that it fulfills two different types of function: membrane depolarization, resembling sensory transduction TRPs, and mediation of sustained increases in intracellular Ca2+. The mechanism(s) by which the C-class of TRP channels-the TRPCs-are activated is poorly understood and their role in mediating intracellular Ca2+ increases is being questioned. Both of these questions-mechanism of activation and participation in Ca2+ entry-are the topics of this review. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov FU Intramural Research Program of the VIII FX L.B. is supported by the Intramural Research Program of the VIII. NR 138 TC 134 Z9 140 U1 1 U2 14 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0448-5 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2009 VL 49 BP 395 EP 426 DI 10.1146/annurev.pharmtox.48.113006.094928 PG 32 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 410GQ UT WOS:000263565900018 PM 19281310 ER PT S AU London, SJ Romieu, I AF London, Stephanie J. Romieu, Isabelle TI Gene by Environment Interaction in Asthma SO ANNUAL REVIEW OF PUBLIC HEALTH SE Annual Review of Public Health LA English DT Review; Book Chapter DE genetic polymorphism endotoxin; air pollution; tobacco smoke pollution; environmental pollutants ID S-TRANSFERASE M1; GENOME-WIDE ASSOCIATION; PEAK EXPIRATORY FLOW; CHILDHOOD ASTHMA; TOBACCO-SMOKE; LUNG-FUNCTION; BRONCHIAL HYPERRESPONSIVENESS; ALLERGIC RESPONSES; CD14 POLYMORPHISMS; ORMDL3 EXPRESSION AB Marked international differences in rates of asthma and allergies and the importance of family history highlight the primacy of interactions between genetic variation and the environment in asthma etiology. Environmental tobacco smoke (or secondhand smoke), ambient air pollutants, and endotoxin and/or other pathogen-associated molecular patterns are the ambient exposures studied most frequently for interactions with genetic polymorphisms in asthma. To date, results from the literature remain inconclusive. Most published Studies are underpowered to study interactions between genetic polymorphisms and ambient exposures, each with weak effects. Strategies to increase power include cooperation across studies to increase sample sizes and improve measures of both exposure and asthma phenotypes. Genome-wide association studies hold promise for identifying unexpected gene environment interactions, but given the statistical power issues, candidate gene association studies will remain important. New tools are enabling die study of epigenetic mechanisms for environmental interactions. C1 [London, Stephanie J.] NIEHS, NIH, Div Intramural Res, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Romieu, Isabelle] Natl Inst Publ Hlth, Cuernavaca 62508, Morelos, Mexico. RP London, SJ (reprint author), NIEHS, NIH, Div Intramural Res, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov; iromieu@insp.mx OI London, Stephanie/0000-0003-4911-5290 FU National Institute of Environmental Health Sciences; National Institutes of Health, Department of Health and Human Services; Centers for Disease Control and Prevention, Department of Health and Human Services FX Dr. London is supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. Dr. Rornieu is supported by the National Center for Environmental Health from the Centers for Disease Control and Prevention, Department of Health and Human Services. NR 92 TC 44 Z9 47 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 BN 978-0-8243-2730-9 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2009 VL 30 BP 55 EP 80 DI 10.1146/annurev.publhealth.031308.100151 PG 26 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 471PZ UT WOS:000268071900005 PM 18980546 ER PT S AU Ho, M Pastan, I AF Ho, Mitchell Pastan, Ira BE Aitken, R TI Display and Selection of scFv Antibodies on HEK-293T Cells SO ANTIBODY PHAGE DISPLAY: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Mammalian cell display; Antibody engineering; Antibody affinity maturation; Single-chain Fv or scFv; Phage display; Yeast display; Cell display; HEK-293T; Flow cytometry; B-cell malignancy ID SURFACE DISPLAY; LIBRARIES; AFFINITY; CANCER; PHAGE AB We describe a human cell display strategy to isolate high-affinity single-chain antibody fragments (scFvs) specific for CD22 for the treatment of B-cell malignancies. Our strategy uses flow cytometry and human embryonic kidney 293T (HEK-293T) cells that are widely used for transient protein expression. Flow cytometry enhances the screen's sensitivity thereby allowing LIS to isolate high-affinity scFvs. Using human cell display, one could isolate and engineer scFvs, single domains, Fabs, or whole IgGs for increased affinity and other biological functions. C1 [Ho, Mitchell; Pastan, Ira] NCI, NIH, Bethesda, MD 20892 USA. RP Ho, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. RI Ho, Mitchell/F-5059-2015 FU Intramural NIH HHS [ZIA BC008753-27] NR 14 TC 14 Z9 15 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-301-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 562 BP 99 EP 113 DI 10.1007/978-1-60327-302-2_8 D2 10.1007/978-1-60327-302-2 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY58 UT WOS:000269619000008 PM 19554290 ER PT S AU Zhang, MY Dimitrov, DS AF Zhang, Mei-Yun Dimitrov, Dimiter S. BE Aitken, R TI Sequential Antigen Panning for Selection of Broadly Cross-Reactive HIV-1-Neutralizing Human Monoclonal Antibodies SO ANTIBODY PHAGE DISPLAY: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Selection Fab; HIV gp120; gp140; Cross-reaction ID PHAGE-DISPLAY TECHNOLOGY; LIBRARIES AB Many phage display techniques drive selection toward the isolation of highly specific antibodies. However, the identification of monoclonal antibodies that are cross-reactive has implications for the development of diagnostics, therapeutics, and vaccines against pathogens or cancer cells that are able to rapidly generate variants and escape mutants. To identify human monoclonal antibodies with high activity against HIV and broad-spectrum activity, we developed a technique termed sequential antigen panning. This methodology could be used to isolated recombinant antibodies against any antigen that shares epitopes with other antigens. C1 [Zhang, Mei-Yun; Dimitrov, Dimiter S.] NCI, NIH, Frederick, MD 21701 USA. RP Zhang, MY (reprint author), NCI, NIH, Frederick, MD 21701 USA. FU Intramural NIH HHS [Z99 CA999999] NR 12 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-301-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 562 BP 143 EP 154 DI 10.1007/978-1-60327-302-2_11 D2 10.1007/978-1-60327-302-2 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY58 UT WOS:000269619000011 PM 19554293 ER PT B AU O'Shaughnessy, EM Lyman, CA Walsh, TJ AF O'Shaughnessy, Elizabeth M. Lyman, Caron A. Walsh, Thomas J. BE Mayers, DL TI Amphotericin B: Polyene Resistance Mechanisms SO ANTIMICROBIAL DRUG RESISTANCE, VOL 1: MECHANISMS OF DRUG RESISTANCE SE Infectious Disease LA English DT Article; Book Chapter ID ANTIFUNGAL DRUG-RESISTANCE; CANDIDA-ALBICANS MUTANTS; WALL CHITIN CONTENT; OF-THE-LITERATURE; IN-VITRO; SCEDOSPORIUM-PROLIFICANS; ASPERGILLUS-FUMIGATUS; EMERGING PATHOGEN; OXIDATIVE DAMAGE; PULMONARY ASPERGILLOSIS C1 [Lyman, Caron A.; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 105 TC 2 Z9 2 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-592-7 J9 INFECT DIS PY 2009 BP 295 EP 305 DI 10.1007/978-1-59745-180-2_25 PG 11 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA BKN91 UT WOS:000268730400025 ER PT B AU Helweg-Larsen, J Benfield, T Kovacs, J Masur, H AF Helweg-Larsen, Jannik Benfield, Thomas Kovacs, Joseph Masur, Henry BE Mayers, DL TI Drug Resistance in Pneumocystis jirovecii SO ANTIMICROBIAL DRUG RESISTANCE, VOL 2: CLINICAL AND EPIDEMIOLOGICAL ASPECTS SE Infectious Disease LA English DT Article; Book Chapter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; DIHYDROPTEROATE SYNTHASE GENE; DIHYDROFOLATE-REDUCTASE GENE; F-SP HOMINIS; CARINII PNEUMONIA PROPHYLAXIS; MAJOR SURFACE GLYCOPROTEIN; CYTOCHROME-B MUTATIONS; FOLIC-ACID SYNTHESIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; SACCHAROMYCES-CEREVISIAE C1 [Helweg-Larsen, Jannik] Copenhagen Univ Hosp, Rigshosp, Dept Infect Dis, Copenhagen, Denmark. [Benfield, Thomas] Hvidovre Univ Hosp, Dept Infect Dis, Copenhagen, Denmark. [Kovacs, Joseph] NIH, CCMD, Bethesda, MD 20892 USA. [Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Helweg-Larsen, J (reprint author), Copenhagen Univ Hosp, Rigshosp, Dept Infect Dis, Copenhagen, Denmark. EM jhelweg@dadlnet.dk NR 127 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-594-1 J9 INFECT DIS PY 2009 BP 993 EP 1007 DI 10.1007/978-1-60327-595-8_68 D2 10.1007/978-1-60327-595-8 PG 15 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BKN89 UT WOS:000268730200022 ER PT B AU Henderson, DK AF Henderson, David K. BE Mayers, DL TI Controlling the Spread of Resistant Pathogens in the Intensive Care Unit SO ANTIMICROBIAL DRUG RESISTANCE, VOL 2: CLINICAL AND EPIDEMIOLOGICAL ASPECTS SE Infectious Disease LA English DT Article; Book Chapter ID BLOOD-STREAM INFECTIONS; STAPHYLOCOCCUS-AUREUS MRSA; CRITICALLY-ILL PATIENTS; PREVENTING NOSOCOMIAL TRANSMISSION; VENTILATOR-ASSOCIATED PNEUMONIA; DIFFICILE-ASSOCIATED DIARRHEA; CLOSTRIDIUM-DIFFICILE; ANTIMICROBIAL RESISTANCE; ACINETOBACTER-BAUMANNII; PSEUDOMONAS-AERUGINOSA C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM dkh@nih.gov NR 124 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-594-1 J9 INFECT DIS PY 2009 BP 1295 EP 1314 DI 10.1007/978-1-60327-595-8_89 D2 10.1007/978-1-60327-595-8 PG 20 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BKN89 UT WOS:000268730200043 ER PT J AU Nekhai, S Jeang, KT AF Nekhai, Sergei Jeang, Kuan-Teh BE LaFemina, RL TI Human Immunodeficiency Virus Type 1 Tat and Rev as Potential Targets for Drug Development SO ANTIVIRAL RESEARCH: STRATEGIES IN ANTIVIRAL DRUG DISCOVERY LA English DT Article; Book Chapter ID PHASE-II TRIAL; P-TEFB COMPLEX; HELICASE-PRIMASE INHIBITORS; DEPENDENT KINASE INHIBITOR; BLOCKS HIV-1 REPLICATION; RNA-PROTEIN INTERACTIONS; HUMAN T-CELLS; RESPONSE ELEMENT; IN-VITRO; STRUCTURAL BASIS C1 [Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Dept Med, Washington, DC 20001 USA. [Nekhai, Sergei] Howard Univ, Dept Biochem & Mol Biol, Washington, DC 20059 USA. [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Nekhai, S (reprint author), Howard Univ, Ctr Sickle Cell Dis, Dept Med, 1840 7th St NW,HURB1,Suite 202, Washington, DC 20001 USA. NR 131 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-439-7 PY 2009 BP 97 EP 111 PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA BPJ56 UT WOS:000279002800007 ER PT J AU LaFemina, RL Whitley, R Collett, MS Hughes, S Colacino, J AF LaFemina, Robert L. Whitley, Richard Collett, Marc S. Hughes, Stephen Colacino, Joseph BE LaFemina, RL TI Afterword and Future Directions SO ANTIVIRAL RESEARCH: STRATEGIES IN ANTIVIRAL DRUG DISCOVERY LA English DT Editorial Material; Book Chapter C1 [Whitley, Richard] Univ Alabama, Birmingham, AL 35233 USA. [Collett, Marc S.] ViroDefense Inc, Rockville, MD 20850 USA. [Hughes, Stephen] Natl Canc Inst, Frederick, MD 21702 USA. [Colacino, Joseph] PTC Therapeut, S Plainfield, NJ 07080 USA. RP LaFemina, RL (reprint author), 2020 Serendip Way, Schwenksville, PA 19473 USA. EM robert.lafemina@gmail.com; robert.lafemina@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-439-7 PY 2009 BP 363 EP 366 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA BPJ56 UT WOS:000279002800022 ER PT J AU Reynolds, SJ Kityo, C Mbamanya, F Dewar, R Ssali, F Quinn, TC Mugyenyi, P Dybul, M AF Reynolds, Steven J. Kityo, Cissy Mbamanya, Frank Dewar, Robin Ssali, Francis Quinn, Thomas C. Mugyenyi, Peter Dybul, Mark TI Evolution of drug resistance after virological failure of a first-line highly active antiretroviral therapy regimen in Uganda SO ANTIVIRAL THERAPY LA English DT Article ID HIV-INFECTED PATIENTS; MUTATIONS; COMBINATION; PREVALENCE; COUNTRIES; AFRICA AB Background: This study aimed to determine the extent of viral resistance over time among non-Glade B HIV type-1-infected patients in Uganda who were maintained on first-line highly active antiretroviral therapy (HAART) following virological failure. Methods: Genotyping was performed on 16 patients with virological failure who were enrolled in an open-label randomized clinical trial of short-cycle treatment interruption. Results: All patients receiving efavirenz-containing HAART had >= 1 efavirenz resistance mutation develop during follow-up. The majority (13/15, 86%) developed lamivudine resistance during follow-up, but no thymidine analogue mutations (TAMS) developed during a median duration of virological failure of 325.5 days. Conclusions: Genotype resistance to both efavirenz and lamivudine developed early during the course of treatment after virological failure. TAMS did not emerge early despite moderate exposure time to thymidine analogues during virological failure. C1 [Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Kityo, Cissy; Mbamanya, Frank; Ssali, Francis; Mugyenyi, Peter] Joint Clin Res Ctr, Kampala, Uganda. [Dewar, Robin] NCI, NIH, Bethesda, MD 20892 USA. [Dybul, Mark] Georgetown Univ, Ctr Law, ONeill Inst Natl & Global Hlth Law, Washington, DC USA. RP Reynolds, SJ (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sjr@jhmi.edu FU 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, and was presented in part at the International AIDS,Society Conference on HIV Pathogenesis, Treatment and Prevention, 22-2-5 July 2007, Sydney, Australia. NR 14 TC 20 Z9 21 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 2 BP 293 EP 297 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 439JZ UT WOS:000265624700017 PM 19430104 ER PT J AU Cossarini, F Wiegand, A Mican, J Polis, M Rehm, C O'Shea, A Poethke, C Spindler, J Dewar, R Higgins, J Kearney, M Coffin, J Mellors, J Maldarelli, F AF Cossarini, F. Wiegand, A. Mican, J. Polis, M. Rehm, C. O'Shea, A. Poethke, C. Spindler, J. Dewar, R. Higgins, J. Kearney, M. Coffin, J. Mellors, J. Maldarelli, F. TI Markers of cellular immune activation do not correlate with levels of residual viremia in patients on long-term suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Cossarini, F.; Wiegand, A.; Poethke, C.; Spindler, J.; Kearney, M.; Coffin, J.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Cossarini, F.] Ist Sci San Raffaele, Dept Infect Dis, I-20132 Milan, Italy. [Mican, J.; O'Shea, A.] NIAID, NIH, Bethesda, MD 20892 USA. [Polis, M.; Rehm, C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Dewar, R.; Higgins, J.] NIAID, Collaborat Clin Res Branch, SAIC, Immunoregulat Lab,NIH, Frederick, MD USA. [Coffin, J.] Tufts Univ, Dept Microbiol & Immunol, Boston, MA 02111 USA. [Mellors, J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 8 BP A10 EP A10 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900025 ER PT J AU Das, K Bandwar, R Bauman, J Tuske, S Hughes, SH Arnold, E AF Das, K. Bandwar, R. Bauman, J. Tuske, S. Hughes, S. H. Arnold, E. TI High-resolution structures of HIV-1 RT/RNA:DNA ternary complexes with tenofovir diphosphate and dATP SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Das, K.; Bandwar, R.; Bauman, J.; Tuske, S.; Arnold, E.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. [Das, K.; Bandwar, R.; Bauman, J.; Tuske, S.; Arnold, E.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Hughes, S. H.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 17 BP A19 EP A19 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900034 ER PT J AU Delviks-Frankenberry, KA Nikolenko, GN Maldarelli, F Hase, S Takebe, Y Pathak, VK AF Delviks-Frankenberry, K. A. Nikolenko, G. N. Maldarelli, F. Hase, S. Takebe, Y. Pathak, V. K. TI Subtype-specific amino acid polymorphisms in the HIV-1 reverse transcriptase connection subdomain of CRF01_AE are associated with higher 3 '-azido-3 '-deoxythymidine resistance SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Delviks-Frankenberry, K. A.; Nikolenko, G. N.; Pathak, V. K.] NCI, Viral Mutat Sect, Host Virus Interact Branch, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Hase, S.; Takebe, Y.] Natl Inst Infect Dis, AIDS Res Ctr, Lab Mol Virol & Epidemiol, Tokyo, Japan. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 29 BP A31 EP A31 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900046 ER PT J AU Dimock, D Vakkalanka, S Kopp, J Purdy, J Hazra, R Hadigan, C AF Dimock, D. Vakkalanka, S. Kopp, J. Purdy, J. Hazra, R. Hadigan, C. TI Microalbuminuria in a longitudinal cohort of adolescents and young adults with HIV infection acquired in infancy or childhood SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 11th International Workshop on AdverseDrug Reactions and Co-Morbidities in HIV CY OCT 26-28, 2009 CL Philadelphia, PA C1 [Dimock, D.; Hadigan, C.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Vakkalanka, S.; Hazra, R.] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Kopp, J.] NIDDKD, Kidney Dis Branch, Bethesda, MD 20892 USA. [Purdy, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. [Hazra, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 7 BP A47 EP A48 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 523GH UT WOS:000272060000066 ER PT J AU Dinoso, J Jones, J McMahon, D Wiegand, A Kearney, M Spindler, J Palmer, S McNulty, S Metcalf, J Acosta, E Siliciano, R Coffin, J Mellors, J Maldarelli, F AF Dinoso, J. Jones, J. McMahon, D. Wiegand, A. Kearney, M. Spindler, J. Palmer, S. McNulty, S. Metcalf, J. Acosta, E. Siliciano, R. Coffin, J. Mellors, J. Maldarelli, F. TI Antiretroviral intensification does not reduce persistent HIV-1 viremia on therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Dinoso, J.; Siliciano, R.] Johns Hopkins Univ, Baltimore, MD USA. [Jones, J.; McMahon, D.; McNulty, S.; Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Wiegand, A.; Kearney, M.; Spindler, J.; Palmer, S.; Coffin, J.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Metcalf, J.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Acosta, E.] Univ Alabama, Birmingham, AL USA. [Coffin, J.] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 10 BP A12 EP A12 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900027 ER PT J AU Hunt, PW Hatano, H Sinclair, E Delwart, EL Lee, TH Busch, MP Hoh, R Grossman, Z Martin, JN Deeks, SG AF Hunt, P. W. Hatano, H. Sinclair, E. Delwart, E. L. Lee, T. H. Busch, M. P. Hoh, R. Grossman, Z. Martin, J. N. Deeks, S. G. TI HIV-specific CD4(+) T-cells may contribute to viral persistence in HIV-infected elite controllers SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Hunt, P. W.; Hatano, H.; Sinclair, E.; Delwart, E. L.; Busch, M. P.; Hoh, R.; Martin, J. N.; Deeks, S. G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Delwart, E. L.; Lee, T. H.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Grossman, Z.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 5 BP A7 EP A7 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900022 ER PT J AU Kearney, M Yu, S Shao, W Mellors, JW Coffin, JM Maldarelli, F AF Kearney, M. Yu, S. Shao, W. Mellors, J. W. Coffin, J. M. Maldarelli, F. TI HIV-1 plasma virus diversity persists despite suppression with antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Kearney, M.; Yu, S.; Shao, W.; Coffin, J. M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Mellors, J. W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 6 BP A8 EP A8 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900023 ER PT J AU Kim, PS Woods, C Dutcher, L Georgoff, P Rosenberg, A Mican, JAM Kopp, J Smith, MA Hadigan, C AF Kim, P. S. Woods, C. Dutcher, L. Georgoff, P. Rosenberg, A. Mican, J. A. M. Kopp, J. Smith, M. A. Hadigan, C. TI Increased microalbuminuria in HIV-infected adults with diabetes is associated with abacavir and viral load SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 11th International Workshop on AdverseDrug Reactions and Co-Morbidities in HIV CY OCT 26-28, 2009 CL Philadelphia, PA C1 [Kim, P. S.; Rosenberg, A.; Mican, J. A. M.; Hadigan, C.] NIAID, NIH, Bethesda, MD 20892 USA. [Woods, C.; Smith, M. A.] Washington Hosp Ctr, Dept Infect Dis, Washington, DC 20010 USA. [Dutcher, L.; Georgoff, P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Kopp, J.] NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 7 BP A7 EP A7 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 523GH UT WOS:000272060000024 ER PT J AU Lidstrom, J Kumwenda, N Kafulafula, G Hoover, DR Kumwenda, J Mofenson, LM Fowler, MG Thigpen, MC Taha, TE Eshleman, SH AF Lidstrom, J. Kumwenda, N. Kafulafula, G. Hoover, D. R. Kumwenda, J. Mofenson, L. M. Fowler, M. G. Thigpen, M. C. Taha, T. E. Eshleman, S. H. TI Antiretroviral treatment of HIV-infected women can induce multiclass drug resistance in their breastfeeding infants SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Lidstrom, J.; Fowler, M. G.; Eshleman, S. H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kumwenda, N.; Taha, T. E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Kafulafula, G.; Kumwenda, J.] Univ Malawi, Coll Med, Blantyre, Malawi. [Hoover, D. R.] Rutgers State Univ, Piscataway, NJ USA. [Mofenson, L. M.] NIH, Rockville, MD USA. [Fowler, M. G.; Thigpen, M. C.] Ctr Dis Control & Prevent CDC, Atlanta, GA USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 135 BP A158 EP A158 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900152 ER PT J AU Lidstrom, J Kumwenda, N Hoover, DR Kafulafula, G Li, Q Mofenson, LM Fowler, MG Thigpen, MC Taha, TE Eshleman, SH AF Lidstrom, J. Kumwenda, N. Hoover, D. R. Kafulafula, G. Li, Q. Mofenson, L. M. Fowler, M. G. Thigpen, M. C. Taha, T. E. Eshleman, S. H. TI Addition of extended zidovudine to extended nevirapine prophylaxis reduces resistance in infants who were HIV-infected in utero: the PEPI-Malawi Study SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Lidstrom, J.; Fowler, M. G.; Eshleman, S. H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kumwenda, N.; Li, Q.; Taha, T. E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hoover, D. R.] Rutgers State Univ, Piscataway, NJ USA. [Kafulafula, G.] Univ Malawi, Blantyre, Malawi. [Mofenson, L. M.] NIH, Rockville, MD USA. [Fowler, M. G.; Thigpen, M. C.] CDC, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 40 BP A42 EP A42 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900057 ER PT J AU Marchand, B Michailidis, L Kodama, EI Ryan, E Do, R Matsuoka, M Ashida, N Nagy, E Mirsuya, H Parniak, MA Sarafianos, SG AF Marchand, B. Michailidis, L. Kodama, E. I. Ryan, E. Do, R. Matsuoka, M. Ashida, N. Nagy, E. Mirsuya, H. Parniak, M. A. Sarafianos, S. G. TI Mechanisms of inhibition and resistance to translocation deficient reverse transcriptase inhibitors SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Marchand, B.; Michailidis, L.; Ryan, E.; Do, R.; Sarafianos, S. G.] Univ Missouri, Columbia, MO USA. [Kodama, E. I.; Matsuoka, M.] Kyoto Univ, Kyoto, Japan. [Ashida, N.] Yamasa Corp, Chiba, Japan. [Nagy, E.; Parniak, M. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Mirsuya, H.] Kumamoto Univ, Kumamoto, Japan. [Mirsuya, H.] NIH, Bethesda, MD 20892 USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 20 BP A22 EP A22 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900037 ER PT J AU Morse, C Voss, J Rakocevic, G Huber, C Vinton, C Mclaughlin, M Dalakas, M Kovacs, J AF Morse, C. Voss, J. Rakocevic, G. Huber, C. Vinton, C. Mclaughlin, M. Dalakas, M. Kovacs, J. TI Effects of HIV and anti-retroviral therapy on mitochondrial DNA levels in muscle, adipose tissue, and PBMCs SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 11th International Workshop on AdverseDrug Reactions and Co-Morbidities in HIV CY OCT 26-28, 2009 CL Philadelphia, PA C1 [Morse, C.; Mclaughlin, M.] NIAID, Bethesda, MD 20892 USA. [Voss, J.] Univ Washington, Seattle, WA 98195 USA. [Rakocevic, G.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Huber, C.; Vinton, C.; Kovacs, J.] Natl Inst Hlth, Ctr Clin, Bethesda, MD USA. [Dalakas, M.] Univ London Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 7 BP A62 EP A63 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 523GH UT WOS:000272060000084 ER PT J AU Nikolenko, GN Delviks-Frankenberry, KA Pathak, VK AF Nikolenko, G. N. Delviks-Frankenberry, K. A. Pathak, V. K. TI A novel molecular mechanism of dual resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Nikolenko, G. N.; Delviks-Frankenberry, K. A.; Pathak, V. K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 31 BP A33 EP A33 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900048 ER PT J AU Nissley, DV Alpturk, O Ambrose, Z Eaton, K Strathern, JN Sluis-Cremer, N AF Nissley, D. V. Alptuerk, O. Ambrose, Z. Eaton, K. Strathern, J. N. Sluis-Cremer, N. TI HIV-1 reverse transcriptase fidelity variants alter levels of mutation during replication SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Nissley, D. V.] NCI, BSP, SAIC Frederick Inc, Frederick, MD 21701 USA. [Nissley, D. V.; Eaton, K.; Strathern, J. N.] NCI, GRCBL, Frederick, MD 21701 USA. [Ambrose, Z.; Sluis-Cremer, N.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 22 BP A24 EP A24 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900039 ER PT J AU Palmer, S Josefsson, L Brannstrom, J Maldarelli, F Kearney, M Shao, W Rock, D Mellors, J Albert, J Coffin, J AF Palmer, S. Josefsson, L. Brannstrom, J. Maldarelli, F. Kearney, M. Shao, W. Rock, D. Mellors, J. Albert, J. Coffin, J. TI Analysis of HIV DNA molecules in single infected cells from recently and chronically infected patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Palmer, S.; Josefsson, L.; Brannstrom, J.; Albert, J.] Karolinska Inst, Dept Virol, Swedish Inst Infect Dis Control, Solna, Sweden. [Palmer, S.; Maldarelli, F.; Kearney, M.; Shao, W.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Rock, D.] NIAID CCMD Clin, Bethesda, MD USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 84 BP A99 EP A99 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900101 ER PT J AU Palmer, S King, M Wiegand, A Miura, T Block, B Pereyra, F Maldarelli, F Dahl, V Mellors, J Walker, B Coffin, JM AF Palmer, S. King, M. Wiegand, A. Miura, T. Block, B. Pereyra, F. Maldarelli, F. Dahl, V. Mellors, J. Walker, B. Coffin, J. M. TI Longitudinal dynamics of persistent viremia in elite controller patients versus patients on suppressive therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Palmer, S.; Dahl, V.] Karolinska Inst, Swedish Inst Infect Dis Control, S-10401 Stockholm, Sweden. [Palmer, S.; Wiegand, A.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [King, M.] Abbott Labs, Abbott Pk, IL 60064 USA. [Miura, T.; Block, B.; Pereyra, F.; Walker, B.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 4 BP A6 EP A6 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900021 ER PT J AU Parkin, NT Fitzgibbon, J Bremer, J Bertagnolio, S AF Parkin, N. T. Fitzgibbon, J. Bremer, J. Bertagnolio, S. TI HIV drug resistance genotyping external quality assurance (EQA) for laboratories in the World Health Organization (WHO) ResNet during 2007-2009 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Parkin, N. T.; Bertagnolio, S.] WHO, CH-1211 Geneva, Switzerland. [Fitzgibbon, J.] NIAID, NIH, Bethesda, MD 20892 USA. [Bremer, J.] Rush Univ, VQA, Chicago, IL 60612 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 139 BP A162 EP A162 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900156 ER PT J AU Shao, W Boltz, VF Kearney, M Maldarelli, F Mellors, JW Stewart, C Levitsky, A Volfovsky, N Stephens, RM Coffin, JM AF Shao, W. Boltz, V. F. Kearney, M. Maldarelli, F. Mellors, J. W. Stewart, C. Levitsky, A. Volfovsky, N. Stephens, R. M. Coffin, J. M. TI Characterization of HIV-1 sequence artifacts introduced by bulk PCR and detected by 454 sequencing SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Shao, W.; Levitsky, A.; Volfovsky, N.; Stephens, R. M.] NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. [Boltz, V. F.; Kearney, M.; Maldarelli, F.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Mellors, J. W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. [Stewart, C.] NCI, LMT, SAIC Frederick, Frederick, MD 21701 USA. [Coffin, J. M.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 104 BP A123 EP A123 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900121 ER PT J AU Tchesnokov, EP Obikhod, A Massud, I Lisco, A Vanpouille, C Brichacek, B Balzarini, J McGuigan, C Derudas, M Margolis, L Schinazi, RF Gotte, M AF Tchesnokov, E. P. Obikhod, A. Massud, I. Lisco, A. Vanpouille, C. Brichacek, B. Balzarini, J. McGuigan, C. Derudas, M. Margolis, L. Schinazi, R. F. Goette, M. TI Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 18th International HIV Drug Resistance Workshop CY JUN 09-13, 2009 CL Ft Myers, FL C1 [Tchesnokov, E. P.; Goette, M.] McGill Univ, Montreal, PQ, Canada. [Obikhod, A.; Massud, I.; Schinazi, R. F.] Emory Univ, Sch Med, Atlanta, GA USA. [Obikhod, A.; Massud, I.; Schinazi, R. F.] Vet Affairs Med Res, Atlanta, GA USA. [Lisco, A.; Vanpouille, C.; Brichacek, B.; Margolis, L.] NIH, Bethesda, MD 20892 USA. [Balzarini, J.] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. [McGuigan, C.; Derudas, M.] Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales. RI McGuigan, Chris/P-1580-2014 OI McGuigan, Chris/0000-0001-8409-710X NR 0 TC 1 Z9 1 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2009 VL 14 IS 4 MA 19 BP A21 EP A21 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 471FA UT WOS:000268039900036 ER PT J AU Lott, SN Sperling, AJ Watson, NL Friedman, RB AF Lott, Susan Nitzberg Sperling, Anne J. Watson, Nora L. Friedman, Rhonda B. TI Repetition priming in oral text reading: A therapeutic strategy for phonologic text alexia SO APHASIOLOGY LA English DT Article ID CLOSED-CLASS WORDS; NEURAL MECHANISMS; MEMORY; CONTINUUM; BRAIN; COMPREHENSION; COMPONENTS; ACTIVATION; DIFFICULTY; FREQUENCY AB Background: Phonologic text alexia (PhTA) is a reading disorder in which reading of pseudowords is impaired, but reading of real words is impaired only when reading text. Oral reading accuracy remains well preserved when words are presented individually, but when presented in text the part-of-speech effect that is often seen in phonologic alexia (PhA) emerges. Aims: To determine whether repetition priming could strengthen and/or maintain the activation of words during text reading. Methods Procedures: We trained NYR, a patient with PhTA, to use a strategy, sentence building, designed to improve accuracy of reading words in text. The strategy required NYR to first read the initial word, and then build up the sentence by adding on sequential words, in a step-wise manner, utilising the benefits of repetition priming to enhance accuracy. Outcomes Results: When using the strategy, NYR displayed improved accuracy not only for sentences she practised using the strategy, but unpractised sentences as well. Additionally, NYR performed better on a test of comprehension when using the strategy, as compared to without the strategy. Conclusions: In light of research linking repetition priming to increased neural processing efficiency, our results suggest that use of this compensatory strategy improves reading accuracy and comprehension by temporarily boosting phonologic activation levels. C1 [Lott, Susan Nitzberg; Sperling, Anne J.; Watson, Nora L.; Friedman, Rhonda B.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA. [Sperling, Anne J.] NIMH, Bethesda, MD 20892 USA. RP Lott, SN (reprint author), Georgetown Univ, Med Ctr, Bldg D,Suite 207,4000 Reservoir Rd NW, Washington, DC 20057 USA. EM lotts@georgetown.edu FU NICHD [HD036019]; Georgetown University Medical Center FX The first and second authors contributed equally to this paper. This study was supported by NICHD grant # HD036019 to the last author. Anne Sperling contributed to this research as part of a postdoctoral fellowship at Georgetown University Medical Center. No official support or endorsement by the National Institute of Mental Health is intended or should be inferred. NR 39 TC 3 Z9 3 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2009 VL 23 IS 6 BP 659 EP 675 AR PII 793360098 DI 10.1080/02687030801969539 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 450XT UT WOS:000266436000001 PM 20664804 ER PT J AU Metter, EJ Mlcoch, A AF Metter, E. Jeffrey Mlcoch, Anthony TI The contribution of the Department of Veterans Affairs to neuroimaging of aphasia: One perspective SO APHASIOLOGY LA English DT Article DE neuroimaging; Veterans Affairs; aphasia; positron emission tomography; MRI; computed tomography ID POSITRON-EMISSION-TOMOGRAPHY; LANGUAGE COMPREHENSION; COMPUTED-TOMOGRAPHY; CEREBRAL INFARCTION; GLUCOSE-METABOLISM; TEMPOROPARIETAL CORTEX; LESION LOCALIZATION; MAGNETIC-RESONANCE; ACUTE STROKE; RECOVERY AB Background: The Department of Veterans Affairs (VA) has made important contributions to the neuroimaging of aphasia. Through the affiliations of VA researchers with medical faculties, a broad range of questions has been addressed regarding the structural, metabolic, and functional changes that occur in the brain of individuals who develop aphasia. Aims: This report examines some of the work that has been accomplished by VA researchers using CT, MRI, SPECT, and PET imaging approaches. Main Contribution and Conclusions: The reviewed VA research demonstrates that aphasia results from the dynamic relationships that exist between the impact of structural brain damage on brain function in both damaged and non-damaged regions of the brain. The resulting concepts have led to innovative strategies for the neurorehabilitation of aphasia. C1 [Metter, E. Jeffrey] Harbor Hosp, Clin Res Branch, NIA, Baltimore, MD 21225 USA. [Mlcoch, Anthony] Hines Vet Affairs Hosp, Hines, IL USA. RP Metter, EJ (reprint author), Harbor Hosp, Clin Res Branch, NIA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM metterj@mail.nih.gov FU NIH, National Institute on Aging FX This research review was supported (in part) by the Intramural Research Program of the NIH, National Institute on Aging. NR 41 TC 1 Z9 1 U1 4 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2009 VL 23 IS 9 BP 1086 EP 1100 AR PII 782652598 DI 10.1080/02687030701584982 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 493HN UT WOS:000269727500002 ER PT J AU Bodenreider, O AF Bodenreider, Olivier TI Special Issue: Biomedical Ontology in Action SO APPLIED ONTOLOGY LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Bodenreider, O (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov NR 28 TC 2 Z9 2 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5838 J9 APPL ONTOL JI Appl. Ontol. PY 2009 VL 4 IS 1 BP 1 EP 4 DI 10.3233/AO-2009-0066 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA V17KQ UT WOS:000207936500001 ER PT J AU Brown, RJ Rother, KI Artman, H Mercurio, MG Wang, R Looney, RJ Cowen, EW AF Brown, Rebecca J. Rother, Kristina I. Artman, Henry Mercurio, Mary Gail Wang, Roger Looney, R. John Cowen, Edward W. TI Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae SO ARCHIVES OF DERMATOLOGY LA English DT Article ID TYPE-1 DIABETES-MELLITUS; ACNE-VULGARIS; ASSOCIATION; REACTIVATION; ALLOPURINOL; ANTIBIOTICS; DISEASES; THERAPY AB Background: Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations: A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjogren syndrome A, and anti-Smith antibodies. Conclusions: Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. C1 [Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Brown, Rebecca J.] Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, Rockville, MD USA. [Rother, Kristina I.] NIDDK, Clin Endocrinol Branch, Bethesda, MD USA. [Artman, Henry] Univ Rochester, Sch Med & Dent, Dept Pediat, Div Endocrinol, Rochester, NY 14642 USA. [Mercurio, Mary Gail] Univ Rochester, Sch Med & Dent, Dept Dermatol, Rochester, NY 14642 USA. [Wang, Roger; Looney, R. John] Univ Rochester, Sch Med & Dent, Dept Med, Sect Allergy Immunol & Rheumatol, Rochester, NY 14642 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU Intramural Research Programs of the National Institutes of Health; Center for Cancer Research; National Cancer Institute; National Institute of Diabetes, Digestive, and Kidney Diseases FX This research was supported in part by the Intramural Research Programs of the National Institutes of Health, Center for Cancer Research, National Cancer Institute, and National Institute of Diabetes, Digestive, and Kidney Diseases. NR 26 TC 38 Z9 38 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2009 VL 145 IS 1 BP 63 EP 66 PG 4 WC Dermatology SC Dermatology GA 395YL UT WOS:000262559300009 PM 19153345 ER PT J AU Epstein, DH Willner-Reid, J Vahabzadeh, M Mezghanni, M Lin, JL Preston, KL AF Epstein, David H. Willner-Reid, Jessica Vahabzadeh, Massoud Mezghanni, Mustapha Lin, Jia-Ling Preston, Kenzie L. TI Real-Time Electronic Diary Reports of Cue Exposure and Mood in the Hours Before Cocaine and Heroin Craving and Use SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; REINSTATEMENT MODEL; RELAPSE PREVENTION; SOCIAL PHOBIA; GROUP-THERAPY; SMOKING; LAPSES; REACTIVITY; CONTRASTS; ALCOHOL AB Context: In ecological momentary assessment (EMA), participants electronically report their activities and moods in their daily environments in real time, enabling a truly prospective approach to the study of acute precipitants of behavioral events. Ecological momentary assessment has greatly enhanced the study of tobacco addiction, but its use has rarely been attempted in individuals with cocaine or heroin addiction. Objective: To prospectively monitor the acute daily life precipitants of craving for and use of cocaine and heroin. Design: Cohort study. Participants: A volunteer sample of 114 cocaine- and heroin-abusing outpatients who were being treated with methadone provided EMA data on handheld electronic devices for 14918 person-days(mean, 130.9; range, 6-189 days per participant). Of these outpatients, a total of 102(63 men, 39 women) provided acute precraving and/or preuse data and were thus included in the present analyses. Main Outcome Measures: Changes in reports of mood and exposure to 12 putative drug-use triggers at random intervals during the 5 hours preceding each self-reported episode of drug craving or use, analyzed via repeated measures logistic regression (generalized linear mixed models). Results: During the 5 hours preceding cocaine use or heroin craving, most of the 12 putative triggers showed linear increases. Cocaine use was most robustly associated with increases in participants reporting that they "saw [the] drug" (P < .001), were "tempted to use out of the blue" (P < .001), "wanted to see what would happen if I used" (P < .001), and were in a good mood (P < .001). Heroin craving was most robustly associated with increases in reports of feeling sad (P < .001) or angry (P = .01). Cocaine craving and heroin use showed few reliable associations with any of the putative triggers assessed. Conclusions: These findings confirm that polydrug-abusing individuals can provide behavioral data in their daily environments using handheld electronic devices and that those data can reveal orderly patterns, including prospectively detectable harbingers of craving and use, which may differ across drugs. C1 [Epstein, David H.; Willner-Reid, Jessica; Preston, Kenzie L.] Natl Inst Drug Abuse, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch,NIH,Dept Hlth &, Baltimore, MD 21224 USA. [Vahabzadeh, Massoud; Mezghanni, Mustapha; Lin, Jia-Ling] Natl Inst Drug Abuse, Biomed Informat Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Biomed Informat Sect, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Epstein, DH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch,NIH,Dept Hlth &, Room 01B 606,251 Bayview Blvd,Ste 200, Baltimore, MD 21224 USA. EM depstein@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 28 TC 122 Z9 124 U1 9 U2 18 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 JAN PY 2009 VL 66 IS 1 BP 88 EP 94 PG 7 WC Psychiatry SC Psychiatry GA 390QJ UT WOS:000262178500011 PM 19124692 ER PT J AU Chiu, AW Richert, N Ehrmantraut, M Ohayon, J Gupta, S Bomboi, G Gaindh, D Cantor, FK Frank, JA McFarland, HF Bagnato, F AF Chiu, Annie W. Richert, Nancy Ehrmantraut, Mary Ohayon, Joan Gupta, Shiva Bomboi, Giuseppe Gaindh, Deeya Cantor, Fredric K. Frank, Joseph A. McFarland, Henry F. Bagnato, Francesca TI Heterogeneity in Response to Interferon Beta in Patients With Multiple Sclerosis A 3-Year Monthly Imaging Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID MRI RESPONSE; MS; THERAPY; IMPAIRMENT; DISABILITY; TRIAL AB Objectives: To investigate the heterogeneity in magnetic resonance image (MRI) patterns of response to interferon beta across patients with multiple sclerosis or within an individual patient over time. Design, Setting, and Patients: Fifteen patients with relapsing-remitting multiple sclerosis underwent monthly MRIs and clinical examinations (6-month pretherapy phase and 36-month therapy phase) and bimonthly neutralizing antibody tests. On each MRI, the total number of contrast-enhancing lesions was noted. Therapy MRI responders were defined as those with a reduction of 60% or more in the total number of contrast-enhancing lesions during each semester of therapy. Intervention: Subcutaneous administration of interferon beta-1b, 250 mu g, every other day for 3 years. Main Outcome Measure: Reduction in the number of contrast-enhancing lesions. Results: Eight patients (53.3%) were MRI responders and 7 (46.7%) were nonresponders. Of those 7, 3 (20.0%) had only an initial optimal reduction of the total number of contrast-enhancing lesions, 2 (13.3%) never reached an optimal response, and 2 ( 13.3%) had a delayed optimal response. No clear association between neutralizing antibody profile and MRI response was evident. Conclusions: Multiple MRI evaluations disclose that approximately only half of the patients treated with interferon beta achieve and maintain a full response to the drug over time, although an additional small number of individuals may still restore an optimal response to the drug after an initial failure. C1 [Chiu, Annie W.; Richert, Nancy; Ehrmantraut, Mary; Ohayon, Joan; Gupta, Shiva; Bomboi, Giuseppe; Gaindh, Deeya; Cantor, Fredric K.; McFarland, Henry F.; Bagnato, Francesca] NINCDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Frank, Joseph A.] NINCDS, Lab Diagnost Radiol & Res, NIH, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), NINCDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. Dr Bomboi's contribution was sustained by a public-private partnership supported jointly by the University La Sapienza, Rome, Italy, and a grant from the Bayer-Schering Pharmaceuticals Group. NR 20 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2009 VL 66 IS 1 BP 39 EP 43 DI 10.1001/archneur.66.1.noc80047 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 393UM UT WOS:000262398900004 PM 19001157 ER PT J AU Pardini, M Huey, ED Cavanagh, AL Grafman, J AF Pardini, Matteo Huey, Edward D. Cavanagh, Alyson L. Grafman, Jordan TI Olfactory Function in Corticobasal Syndrome and Frontotemporal Dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BRAIN ACTIVATION; IDENTIFICATION; DEGENERATION; DYSFUNCTION; MEMORY; MRI AB Background: Formal olfactory testing may be useful as a bedside tool to help differentiate between conditions such as atypical parkinsonism, dementia, and psychiatric conditions. However, the neural basis of olfactory dysfunction, the effect of concurrent cognitive deficits on olfactory testing results, and the exact prevalence of olfactory deficits in populations with corticobasal syndrome (CBS) and the frontal variant of frontotemporal dementia (FTD-FV) are to date unclear. Objective: To assess the prevalence and the neural basis of olfactory recognition deficits in patients with a clinical diagnosis of CBS or FTD-FV. Design: Retrospective study of clinical, neuropsychological, and imaging data. Setting: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Participants: Twenty-five patients with CBS, 22 with FTD-FV, and 12 age-matched control subjects. Main Outcome Measures: Results of neuropsychological evaluation, formal olfactory recognition testing ( University of Pennsylvania Smell Identification Test [UPSIT]), and voxel-based morphometry analysis of structural magnetic resonance images of the brain. Results: Mean UPSIT percentile scores were 31.6% for the CBS group and 9.5% for the FTD-FV group. The voxel-based morphometry correlations between local gray matter and UPSIT scores showed a significant volume effect in the right midfrontal gyrus for the FTD-FV patients and in the right insula, right midfrontal gyrus, and bilateral inferior frontal gyrus for the patients with CBS. A linear regression analysis of the UPSIT scores revealed as significant predictors the general memory score of the Wechsler Memory Scale and the Boston Naming Test total score for the patients with FTD-FV and the Mattis Dementia Rating Scale total score for the patients with CBS. Conclusions: Our data showed a more severe olfactory impairment for CBS patients than previously reported. We also showed a significant relationship between formal olfactory recognition testing scores and specific cognitive domains. These findings could be useful to clinically differentiate FTD-FV and CBS from other dementing illnesses and movement disorders. C1 [Pardini, Matteo; Huey, Edward D.; Cavanagh, Alyson L.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Pardini, Matteo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanJ@ninds.nih.gov RI Pardini, Matteo/F-8414-2010; OI Pardini, Matteo/0000-0002-4740-1982; Grafman, Jordan H./0000-0001-8645-4457 FU National Institutes of Health; National Institute of Neurological Disorders and Stroke FX This study was supported by the intramural program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 23 TC 31 Z9 31 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2009 VL 66 IS 1 BP 92 EP 96 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 393UM UT WOS:000262398900012 PM 19139305 ER PT J AU SanGiovanni, JP Agron, E Clemons, TE Chew, EY AF SanGiovanni, John Paul Agron, Elvira Clemons, Traci E. Chew, Emily Y. TI omega-3 Long-Chain Polyunsaturated Fatty Acid Intake Inversely Associated With 12-Year Progression to Advanced Age-Related Macular Degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID DIETARY; DISEASE; AREDS C1 [SanGiovanni, John Paul] NEI, Clin Trials Branch, CRC, Bethesda, MD 20892 USA. RP SanGiovanni, JP (reprint author), NEI, Clin Trials Branch, CRC, 10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM jpsangio@post.harvard.edu FU Intramural NIH HHS [Z99 EY999999, ZIA EY000489-01] NR 8 TC 31 Z9 31 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2009 VL 127 IS 1 BP 110 EP 112 PG 4 WC Ophthalmology SC Ophthalmology GA 393UN UT WOS:000262399000019 PM 19139352 ER PT J AU Pacher, P AF Pacher, Pal TI Cannabinoid CB1 Receptor Antagonists for Atherosclerosis and Cardiometabolic Disorders New Hopes, Old Concerns? SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; ENDOCANNABINOID SYSTEM; OVERWEIGHT PATIENTS; RIO-EUROPE; RIMONABANT; WEIGHT; PROGRESSION; MONOCYTES; DISEASE C1 NIAAA, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, NIH, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z99 AA999999, Z01 AA000375-02] NR 22 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2009 VL 29 IS 1 BP 7 EP 9 DI 10.1161/ATVBAHA.108.178129 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 385EV UT WOS:000261797200003 PM 19092136 ER PT J AU Desai, A Glaser, A Liu, DL Raghavachari, N Blum, A Zalos, G Lippincott, M McCoy, JP Munson, PJ Solomon, MA Danner, RL Cannon, RO AF Desai, Aditi Glaser, Alexander Liu, Delong Raghavachari, Nalini Blum, Arnon Zalos, Gloria Lippincott, Margaret McCoy, J. Philip Munson, Peter J. Solomon, Michael A. Danner, Robert L. Cannon, Richard O., III TI Microarray-Based Characterization of a Colony Assay Used to Investigate Endothelial Progenitor Cells and Relevance to Endothelial Function in Humans SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE exercise; gene expression; endothelial function; endothelial progenitor cell; T lymphocyte ID HEMATOPOIETIC STEM-CELLS; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; POSTNATAL VASCULOGENESIS; IN-VITRO; CARDIOVASCULAR RISK; TRAINING INCREASES; PERIPHERAL-BLOOD; GENE-EXPRESSION; T-CELLS AB Objective-An assay proposed to quantify endothelial progenitor cell (EPC) colonies in humans was investigated to determine the phenotype of recovered cells and their relevance to in vivo endothelial function. Methods and Results-Twelve sedentary subjects participating in a worksite wellness program underwent endothelial flow-mediated dilation (FMD) testing of the brachial artery and blood sampling for EPC colony assay. Microarray-based genotypic characterization of colonies showed surface markers consistent with T lymphocyte phenotype, but not with an EPC (CD34, CD133, VEGFR-2) or endothelial (CD146) phenotype. Gene expression patterns more closely matched T lymphocytes (r = 0.87) than endothelial cells (r = 0.66) in our microarray database. Flow cytometry of colonies confirmed large populations of CD3+CD45+ T cells (> 75%) and few CD146+CD45- endothelial cells (< 1%). Further, there was no correlation between colony number and the magnitude of FMD (r = -0.1512, P = 0.6389). After exercise training, subjects improved FMD, from 6.7 +/- 2.0 to 8.7 +/- 1.9% (P = 0.0043). Colonies also increased (P = 0.0210), but without relation to FMD (r = 0.1074, P = 0.7396). T lymphocyte phenotype persisted after exercise (r = 0.87). Conclusions-Cells in a commonly used EPC colony assay have a gene expression and cell surface marker profile consistent with a predominance of T lymphocytes and have an unclear relevance to endothelial function, either before or after exercise training. (Arterioscler Thromb Vasc Biol. 2009; 29: 121-127.) C1 [Desai, Aditi; Glaser, Alexander; Blum, Arnon; Zalos, Gloria; Lippincott, Margaret; Solomon, Michael A.; Cannon, Richard O., III] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Raghavachari, Nalini; Solomon, Michael A.; Danner, Robert L.] NIH, Ctr Clin, Dept Crit Care Med, Funct Genom & Prote Facil, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10 CRC,Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@nih.gov OI Lippincott, Margaret/0000-0002-3533-1999; Glaser, Alexander/0000-0003-1781-9023 FU National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 43 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2009 VL 29 IS 1 BP 121 EP 127 DI 10.1161/ATVBAHA.108.174573 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 385EV UT WOS:000261797200020 PM 19092138 ER PT J AU Ryan, JG Aksentijevich, I AF Ryan, John G. Aksentijevich, Ivona TI Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Toward a Molecular Understanding of the Systemic Autoinflammatory Diseases SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID TNF-RECEPTOR; SYNDROME TRAPS; MUTANT; MUTATIONS C1 [Ryan, John G.] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. RP Ryan, JG (reprint author), NIAMSD, Genet & Genom Branch, NIH, Bldg 9 Room 1W108,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ryanj2@mail.nih.gov FU NIH (Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases) FX Supported by te NIH (Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases). NR 16 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2009 VL 60 IS 1 BP 8 EP 11 DI 10.1002/art.24145 PG 4 WC Rheumatology SC Rheumatology GA 394AC UT WOS:000262416600003 PM 19116899 ER PT J AU Korman, BD Seldin, MF Taylor, KE Le, JM Lee, AT Plenge, RM Amos, CI Criswe, LA Gregersen, PK Kastner, DL Remmers, EF AF Korman, Benjamin D. Seldin, Michael F. Taylor, Kimberly E. Le, Julie M. Lee, Annette T. Plenge, Robert M. Amos, Christopher I. Criswe, Lindsey A. Gregersen, Peter K. Kastner, Daniel L. Remmers, Elaine F. TI The Chromosome 7q Region Association With Rheumatoid Arthritis in Females in a British Population Is Not Replicated in a North American Case-Control Series SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GENOME-WIDE ASSOCIATION; RISK; ALLELES; 6Q23 AB Objective. The single-nucleotide polymorphism (SNP) rs11761231 on chromosome 7q has been reported to be sexually dimorphic marker for rheumatoid arthritis (RA) susceptibility in a British population. We sought to replicate this finding and to better characterize susceptibility alleles in the region in a North American population. Methods. DNA from 2 North American collections of RA patients and controls (1,605 cases and 2,640 controls) was genotyped for rs11761231 and 16 additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests were performed for each collection and also separately, contrasting male cases with male controls and female cases with female controls. Principal components analysis (EigenStrat) was used to determine association with RA before and after adjusting for population stratification in the subset of the samples for which there were whole-genome SNP data (772 cases and 1,213 controls). Results. We failed to replicate an association of the 7q region with RA. Initially, rs11761231 showed evidence for association with RA in the North American Rheumatoid Arthritis Consortium (NARAC) collection (P = 0.0073), and rs11765576 showed association with RA in both the NARAC (P = 0.038) and RA replication (P = 0.0013) collections. These markers also exhibited sex differentiation. However, in the whole-genome subset, neither SNP showed significant association with RA after correction for population stratification. Conclusion. While 2 SNPs on chromosome 7q appeared to be associated with RA in a North American cohort, the significance of this finding did not withstand correction for population substructure. Our results emphasize the need to carefully account for population structure to avoid false-positive disease associations. C1 [Korman, Benjamin D.; Le, Julie M.; Kastner, Daniel L.; Remmers, Elaine F.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Seldin, Michael F.] Univ Calif Davis, Davis, CA 95616 USA. [Taylor, Kimberly E.; Criswe, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lee, Annette T.; Gregersen, Peter K.] Feinstein Inst Med Res, New York, NY USA. [Plenge, Robert M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Plenge, Robert M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Amos, Christopher I.] Univ Texas Houston, Houston, TX USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Remmers, EF (reprint author), NIAMSD, NIH, 10 Ctr Dr,10-C101,MSC 1849, Bethesda, MD 20892 USA. EM remmerse@mail.nih.gov FU NIH Clinical Research Training Program; Research and Education Foundation of the American College of Rheumatology [KOS-AI-55314-3]; NIH [R01-AR-44422, R01-AI-065841, K24-AR-02175, N01-AR-7-3232, N01-AI-95386]; National Center for Research Resources, USPHS; General Clinical Research Center, Moffitt Hospital, University of California. San Francisco [5-M01-RR00079]; General Clinical Research Center, Feinstein Institute for Medical Research [M01-RR-018535] FX Supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH. Mr. Korman's work was supported hy the NIH Clinical Research Training Program. a public-private partnership between the Foundation for the NIH and Pfizer. Inc. Dr. PIcnge's work was supported by the NIH (grant KOS-AI-55314-3), the Research and Education Foundation of the American College of Rheumatology, the Burroughs Wellcome Fund (Career Awards for Medical Scientists). and the William Randolph Hearst Fund of Harvard University. Dr. Amos' work was supported by the NIH (grant R01-AR-44422). Dr. Criswell's work was supported by the NIH (grants R01-AI-065841, K24-AR02175. and N01-AR-7-3232) and by the Rosalind Russell Medical Research Center for Arthritis. Dr. Gregersen's work was supported by the NIH (grants R01-AR-44422 and N01-AI-95386). The studies were funded by the National Center for Research Resources, USPHS, and carried out in part at the General Clinical Research Center, Moffitt Hospital. University of California. San Francisco (grant 5-M01-RR00079) and at the General Clinical Research Center, Feinstein Institute for Medical Research (grant M01-RR-018535). NR 21 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2009 VL 60 IS 1 BP 47 EP 52 DI 10.1002/art.24180 PG 6 WC Rheumatology SC Rheumatology GA 394AC UT WOS:000262416600008 PM 19116934 ER PT J AU Brionez, TF Assassi, S Reveille, JD Learch, TJ Diekman, L Ward, MM Davis, JC Weisman, MH Nicassio, P AF Brionez, Tamar F. Assassi, Shervin Reveille, John D. Learch, Thomas J. Diekman, Laura Ward, Michael M. Davis, John C., Jr. Weisman, Michael H. Nicassio, Perry TI Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS PATIENTS; PASSIVE COPING STRATEGIES; CHRONIC PAIN PATIENTS; DISEASE-ACTIVITY; HELPLESSNESS INDEX; WORK DISABILITY; RISK-FACTORS; PREDICTORS; DEPRESSION AB Introduction Functional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables. Methods 294 AS patients meeting modified New York Criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality and helplessness at the baseline visit. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of correlation of psychological variables with functional limitation, as measured by the Bath AS Functional Index (BASFI). Results In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASFI scores, adding an additional 24% to the overall Rsquare beyond that accounted by demographic and medical variables (R-square 32%), resulting in a final R-square of 56%. Specifically, arthritis helplessness, depression and passive coping beside age, ESR and the Bath AS Radiograph Index accounted for a significant portion of the variance in BASFI scores in the final model. Conclusions Arthritis helplessness, depression, and passive coping accounted for significant variability in self-reported functional limitation beyond demographic and clinical variables in patients with AS. Psychological health should be examined and accounted for when assessing functional status in the AS patients. C1 [Brionez, Tamar F.; Assassi, Shervin; Reveille, John D.; Diekman, Laura] Univ Texas Houston, Div Rheumatol, Dept Med, Houston, TX 77030 USA. [Learch, Thomas J.; Weisman, Michael H.] Cedars Sinai Med Ctr, Div Rheumatol, Dept Med, Los Angeles, CA 90048 USA. [Ward, Michael M.] NIAMS, Dept Med, Div Rheumatol, NIH, Bethesda, MD 20892 USA. [Davis, John C., Jr.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94122 USA. [Nicassio, Perry] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. RP Assassi, S (reprint author), Univ Texas Houston, Div Rheumatol, Dept Med, 6431 Fannin, Houston, TX 77030 USA. EM shervin.assassi@uth.tmc.edu FU United States Department of Health and Human Services, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P01-AR-052915-01]; NIH-KL2RR024149-04; NIAMS/NIH FX Supported by grants from the United States Department of Health and Human Services, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), P01-AR-052915-01; NIH-KL2RR024149-04; the Intramural Research Program, NIAMS/NIH. The authors also thank Ms. Vera Wirawan, Ms. Stephanie Brown, Ms. Lori Guthrie, Dr. Mamatha Hanumanthaiah, Ms. Stephanie Morgan and Mr. Robert Sandoval for their assistance with data collection and management. NR 45 TC 28 Z9 29 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 6 AR R182 DI 10.1186/ar2874 PG 9 WC Rheumatology SC Rheumatology GA 604MC UT WOS:000278282100022 PM 19968879 ER PT J AU Dorner, T Jacobi, AM Lipsky, PE AF Doerner, Thomas Jacobi, Annett M. Lipsky, Peter E. TI B cells in autoimmunity SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COMMON VARIABLE IMMUNODEFICIENCY; FC-GAMMA-RIIB; ANTI-CD4 MONOCLONAL-ANTIBODY; PLASMA-CELLS; RHEUMATOID-ARTHRITIS; SJOGRENS-SYNDROME; PERIPHERAL-BLOOD; MURINE LUPUS; UNDIFFERENTIATED ARTHRITIS AB B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of certain stages of B-cell development as well as plasmablasts/plasma cells in immune regulation under normal and autoimmune conditions with particular emphasis on systemic lupus erythematosus. Based on preclinical and clinical data, B cells have emerged increasingly as both effector cells as well as cells with immunoregulatory potential. C1 [Doerner, Thomas; Jacobi, Annett M.] Charite, Charite Ctr 12 & 14, D-10098 Berlin, Germany. [Doerner, Thomas; Jacobi, Annett M.] DRFZ Berlin, D-10098 Berlin, Germany. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Charite, Charite Ctr 12 & 14, Charitepl 01, D-10098 Berlin, Germany. EM thomas.doerner@charite.de NR 80 TC 53 Z9 60 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 5 AR 247 DI 10.1186/ar2780 PG 11 WC Rheumatology SC Rheumatology GA 540ND UT WOS:000273338400014 PM 19849820 ER PT J AU Eidelman, N Boyde, A Bushby, AJ Howell, PGT Sun, JR Newbury, DE Miller, FW Robey, PG Rider, LG AF Eidelman, Naomi Boyde, Alan Bushby, Andrew J. Howell, Peter G. T. Sun, Jirun Newbury, Dale E. Miller, Frederick W. Robey, Pamela G. Rider, Lisa G. TI Microstructure and mineral composition of dystrophic calcification associated with the idiopathic inflammatory myopathies SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SCANNING-ELECTRON-MICROSCOPY; MONTE-CARLO-SIMULATION; MEAN ATOMIC-NUMBER; X-RAY-DIFFRACTION; JUVENILE DERMATOMYOSITIS; ATHEROSCLEROTIC PLAQUES; MECHANICAL-PROPERTIES; CALCINOSIS CUTIS; ELASTIC-MODULUS; PULP STONES AB Introduction Calcified deposits (CDs) in skin and muscles are common in juvenile dermatomyositis (DM), and less frequent in adult DM. Limited information exists about the microstructure and composition of these deposits, and no information is available on their elemental composition and contents, mineral density (MD) and stiffness. We determined the microstructure, chemical composition, MD and stiffness of CDs obtained from DM patients. Methods Surgically-removed calcinosis specimens were analyzed with fourier transform infrared microspectroscopy in reflectance mode (FTIR-RM) to map their spatial distribution and composition, and with scanning electron microscopy/silicon drift detector energy dispersive X-ray spectrometry (SEM/SDDEDS) to obtain elemental maps. X-ray diffraction (XRD) identified their mineral structure, X-ray micro-computed tomography (mu CT) mapped their internal structure and 3D distribution, quantitative backscattered electron (qBSE) imaging assessed their morphology and MD, nanoindentation measured their stiffness, and polarized light microscopy (PLM) evaluated the organic matrix composition. Results Some specimens were composed of continuous carbonate apatite containing small amounts of proteins with a mineral to protein ratio much higher than in bone, and other specimens contained scattered agglomerates of various sizes with similar composition (FTIR-RM). Continuous or fragmented mineralization was present across the entire specimens (mu CT). The apatite was much more crystallized than bone and dentin, and closer to enamel (XRD) and its calcium/phophorous ratios were close to stoichiometric hydroxyapatite (SEM/SDD-EDS). The deposits also contained magnesium and sodium (SEM/SDD-EDS). The MD (qBSE) was closer to enamel than bone and dentin, as was the stiffness (nanoindentation) in the larger dense patches. Large mineralized areas were typically devoid of collagen; however, collagen was noted in some regions within the mineral or margins (PLM). qBSE, FTIR-RM and SEM/SDD-EDS maps suggest that the mineral is deposited first in a fragmented pattern followed by a wave of mineralization that incorporates these particles. Calcinosis masses with shorter duration appeared to have islands of mineralization, whereas longstanding deposits were solidly mineralized. Conclusions The properties of the mineral present in the calcinosis masses are closest to that of enamel, while clearly differing from bone. Calcium and phosphate, normally present in affected tissues, may have precipitated as carbonate apatite due to local loss of mineralization inhibitors. C1 [Eidelman, Naomi] NIST, Paffenbarger Res Ctr, Amer Dent Assoc Fdn, Gaithersburg, MD 20899 USA. [Boyde, Alan] Queen Mary Univ London, Inst Dent, Biophys OGD, London E1 1BB, England. [Bushby, Andrew J.] Queen Mary Univ London, Dept Mat, London E1 4NS, England. [Howell, Peter G. T.] UCL Eastman Dent Inst, Prosthet Dent Unit, London WC1X 8LD, England. [Sun, Jirun] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Newbury, Dale E.] NIST, Surface & Microanal Sci Div, Gaithersburg, MD 20899 USA. [Miller, Frederick W.; Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. [Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Eidelman, N (reprint author), NIST, Paffenbarger Res Ctr, Amer Dent Assoc Fdn, 100 Bur Dr,Stop 8546, Gaithersburg, MD 20899 USA. EM naomi.eidelman@nist.gov RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIEHS; NIDCR; ADAF; NIST; Medical Research Council, UK; Horserace Betting Levy Board, UK FX This work was supported in part by the intramural research programs of NIEHS (FWM, LGR) and NIDCR (PGR), ADAF (NE), NIST (NE, JS), the Medical Research Council, UK (AB through the provision of the facility for the determination of mineralization density at the microscopic scale from BSE imaging) and the Veterinary Advisory Committee of the Horserace Betting Levy Board, UK (AB via support of M Arora). NR 60 TC 14 Z9 15 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 5 AR R159 DI 10.1186/ar2841 PG 21 WC Rheumatology SC Rheumatology GA 540ND UT WOS:000273338400052 PM 19857267 ER PT J AU Nanki, T Takada, K Komano, Y Morio, T Kanegane, H Nakajima, A Lipsky, PE Miyasaka, N AF Nanki, Toshihiro Takada, Kazuki Komano, Yukiko Morio, Tomohiro Kanegane, Hirokazu Nakajima, Atsuo Lipsky, Peter E. Miyasaka, Nobuyuki TI Chemokine receptor expression and functional effects of chemokines on B cells: implication in the pathogenesis of rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SYNOVIAL T-CELLS; DENDRITIC CELLS; NECROSIS-FACTOR; FACTOR-I; ACTIVATION; ACCUMULATION; COSTIMULATOR; LYMPHOCYTES; IMMUNITY; PATHWAY AB Introduction Accumulation of B cells in the rheumatoid arthritis (RA) synovium has been reported, and it has been thought that these cells might contribute to the pathogenesis of RA by antigen presentation, autoantibody production, and/or inflammatory cytokine production. Chemokines could enhance the accumulation of B cells in the synovium. The aims of this study were to determine chemokine receptor expression by B cells both in the peripheral blood of normal donors and subjects with RA, and at the inflammatory site in RA, and the effects of chemokines on B cell activation. Methods Cell surface molecule expression was analyzed by flow cytometry. Cellular migration was assessed using chemotaxis chambers. Cellular proliferation was examined by (3)H-thymidine incorporation. Tumor necrosis factor (TNF) production was assayed by enzyme-linked immunosorbent assay. Results Significant numbers of peripheral blood B cells of healthy donors and subjects with RA expressed CC chemokine receptor (CCR)5 and CXCR3, and most B cells expressed CCR6, CCR7, CXCR4 and CXCR5. CCR5 expression was more frequent on CD27(+) than CD27(-) peripheral blood B cells of healthy donors and RA. Synovial B cells more frequently expressed CCR5, but less often expressed CCR6, CCR7 and CXCR5 compared to peripheral blood in RA. Further functional analyses were performed on peripheral blood B cells from healthy donors. Migration of peripheral blood B cells, especially CD27(+) B cells, was enhanced by CC chemokine ligand (CCL)20, CCL19, CCL21 and CXCL12. All four chemokines alone induced B cell proliferation; with CCL21 being the most effective. CCL21 also enhanced the proliferation of anti-immunoglobulin (Ig) M-stimulated B cells and blockade of CCR7 inhibited this effect. CCL20, CCL21 and CXCL12 enhanced TNF production by anti-IgM mAb-stimulated B cells. Finally, stimulation with CXCL12, but not CCL20, CCL19 and CCL21, enhanced inducible costimulator-ligand (ICOSL) expression by peripheral blood B cells of healthy donors and RA, but did not increase B cell-activating factor receptor or transmembrane activator and CAML-interactor. Conclusions The data suggest that CCR5, CCR6, CCR7, CXCR3, CXCR4 and CXCR5 may be important for the B cell migration into the synovium of RA patients, and also their local proliferation, cytokine production and ICOSL expression in the synovium. C1 [Nanki, Toshihiro; Takada, Kazuki; Komano, Yukiko; Miyasaka, Nobuyuki] Tokyo Med & Dent Univ, Grad Sch, Dept Med, Bunkyo Ku, Tokyo 1138519, Japan. [Nanki, Toshihiro; Takada, Kazuki; Komano, Yukiko; Miyasaka, Nobuyuki] Tokyo Med & Dent Univ, Grad Sch, Dept Rheumatol, Bunkyo Ku, Tokyo 1138519, Japan. [Nanki, Toshihiro; Komano, Yukiko] Tokyo Med & Dent Univ, Grad Sch, Dept Pharmacovigilance, Bunkyo Ku, Tokyo 1138519, Japan. [Morio, Tomohiro] Tokyo Med & Dent Univ, Grad Sch, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138519, Japan. [Kanegane, Hirokazu] Toyama Univ, Grad Sch Med, Dept Pediat, Toyama 9300194, Japan. [Nakajima, Atsuo] Nippon Med Sch, Dept Joint Dis & Rheumatism, Bunkyo Ku, Tokyo 1138603, Japan. [Nakajima, Atsuo] Tokyo Metropolitan Police Hosp, Dept Rheumatol, Nakano Ku, Tokyo 1648541, Japan. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Miyasaka, Nobuyuki] Tokyo Med & Dent Univ, Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence GCOE Program, Bunkyo Ku, Tokyo 1138519, Japan. RP Nanki, T (reprint author), Tokyo Med & Dent Univ, Grad Sch, Dept Med, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan. EM nanki.rheu@tmd.ac.jp FU Ministry of Health, Labor and Welfare; Ministry of Education, Science, Sports and Culture, Japan; Japanese Ministry of Education, Global Center of Excellence ( GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases FX We thank Fumiko Inoue and Aya Sato for the excellent technical support. This work was supported in part by grants-in-aid from the Ministry of Health, Labor and Welfare, and the Ministry of Education, Science, Sports and Culture, Japan, and the Japanese Ministry of Education, Global Center of Excellence ( GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases. NR 38 TC 47 Z9 48 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 5 AR R149 DI 10.1186/ar2823 PG 11 WC Rheumatology SC Rheumatology GA 540ND UT WOS:000273338400042 PM 19804625 ER PT J AU Perruche, S Saas, P Chen, WJ AF Perruche, Sylvain Saas, Philippe Chen, Wanjun TI Apoptotic cell-mediated suppression of streptococcal cell wall-induced arthritis is associated with alteration of macrophage function and local regulatory T-cell increase: a potential cell-based therapy? SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; TGF-BETA; CYTOKINE PRODUCTION; IMMUNE TOLERANCE; DENDRITIC CELLS; PHOTOPHERESIS; INDUCTION; MICE; TRANSFUSION; MECHANISMS AB Introduction Experimental streptococcal cell wall (SCW)-induced arthritis is characterized by two successive phases of the disease. The acute phase occurs early and is associated with an inflammatory process and neutrophil infiltration into the synovium. The second chronic phase is related to effector T-cell activation and the dysregulation of macrophage function. Creation of an immunomodulatory environment has been attributed to apoptotic cells themselves, apoptotic cell uptake by phagocytes as well as a less sensibility of phagocytes capturing apoptotic bodies to activation. Therefore we evaluated the potential of apoptotic cell injection to influence the course of inflammation in SCW-induced arthritis in rats. Methods Rat apoptotic thymocytes were injected intraperitoneally (2 x 10(8)) in addition to an arthritogenic dose of systemic SCW in LEW female rats. Control rats received SCW immunization and PBS. Rats were then followed for arthritis occurrence and circulating cytokine detection. At sacrifice, regulatory T cells (Tregs) and macrophages were analyzed. Results Apoptotic cell injection profoundly suppressed joint swelling and destruction typically observed during the acute and chronic phases of SCW-induced arthritis. Synovial inflammatory cell infiltration and bone destruction were also markedly suppressed. Ex vivo experiments revealed reduced levels of TNF in cultures of macrophages from rats challenged with SCW in the presence of apoptotic thymocytes as well as reduced macrophage response to lipopolysaccharide. Moreover, apoptotic cell injection induced higher Foxp3(+) Tregs in the lymphoid organs, especially in the draining lymph nodes. Conclusions Our data indicate that apoptotic cells modulate macrophage function and result in Treg generation/increase. This may be involved in inhibition of inflammation and amelioration of arthritis. This highlights and confirms previous studies showing that in vivo generation of Tregs using apoptotic cell injection may be a useful tool to prevent and treat inflammatory autoimmune responses. C1 [Perruche, Sylvain; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Perruche, Sylvain; Saas, Philippe] Univ Franche Comte, INSERM, EFS BFC, UMR645,IFR133, F-25020 Besancon, France. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Convent Dr, Bethesda, MD 20892 USA. EM wchen@dir.nidcr.nih.gov RI SAAS, Philippe/M-3550-2015; OI SAAS, Philippe/0000-0002-8857-9939 FU Intramural Research Program of the National Institutes of Health; National Institute of Dental and Craniofacial Research; Association pour la Recherche sur le Cancer (ARC) [3851]; INCa [PL098] FX The present research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. PS was supported by grants from the Association pour la Recherche sur le Cancer (ARC #3851) and from INCa (#PL098). NR 30 TC 16 Z9 18 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 4 AR R104 DI 10.1186/ar2750 PG 8 WC Rheumatology SC Rheumatology GA 508MU UT WOS:000270936400019 PM 19570235 ER PT J AU Souto-Carneiro, MM Mahadevan, V Takada, K Fritsch-Stork, R Nanki, T Brown, M Fleisher, TA Wilson, M Goldbach-Mansky, R Lipsky, PE AF Souto-Carneiro, M. Margarida Mahadevan, Vijayabhanu Takada, Kazuki Fritsch-Stork, Ruth Nanki, Toshihiro Brown, Margaret Fleisher, Thomas A. Wilson, Mildred Goldbach-Mansky, Raphaela Lipsky, Peter E. TI Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHEMOKINE RECEPTORS; GERMINAL CENTER; FACTOR-ALPHA; DIFFERENTIAL EXPRESSION; ATTRACTING CHEMOKINE-1; LYMPHOID NEOGENESIS; ADHESION MOLECULES; SJOGRENS-SYNDROME; SYNOVIAL TISSUES AB Introduction Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear. Methods The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab. Results RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD(+)CD27(+) memory B cells than healthy individuals, whereas post-switch IgD-CD27(+) accumulate with increased disease duration. Notably, both pre-switch IgD(+)CD27(+) and post-switch IgD-CD27(+) memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD(+)CD27 memory B cells in the peripheral blood. Conclusions The data suggest that decreases in peripheral blood IgD(+)CD27(+) pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF. C1 [Mahadevan, Vijayabhanu; Wilson, Mildred; Goldbach-Mansky, Raphaela; Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Souto-Carneiro, M. Margarida] Univ Coimbra, Dept Zool, Ctr Neurociencias & Biol Celular, P-3004517 Coimbra, Portugal. [Takada, Kazuki; Nanki, Toshihiro] Tokyo Med & Dent Univ, Grad Sch, Dept Med & Rheumatol, Bunkyo Ku, Tokyo 1138519, Japan. [Fritsch-Stork, Ruth] UMC Utrecht, Dept Rheumatol, NL-3584 CX Utrecht, Netherlands. [Brown, Margaret; Fleisher, Thomas A.] NIH, Dept Lab Med, Warren Magnuson Ctr, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM peterlipsky@comcast.net RI Fritsch-sTork, Ruth/G-9702-2012; Souto-Carneiro, Margarida/C-4386-2016 OI Souto-Carneiro, Margarida/0000-0001-6923-0590 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program; Marie Curie Intra-European Fellowship [LIF-025885]; EULAR Young Investigator Award FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program. MMSC was supported by the Marie Curie Intra-European Fellowship, LIF-025885 and EULAR Young Investigator Award. NR 62 TC 55 Z9 58 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 3 AR R84 DI 10.1186/ar2718 PG 12 WC Rheumatology SC Rheumatology GA 484BW UT WOS:000269019300050 PM 19500335 ER PT J AU Thwin, MM Douni, E Arjunan, P Kollias, G Kumar, PV Gopalakrishnakone, P AF Thwin, Maung-Maung Douni, Eleni Arjunan, Pachiappan Kollias, George Kumar, Prem V. Gopalakrishnakone, Ponnampalam TI Suppressive effect of secretory phospholipase A(2) inhibitory peptide on interleukin-1 beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts, and its antiarthritic activity in hTNFtg mice SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; COLLAGEN-INDUCED ARTHRITIS; ARACHIDONIC-ACID RELEASE; GROUP-IIA; MESANGIAL CELLS; P38 MAPK; PROSTAGLANDIN PRODUCTION; DIFFERENTIAL REGULATION; INFLAMMATORY ARTHRITIS AB Introduction Secretory phospholipase A(2) (sPLA(2)) and matrix metalloproteinase (MMP) inhibitors are potent modulators of inflammation with therapeutic potential, but have limited efficacy in rheumatoid arthritis (RA). The objective of this study was to understand the inhibitory mechanism of phospholipase inhibitor from python (PIP)-18 peptide in cultured synovial fibroblasts (SF), and to evaluate its therapeutic potential in a human tumor necrosis factor (hTNF)-driven transgenic mouse (Tg197) model of arthritis. Methods Gene and protein expression of sPLA(2)-IIA, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by real time PCR and ELISA respectively, in interleukin (IL)-1 beta stimulated rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts cells treated with or without inhibitors of sPLA2 (PIP-18, LY315920) or MMPs (MMP Inhibitor II). Phosphorylation status of mitogen-activated protein kinase (MAPK) proteins was examined by cell-based ELISA. The effect of PIP-18 was compared with that of celecoxib, methotrexate, infliximab and antiflamin-2 in Tg197 mice after ip administration (thrice weekly for 5 weeks) at two doses (10, 30 mg/kg), and histologic analysis of ankle joints. Serum sPLA(2) and cytokines (tumor necrosis factor (TNF)alpha, IL-6) were measured by Escherichia coli (E coli) assay and ELISA, respectively. Results PIP-18 inhibited sPLA(2)-IIA production and enzymatic activity, and suppressed production of MMPs in IL-1 beta-induced RA and OA SF cells. Treatment with PIP-18 blocked IL-1 beta-induced p38 MAPK phosphorylation and resulted in attenuation of sPLA(2)-IIA and MMP mRNA transcription in RA SF cells. The disease modifying effect of PIP-18 was evidenced by significant abrogation of synovitis, cartilage degradation and bone erosion in hTNF Tg197 mice. Conclusions Our results demonstrate the benefit that can be gained from using sPLA(2) inhibitory peptide for RA treatment, and validate PIP-18 as a potential therapeutic in a clinically relevant animal model of human arthritis. C1 [Thwin, Maung-Maung; Gopalakrishnakone, Ponnampalam] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, Singapore 117597, Singapore. [Douni, Eleni; Kollias, George] Biomed Sci Res Ctr, Inst Immunol, Vari 16672, Greece. [Arjunan, Pachiappan] NEI, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Kumar, Prem V.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Orthopaed Surg, Singapore 117597, Singapore. RP Gopalakrishnakone, P (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Anat, 4 Med Dr, Singapore 117597, Singapore. EM antgopal@nus.edu.sg RI Kollias, George/A-7079-2012 OI Kollias, George/0000-0003-1867-3150 FU Singapore Economic Development Board ( EDB); Biomedical Sciences Proof-of-Concept Scheme [S05/1-25277273]; National University of Singapore [R-181-000087-414] FX We thank Mr. Nikos Giannakas, Biomedical Sciences Research Centre, Institute of Immunology, Fleming, Greece, for assistance with the Tg197 mice experiments, and Dr. B. Susithra, Department of Anatomy, National University of Singapore, for histology. This study was funded by the Singapore Economic Development Board ( EDB), Biomedical Sciences Proof-of-Concept Scheme ( POC project S05/1-25277273) and supported by the National University of Singapore ( Grant No: R-181-000087-414). NR 67 TC 10 Z9 10 U1 6 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 5 AR R138 DI 10.1186/ar2810 PG 16 WC Rheumatology SC Rheumatology GA 540ND UT WOS:000273338400031 PM 19765281 ER PT J AU Vosters, JL Yin, HE Roescher, N Kok, MR Tak, PP Chiorini, JA AF Vosters, Jelle L. Yin, Hongen Roescher, Nienke Kok, Marc R. Tak, Paul P. Chiorini, John A. TI Local expression of tumor necrosis factor-receptor 1:immunoglobulin G can induce salivary gland dysfunction in a murine model of Sjogren's syndrome SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID NOD MICE; FACTOR-ALPHA; AUTOIMMUNE EXOCRINOPATHY; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; DIABETES-MELLITUS; B-LYMPHOCYTES; GENE-TRANSFER; THERAPY; DISEASE AB Introduction Tumor necrosis factor is a pleiotropic cytokine with potent immune regulatory functions. Although tumor necrosis factor inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjogren's syndrome. The aim of this study was to assess the effect of a locally expressed tumor necrosis factor inhibitor on the salivary gland function and histopathology in an animal model of Sjogren's syndrome. Methods Using in vivo adeno associated viral gene transfer, we have stably expressed soluble tumor necrosis factor-receptor 1-Fc fusion protein locally in the salivary glands in the Non Obese Diabetic model of Sjogren's syndrome. Pilocarpine stimulated saliva flow was measured to address the salivary gland function and salivary glands were analyzed for focus score and cytokine profiles. Additionally, cytokines and autoantibody levels were measured in plasma. Results Local expression of tumor necrosis factor-receptor 1:immunoglobulin G fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of tumor growth factor-beta 1 and decreased levels of interleukin-5, interleukin-12p70 and interleukin -17 were detected in the salivary glands. In contrast, plasma levels showed significantly decreased levels of tumor growth factor-beta 1 and increased levels of interleukin-4, interferon-gamma, interleukin-10 and interleukin-12p70. Conclusions Our findings suggest that expression of tumor necrosis factor inhibitors in the salivary gland can have a negative effect on salivary gland function and that other cytokines should be explored as points for therapeutic intervention in Sjogren's syndrome. C1 [Vosters, Jelle L.; Yin, Hongen; Roescher, Nienke; Kok, Marc R.; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Vosters, Jelle L.; Roescher, Nienke; Kok, Marc R.; Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1100 DD Amsterdam, Netherlands. RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov RI e-, a/F-9947-2012 FU Dutch Arthritis Association [NR 07-1-406]; NIH, NIDCR FX The authors thank Bruce J. Baum and Gabor G. Illei for critical review and helpful discussion of this manuscript and Beverly Handelman for the virus preparations. This work is supported by a Dutch Arthritis Association grant [NR 07-1-406] to JLV and an NIH, NIDCR intramural research grant to JAC. NR 45 TC 14 Z9 14 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2009 VL 11 IS 6 AR R189 DI 10.1186/ar2888 PG 11 WC Rheumatology SC Rheumatology GA 604MC UT WOS:000278282100029 PM 20003451 ER PT J AU Garg, S Nichols, JR Esen, N Liu, SL Phulwani, NK Syed, MM Wood, WH Zhang, YQ Becker, KG Aldrich, A Kielian, T AF Garg, Sarita Nichols, Jessica R. Esen, Nilufer Liu, Shuliang Phulwani, Nirmal K. Syed, Mohsin Md. Wood, William H. Zhang, Yongqing Becker, Kevin G. Aldrich, Amy Kielian, Tammy TI MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses SO ASN NEURO LA English DT Article DE bone marrow chimaera mice; brain abscess; central nervous system; MyD88; Staphylococcus aureus; Toll-like receptor ID NF-KAPPA-B; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYCOBACTERIUM-TUBERCULOSIS INFECTION; CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTOR-4; STAPHYLOCOCCUS-AUREUS; BONE-MARROW; TNF-ALPHA; NEUTROPHIL GELATINASE; MYD88-DEFICIENT MICE AB MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, in our previous studies it has been impossible to determine the relative contribution of MyD88-dependent signalling in the CNS compared with the peripheral immune cell compartments. In the present study we addressed this by examining the course of S. aureus infection in MyD88 bone marrow chimaera mice. Interestingly, chimaeras where MyD88 was present in the CNS, but not bone marrow-derived cells, mounted pro-inflammatory mediator expression profiles and neutrophil recruitment equivalent to or exceeding that detected in WT (wild-type) mice. These results implicate CNS MyD88 as essential in eliciting the initial wave of inflammation during the acute response to parenchymal infection. Microarray analysis of infected MyD88 KO compared with WT mice revealed a preponderance of differentially regulated genes involved in apoptotic pathways, suggesting that the extensive tissue damage characteristic of brain abscesses from MyD88 KO mice could result from dysregulated apoptosis. Collectively, the findings of the present study highlight a novel mechanism for CNS-resident cells in initiating a protective innate immune response in the infected brain and, in the absence of MyD88 in this compartment, immunity is compromised. C1 [Aldrich, Amy; Kielian, Tammy] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Garg, Sarita] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. [Nichols, Jessica R.] Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. [Esen, Nilufer] Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA. [Liu, Shuliang; Phulwani, Nirmal K.; Syed, Mohsin Md.] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA. [Wood, William H.; Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. RP Kielian, T (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. EM tkielian@unmc.edu OI Becker, Kevin/0000-0002-6794-6656 FU National Institutes of Health National Institute of Neurological Disorders and Stroke [RO1 NS NS055385]; National Institute of Neurological Disorders and Stroke supported Core Facility at the University of Arkansas for Medical Sciences [P30 NS047546]; National Institutes of Health, National Institute on Aging FX This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [grant number RO1 NS NS055385 (to T. K.)]; the National Institute of Neurological Disorders and Stroke supported Core Facility at the University of Arkansas for Medical Sciences [grant number P30 NS047546]; and the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 77 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2009 VL 1 IS 2 AR e00007 DI 10.1042/AN20090004 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 577AS UT WOS:000276192800002 ER PT J AU Greggio, E Cookson, MR AF Greggio, Elisa Cookson, Mark R. TI Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions SO ASN NEURO LA English DT Review DE GTPase; leucine-rich repeat kinase 2 (LRRK2); Lewy body; neurotoxicity; Parkinson's disease ID LRRK2 G2019S MUTATION; AUTOSOMAL-DOMINANT PARKINSONISM; LEWY BODY DISEASE; ALPHA-SYNUCLEIN; LEUCINE-RICH-REPEAT-KINASE-2 LRRK2; DOPAMINERGIC-NEURONS; ROC DOMAIN; GENE LRRK2; SPANISH PATIENTS; GTP-BINDING AB Mutations in the gene encoding LRRK2 (leucine-rich repeat kinase 2) were first identified in 2004 and have since been shown to be the single most common cause of inherited Parkinson's disease. The protein is a large GTP-regulated serine/threonine kinase that additionally contains several protein-protein interaction domains. In the present review, we discuss three important, but unresolved, questions concerning LRRK2. We first ask: what is the normal function of LRRK2? Related to this, we discuss the evidence of LRRK2 activity as a GTPase and as a kinase and the available data on protein-protein interactions. Next we raise the question of how mutations affect LRRK2 function, focusing on some slightly controversial results related to the kinase activity of the protein in a variety of in vitro systems. Finally, we discuss what the possible mechanisms are for LRRK2-mediated neurotoxicity, in the context of known activities of the protein. C1 [Greggio, Elisa; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20982 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20982 USA. EM Cookson@mail.nih.gov RI Greggio, Elisa/H-6119-2013 OI Greggio, Elisa/0000-0002-8172-3598 FU National Institute of Aging of the National Institutes of Health [AG000948-01] FX This work was funded by the Intramural Research Program of the National Institute of Aging of the National Institutes of Health [project number AG000948-01]. NR 98 TC 111 Z9 111 U1 1 U2 10 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PY 2009 VL 1 IS 1 AR e00002 DI 10.1042/AN20090007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 577AR UT WOS:000276192700002 ER PT J AU Groll, AH Walsh, TJ AF Groll, Andreas H. Walsh, Thomas J. BE Latge, JP Steinbach, WJ TI Antifungal Polyenes SO ASPERGILLUS FUMIGATUS AND ASPERGILLOSIS LA English DT Article; Book Chapter ID LIPOSOMAL AMPHOTERICIN-B; INVASIVE FUNGAL-INFECTIONS; EXPERIMENTAL PULMONARY ASPERGILLOSIS; OF-THE-LITERATURE; MEDITERRANEAN VISCERAL LEISHMANIASIS; PERSISTENTLY NEUTROPENIC RABBITS; MARROW TRANSPLANT RECIPIENTS; FAT EMULSION FORMULATION; CRITICALLY-ILL PATIENTS; COMPLEX INJECTION ABLC C1 [Groll, Andreas H.; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Groll, Andreas H.; Walsh, Thomas J.] Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, D-48149 Munster, Germany. [Groll, Andreas H.; Walsh, Thomas J.] Univ Childrens Hosp, Dept Pediat Hematol Oncol, D-48149 Munster, Germany. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 216 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-552-3 PY 2009 BP 391 EP 415 PG 25 WC Microbiology; Mycology SC Microbiology; Mycology GA BOY46 UT WOS:000278059700031 ER PT S AU Gregoriou, GG Gotts, SJ Zhou, HH Desimone, R AF Gregoriou, Georgia G. Gotts, Stephen J. Zhou, Huihui Desimone, Robert BE Srinivasan, N TI Long-range neural coupling through synchronization with attention SO ATTENTION SE Progress in Brain Research LA English DT Review; Book Chapter DE attention; frontal eye field; area V4; synchrony; top-down; lateral intraparietal area ID FRONTAL EYE FIELD; MACAQUE AREA V4; SELECTIVE VISUAL-ATTENTION; LATERAL INTRAPARIETAL AREA; PARIETAL CORTEX; TOP-DOWN; PREFRONTAL CORTEX; SPATIAL ATTENTION; NEURONAL SYNCHRONIZATION; GAMMA-OSCILLATIONS AB In a crowded visual scene, we typically employ attention to select stimuli that are behaviorally relevant. Two likely cortical sources of top-down attentional feedback to cortical visual areas are the prefrontal (PFC) and posterior parietal (PPC) cortices. Recent neurophysiological studies show that areas in PFC and PPC process signals about the locus of attention earlier than in extrastriate visual areas and are therefore likely to mediate attentional selection. Moreover, attentional selection appears to be mediated in part by neural synchrony between neurons in PFC/PPC and early visual areas, with phase relationships that seem optimal for increasing the impact of the top-down inputs to the visual cortex. C1 [Zhou, Huihui; Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Gregoriou, Georgia G.] Univ Crete, Sch Med, Dept Basic Sci, Iraklion, Crete, Greece. [Gotts, Stephen J.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Desimone, R (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM desimone@mit.edu RI Gregoriou, Georgia/F-7759-2011; Gotts, Stephen/J-4842-2012 OI Gregoriou, Georgia/0000-0002-4002-6657; FU Intramural NIH HHS; NEI NIH HHS [EY017921, EY017292]; NIMH NIH HHS [MH64445] NR 81 TC 40 Z9 40 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53426-2 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2009 VL 176 BP 35 EP 45 DI 10.1016/S0079-6123(09)17603-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BQC06 UT WOS:000280608300004 PM 19733748 ER PT B AU Greydanus, DE Merrick, J AF Greydanus, Donald E. Merrick, Joav BE Gordon, SM Mitchell, AE TI Psychopharmacology in Children, Adolescents and Adults with Attention Deficit Hyperactivity Disorder (ADHD) SO ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) SE Psychiatry Theory Applications and Treatment LA English DT Article; Book Chapter ID DEFICIT/HYPERACTIVITY DISORDER; COLLEGE-STUDENTS; STIMULANTS; TOMOXETINE; ABUSE AB Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder affecting several percent of the population, which usually presents itself during childhood, but can persist into adulthood or be diagnosed in adulthood also. Treatment of the male or female child, adolescent, young adult, or older adult with ADHD begins with a careful assessment to establish a correct diagnosis and what potential co-morbid conditions may also complicate the clinical picture. If a psychopharmacologic approach is chosen as part of the management strategy for this common conundrum, the clinician should understand that the medications noted by research to help many patients improve their attention dysfunction are stimulants, norepinephrine reuptake inhibitors, and antidepressants; alpha-2 agonists may improve the classic insomniac effect of stimulants. The most popular drugs and the ones with the most underlying research support are the stimulants, methylphenidate (available since 1957) and amphetamine (with observational data on its effectiveness starting in 1937). A number of newer, long-acting stimulants have been introduced in the past decade. C1 [Greydanus, Donald E.] Michigan State Univ, Coll Human Med, Pediat Program, Kalamazoo, MI 49008 USA. [Greydanus, Donald E.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI 49008 USA. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, IL-91012 Jerusalem, Israel. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY 40506 USA. [Merrick, Joav] NICHHD, Off Med, Bethesda, MD 20892 USA. RP Greydanus, DE (reprint author), Michigan State Univ, Coll Human Med, Pediat Program, 1000 Oakland Dr, Kalamazoo, MI 49008 USA. EM Greydanus@kcms.msu.edu; jmerrick@zahav.net.il NR 35 TC 2 Z9 2 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-581-7 J9 PSYCHIAT THEOR APPL PY 2009 BP 257 EP 272 PG 16 WC Psychiatry SC Psychiatry GA BMS41 UT WOS:000273461200011 ER PT B AU Carmeli, E Merrick, J AF Carmeli, Eli Merrick, Joav BE Gordon, SM Mitchell, AE TI Attention Deficit Hyperactivity Disorder and Persons with Intellectual Disability SO ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) SE Psychiatry Theory Applications and Treatment LA English DT Article; Book Chapter ID MENTAL-RETARDATION; CHILDREN; ADOLESCENTS; ADHD AB In this chapter we want to demonstrate a correlation between social skills and attention deficit hyperactivity disorder (ADHD) among adolescents with intellectual disability (ID). In a recent pilot study of adolescents dually diagnosed with mild intellectual disabilities and comorbid pathology of ADHD we defined three age-and IQ-match groups (males, n=12 in each group) with group I - composed of adolescent diagnosed with mild ID, group II - adolescents diagnosed with ADHD, and group III - adolescents diagnosed with ID and ADHD. The instruments used in the study were Wechsler Intelligence Scale for Children (WISC, according to the chronological age of the subjects) and the short version of the Developmental Behavior Checklist (DBC). We found that comorbidity was a factor differentiating. ADHD strongly increased the impairment of social skills, while behavioral disorders were less damaging in ID performance. The WISC and DBC instruments should be used with confidence in clinical and service settings, to allow a better assessment of co-occurrence morbidity in adolescents with ID. The interactions between intellectual disability and psychopathology behavior highlight the need to plan a more accurate diagnosis and appropriate rehabilitative intervention program, essential for improving the quality of life of the ID population. C1 [Carmeli, Eli] Tel Aviv Univ, Sackler Fac Med, Dept Phys Therapy, Stanley Steyer Sch Hlth Profess, IL-69978 Ramat Aviv, Israel. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, IL-91012 Jerusalem, Israel. [Merrick, Joav] NICHHD, Off Med, Bethesda, MD 20892 USA. [Merrick, Joav] Soroka Univ, Med Ctr, Zusman Child Dev Ctr, Beer Sheva, Israel. [Merrick, Joav] Interuniv Coll Hlth & Dev, Castle Seggau, Graz, Austria. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY 40506 USA. RP Carmeli, E (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Phys Therapy, Stanley Steyer Sch Hlth Profess, IL-69978 Ramat Aviv, Israel. EM elie@post.tau.ac.il; jmerrick@zahav.net.il NR 13 TC 0 Z9 0 U1 1 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-581-7 J9 PSYCHIAT THEOR APPL PY 2009 BP 297 EP 302 PG 6 WC Psychiatry SC Psychiatry GA BMS41 UT WOS:000273461200014 ER PT J AU O'Brien, SJ AF O'Brien, Stephen J. TI Comparative genomics in vertebrates: a role for the platypus SO AUSTRALIAN JOURNAL OF ZOOLOGY LA English DT Editorial Material ID SEX-CHROMOSOMES; EVOLUTION C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM stephen.obrien@nih.gov NR 16 TC 2 Z9 2 U1 0 U2 7 PU CSIRO PUBLISHING PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD, VICTORIA 3066, AUSTRALIA SN 0004-959X J9 AUST J ZOOL JI Aust. J. Zool. PY 2009 VL 57 IS 3-4 BP VII EP IX DI 10.1071/ZOv57n4_IN PG 3 WC Zoology SC Zoology GA 510DI UT WOS:000271067800002 ER PT J AU Raben, N Baum, R Schreiner, C Takikita, S Mizushima, N Ralston, E Plotz, P AF Raben, Nina Baum, Rebecca Schreiner, Cynthia Takikita, Shoichi Mizushima, Noboru Ralston, Evelyn Plotz, Paul TI When more is less Excess and deficiency of autophagy coexist in skeletal muscle in Pompe disease SO AUTOPHAGY LA English DT Article DE Pompe disease; lysosome; muscle-specific autophagy deficiency; protein inclusions ID ACID ALPHA-GLUCOSIDASE; SELF-DIGESTION; LC3; GLYCOGEN; MICE; DEGRADATION; STARVATION; FIBERS; MARKER; CELLS AB The role of autophagy, a catabolic lysosome-dependent pathway, has recently been recognized in a variety of disorders, including Pompe disease, which results from a deficiency of the glycogen-degrading lysosomal hydrolase acid-alpha glucosidase (GAA). Skeletal and cardiac muscle are most severely affected by the progressive expansion of glycogen-filled lysosomes. In both humans and an animal model of the disease (GAA KO), skeletal muscle pathology also involves massive accumulation of autophagic vesicles and autophagic buildup in the core of myofibers, suggesting an induction of autophagy. Only when we suppressed autophagy in the skeletal muscle of the GAA KO mice did we realize that the excess of autophagy manifests as a functional deficiency. This failure of productive autophagy is responsible for the accumulation of potentially toxic aggregate-prone ubiquitinated proteins, which likely cause profound muscle damage in Pompe mice. Also, by generating muscle-specific autophagy-deficient wild-type mice, we were able to analyze the role of autophagy in healthy skeletal muscle. C1 [Raben, Nina; Baum, Rebecca; Schreiner, Cynthia; Takikita, Shoichi; Plotz, Paul] NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. [Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan. [Ralston, Evelyn] NIAMS, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD USA. RP Raben, N (reprint author), NIAMS, Arthrit & Rheumatism Branch, NIH, 50 S Dr Bld 50-1345, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov RI Mizushima, Noboru/C-3635-2009 OI Mizushima, Noboru/0000-0002-6258-6444 FU National Institute of Arthritis and Musculoskeletal and Skill Diseases of the National Institutes of Health FX This research was Supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skill Diseases of the National Institutes of Health. Dr. Takikita was supported in part by a CRADA between the NIH and Genzyme Corporation (Framingham, MA). NR 23 TC 26 Z9 26 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN PY 2009 VL 5 IS 1 BP 111 EP 113 PG 3 WC Cell Biology SC Cell Biology GA 400CE UT WOS:000262844800019 PM 19001870 ER PT S AU Otto, M AF Otto, Michael BE Collin, M Schuch, R TI Bacterial Sensing of Antimicrobial Peptides SO BACTERIAL SENSING AND SIGNALING SE Contributions to Microbiology LA English DT Article; Book Chapter ID 2-COMPONENT REGULATORY SYSTEM; VANCOMYCIN-INTERMEDIATE RESISTANCE; HOST-DEFENSE PEPTIDES; STAPHYLOCOCCUS-AUREUS; SALMONELLA-TYPHIMURIUM; PHOP-PHOQ; ANTIBACTERIAL PEPTIDES; STREPTOCOCCUS-PYOGENES; NEISSERIA-GONORRHOEAE; LIPOTEICHOIC ACID AB Antimicrobial peptides (AMPs) form a crucial part of human innate host defense, especially in neutrophil phagosomes and on epithelial surfaces. Bacteria have a variety of efficient resistance mechanisms to human AMPs, such as efflux pumps, secreted proteases, and alterations of the bacterial cell surface that are aimed to minimize attraction of the typically cationic AMPs. In addition, bacteria have specific sensors that activate AMP resistance mechanisms when AMPs are present. The prototypical Gram-negative PhoP/PhoQ and the Gram-positive Aps AMP-sensing systems were first described and investigated in Salmonella typhimurium and Staphylococcus epidermidis, respectively. Both include a classical bacterial two-component sensor/regulator system, but show many structural, mechanistic, and functional differences. The PhoP/PhoQ regulon controls a variety of genes not necessarily limited to AMP resistance mechanisms, but apparently aimed to combat innate host defense on a broad scale. In contrast, the staphylococcal Aps system predominantly upregulates AMP resistance mechanisms, namely the D-alanylation of teichoic acids, inclusion of lysyl-phosphatidylglycerol in the cytoplasmic membrane, and expression of the putative VraFG AMP efflux pump. Notably, both systems are crucial for virulence and represent possible targets for antimicrobial therapy. Copyright (C) 2009 S. Karger AG, Basel C1 [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS [Z99 AI999999, ZIA AI000904-08] NR 75 TC 44 Z9 45 U1 3 U2 7 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1420-9519 BN 978-3-8055-9132-4 J9 CONTRIB MICROBIOL JI Contrib. Microbiol. PY 2009 VL 16 BP 136 EP 149 PG 14 WC Microbiology SC Microbiology GA BKK46 UT WOS:000268384300008 PM 19494583 ER PT S AU Walters, JR Tierney, PL Bergstrom, DA AF Walters, Judith R. Tierney, Patrick L. Bergstrom, Debra A. BE Groenewegen, HJ Berendse, HW Cools, AR Voorn, P Mulder, AB TI Oscillatory Activity and Synchronization in the Basal Ganglia Network in Rodent Models of Parkinson's Disease SO BASAL GANGLIA IX SE Advances in Behavioral Biology LA English DT Proceedings Paper CT 9th Triennial Meeting of the International-Basal-Ganglia-Society CY SEP 02-06, 2007 CL Egmond aan Zee, NETHERLANDS SP Int Basal Ganglia Soc ID RAT GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS NEURONS; DOPAMINE-RECEPTOR STIMULATION; MOVEMENT-RELATED CHANGES; DEEP-BRAIN-STIMULATION; MEDIUM SPINY NEURONS; CEREBRAL-CORTEX; PEDUNCULOPONTINE NUCLEUS; BETA-OSCILLATIONS; SUBSTANTIA-NIGRA AB The efficacy of deep brain stimulation (DBS) in the subthalamic nucleus (STN) in Parkinson's disease (PD) has focused attention on the role of STN tiring patterns in PD symptomatology. Oscillatory activity in the beta frequency range is of special interest as local field potential (LFP) recordings in the STN in bradykinetic PD patients during DBS electrode placement show prominent activity in this frequency range. As increased synchronization between the globus pallidus pars externus (GP) and STN has been implicated in the emergence of oscillatory activity in the STN, the effect of dopamine loss and increased dopamine stimulation on beta range activity in paired GP-STN single unit and UP recordings was examined in intact or nigrostriatally lesioned, locally anesthetized, and immobilized rats. Spike-triggered waveform averages (STWAs) show that GP spiking becomes significantly more synchronized with STN UP oscillations in the beta range after dopamine cell lesion. Coherences between GP spiking and STN UP and between STN spiking and STN LFP are increased after dopamine cell lesion. A desynchronizing effect of increased dopamine receptor stimulation with apomorphine on GP-STN relationships in both intact and lesioned rats is observed. Results support a role for increased synchronization between STN and GP in the emergence of beta range activity in the STN and a greater impact of GP on STN activity after decreased dopamine receptor stimulation. C1 [Walters, Judith R.; Tierney, Patrick L.; Bergstrom, Debra A.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, Bldg 35,Room 1C905,35 Convent Dr, Bethesda, MD 20892 USA. EM waltersj@ninds.nih.gov RI Tierney, Patrick/E-5860-2010 NR 92 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0099-9962 BN 978-1-4419-0339-6 J9 ADV BEHAV BIOL JI Adv. Behav. Biol. PY 2009 VL 58 BP 443 EP 459 DI 10.1007/978-1-4419-0340-2_34 PG 17 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BMS42 UT WOS:000273461800034 ER PT J AU Chen, MH Kim, S AF Chen, Ming-Hui Kim, Sungduk TI Bayesian Generalized Method of Moments Comments SO BAYESIAN ANALYSIS LA English DT Editorial Material C1 [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Kim, Sungduk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Chen, MH (reprint author), Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. EM mhchen@stat.uconn.edu; kims2@mail.nih.gov NR 4 TC 0 Z9 0 U1 1 U2 2 PU INT SOC BAYESIAN ANALYSIS PI PITTSBURGH PA CARNEGIE MELLON UNIV, DEPT STTISTICS, PITTSBURGH, PA 15213 USA SN 1931-6690 J9 BAYESIAN ANAL JI Bayesian Anal. PY 2009 VL 4 IS 2 BP 209 EP 212 DI 10.1214/09-BA407A PG 4 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 542HK UT WOS:000273483400002 ER PT J AU Ferrell, CB AF Ferrell, Courtney B. TI Reengineering Clinical Research Science A Focus on Translational Research SO BEHAVIOR MODIFICATION LA English DT Article DE translational research; NIH; clinical research ID NIH ROADMAP; HEALTH; DISCOVERY AB The burden of disease in the United States is high. Mental illness is currently the leading cause of disease burden among 15- to 44-year-olds. This phenomenon is occurring despite the many advances that have been made in clinical research. Several efficacious interventions are available to treat many of these disorders; however, they are greatly underutilized within community settings. Achievements in basic science such as the completion of the Human Genome project have provided access to the examination of the neurobiology of mental disorders. To address the overall burden of disease, a reengineering of clinical science must take place. Adopting a translational framework will capitalize on the synergy of integrating basic science and clinical knowledge to inform real-world practices. This article will define and discuss translational research and the current National Institutes of Health initiatives that have been developed to support its implementation. C1 NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. RP Ferrell, CB (reprint author), NIMH, Div Dev Translat Res, 6001 Execut Blvd,MSC 9617,Room 6162, Bethesda, MD 20892 USA. EM cferrell@mail.nih.gov NR 41 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD JAN PY 2009 VL 33 IS 1 BP 7 EP 23 DI 10.1177/0145445508322616 PG 17 WC Psychology, Clinical SC Psychology GA 381OT UT WOS:000261546500002 PM 18776172 ER PT S AU Justinova, Z Panlilio, LV Goldberg, SR AF Justinova, Zuzana Panlilio, Leigh V. Goldberg, Steven R. BE Kendall, D Alexander, S TI Drug Addiction SO BEHAVIORAL NEUROBIOLOGY OF THE ENDOCANNABINOID SYSTEM SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Drug addiction; Cannabinoids; Endocannabinoids; Self-administration; Relapse; Reward; THC ID CONDITIONED PLACE PREFERENCE; CANNABINOID RECEPTOR ANTAGONIST; ACID AMIDE HYDROLASE; VENTRAL TEGMENTAL AREA; RAT NUCLEUS-ACCUMBENS; INDUCED DOPAMINE RELEASE; LONG-TERM DEPRESSION; CHRONIC DELTA(9)-TETRAHYDROCANNABINOL TREATMENT; INDUCED BEHAVIORAL SENSITIZATION; FOOD-REINFORCED BEHAVIOR AB Many drugs of abuse, including cannabinoids, opioids, alcohol and nicotine, can alter the levels of endocannabinoids in the brain. Recent studies show that release of endocannabinoids in the ventral tegmental area can modulate the reward-related effects of dopamine and might therefore be an important neurobiological mechanism underlying drug addiction. There is strong evidence that the endocannabinoid system is involved in drug-seeking behavior (especially behavior that is reinforced by drug-related cues), as well as in the mechanisms that underlie relapse to drug use. The cannabinoid CB1 antagonist/inverse agonist rimonabanthas been shown to reduce the behavioral effects of stimuli associated with drugs of abuse, including nicotine, alcohol, cocaine, and marijuana. Thus, the endocannabinoid system represents a promising target for development of new treatments for drug addiction. C1 [Justinova, Zuzana; Panlilio, Leigh V.; Goldberg, Steven R.] NIDA, US Dept HHS, Preclin Pharmacol Sect,NIH, Behav Neurosci Res Branch,Intramural Res Program, Baltimore, MD 21224 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. RP Goldberg, SR (reprint author), NIDA, US Dept HHS, Preclin Pharmacol Sect,NIH, Behav Neurosci Res Branch,Intramural Res Program, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU Intramural NIH HHS [Z99 DA999999, ZIA DA000001-26, ZIA DA000003-25]; NIDA NIH HHS [N01 DA059909] NR 250 TC 12 Z9 12 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-540-88954-0 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2009 VL 1 BP 309 EP 346 DI 10.1007/978-3-540-88955-7_13 D2 10.1007/978-3-540-88955-7 PG 38 WC Neurosciences SC Neurosciences & Neurology GA BMW95 UT WOS:000273776600013 PM 21104390 ER PT B AU Csokmay, JM DeCherney, AH AF Csokmay, John M. DeCherney, Alan H. BE Carrell, DT Racowsky, C Schlegel, PN VanVoorhis, BJ TI Discriminate Use of Varicocelectomy in Light of Advances in Assisted Reproductive Technologies SO BIENNIAL REVIEW OF INFERTILITY, VOL 1 LA English DT Article; Book Chapter DE Varicocele; Varicocelectomy; Infertility; Male factor; Assisted reproductive technologies (ART); In vitro fertilization (IVF); Intra-cytoplasmic sperm injection (ICSI); Semen analysis; Oligospermia; Anti-sperm antibodies ID SPERMATIC VEIN LIGATION; SEMEN QUALITY; MICROSURGICAL VARICOCELECTOMY; NONOBSTRUCTIVE AZOOSPERMIA; SUBCLINICAL VARICOCELE; STATISTICAL-ANALYSIS; SCROTAL TEMPERATURE; MALE-INFERTILITY; VENA SPERMATICA; MALE-FERTILITY AB Varicoceles are common in the population and pose a challenge to infertility providers. The data to support varicocelectomy in infertile males is limited and controversial. Varicocelectomy does demonstrate improvement in semen parameters and may be considered the sole infertility management in only a limited subset of the infertile population. Current advances in assisted reproductive technologies (ART) have demonstrated superior success rates and shorter time to pregnancy compared to surgical repair of varicocele in the sub-fertile male and should be considered the primary treatment. C1 [Csokmay, John M.; DeCherney, Alan H.] NICHHD, NIH, Bethesda, MD 20892 USA. RP DeCherney, AH (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM decherna@mail.nih.gov NR 54 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-391-6 PY 2009 BP 249 EP 257 DI 10.1007/978-1-60327-392-3_17 D2 10.1007/978-1-60327-392-3 PG 9 WC Andrology; Obstetrics & Gynecology; Urology & Nephrology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Urology & Nephrology GA BKD24 UT WOS:000267802400017 ER PT J AU Barak, D Ordentlich, A Stein, D Yu, QS Greig, NH Shafferman, A AF Barak, Dov Ordentlich, Arie Stein, Dana Yu, Qian-sheng Greig, Nigel H. Shafferman, Avigdor TI Accommodation of physostigmine and its analogues by acetylcholinesterase is dominated by hydrophobic interactions SO BIOCHEMICAL JOURNAL LA English DT Article DE Alzheimer's disease; carbamate; hydrophobic subsite; non-covalent inhibition; oxyanion hole ID PERIPHERAL ANIONIC SITE; ACTIVE-CENTER; ALZHEIMERS-DISEASE; ANTICHOLINESTERASE ACTIVITY; CHOLINESTERASE INHIBITOR; ALLOSTERIC MODULATION; TORPEDO-CALIFORNICA; ACYL POCKET; RESIDUES; BUTYRYLCHOLINESTERASE AB The role of the functional architecture of the HuAChE (human acetylcholinesterase) in reactivity toward the carbamates pyridostigmine, rivastigmine and several analogues of physostigmine, that are Currently used or considered for use as drugs for Alzheimer's disease, was analysed using over 20 mutants of residues that constitute the interaction subsites in the active centre. Both steps of the HuAChE carbamylation reaction, formation of the Michaelis complex as well as the nucleophilic process, are sensitive to accommodation of the ligand by the enzyme. For certain carbamate/HuAChE combinations, the mode of inhibition shifted from a covalent, to a noncovalent type, according to the balance between dissociation and covalent reaction rates. Whereas the charged moieties of pyridostigmine and rivastigmine contribute significantly to the stability of the corresponding HuAChE complexes, no Such effect was observed for physostigmine and its analogues, phenserine and cymserine. Moreover, physostigmine-like ligands carrying oxygen instead of nitrogen at position -1 of the tricyclic moiety (physovenine and tetrahydrofuro-benzofuran analogues) displayed comparable structure-function characteristics toward the various HuAChE enzymes. The essential role of the HuAChE hydrophobic pocket, comprising mostly residues Trp(86) and Tyr(337) in accommodating (-)-physostigmine and in conferring similar to 300-fold stereoselectivity toward physostigmines, Was elucidated through examination of the reactivity of: selected HuAChE mutations toward enantiomeric pairs of different physostigmine analogues. The present study demonstrates that certain charged and uncharged ligands, like analogues of physostigmine and physovenine, seem to be accommodated by the enzyme mostly through hydrophobic interactions. C1 [Barak, Dov; Ordentlich, Arie; Stein, Dana; Shafferman, Avigdor] Israel Inst Biol Res, IL-74100 Ness Ziona, Israel. [Yu, Qian-sheng; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Shafferman, A (reprint author), Israel Inst Biol Res, IL-74100 Ness Ziona, Israel. EM avigdors@iibr.gov.il FU US Army Medical Research and Material Command [DAMD17-00-C-0021]; National Institute on Aging, National Institutes of Health FX This work was supported by the US Army Medical Research and Material Command [contract number DAMD17-00-C-0021 (to A.S.)] and the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 40 TC 14 Z9 18 U1 2 U2 8 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2009 VL 417 BP 213 EP 222 DI 10.1042/BJ20081276 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 391JX UT WOS:000262230700021 PM 18729824 ER PT J AU Ramirez, DC Gomez-Mejiba, SE Corbett, JT Deterding, LJ Tomer, KB Mason, RP AF Ramirez, Dario C. Gomez-Mejiba, Sandra E. Corbett, Jean T. Deterding, Leesa J. Tomer, Kenneth B. Mason, Ronald P. TI Cu,Zn-superoxide dismutase-driven free radical modifications: copper- and carbonate radical anion-initiated protein radical chemistry SO BIOCHEMICAL JOURNAL LA English DT Article DE carbonate radical anion; immuno-spin trapping; nitrone adduct; peroxymonocarbonate; protein radical; superoxide dismutase ID ZINC SUPEROXIDE-DISMUTASE; AMYOTROPHIC-LATERAL-SCLEROSIS; ENHANCED PEROXIDASE-ACTIVITY; HYDROGEN-PEROXIDE; COVALENT AGGREGATION; OXIDATION-PRODUCTS; DNA RADICALS; BICARBONATE; IDENTIFICATION; INTERMEDIACY AB The understanding of file mechanism, oxidant(s) involved and flow and what protein radicals are produced during the reaction of wild-type SOD1 (Cu,Zn-superoxide dismutase) with H(2)O(2) and their fate is incomplete, but a better understanding of the role of this reaction is needed. We have used immuno-spin trapping and MS analysis to study the protein oxidations driven by human (h) and bovine (b) SOD1 when reacting with H(2)O(2) using HSA (human serum albumin) and mBH (mouse brain homogenate) as target models. In order to gain mechanistic information about this reaction, we considered both copper- and CO(3)(center dot-) (carbonate radical anion)-initiated protein oxidation. We chose experimental conditions that clearly Separated SOD1-driven oxidation via CO(3)(center dot-) from that initiated by copper released from the SOD1 active site. In file absence of (bi)carbonate, site-specific radical-mediated fragmentation is produced by SOD1 active-site copper. In the presence of (bi)carbonate and DTPA (diethylenetriaminepenta-acetic acid (to suppress copper chemistry), CO(3)(center dot-) produced distinct radical sites in both SOD1 and HSA, which Caused protein aggregation without causing protein fragmentation. CO produced by the reaction of hSOD1 with H(2)O(2) also produced distinctive DMPO (5,5-dimethylpyrroline-N-oxide) nitrone adduct-positive protein bands in the mBH. Finally, we propose a biochemical mechanism to explain CO(3)(center dot-) production from CO, enhanced protein radical formation and protection by (bi)carbonate against H(2)O(2)-induced fragmentation of the SOD1 active site. Our present Study is important for establishing experimental conditions for studying the Molecular mechanism and targets of oxidation during the reverse reaction of SOD1 with H(2)O(2); these results are the first step in analysing the critical targets of SOD1-driven oxidation during pathological processes such as neuroinflammation. C1 [Corbett, Jean T.; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Ramirez, Dario C.; Gomez-Mejiba, Sandra E.] Oklahoma Med Res Fdn, Free Rad Biol & Aging Res Program, Oklahoma City, OK 73104 USA. [Deterding, Leesa J.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Pharmacol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov RI RAMIREZ, DARIO/K-3312-2013; Tomer, Kenneth/E-8018-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326; FU National Institute of Environmental Health Sciences of the National Institutes of Health; National Institute of Environmental Health Sciences [R00ES015415]; Presbyterian Health Foundation FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences of the National Institutes of Health. D.C.R. acknowledges support from the National Institute of Environmental Health Sciences [grant number R00ES015415] and the start-up funds from the Presbyterian Health Foundation. NR 45 TC 24 Z9 24 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2009 VL 417 BP 341 EP 353 DI 10.1042/BJ20070722 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 391JX UT WOS:000262230700034 PM 18764780 ER PT J AU Li, Y Limmon, GV Imani, F Teng, C AF Li, Yin Limmon, Gino V. Imani, Farhad Teng, Christina TI Induction of lactoferrin gene expression by innate immune stimuli in mouse mammary epithelial HC-11 cells SO BIOCHIMIE LA English DT Article DE Lactoferrin; LPS; dsRNA; HC-11 cells; PKC; MAPK; NF-kappa B; Inhibitors ID DOUBLE-STRANDED-RNA; NF-KAPPA-B; TOLL-LIKE RECEPTORS; EPIDERMAL-GROWTH-FACTOR; BOVINE LACTOFERRIN; MESSENGER-RNA; RESPONSE-ELEMENT; HOST-DEFENSE; 3 FINGERS; ESTROGEN AB Lactoferrin (LF) is a multifunctional protein. While its functions and mechanism of actions are actively being investigated, the cellular signals that regulate LF expression have not been as explored. We have previously demonstrated that LF is upregulated by estrogen in the reproductive system. In this study, we show that the expression of LF was stimulated by bacterial lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) in normal mouse mammalian HC-11 cells. When cells were exposed to either LPS or dsRNA, the mRNA and protein of LF were increased in a dose- and time-dependent manner, yet the kinetics of LF induction by dsRNA or LPS were different. The LPS and dsRNA-induced LF was mainly released into the culture medium where it blocked TNF-alpha production in exposed cells. We explored the mechanisms of LF induction by LPS and dsRNA using specific inhibitors and found that the induction could be attenuated by inhibitors to PKC, NF-kappa B, p38 and JNK, but not by an inhibitor to PKA. Interestingly, ERK inhibitor was effective against dsRNA but not against LPS induction of LF. These data suggest that LF was induced by LPS and dsRNA through PKC, NF-kappa B and MAPK pathways which in turn play an inhibitory role in the continuation of innate inflammation. Published by Elsevier Masson SAS. C1 [Li, Yin; Teng, Christina] NIEHS, Gene Regulat Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. [Limmon, Gino V.; Imani, Farhad] NIEHS, Immunol Grp, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, C (reprint author), NIEHS, Gene Regulat Sect, LRDT, NIH, 111 TW Alexander Dr,POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) FX We thank Dr David Kerr (Department of Animal Science, University of Vermont Medical School) for providing the mouse mammary epithelial HC-11 cells. We acknowledge the critical reading of this manuscript by Dr M. Fessler and S. Garantziotis. This research was supported by the intramural research program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). The paper was edited by Dr Peggy Kaminski. NR 54 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JAN PY 2009 VL 91 IS 1 BP 58 EP 67 DI 10.1016/j.biochi.2008.04.014 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 402NA UT WOS:000263019200009 PM 18534195 ER PT J AU Ogawa, M Kosaka, N Choyke, PL Kobayashi, H AF Ogawa, Mikako Kosaka, Nobuyuki Choyke, Peter L. Kobayashi, Hisataka TI Tumor-Specific Detection of an Optically Targeted Antibody Combined with a Quencher-Conjugated Neutravidin "Quencher-Chaser": A Dual "Quench and Chase" Strategy to Improve Target to Nontarget Ratios for Molecular Imaging of Cancer SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; AVIDIN CHASE; MONOCLONAL-ANTIBODY; CONTRAST AGENTS; BLOOD CLEARANCE; STREPTAVIDIN; ACCUMULATION; BIOTIN; IGG; PHARMACOKINETICS AB In vivo molecular cancer imaging with monoclonal antibodies has great potential not only for cancer detection, but also for cancer characterization. However, the prolonged retention of intravenously injected antibody in the blood causes low target tumor-to-background ratio (TBR). Avidin has been used as a "chase" to clear the unbound, circulating biotinylated antibody and decrease the background signal. Here, we utilize a combined approach of a fluorescence resonance energy transfer (FRET) quenched antibody with an "avidin chase" to increase TBR. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type 2 (HER2), was biotinylated and conjugated with the near-infrared (NIR) fluorophore Alexa680 to synthesize Tra-Alexa680-biotin. Next, the FRET quencher, QSY-21, was conjugated to avidin, neutravidin (nAv), or streptavidin (sAv), thus creating Av-QSY21, nAv-QSY21, or sAv-QSY21 as "chasers". The fluorescence was quenched in vitro by binding Tra-Alexa680-biotin to Av-QSY21, nAv-QSY21, or sAv-QSY21. To evaluate if the injection of quencher-conjugated avidin derivatives can improve target TBR by using a dual "quench and chase" strategy, both target (3T3/HER2+) and nontarget (Balb3T3/ZsGreen) tumor-bearing mice were employed. The "FRET quench" effect induced by all the QSY21 avidin-based conjugates reduced but did not totally eliminate background signal from the blood pool. The addition of nAv-QSY21 administration increased target TBR mainly because of the "chase" effect where unbound conjugated antibody was preferentially cleared to the liver. The relatively slow clearance of unbound nAv-QSY21 leads to further reductions in background signal by leaking out of the vascular space and binding to unbound antibodies in the extravascular space of tumors, resulting in decreased nontarget tumor-to-background ratios but increased target TBR due to the "FRET quench" effect, because target-bound antibodies were internalized and could not bind to nAv-QSY21. In conclusion, the proposed "quench-and-chase" system combines two strategies, fluorescent quenching and avidin chasing, to improve target TBR and reduce nontarget TBR, which should result in both improved tumor sensitivity and improved specificity. C1 [Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room IB40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 20 TC 21 Z9 21 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2009 VL 20 IS 1 BP 147 EP 154 DI 10.1021/bc8003765 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 397JT UT WOS:000262659700019 PM 19072537 ER PT J AU Kreitman, RJ AF Kreitman, Robert J. TI Recombinant Immunotoxins Containing Truncated Bacterial Toxins for the Treatment of Hematologic Malignancies SO BIODRUGS LA English DT Review ID HAIRY-CELL LEUKEMIA; PHASE-I TRIAL; CHRONIC LYMPHOCYTIC-LEUKEMIA; PSEUDOMONAS EXOTOXIN-A; COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; TOXIN-INTERLEUKIN-3 FUSION PROTEIN; SINGLE-CHAIN IMMUNOTOXIN; NICOTINAMIDE ADENINE-DINUCLEOTIDE; RIBOSOME-INACTIVATING PROTEINS AB Immunotoxins are molecules that contain a protein toxin and a ligand that is either an antibody or a growth factor. The ligand binds to a target cell antigen, and the target cell internalizes the immunotoxin, allowing the toxin to migrate to the cytoplasm where it can kill the cell. In the case of recombinant immunotoxins, the ligand and toxin are encoded in DNA that is then expressed in bacteria, and the purified immunotoxin contains the ligand and toxin fused together. Among the most active recombinant immunotoxins clinically tested are those that are targeted to hematologic malignancies. One agent, containing human interleukin-2 and truncated diphtheria toxin (denileukin diftitox), has been approved for use in cutaneous T-cell lymphoma, and has shown activity in other hematologic malignancies, including leukemias and lymphomas. Diphtheria toxin has also been targeted by other ligands, including granulocyte-macrophage colony-stimulating factor and interleukin-3, to target myelogenous leukemia cells. Single-chain anti-bodies containing variable heavy and light antibody domains have been fused to truncated Pseudomonas exotoxin to target lymphomas and lymphocytic leukemias. Recombinant immunotoxins anti-Tac(Fv)-PE38 (LMB-2), targeting CD25, and RFB4(dsFv)-PE38 (BL22, CAT-3888), targeting CD22, have each been tested in patients. Major responses have been observed after failure of standard chemotherapy. The most successful application of recombinant immunotoxins today is in hairy cell leukemia, where BL22 has induced complete remissions in most patients who were previously treated with optimal chemotherapy. C1 NCI, Clin Immumotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immumotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU MedImmune, LLC [CAT-3888, CAT-8015]; National Cancer Institute FX Robert Kreitman is a co-inventor on the National Institutes of Health patent for BL22. Clinical development of BL22 (CAT-3888) and HA22 (CAT-8015) is in part supported by MedImmune, LLC. This work was supported by the intramural program of the National Cancer Institute. NR 157 TC 69 Z9 75 U1 2 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2009 VL 23 IS 1 BP 1 EP 13 PG 13 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 436WA UT WOS:000265445600001 PM 19344187 ER PT J AU Irimia, M Rukov, JL Roy, SW Vinther, J Garcia-Fernandez, J AF Irimia, Manuel Rukov, Jakob L. Roy, Scott W. Vinther, Jeppe Garcia-Fernandez, Jordi TI Quantitative regulation of alternative splicing in evolution and development SO BIOESSAYS LA English DT Review DE alternative splicing; evo-devo; post-transcriptional regulation; transcriptome diversity ID MESSENGER-RNA DECAY; GENOME-WIDE DETECTION; CAENORHABDITIS-ELEGANS; SELECTION PRESSURE; GENE-EXPRESSION; ANOPHELES-GAMBIAE; MOUSE; CONSERVATION; EXONS; EVENTS AB Alternative splicing (AS) is a widespread mechanism with an important role in increasing transcriptome and proteome diversity by generating multiple different products from the same gene. Evolutionary studies of AS have focused primarily on the conservation of alternatively spliced sequences or of the AS pattern of those sequences itself. Less is known about the evolution of the regulation of AS, but several studies, working from different perspectives, have recently made significant progress. Here, we categorize the different levels of AS evolution, and summarize the studies on evolution of AS regulation, which point to a high level of evolutionary conservation of the regulation of AS events conserved between related species. This suggests that the quantitative regulation of AS is an intrinsic part of AS function. We discuss the potential role of changes in developmental regulation of AS as an additional layer in complex gene regulatory networks and in the emergence of genetic novelties. C1 [Irimia, Manuel; Garcia-Fernandez, Jordi] Univ Barcelona, Dept Genet, Barcelona, Spain. [Irimia, Manuel; Garcia-Fernandez, Jordi] Univ Barcelona, Inst Biomed, Barcelona, Spain. [Rukov, Jakob L.; Vinther, Jeppe] Univ Copenhagen, Dept Biol, Mol Evolut Grp, Copenhagen N, Denmark. [Roy, Scott W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Irimia, M (reprint author), Univ Barcelona, Dept Genet, Barcelona, Spain. EM mirimia@gmail.com; jordigarcia@ub.edu RI Irimia, Manuel/E-3040-2010; Vinther, Jeppe/A-8172-2012; Garcia-Fernandez, Jordi/B-3839-2013; OI Vinther, Jeppe/0000-0002-3847-3853; Garcia-Fernandez, Jordi/0000-0001-5677-5970; Irimia, Manuel/0000-0002-2179-2567 FU Spanish Ministerio of Educacion y Ciencia through FPI [BFU2005-00252/BFU2008-03776]; Carlsberg Foundation [21-00-0680]; National Library of Medicine at National Institutes of Health/DHHS FX We thank Juan Pascual-Anaya, Signe Olivarius, and Nacho Maeso for critical reading of the manuscript. M. I. and J. L. R. wish to thank Prof. Peter Arctander for a wealth of inspiring discussions. S. W. R. would like to thank Eugene Koonin for intellectual support and for fostering an environment of open intellectual exploration in his group. M. I. and J. G. F are funded by the Spanish Ministerio of Educacion y Ciencia, through the FPI grants (BFU2005-00252/BFU2008-03776), J. L. R. and J. V are supported by a Carlsberg Foundation Grant (21-00-0680), and S. W. R. by the Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS. NR 98 TC 28 Z9 31 U1 1 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2009 VL 31 IS 1 BP 40 EP 50 DI 10.1002/bies.080092 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 406OK UT WOS:000263304600007 PM 19154001 ER PT J AU Tarca, AL Draghici, S Khatri, P Hassan, SS Mittal, P Kim, JS Kim, CJ Kusanovic, JP Romero, R AF Tarca, Adi Laurentiu Draghici, Sorin Khatri, Purvesh Hassan, Sonia S. Mittal, Pooja Kim, Jung-sun Kim, Chong Jai Kusanovic, Juan Pedro Romero, Roberto TI A novel signaling pathway impact analysis SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; COLORECTAL-CANCER; SYSTEMS BIOLOGY; MICROARRAY DATA; DENSITY; LABOR; TERM; MYOMETRIUM; PREGNANCY; CERVIX AB Motivation: Gene expression class comparison studies may identify hundreds or thousands of genes as differentially expressed ( DE) between sample groups. Gaining biological insight from the result of such experiments can be approached, for instance, by identifying the signaling pathways impacted by the observed changes. Most of the existing pathway analysis methods focus on either the number of DE genes observed in a given pathway (enrichment analysis methods), or on the correlation between the pathway genes and the class of the samples (functional class scoring methods). Both approaches treat the pathways as simple sets of genes, disregarding the complex gene interactions that these pathways are built to describe. Results: We describe a novel signaling pathway impact analysis (SPIA) that combines the evidence obtained from the classical enrichment analysis with a novel type of evidence, which measures the actual perturbation on a given pathway under a given condition. A bootstrap procedure is used to assess the significance of the observed total pathway perturbation. Using simulations we show that the evidence derived from perturbations is independent of the pathway enrichment evidence. This allows us to calculate a global pathway significance P-value, which combines the enrichment and perturbation P-values. We illustrate the capabilities of the novel method on four real datasets. The results obtained on these data show that SPIA has better specificity and more sensitivity than several widely used pathway analysis methods. C1 [Tarca, Adi Laurentiu; Draghici, Sorin; Khatri, Purvesh] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Tarca, Adi Laurentiu; Hassan, Sonia S.; Mittal, Pooja; Kim, Jung-sun; Kim, Chong Jai; Kusanovic, Juan Pedro; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, 431 State Hall, Detroit, MI 48202 USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU The Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH/DHHS [NSF DBI 0234806, CCF 0438970, 1R01HG003491, 1U01CA117478, 1R21CA100740, 1R01 NS045207, 5R21EB000990, 2P30 CA022453] FX The Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS (in part); NSF DBI 0234806, CCF 0438970, 1R01HG003491, 1U01CA117478, 1R21CA100740, 1R01 NS045207, 5R21EB000990, 2P30 CA022453 (to S. D.). NR 27 TC 296 Z9 300 U1 4 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2009 VL 25 IS 1 BP 75 EP 82 DI 10.1093/bioinformatics/btn577 PG 8 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 388BX UT WOS:000261996400012 PM 18990722 ER PT S AU Marino-Ramirez, L Tharakaraman, K Spouge, JL Landsman, D AF Marino-Ramirez, Leonardo Tharakaraman, Kannan Spouge, John L. Landsman, David BE Posada, D TI Promoter Analysis: Gene Regulatory Motif Identification with A-GLAM SO BIOINFORMATICS FOR DNA SEQUENCE ANALYSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Promoter regions; transcription factor binding sites; enumerative methods; promoter comparison ID FACTOR-BINDING SITES; HUMAN GENOME; DNA MOTIFS; SEQUENCES; ELEMENTS; DISCOVERY; ALIGNMENTS; ALGORITHM; LOCATION; PATTERNS AB Reliable detection of cis-regulatory elements in promoter regions is a difficult and unsolved problem in computational biology. The intricacy of transcriptional regulation in higher eukaryotes, primarily in metazoans, could be a major driving force of organismal complexity. Eukaryotic genome annotations have improved greatly due to large-scale characterization of full-length cDNAs, transcriptional start sites (TSSs), and comparative genomics. Regulatory elements arc identified in promoter regions using a variety of enumerative or alignment-based methods. Here we present a survey of recent computational methods for eukaryotic promoter analysis and describe the use of an alignment-based method implemented in the A-GLAM program. C1 [Marino-Ramirez, Leonardo; Tharakaraman, Kannan; Spouge, John L.; Landsman, David] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Marino-Ramirez, L (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. RI Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 45 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-910-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 537 BP 263 EP 276 DI 10.1007/978-1-59745-251-9_13 D2 10.1007/978-1-59745-251-9 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKJ93 UT WOS:000268335500013 PM 19378149 ER PT B AU Chervitz, SA Parkinson, H Fostel, JM Causton, HC Sanson, SA Deutsch, EW Field, D Taylor, CF Rocca-Serra, P White, J Stoeckert, CJ AF Chervitz, Stephen A. Parkinson, Helen Fostel, Jennifer M. Causton, Helen C. Sanson, Susanna-Assunta Deutsch, Eric W. Field, Dawn Taylor, Chris F. Rocca-Serra, Philippe White, Joe Stoeckert, Christian J. BE Edwards, D Stajich, J Hansen, D TI Standards for Functional Genomics SO BIOINFORMATICS: TOOLS AND APPLICATIONS LA English DT Article; Book Chapter ID MINIMUM REPORTING STANDARDS; MICROARRAY DATA; GENE-EXPRESSION; PLANT METABOLOMICS; MASS-SPECTROMETRY; WORKING GROUP; DATA EXCHANGE; DATA FORMAT; MAGE-TAB; INFORMATION C1 [Chervitz, Stephen A.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Parkinson, Helen; Sanson, Susanna-Assunta; Taylor, Chris F.; Rocca-Serra, Philippe] European Bioinformat Inst, Cambridge, England. [Fostel, Jennifer M.] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC 27709 USA. [Causton, Helen C.] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. [Deutsch, Eric W.] Inst Syst Biol, Seattle, WA 98105 USA. [Field, Dawn] Ctr Ecol & Hydrol, Nat Environm Res Council, Oxford OX1 3SR, England. [White, Joe] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Joe] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Stoeckert, Christian J.] Univ Penn, Sch Med, Dept Genet, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA. RP Chervitz, SA (reprint author), Affymetrix Inc, Santa Clara, CA 95051 USA. EM Steve_Chervitz@affymetrix.com; parkinson@ebi.ac.uk; fostel@niehs.nih.gov; helen.causton@csc.mrc.ac.uk; sansone@ebi.ac.uk; edeutsch@systemsbiology.org; dfield@cch.ac.uk; christ@ebi.ac.uk; rocca@ebi.ac.uk; jwhite@jimmy.harvard.edu; stoeckrt@pcbi.upenn.edu OI Taylor, Ronald/0000-0001-9777-9767 NR 73 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92737-4 PY 2009 BP 293 EP 329 DI 10.1007/978-0-387-92738-1_15 D2 10.1007/978-0-387-92738-1 PG 37 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology GA BMH82 UT WOS:000272399500015 ER PT B AU Zweigenbaum, P Demner-Fushman, D AF Zweigenbaum, Pierre Demner-Fushman, Dina BE Edwards, D Stajich, J Hansen, D TI Advanced Literature-Mining Tools SO BIOINFORMATICS: TOOLS AND APPLICATIONS LA English DT Article; Book Chapter ID LITERATURE-BASED DISCOVERY; INFORMATION-RETRIEVAL; BIOMEDICAL TEXT; LIFE SCIENCES; NETWORK; SYSTEM; ALGORITHM; KNOWLEDGE; BIOLOGY; MEDLINE C1 [Zweigenbaum, Pierre] CNRS, LIMSI, F-91403 Orsay, France. [Demner-Fushman, Dina] US Natl Lib Med, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Zweigenbaum, P (reprint author), CNRS, LIMSI, BP 133, F-91403 Orsay, France. EM pz@limsi.fr; ddemner@mail.nih.gov NR 87 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92737-4 PY 2009 BP 347 EP 380 DI 10.1007/978-0-387-92738-1_17 D2 10.1007/978-0-387-92738-1 PG 34 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology GA BMH82 UT WOS:000272399500017 ER PT J AU Williams, CJ Jefferson, WN Padilla-Banks, E Goulding, EH Newbold, RR AF Williams, Carmen J. Jefferson, Wendy N. Padilla-Banks, Elizabeth Goulding, Eugenia H. Newbold, Retha R. TI Long-Term Impact of Neonatal Genistein Exposure on Adult Oviductal Function in the Mouse. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Williams, Carmen J.; Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Goulding, Eugenia H.; Newbold, Retha R.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 59 BP 61 EP 61 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500059 ER PT J AU Jefferson, W Kinyamu, H Archer, T Newbold, R AF Jefferson, Wendy Kinyamu, Harriet Archer, Trevot Newbold, Retha TI Developmental Exposure to Estrogens and Uterine Disease Later in Life. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Jefferson, Wendy; Kinyamu, Harriet; Archer, Trevot; Newbold, Retha] NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 70 BP 63 EP 63 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500070 ER PT J AU Schoendorf, KC AF Schoendorf, Kenneth C. TI The National Children's Study: A Life Course Investigation of Early Origins of Health and Disease. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Schoendorf, Kenneth C.] NICHD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 115 BP 73 EP 73 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500114 ER PT J AU Fan, HY Liu, ZL Shimada, M Sterneck, E Johnson, PF Richards, JS AF Fan, Heng-Yu Liu, Zhilin Shimada, Masayuki Sterneck, Esta Johnson, Peter F. Richards, JoAnne S. TI ERK1/2 in Ovarian Granulosa Cells Are Essential for Female Fertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 Baylor Coll Med, Houston, TX 77030 USA. Hiroshima Univ, Hiroshima, Japan. NCI, Frederick, MD 21701 USA. RI Johnson, Peter/A-1940-2012; Shimada, Masayuki/Q-3673-2016 OI Johnson, Peter/0000-0002-4145-4725; Shimada, Masayuki/0000-0002-6500-2088 NR 0 TC 0 Z9 0 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. PY 2009 SU S MA 153 BP 82 EP 82 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500152 ER PT J AU Hewitt, SC Li, Y Li, LP Kotach, KS AF Hewitt, Sylvia Curtis Li, Yin Li, Leping Kotach, Kenneth S. TI Estrogen Regulation of Igf1 and Uterine Growth Involves Direct Binding of Estrogen Receptors to Estrogen Responsive Elements. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Hewitt, Sylvia Curtis; Li, Yin; Li, Leping; Kotach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 163 BP 84 EP 85 PG 2 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500162 ER PT J AU Kwmtkiewicz, J Padilla-Banks, E Jefferson, WN Williams, CJ AF Kwmtkiewicz, Jakub Padilla-Banks, Elizabeth Jefferson, Wendy N. Williams, Carmen J. TI Characterization of Metastasis Associated Protein 3 (MTA3) in Mouse Oocytes and Pre-Implantation Embryos SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Kwmtkiewicz, Jakub; Padilla-Banks, Elizabeth; Jefferson, Wendy N.; Williams, Carmen J.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 223 BP 99 EP 99 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500221 ER PT J AU Odet, F Karusa, A Gabel, SA Willis, WD Eddy, M AF Odet, Fanny Karusa, Ankunda Gabel, Scott A. Willis, William D. Eddy, Mitch TI Glycolysis and Respiration in Mouse Ldhc(-/-) Sperm. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Odet, Fanny; Karusa, Ankunda; Gabel, Scott A.; Willis, William D.; Eddy, Mitch] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 460 BP 152 EP 152 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500441 ER PT J AU Nakamura, N Goulding, E Willis, W Eddy, M AF Nakamura, Noriko Goulding, Eugenia Willis, William Eddy, Mitch TI Disruption of a Mouse Enolase 1-Like Gene Causes Abnormal Sperm Morphology and Male Infertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 [Nakamura, Noriko; Goulding, Eugenia; Willis, William; Eddy, Mitch] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 463 BP 153 EP 153 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500444 ER PT J AU Trevino, LS Wang, W Urick, ME Johnson, PA AF Trevino, Lindsey S. Wang, Wei Urick, Mary Ellen Johnson, Patricia A. TI Global Gene Expression Analysis in Ovarian Cancer of the Hen. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 Cornell Univ, Ithaca, NY USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 535 BP 169 EP 170 PG 2 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500512 ER PT J AU Gray, LE Rider, CV Howdeshell, KL Hotchkiss, AK Wilson, VS Foster, PMD Furr, J AF Gray, L. Earl, Jr. Rider, Cynthia V. Howdeshell, Kembra L. Hotchkiss, Andrew K. Wilson, Vickie S. Foster, Paul M. D. Furr, Johnathan TI Cumulative Effects of Administration Mixtures of "Antiandrogens" in Rats: A New Framework Based upon Common Systems Rather Than Common Mechanisms SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 US EPA, Res Triangle Pk, NC USA. Duke Univ, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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. PY 2009 SU S MA 634 BP 193 EP 193 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500606 ER PT S AU Petralia, RS Al-Hallaq, RA Wenthold, RJ AF Petralia, Ronald S. Al-Hallaq, Rana A. Wenthold, Robert J. BE VanDongen, AM TI Trafficking and Targeting of NMDA Receptors SO BIOLOGY OF THE NMDA RECEPTOR SE Frontiers in Neuroscience-Series LA English DT Article; Book Chapter ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; PROTEIN-KINASE-C; SUBUNIT MESSENGER-RNA; CELL-ADHESION MOLECULE; SYNAPTIC SCAFFOLDING MOLECULE; POSTSYNAPTIC DENSITY PROTEINS; CEREBELLAR GRANULE NEURONS; CYCLIN-DEPENDENT KINASE-5; ER RETENTION SIGNAL C1 [Petralia, Ronald S.; Al-Hallaq, Rana A.; Wenthold, Robert J.] NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 407 TC 19 Z9 19 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-5723 BN 978-1-4200-4414-0 J9 FRONT NEUROSCI JI Front. Neurosci. PY 2009 BP 149 EP 200 PG 52 WC Neurosciences SC Neurosciences & Neurology GA BKW97 UT WOS:000269498700010 ER PT S AU Asanuma, D Kobayashi, H Nagano, T Urano, Y AF Asanuma, Daisuke Kobayashi, Hisataka Nagano, Tetsuo Urano, Yasuteru BE Rich, PB Douillet, C TI Fluorescence Imaging of Tumors with "Smart" pH-Activatable Targeted Probes SO BIOLUMINESCENCE: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Optical tumor imaging; fluorescence; molecular probes; pH; receptor-mediated endocytosis ID CANCER-CELLS; CONJUGATE; AVIDIN AB One goal of molecular imaging is to establish a widely applicable technique for specific detection Of tumors With minimal background originated from non-target tissues. In this study, a "smart" activatable strategy for specific tumor imaging is proposed in which pH-activatable targeted probes specifically detect tumors after binding to the target cell surface proteins, internalization, and eventual acidic pH activation within the acidic organelles. We successfully visualized submillimeter-sized tumors using this strategy, in two different tumor mouse models. Since the design of pH-activatable targeted probes can be applied to any target molecules on the cell surface that are to be internalized after ligand binding, this imaging strategy can afford a general and powerful method to diagnose and monitor the target tumors. C1 [Asanuma, Daisuke; Nagano, Tetsuo; Urano, Yasuteru] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. [Kobayashi, Hisataka] NCI, Mol Imaging Program, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Asanuma, D (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. NR 14 TC 11 Z9 11 U1 1 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-320-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 574 BP 47 EP 62 DI 10.1007/978-1-60327-321-3_5 D2 10.1007/978-1-60327-321-3 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY56 UT WOS:000269617700005 PM 19685299 ER PT J AU Watters, JL Satia, JA da Costa, KA Boysen, G Collins, LB Morrow, JD Milne, GL Swenberg, JA AF Watters, Joanne L. Satia, Jessie A. da Costa, Kerry-Ann Boysen, Gunnar Collins, Leonard B. Morrow, Jason D. Milne, Ginger L. Swenberg, James A. TI Comparison of three oxidative stress biomarkers in a sample of healthy adults SO BIOMARKERS LA English DT Article DE Oxidation DNA damage; lipid peroxidation; 8-hydroxy-2-deoxyguanosine; comet assay; isoprostanes ID DNA-DAMAGE; IN-VIVO; SMOKING STATUS; COMET ASSAY; HUMANS; ISOPROSTANES; CANCER; CARCINOGENESIS; POPULATION; MARKERS AB Oxidative stress is a potentially important aetiological factor for many chronic diseases, including cardio vascular disease, neurodegenerative disease and cancer, yet studies often find inconsistent results. The associations between three of the most widely used biomarkers of oxidative stress, i.e. F-2-isoprostanes for lipid peroxidation and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the comet assay with FPG for oxidative DNA damage, were compared in a sample of 135 healthy African-American and white adults. Modest associations were observed between F 2-isoprostanes and the comet assay (r=0.22, p=0.01), but there were no significant correlations between 8-oxo-dG and the comet assay (r=-0.09) or F-2-IsoP (r=-0.04). These results are informative for researchers seeking to compare results pertaining to oxidative stress across studies and/or assessment methods in healthy disease-free populations. The development and use of oxidative stress biomarkers is a promising field; however, additional validation studies are necessary to establish accuracy and comparability across oxidative stress biomarkers. C1 [Watters, Joanne L.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Watters, Joanne L.; Satia, Jessie A.; da Costa, Kerry-Ann; Swenberg, James A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Boysen, Gunnar; Collins, Leonard B.; Swenberg, James A.] Univ N Carolina, CEHS, Chapel Hill, NC USA. [Boysen, Gunnar; Swenberg, James A.] Univ N Carolina, Dept Environm Sci & Physiol, Chapel Hill, NC USA. [Morrow, Jason D.; Milne, Ginger L.] Vanderbilt Univ, Sch Med, Dept Med, Div Clin Pharmacol, Nashville, TN 37212 USA. RP Watters, JL (reprint author), NCI, NIH, DCEG, Nutr Epidemiol Branch, 6120 Execut Blvd,EPS Suite 320, Bethesda, MD 20892 USA. EM wattersj@mail.nih.gov RI Milne, Ginger/D-7648-2014; OI Milne, Ginger/0000-0003-3890-151X; Boysen, Gunnar/0000-0001-8364-9881 FU [RO3 CA108276]; [K22 CA96556]; [T32 CA72319]; [P30ES010126]; [DK56350]; [RR00046] FX This study was supported in part by the following grants: RO3 CA108276, K22 CA96556, T32 CA72319, P30ES010126, DK56350 and RR00046. The authors would also like to gratefully acknowledge Corneliu N. Craciunescu's technical assistance regarding the comet assay. NR 40 TC 11 Z9 11 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X EI 1366-5804 J9 BIOMARKERS JI Biomarkers PY 2009 VL 14 IS 8 BP 587 EP 595 DI 10.3109/13547500903183954 PG 9 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 532BD UT WOS:000272717400006 PM 20001708 ER PT S AU Taube, SE AF Taube, Sheila E. BE Lovestone, S TI Biomarkers in Oncology Trials and Tribulations SO BIOMARKERS IN BRAIN DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Biomarkers in Brain Disease CY JAN 26-28, 2009 CL Oxford, ENGLAND SP New York Acad Sci, Global Med Excellence Cluster DE oncology biomarkers; biomarker assay development; predictive markers ID POSITIVE BREAST-CANCER; GENE-EXPRESSION; TUMOR-MARKERS; RECOMMENDATIONS; CHEMOTHERAPY; RECURRENCE; TAMOXIFEN; MORTALITY; UPDATE; ASSAY AB Few apparently promising oncology biomarkers actually make their way into routine clinical use. There are many reasons for this lack of success, and the complexity of cancer biology is only one of the reasons. Challenges involved in evaluating the analytical and the clinical performance of cancer biomarkers account for the lack of successful translation to the clinic. The lack of clear definition of the clinical need often results in tests that may perform reproducibly but are not used because they do not help with important patient care decisions. The National Cancer Institute Cancer Diagnosis Program launched the Program for the Assessment of Clinical Cancer Tests in an effort to move biomarkers more efficiently and effectively into the clinic. A development pathway is proposed that defines the steps required for evaluation of a biomarker assay's analytical and clinical performance. Several pilot projects are ongoing to test the process, and these are described. C1 [Taube, Sheila E.] ST Consulting, Glen Echo, MD 20812 USA. [Taube, Sheila E.] NCI, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. [Taube, Sheila E.] NCI, Canc Diag Program, Bethesda, MD 20892 USA. RP Taube, SE (reprint author), ST Consulting, POB 260, Glen Echo, MD 20812 USA. EM taubese63@alumni.brandeis.edu RI Lovestone, Simon/E-8725-2010 NR 18 TC 4 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-772-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1180 BP 111 EP 118 DI 10.1111/j.1749-6632.2009.05019.x PG 8 WC Medicine, Research & Experimental; Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Research & Experimental Medicine; Science & Technology - Other Topics; Neurosciences & Neurology GA BOV07 UT WOS:000277729900011 PM 19906265 ER PT J AU Mejia, R AF Mejia, R. BE Mondaini, RP TI MATHEMATICAL BIOLOGY: SOME OPPORTUNITIES IN INTEGRATIVE BIOLOGY SO BIOMAT 2008 LA English DT Proceedings Paper CT International Symposium on Mathematical and Computational Biology CY NOV 22-27, 2008 CL Campos do Jordao, BRAZIL SP CAPES, Natl Res Council, PETROBRAS Oil Co, PETROBRAS - CENPES Res Ctr ID URINE CONCENTRATING MECHANISM; BIOCHEMICAL NETWORK MODELS; RENAL INNER MEDULLA; THIN LIMB SEGMENTS; COLLECTING DUCT; 3-DIMENSIONAL ARCHITECTURE; INVITRO PERFUSION; PHYSIOME PROJECT; CORE MODEL; CELL-CYCLE AB Integrative Biology is the study of an organism within a framework in an integrated, systematic manner in order to discern governing principles or mechanisms. Quantitative tools applied in the study of biological organisms include, in addition to statistical analyzes and hypothesis testing, mathematical modeling. Computational tools used include databases to organize both the data and models into a form that is linked and readily usable. I will describe mathematical models integrated into research in physiology as well as tools being developed by the Physiome Project with the support of the International Union of Physiological Sciences. The goal of the Physiome Project is the quantitative description of the integrated function of living organisms, and for the human physiome, to develop quantitative biology to improve medical science from genes to health. The "model validate" cycle used in Mathematical Biology is iterated to refine our understanding of the biology as illustrated here with experiments, databases and modeling in kidney physiology. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Mejia, R (reprint author), NHLBI, NIH, 10 Ctr Dr,Room B1D416, Bethesda, MD 20892 USA. EM ray@helix.nih.gov NR 58 TC 0 Z9 0 U1 1 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE PY 2009 BP 338 EP 350 DI 10.1142/9789814271820_0020 PG 13 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA BMO60 UT WOS:000273131300020 ER PT B AU Zhu, YY Huang, XL Wang, W Lopresti, D Long, R Antani, S Xue, ZY Thoma, G AF Zhu, Yaoyao Huang, Xiaolei Wang, Wei Lopresti, Daniel Long, Rodney Antani, Sameer Xue, Zhiyun Thoma, George BE Lin, F Olivo, M Kung, SY TI Balancing the Role of Priors in Multi-Observer Segmentation Evaluation SO BIOMEDICAL IMAGING LA English DT Review; Book Chapter DE Ground truth; Bayesian decision; Precision; Segmentation; Multi-observer; Sensitivity; Specificity; STAPLE; Validation ID IMAGE SEGMENTATION AB Comparison of a group of multiple observer segmentations is known to be a challenging problem. A good segmentation evaluation method would allow different segmentations not only to be compared, but to be combined to generate a "true" segmentation with higher consensus. Numerous multi-observer segmentation evaluation approaches have been proposed in the literature, and STAPLE in particular probabilistically estimates the true segmentation by optimal combination of observed segmentations and a prior model of the truth. An Expectation-Maximization (EM) algorithm, STAPLE's convergence to the desired local minima depends on good initializations for the truth prior and the observer-performance prior. However, accurate modeling of the initial truth prior is nontrivial. Moreover, among the two priors, the truth prior always dominates so that in certain scenarios when meaningful observer-performance priors are available, STAPLE can not take advantage of that information. In this paper, we propose a Bayesian decision formulation of the problem that permits the two types of prior knowledge to be integrated in a complementary manner in four cases with differing application purposes: (1) with known truth prior; (2) with observer prior; (3) with neither truth prior nor observer prior; and (4) with both truth prior and observer prior. The third and fourth cases are not discussed (or effectively ignored) by STAPLE, and in our research we propose a new method to combine multiple-observer segmentations based on the maximum a posterior (MAP) principle, which respects the observer prior regardless of the availability of the truth prior. Based on the four scenarios, we have developed a web-based software application that implements the flexible segmentation evaluation framework for digitized uterine cervix images. Experiment results show that our framework has flexibility in effectively integrating different priors for multi-observer segmentation evaluation and it also generates results comparing favorably to those by the STAPLE algorithm and the Majority Vote Rule. C1 [Zhu, Yaoyao; Huang, Xiaolei; Wang, Wei; Lopresti, Daniel] Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. [Long, Rodney; Antani, Sameer; Xue, Zhiyun; Thoma, George] Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Zhu, YY (reprint author), Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. EM yaz304@lehigh.edu; xih206@lehigh.edu; wew305@lehigh.edu; dal9@lehigh.edu; rlong@mail.nih.gov; santani@mail.nih.gov; xuez@mail.nih.gov; gthoma@mail.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1165-0 PY 2009 BP 423 EP 445 DI 10.1007/s11265-008-0215-5 PG 23 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLV78 UT WOS:000271190000033 ER PT S AU Henry, ER Eaton, WA AF Henry, Eric R. Eaton, William A. BE Puglisi, JD TI A SIMPLE MODEL FOR PROTEIN FOLDING SO BIOPHYSICS AND THE CHALLENGES OF EMERGING THREATS SE NATO Science for Peace and Security Series B - Physics and Biophysics LA English DT Proceedings Paper CT NATO Advanced Study Institute on Biophysics and the Challenges of Emerging Threats CY JUN 19-30, 2007 CL Erice, ITALY SP NATO ID INTRAMOLECULAR CONTACT FORMATION; TRANSITION-STATE; SPEED LIMIT; SH3 DOMAIN; 2-STATE TRANSITION; LOOP FORMATION; KINETICS; DYNAMICS; PATHWAYS; RATES AB We describe a simple Ising-like statistical mechanical model for folding proteins based on the alpha-carbon contact map of the native structure. In this model residues can adopt two microscopic states corresponding to the native and non-native conformations. In order to exactly enumerate the large number of possible configurations, structure is considered to grow as continuous sequences of native residues, with no more than two sequences in each molecule. Inter-residue contacts can only form within each sequence and between residues of the two native sequences, As structure grows there is a tradeoff between the stabilizing effect of inter-residue contacts and the entropy losses from ordering residues in their native conformation and from forming a disordered loop to connect two continuous sequences. Folding kinetics are calculated from the dynamics on the free energy profile, as in Kramers' reaction rate theory. Although non-native interactions responsible for roughness in the energy landscape are not explicitly considered in the model, they are implicitly included by determining the absolute rates for motion on the free energy profile. With the exception of alpha-helical proteins, the kinetic progress curves exhibit single exponential time courses, consistent with two state behavior, as observed experimentally. The calculated folding rates are in remarkably good agreement with the measured values for the 25 two-state proteins investigated, with a correlation coefficient of 0.8. With its coarse-grained description of both the energy and entropy, and only three independently adjustable parameters, the model may be regarded as the simplest possible analytical model of protein folding capable of predicting experimental properties of specific proteins. C1 [Henry, Eric R.; Eaton, William A.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 65 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-465X BN 978-90-481-2367-4 J9 NATO SCIENCE PEACE S PY 2009 BP 1 EP 20 DI 10.1007/978-90-481-2368-1_1 PG 20 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BKC56 UT WOS:000267755300001 ER PT J AU Zanuy, D Curco, D Nussinov, R Aleman, C AF Zanuy, David Curco, David Nussinov, Ruth Aleman, Carlos TI Influence of the Dye Presence on the Conformational Preferences of CREKA, a Tumor Homing Linear Pentapeptide SO BIOPOLYMERS LA English DT Article DE tumor-homing; molecular dynamics; conformation; fluorescein ID MOLECULAR-DYNAMICS; SOLVATION MODEL; DENSITY; ENERGY; WATER; SIMULATION; SOLVENT AB The conformational properties of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence labeled with fluorescein, a fluorescent dye attached to the Cys through a flexible linker have been examined using molecular dynamics simulations. The CREKA sequence has been identified as a tumor-homing peptide that effectively binds to clotted plasma proteins. Before conformational exploration, the molecular geometry, basicity and spectroscopic properties of this dye, which is essential for the imaging the peptide activity, have been examined using quantum mechanical calculations, with the results also allowing determination of the force-field parameters required for classical simulations. Minimum energy conformations derived from the conformational search have been classified using clustering analyses with criteria based on both the existence of interactions and backbone geometric similarity. The results have been compared with those reported for isolated CREKA (peptide without dye). We found that the fluorescein affects the energy distribution of the minimum energy conformations, with the repulsive steric interactions induced by the dye producing shifting the distribution towards higher energy values. Interestingly, although the structural characteristics of the bioactive conformation identified for CREKA are not perturbed by the dye, it is less stable when the peptide is attached to the dye than in other chemical environments previously studied (isolated peptide, peptide attached to the surface of a protein, and peptide inserted in a phage display protein). (c) 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 83-93, 2009. C1 [Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, ETS Enginyeria Ind Barcelona, Dept Enginyeria Quim, E-08028 Barcelona, Spain. [Curco, David] Univ Barcelona, Fac Quim, Dept Enginyeria Quim, E-08028 Barcelona, Spain. [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. RP Zanuy, D (reprint author), Univ Politecn Cataluna, ETS Enginyeria Ind Barcelona, Dept Enginyeria Quim, Diagonal 647, E-08028 Barcelona, Spain. EM david.zanuy@upc.edu; carlos.aleman@upc.edu RI Zanuy, David/G-3930-2014 OI Zanuy, David/0000-0001-7704-2178 FU NCI NIH HHS [N01-CO-12400] NR 28 TC 8 Z9 8 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 2 BP 83 EP 93 DI 10.1002/bip.21122 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 426ES UT WOS:000264691400002 PM 19051312 ER PT J AU Liu, YA Carroll, JR Holt, LA McMahon, J Giomarelli, B Ghirlanda, G AF Liu, Yinan Carroll, Jacob R. Holt, Lindsey A. McMahon, James Giomarelli, Barbara Ghirlanda, Giovanna TI Multivalent Interactions with gp120 Are Required for the Anti-HIV Activity of Cyanovirin SO BIOPOLYMERS LA English DT Article DE Cyanovirin; lectin; antiviral protein; HIV; multivalency ID VIRUS-INACTIVATING PROTEIN; DOMAIN-SWAPPED STRUCTURE; CARBOHYDRATE-BINDING; ANTIVIRAL ACTIVITY; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; VIRAL ENTRY; CV-N; INHIBITION; FUSION AB Cyanovirin-N (CV-N) is a cyanobacterial lectin that binds to specific oligomannoses on the surface of gp120, resulting in nanomolar antiviral activity against HIV fit its monomeric form, CV-N contains two functional carbohydrate-binding domains, A and B. When refolded at high concentration, the protein can form a domain-swapped dimer. To clarify the role of multiple-binding sites in CV-N, we previously designed a monomeric mutant, P51G-m4-CVN, in which the binding site on domain A was rendered ineffective by four mutations (m4); in addition, a hinge region mutation (P51G) hinders the formation of a domain swapped dimer. The protein bound gp120 with diminished affinity and was completely inactive against HIV Here, we present two mutants, Delta Q50-m4-CVN and S52P-m4-CVN, which fold exclusively as domain-swapped dimers while containing the four mutations that abolish domain A. The dimers contain two intact B domains, thus restoring multivalency. Delta Q50-m4-CVN and S52P-m4-CVN bind gp120 at low-nanomolar concentrations and recover in part the antiviral activity of wt CV-N. These results indicate that the number of carbohydrate binding domains, rather than their identity, is crucial to CV-N functionality. (C) 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 194-200, 2009. C1 [Liu, Yinan; Carroll, Jacob R.; Holt, Lindsey A.; Ghirlanda, Giovanna] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. [McMahon, James; Giomarelli, Barbara] NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Ghirlanda, G (reprint author), Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. EM gghirlanda@asu.edu FU ASU-Mayo; Intramural Research Program, NIH, National Cancer Institute, Center for Cancer Research FX Contract grant sponsors: ASU-Mayo; Intramural Research Program, NIH, National Cancer Institute, Center for Cancer Research NR 36 TC 14 Z9 14 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 3 BP 194 EP 200 DI 10.1002/bip.21173 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 438PX UT WOS:000265568900007 PM 19235857 ER PT J AU Liu, F Park, J Shenoy, S Soung, N McMahon, J Lee, K Burke, T AF Liu, F. Park, J. Shenoy, S. Soung, N. McMahon, J. Lee, K. Burke, T., Jr. TI APPLICATION OF OXIME-BASED POST SOLID-PHASE DIVERSIFICATION TO OPTIMIZATION OF POLO BOX DOMAIN-BINDING PEPTIDES SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc C1 [Liu, F.; Burke, T., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Park, J.; Soung, N.; Lee, K.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shenoy, S.; McMahon, J.] NCI, Mol Targets Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 338 EP 338 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100222 ER PT J AU Liu, F Stephen, A Waheed, A Freed, E Fisher, R Burke, T AF Liu, F. Stephen, A. Waheed, A. Freed, E. Fisher, R. Burke, T., Jr. TI MACROCYCLIC PEPTIDE-PEPTOID HYBRIDS DESIGNED AS PPII HELIX MIMETICS SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc C1 [Liu, F.; Burke, T., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Stephen, A.; Fisher, R.] SAIC Frederick Inc, Prot Chem Lab, Frederick, MD USA. [Waheed, A.; Freed, E.] NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 339 EP 339 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100223 ER PT J AU Kim, S Choi, W Stephen, A Weidlich, I Giubellino, A Liu, F Worthy, K Bindu, L Fivash, M Nicklaus, M Bottaro, D Fisher, R Burke, T AF Kim, S. Choi, W. Stephen, A. Weidlich, I. Giubellino, A. Liu, F. Worthy, K. Bindu, L. Fivash, M. Nicklaus, M. Bottaro, D. Fisher, R. Burke, T., Jr. TI USE OF PEPTOID-PEPTIDE HYBRIDS IN THE DEVELOPMENT OF She SH2 DOMAIN -BINDING INHIBITORS SO BIOPOLYMERS LA English DT Meeting Abstract CT 21st American Peptide Symposium CY JUN 07-12, 2009 CL Bloomington, IN SP Amer Peptide Soc C1 [Kim, S.; Choi, W.; Weidlich, I.; Liu, F.; Nicklaus, M.; Burke, T., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Stephen, A.; Worthy, K.; Bindu, L.; Fisher, R.] SAIC Frederick, Prot Chem Lab, Adv Technol Program, Frederick, MD 21702 USA. [Giubellino, A.; Bottaro, D.] NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Fivash, M.] NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014 OI Bottaro, Donald/0000-0002-5057-5334; NR 0 TC 0 Z9 0 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2009 VL 92 IS 4 BP 352 EP 352 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 455IU UT WOS:000266753100292 ER PT J AU Boudou, T Ohayon, J Picart, C Pettigrew, RI Tracqui, P AF Boudou, Thomas Ohayon, Jacques Picart, Catherine Pettigrew, Roderic I. Tracqui, Philippe TI Nonlinear elastic properties of polyacrylamide gels: Implications for quantification of cellular forces SO BIORHEOLOGY LA English DT Review DE Elastic substrate; finite layer thickness; finite element analysis; micropipette aspiration; cell traction forces AB Because of their tunable mechanical properties, polyacrylamide gels (PAG) are frequently used for studying cell adhesion and migratory responses to extracellular substrate stiffness. Since these responses are known to heavily depend on the tensional balance between cell contractility and substrate mechanical resistance, a precise knowledge of PAG's mechanical properties becomes quite crucial. Using the micropipette aspiration technique, we first exhibited the nonlinear elastic behavior of PAG and then successfully modeled it by an original strain-energy function. This function depends on the Poisson's ratio and on two material parameters, which have been explicitly related to acrylamide and bis-acrylamide concentrations. Implications of these results have been highlighted with regard to traction force microscopy experiments where cellular force quantification is derived from displacements of beads embedded in PAG. We found that considering PAG as a linear elastic medium tends to significantly underestimate traction forces for substrate displacements larger than 2 mu m. Interestingly, we also showed that in the range of cellular force amplitude and PAG stiffness currently used in cell traction force experiments, finite size effects become critical for PAG substrate thickness below 60 mu m. Thus, our improved characterization of PAG nonlinear mechanical properties through a new constitutive law could have significant impact onto biological experimentations where such extracellular substrates experience large strains. C1 [Ohayon, Jacques; Pettigrew, Roderic I.] NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD 20892 USA. [Boudou, Thomas; Ohayon, Jacques; Tracqui, Philippe] Fac Med Grenoble, Inst Ingn & Informat Sante, Lab TIMC IMAG, Equipe DynaCell,CNRS,UMR 5525, La Tronche, France. [Picart, Catherine] Univ Montpellier 2, Lab Dynam Mol Interact Membranaires, CNRS, UMR 5539, F-34095 Montpellier 5, France. RP Ohayon, J (reprint author), NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD 20892 USA. EM Ohayonj2@mail.nih.gov; Philippe.Tracqui@imag.fr RI Boudou, Thomas/A-9089-2013; PICART, Catherine/C-9132-2011; Ohayon, Jacques/M-6576-2014; OI PICART, Catherine/0000-0002-4854-6366; Boudou, Thomas/0000-0002-6821-2937 FU National Institutes of Health (NIH); European Community; Cluster I3M 2007 and Emergence 2005 Rhone-Alpes Region, France FX This research was supported in part by an appointment (J. Ohayon) to the Senior Fellow Program at the National Institutes of Health (NIH). This program is administered by Oak Ridge Institute for Science and Education through an interagency agreement between NIH and the US Department of Energy. J. Ohayon and P. Tracqui were supported by grants from the European Community (Disheart Co-operative Research Project 2004-2006), Cluster I3M 2007 and Emergence 2005 Rhone-Alpes Region, France. NR 35 TC 17 Z9 17 U1 3 U2 24 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0006-355X J9 BIORHEOLOGY JI Biorheology PY 2009 VL 46 IS 3 BP 191 EP 205 DI 10.3233/BIR-2009-0540 PG 15 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA 480JO UT WOS:000268730800003 PM 19581727 ER PT J AU Rodriguez, A Dunson, DB Taylor, J AF Rodriguez, Abel Dunson, David B. Taylor, Jack TI Bayesian hierarchically weighted finite mixture models for samples of distributions SO BIOSTATISTICS LA English DT Article ID DIRICHLET PROCESSES; UNKNOWN NUMBER; PRIORS; COMPONENTS; REGRESSION; INFERENCE; OUTCOMES; CELLS AB Finite mixtures of Gaussian distributions are known to provide an accurate approximation to any unknown density. Motivated by DNA repair studies in which data are collected for samples of cells from different individuals, we propose a class of hierarchically weighted finite mixture models. The modeling framework incorporates a collection of k Gaussian basis distributions, with the individual-specific response densities expressed as mixtures of these bases. To allow heterogeneity among individuals and predictor effects, we model the mixture weights, while treating the basis distributions as unknown but common to all distributions. This results in a flexible hierarchical model for samples of distributions. We consider analysis of variance-type structures and a parsimonious latent factor representation, which leads to simplified inferences on non-Gaussian covariance structures. Methods for posterior computation are developed, and the model is used to select genetic predictors of baseline DNA damage, susceptibility to induced damage, and rate of repair. C1 [Rodriguez, Abel] Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Taylor, Jack] Natl Inst Environm Hlth Sci, Epidemiol Branch, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Rodriguez, A (reprint author), Univ Calif Santa Cruz, Dept Appl Math & Stat, Santa Cruz, CA 95064 USA. EM abel@ams.ucsc.edu OI taylor, jack/0000-0001-5303-6398 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences FX This research was partially supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 36 TC 9 Z9 9 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2009 VL 10 IS 1 BP 155 EP 171 DI 10.1093/biostatistics/kxn024 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 383MU UT WOS:000261678500014 PM 18708650 ER PT J AU Shi, M Mostowska, A Jugessur, A Johnson, MK Mansilla, MA Christensen, K Lie, RT Wiicox, AJ Murray, JC AF Shi, Min Mostowska, Adrianna Jugessur, Astanand Johnson, Marla K. Mansilla, Maria Adela Christensen, Kaare Lie, Rolv T. Wiicox, Allen J. Murray, Jeffrey C. TI Identification of Microdeletions in Candidate Genes for Cleft Lip and/or Palate SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE cleft lip; cleft palate; microdeletion; SNP; CNV; candidate genes ID MATERNAL SMOKING; HUMAN GENOME; ORAL CLEFTS; REGION AB BACKGROUND: Genome-wide association studies are now used routinely to identify genes implicated in complex traits. The panels used for such analyses can detect single nucleotide polymorphisms and copy number variants, both of which may help to identify small deleted regions of the genome that may contribute to a particular disease. METHODS: We performed a candidate gene analysis involving 1,221 SNPs in 333 candidate genes for orofacial clefting, using 2,823 samples from 725 two- and three-generation families with a proband having cleft lip with or without cleft palate. We used SNP genotyping, DNA sequencing, high-resolution DNA microarray analysis, and long-range PCR to confirm and characterize the deletion events. RESULTS: This dataset, had a high duplicate reproducibility rate (99.98%), high Mendelian consistency rate (99.93%), and low missing data rate (0.55%), which provided a powerful opportunity for deletion detection. Apparent Mendelian inconsistencies between parents and children suggested deletion events in 15 individuals in 11 genomic regions. We confirmed deletions involving CYP1B1, FGF10, SP8, SUMO1, TBX1, TFAP2A, and UGT7A1, including both de novo and familial cases. Deletions of SUMO1, TBX1, and TFAP2A are likely to be etiologic. CONCLUSIONS: These deletions suggest the potential roles of genes or regulatory elements contained within deleted regions in the etiology of clefting. Our analysis took advantage of genotypes from a candidate-gene-based SNP survey and proved to be an efficient analytical approach to interrogate genes potentially involved in clefting. This can serve as a model to find genes playing a role in complex traits in general. Birth Defects Research (Part A) 85:42-51, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Mostowska, Adrianna; Johnson, Marla K.; Mansilla, Maria Adela; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. [Shi, Min] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC USA. [Mostowska, Adrianna] Univ Med Sci, Dept Biochem & Mol Biol, PL-60781 Poznan, Poland. [Jugessur, Astanand] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Christensen, Kaare] Univ So Denmark, Inst Publ Hlth, DK-5000 Odense C, Denmark. [Lie, Rolv T.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, Bergen, Norway. [Wiicox, Allen J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, Carver Coll Med, S Grand Ave,2182 ML, Iowa City, IA 52242 USA. EM jeff-murray@uiowa.edu RI Christensen, Kaare/C-2360-2009; Mostowska, Adrianna/J-6719-2012; OI Christensen, Kaare/0000-0002-5429-5292; Wilcox, Allen/0000-0002-3376-1311 FU NIH [DE08559, P60 DE13076, NIH P30 ES05605, N01-HG-65403]; Norwegian Research Council (NFR); Intramural Research Program of the NIH; National Institute of Environmental Health Sciences (NIEHS); Center for Inherited Disease Research (CIDR); US National Institute of Dental and Craniofacial Research (NIDCR) FX Grant sponsor: NIH; Grant numbers: DE08559, P60 DE13076, NIH P30 ES05605; Grant sponsors: Norwegian Research Council (NFR), Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS); and a donation from the Iowa Order of the Eastern Star. Genotyping services were provided by the Center for Inherited Disease Research (CIDR), funded through it federal contract from the National Institutes of Health to The Johns Hopkins University; Grant number: N01-HG-65403; Grant sponsor: The US National Institute of Dental and Craniofacial Research (NIDCR) underwrote a significant proportion of the genotyping costs by CIDR. NR 20 TC 30 Z9 31 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2009 VL 85 IS 1 BP 42 EP 51 DI 10.1002/bdra.20571 PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 400YH UT WOS:000262904800007 PM 19137569 ER PT J AU Illei, GG AF Illei, Gabor G. TI Resetting the clock SO BLOOD LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS C1 NIH, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2009 VL 113 IS 1 BP 2 EP 3 DI 10.1182/blood-2008-10-184655 PG 4 WC Hematology SC Hematology GA 390KN UT WOS:000262162800002 ER PT J AU Leitner, WW Baker, MC Berenberg, TL Lu, MC Yannie, PJ Udey, MC AF Leitner, Wolfgang W. Baker, Matthew C. Berenberg, Thomas L. Lu, Michael C. Yannie, P. Josef Udey, Mark C. TI Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen SO BLOOD LA English DT Article ID T-CELL LYMPHOMA; VIRUS-INDUCED TUMORS; IMMUNE-RESPONSE; TCR VACCINES; DENDRITIC CELLS; CANCER-THERAPY; CTL EPITOPE; PHASE-I; IMMUNIZATION; ADJUVANTS AB Nucleic acid-based vaccines are effective in infectious disease models but have yielded disappointing results in tumor models when tumor-associated self-antigens are used. Incorporation of helper epitopes from foreign antigens into tumor vaccines might enhance the immunogenicity of DNA vaccines without increasing toxicity. However, generation of fusion constructs encoding both tumor and helper antigens may be difficult, and resulting proteins have unpredictable physical and immunologic properties. Furthermore, simultaneous production of equal amounts of highly immunogenic helper and weakly immunogenic tumor antigens in situ could favor development of responses against the helper antigen rather than the antigen of interest. We assessed the ability of 2 helper antigens (beta-galactosidase or fragment C of tetanus toxin) encoded by one plasmid to augment responses to a self-antigen (lymphoma-associated T-cell receptor) encoded by a separate plasmid after codelivery into skin by gene gun. This approach allowed adjustment of the relative ratios of helper and tumor antigen plasmids to optimize helper effects. Incorporation of threshold (minimally immunogenic) amounts of helper antigen plasmid into a DNA vaccine regimen dramatically increased T cell-dependent protective immunity initiated by plasmid-encoded tumor-associated T-cell receptor antigen. This simple strategy can easily be incorporated into future vaccine trials in experimental animals and possibly in humans. ( Blood. 2009; 113: 37-45) C1 [Leitner, Wolfgang W.; Baker, Matthew C.; Berenberg, Thomas L.; Lu, Michael C.; Yannie, P. Josef; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10-12N238, Bethesda, MD 20892 USA. EM udey@helix.nih.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 54 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2009 VL 113 IS 1 BP 37 EP 45 DI 10.1182/blood-2008-01-136267 PG 9 WC Hematology SC Hematology GA 390KN UT WOS:000262162800010 PM 18832136 ER PT J AU Fenty-Stewart, N Park, JY Roth, SM Hagberg, JM Basu, S Ferrell, RE Brown, MD AF Fenty-Stewart, Nicola Park, Joon-Young Roth, Stephen M. Hagberg, James M. Basu, Samar Ferrell, Robert E. Brown, Michael D. TI Independent and combined influence of AGTR1 variants and aerobic exercise on oxidative stress in hypertensives SO BLOOD PRESSURE LA English DT Article DE AGTR1; angiotensin II; exercise; isoprostanes; oxidative stress ID II TYPE-1 RECEPTOR; ANGIOTENSIN-II; GENE POLYMORPHISM; BLOOD-PRESSURE; NITRIC-OXIDE; NADPH OXIDASE; IN-VITRO; ENDOTHELIUM; PROMOTER; WOMEN AB Angiotensin II (AngII), via the AngII type 1 receptor (AT 1 R), contributes to oxidative stress. Aerobic exercise training (AEXT) reduces the risk of cardiovascular (CV) disease, presumably by reducing the grade of oxidative stress. We investigated the independent and combined influence of the AGTR1 A1166C and -825T/A polymorphisms on oxidative stress and plasma AngII responses to AEXT in pre-and stage 1 hypertensives. Urinary 8-iso-PGF(2 alpha) significantly increased with AEXT (p = 0.002); however, there were no significant changes in superoxide dismutase activity or AngII levels. There was a significant difference in the change in AngII levels with AEXT between A1166C genotype groups (p = 0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEXT on the change in AngII (p = 0.05). Only the TT genotype group of the -825T/A polymorphism had a significant reduction in plasma AngII (p = 0.02). Risk allele analysis revealed a significant reduction in plasma AngII (p = 0.04) and a significant increase in urinary 8-iso-PGF(2 alpha) (p = 0.01) with AEXT in individuals with two risk alleles only. Our findings suggest that variation in the AGTR1 gene is associated with differential changes in plasma AngII but not oxidative stress. C1 [Fenty-Stewart, Nicola; Brown, Michael D.] Temple Univ, Dept Kinesiol, Hypertens Mol & Appl Physiol Lab, Philadelphia, PA 19122 USA. [Fenty-Stewart, Nicola; Park, Joon-Young; Roth, Stephen M.; Hagberg, James M.; Brown, Michael D.] Univ Maryland, Dept Kinesiol, Sch Publ Hlth, College Pk, MD 20742 USA. [Park, Joon-Young] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Basu, Samar] Uppsala Univ, Fac Med, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Ferrell, Robert E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Fenty-Stewart, N (reprint author), Temple Univ, Dept Kinesiol, Hypertens Mol & Appl Physiol Lab, 1800 N Broad St, Philadelphia, PA 19122 USA. EM nicola.fenty@temple.edu OI Roth, Stephen/0000-0002-7841-3695 FU NIH/NIA [KO1AG19640, AG15384, AG17474, AG00268, AG022791]; AHA [0415444U] FX We thank the participants and staff of the Gene Exercise Research Study. We also thank Nancy Petro (University of Pittsburgh) for her technical expertise. This work was supported by NIH/NIA grant #KO1AG19640 (P. I. Michael D Brown), NIH/NIA grant #AG15384, #AG17474 and #AG00268 (P. I. James M. Hagberg), NIH/NIA grant #AG022791 (P. I. Stephen M. Roth) and AHA pre-doctoral Fellowship Grant #0415444U (to Joon-Young Park). NR 35 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0803-7051 J9 BLOOD PRESSURE JI Blood Pressure PY 2009 VL 18 IS 4 BP 204 EP 212 DI 10.1080/08037050903118706 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 488ZQ UT WOS:000269389400007 PM 19593696 ER PT J AU Overby, CL Tarczy-Hornoch, P Demner-Fushman, D AF Overby, Casey Lynnette Tarczy-Hornoch, Peter Demner-Fushman, Dina TI The potential for automated question answering in the context of genomic medicine: an assessment of existing resources and properties of answers SO BMC BIOINFORMATICS LA English DT Article CT 2nd Summit on Translational Bioinformatics CY MAR 15-17, 2009 CL San Francisco, CA SP Amer Med Informat Assoc ID BIOMEDICAL TEXT AB Knowledge gained in studies of genetic disorders is reported in a growing body of biomedical literature containing reports of genetic variation in individuals that map to medical conditions and/or response to therapy. These scientific discoveries need to be translated into practical applications to optimize patient care. Translating research into practice can be facilitated by supplying clinicians with research evidence. We assessed the role of existing tools in extracting answers to translational research questions in the area of genomic medicine. We: evaluate the coverage of translational research terms in the Unified Medical Language Systems (UMLS) Metathesaurus; determine where answers are most often found in full-text articles; and determine common answer patterns. Findings suggest that we will be able to leverage the UMLS in development of natural language processing algorithms for automated extraction of answers to translational research questions from biomedical text in the area of genomic medicine. C1 [Overby, Casey Lynnette; Demner-Fushman, Dina] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, BHHS, Bethesda, MD 20892 USA. [Overby, Casey Lynnette; Tarczy-Hornoch, Peter] Univ Washington, Dept Med Educ & Biomed Informat, Seattle, WA 98195 USA. [Tarczy-Hornoch, Peter] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Tarczy-Hornoch, Peter] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. RP Demner-Fushman, D (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, BHHS, Bldg 10, Bethesda, MD 20892 USA. EM overbyc@uw.edu; pth@uw.edu; ddemner@mail.nih.gov FU NLM NIH HHS [T15 LM07442, T15 LM007442]; PHS HHS [NLM CG/25/833] NR 17 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2009 VL 10 AR S8 DI 10.1186/1471-2105-10-S9-S8 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 501HH UT WOS:000270371700009 PM 19761578 ER PT J AU Burt, DW Carre, W Fell, M Law, AS Antin, PB Maglott, DR Weber, JA Schmidt, CJ Burgess, SC McCarthy, FM AF Burt, David W. Carre, Wilfrid Fell, Mark Law, Andy S. Antin, Parker B. Maglott, Donna R. Weber, Janet A. Schmidt, Carl J. Burgess, Shane C. McCarthy, Fiona M. TI The chicken gene nomenclature committee report SO BMC GENOMICS LA English DT Article CT Avian Genomics Conference and Gene Ontology Annotation Workshop CY MAY 19-20, 2008 CL Mississippi State Univ, Starkville, MS HO Mississippi State Univ ID MAJOR HISTOCOMPATIBILITY B; DATABASE; GENOME; MHC; COMPLEX AB Comparative genomics is an essential component of the post-genomic era. The chicken genome is the first avian genome to be sequenced and it will serve as a model for other avian species. Moreover, due to its unique evolutionary niche, the chicken genome can be used to understand evolution of functional elements and gene regulation in mammalian species. However comparative biology both within avian species and within amniotes is hampered due to the difficulty of recognising functional orthologs. This problem is compounded as different databases and sequence repositories proliferate and the names they assign to functional elements proliferate along with them. Currently, genes can be published under more than one name and one name sometimes refers to unrelated genes. Standardized gene nomenclature is necessary to facilitate communication between scientists and genomic resources. Moreover, it is important that this nomenclature be based on existing nomenclature efforts where possible to truly facilitate studies between different species. We report here the formation of the Chicken Gene Nomenclature Committee (CGNC), an international and centralized effort to provide standardized nomenclature for chicken genes. The CGNC works in conjunction with public resources such as NCBI and Ensembl and in consultation with existing nomenclature committees for human and mouse. The CGNC will develop standardized nomenclature in consultation with the research community and relies on the support of the research community to ensure that the nomenclature facilitates comparative and genomic studies. C1 [Burt, David W.; Carre, Wilfrid; Fell, Mark; Law, Andy S.] Roslin Inst, Dept Genom & Genet, Roslin EH25 9PS, Midlothian, Scotland. [Burt, David W.; Carre, Wilfrid; Fell, Mark; Law, Andy S.] Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland. [Antin, Parker B.] Dept Cell Biol & Anat, Tucson, AZ 85724 USA. [Maglott, Donna R.; Weber, Janet A.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Schmidt, Carl J.] Univ Delaware, Dept Anim & Food Sci, Newark, DE 19706 USA. [Burgess, Shane C.; McCarthy, Fiona M.] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA. [Burgess, Shane C.; McCarthy, Fiona M.] Mississippi State Univ, Inst Digital Biol, Mississippi State, MS 39762 USA. [Burgess, Shane C.] Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Mississippi State, MS 39762 USA. [Burgess, Shane C.] Mississippi State Univ, MSU Life Sci & Biotechnol Inst, Mississippi State, MS 39762 USA. RP Burt, DW (reprint author), Roslin Inst, Dept Genom & Genet, Roslin EH25 9PS, Midlothian, Scotland. EM Dave.Burt@roslin.ed.ac.uk; wilfrid.carre@bbsrc.ac.uk; Mark.Fell@roslin.ed.ac.uk; Andy.Law@roslin.ed.ac.uk; pba@email.arizona.edu; maglott@ncbi.nlm.nih.gov; weber@ncbi.nlm.nih.gov; schmidtc@udel.edu; sburgess@cvm.msstate.edu; fmccarthy@cvm.msstate.edu OI Schmidt, Carl/0000-0002-8386-4781 FU Biotechnology and Biological Sciences Research Council [BBS/E/R/00000690, , BBS/B/05478, BBS/B/05478/2, BBS/B/13500, BBS/E/D/05191130, BBS/E/R/00000685]; Intramural NIH HHS; NIGMS NIH HHS [5R24 GM 079326] NR 21 TC 14 Z9 14 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR S5 DI 10.1186/1471-2164-10-S2-S5 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BW UT WOS:000268635000006 PM 19607656 ER PT J AU Lichtenberg, J Jacox, E Welch, JD Kurz, K Liang, XY Yang, MQ Drews, F Ecker, K Lee, SS Elnitski, L Welch, LR AF Lichtenberg, Jens Jacox, Edwin Welch, Joshua D. Kurz, Kyle Liang, Xiaoyu Yang, Mary Qu Drews, Frank Ecker, Klaus Lee, Stephen S. Elnitski, Laura Welch, Lonnie R. TI Word-based characterization of promoters involved in human DNA repair pathways SO BMC GENOMICS LA English DT Article ID CHAOS GAME REPRESENTATION; HUMAN GENOME; COMPOSITIONAL BIASES; REGULATORY REGIONS; RELATIVE ABUNDANCE; GENE-EXPRESSION; SEQUENCES; IDENTIFICATION; SIGNATURES; ELEMENTS AB Background: DNA repair genes provide an important contribution towards the surveillance and repair of DNA damage. These genes produce a large network of interacting proteins whose mRNA expression is likely to be regulated by similar regulatory factors. Full characterization of promoters of DNA repair genes and the similarities among them will more fully elucidate the regulatory networks that activate or inhibit their expression. To address this goal, the authors introduce a technique to find regulatory genomic signatures, which represents a specific application of the genomic signature methodology to classify DNA sequences as putative functional elements within a single organism. Results: The effectiveness of the regulatory genomic signatures is demonstrated via analysis of promoter sequences for genes in DNA repair pathways of humans. The promoters are divided into two classes, the bidirectional promoters and the unidirectional promoters, and distinct genomic signatures are calculated for each class. The genomic signatures include statistically overrepresented words, word clusters, and co-occurring words. The robustness of this method is confirmed by the ability to identify sequences that exist as motifs in TRANSFAC and JASPAR databases, and in overlap with verified binding sites in this set of promoter regions. Conclusion: The word-based signatures are shown to be effective by finding occurrences of known regulatory sites. Moreover, the signatures of the bidirectional and unidirectional promoters of human DNA repair pathways are clearly distinct, exhibiting virtually no overlap. In addition to providing an effective characterization method for related DNA sequences, the signatures elucidate putative regulatory aspects of DNA repair pathways, which are notably under-characterized. C1 [Lichtenberg, Jens; Welch, Joshua D.; Kurz, Kyle; Liang, Xiaoyu; Drews, Frank; Ecker, Klaus; Welch, Lonnie R.] Ohio Univ, Sch Elect Engn & Comp Sci, Bioinformat Lab, Athens, OH 45701 USA. [Jacox, Edwin; Yang, Mary Qu; Elnitski, Laura] NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD USA. [Lee, Stephen S.] Univ Idaho, Dept Stat, Moscow, ID 83843 USA. [Welch, Lonnie R.] Ohio Univ, Biomed Engn Program, Athens, OH 45701 USA. [Welch, Lonnie R.] Ohio Univ, Mol & Cellular Biol Program, Athens, OH 45701 USA. RP Lichtenberg, J (reprint author), Ohio Univ, Sch Elect Engn & Comp Sci, Bioinformat Lab, Athens, OH 45701 USA. EM lichtenj@ohio.edu; jacoxe@mail.nih.gov; jw156605@ohio.edu; kk372703@ohio.edu; xl187007@ohio.edu; yangma@mail.nih.gov; drews@ohio.edu; ecker@ohio.edu; stevel@uidaho.edu; elnitski@mail.nih.gov; welch@ohio.edu FU Intramural NIH HHS NR 46 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR S18 DI 10.1186/1471-2164-10-S1-S18 PG 27 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BV UT WOS:000268634900019 PM 19594877 ER PT J AU Liu, QZ Sung, AH Qiao, MY Chen, ZX Yang, JY Yang, MQ Huang, XD Deng, YP AF Liu, Qingzhong Sung, Andrew H. Qiao, Mengyu Chen, Zhongxue Yang, Jack Y. Yang, Mary Qu Huang, Xudong Deng, Youping TI Comparison of feature selection and classification for MALDI-MS data SO BMC GENOMICS LA English DT Article ID IMPROVED PEAK DETECTION; SUPPORT VECTOR MACHINE; GENE SELECTION; MASS-SPECTRA; DIMENSIONALITY REDUCTION; WAVELET TRANSFORM; CANCER; SAMPLES; ALGORITHMS AB Introduction: In the classification of Mass Spectrometry (MS) proteomics data, peak detection, feature selection, and learning classifiers are critical to classification accuracy. To better understand which methods are more accurate when classifying data, some publicly available peak detection algorithms for Matrix assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) data were recently compared; however, the issue of different feature selection methods and different classification models as they relate to classification performance has not been addressed. With the application of intelligent computing, much progress has been made in the development of feature selection methods and learning classifiers for the analysis of high-throughput biological data. The main objective of this paper is to compare the methods of feature selection and different learning classifiers when applied to MALDI-MS data and to provide a subsequent reference for the analysis of MS proteomics data. Results: We compared a well-known method of feature selection, Support Vector Machine Recursive Feature Elimination (SVMRFE), and a recently developed method, Gradient based Leave-one-out Gene Selection (GLGS) that effectively performs microarray data analysis. We also compared several learning classifiers including K-Nearest Neighbor Classifier (KNNC), Naive Bayes Classifier (NBC), Nearest Mean Scaled Classifier (NMSC), uncorrelated normal based quadratic Bayes Classifier recorded as UDC, Support Vector Machines, and a distance metric learning for Large Margin Nearest Neighbor classifier (LMNN) based on Mahanalobis distance. To compare, we conducted a comprehensive experimental study using three types of MALDI-MS data. Conclusion: Regarding feature selection, SVMRFE outperformed GLGS in classification. As for the learning classifiers, when classification models derived from the best training were compared, SVMs performed the best with respect to the expected testing accuracy. However, the distance metric learning LMNN outperformed SVMs and other classifiers on evaluating the best testing. In such cases, the optimum classification model based on LMNN is worth investigating for future study. C1 [Liu, Qingzhong; Sung, Andrew H.; Qiao, Mengyu] New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. [Liu, Qingzhong; Sung, Andrew H.] New Mexico Inst Min & Technol, Inst Complex Addit Syst Anal, Socorro, NM 87801 USA. [Chen, Zhongxue] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Houston, TX 77030 USA. [Yang, Jack Y.] Harvard Univ, Cambridge, MA 02140 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept HHS, Rockville, MD 20852 USA. [Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Ctr Adv Med Imaging, Boston, MA 02115 USA. [Huang, Xudong] Brigham & Womens Hosp, Div Nucl Med & Mol Imaging, Conjugate & Med Chem Lab, Boston, MA 02115 USA. [Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Deng, Youping] SpecPro, Vicksburg, MS 39180 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. RP Sung, AH (reprint author), New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. EM liu@cs.nmt.edu; sung@cs.nmt.edu; myuqiao@cs.nmt.edu; zhongxue.chen@uth.tmc.edu; Dr.Yang@JHU.edu; yangma@mail.NIH.GOV; xhuang3@partners.org; youping.deng@usm.edu RI Chen, Zhongxue/K-1372-2013; Qiao, Mengyu/N-4466-2016 OI Chen, Zhongxue/0000-0003-2537-7843; Qiao, Mengyu/0000-0002-7872-0089 FU Mississippi Functional Genomics Network [2P20RR016476-04] FX The authors wish to thank ICASA (Institute for Complex Additive Systems Analysis, a division of New Mexico Tech) for the support of this study. This work was also supported by the Mississippi Functional Genomics Network (DHHS/NIH/NCRR Grant# 2P20RR016476-04). Special thanks go to Ms. Kimberly Lawson of the Department of Radiology, Brigham and Women's Hospital and Harvard Medical School. NR 38 TC 10 Z9 11 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR S3 DI 10.1186/1471-2164-10-S1-S3 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BV UT WOS:000268634900004 PM 19594880 ER PT J AU Romanov, MN Tuttle, EM Houck, ML Modi, WS Chemnick, LG Korody, ML Mork, EMS Otten, CA Renner, T Jones, KC Dandekar, S Papp, JC Da, Y Green, ED Magrini, V Hickenbotham, MT Glasscock, J McGrath, S Mardis, ER Ryder, OA AF Romanov, Michael N. Tuttle, Elaina M. Houck, Marlys L. Modi, William S. Chemnick, Leona G. Korody, Marisa L. Mork, Emily M. Stremel Otten, Christie A. Renner, Tanya Jones, Kenneth C. Dandekar, Sugandha Papp, Jeanette C. Da, Yang Green, Eric D. Magrini, Vincent Hickenbotham, Matthew T. Glasscock, Jarret McGrath, Sean Mardis, Elaine R. Ryder, Oliver A. CA NISC Comparative Sequencing Progra TI The value of avian genomics to the conservation of wildlife SO BMC GENOMICS LA English DT Article CT Avian Genomics Conference and Gene Ontology Annotation Workshop CY MAY 19-20, 2008 CL Mississippi State Univ, Starkville, MS HO Mississippi State Univ ID WHITE-THROATED SPARROW; ALTERNATIVE REPRODUCTIVE STRATEGIES; ZONOTRICHIA-ALBICOLLIS GMELIN; AGGRECAN GENE; CHROMOSOMAL-POLYMORPHISM; CALIFORNIA CONDORS; OVERGO HYBRIDIZATION; PLUMAGE POLYMORPHISM; CHICKEN GENOME; PARENTAL CARE AB Background: Genomic studies in non-domestic avian models, such as the California condor and white-throated sparrow, can lead to more comprehensive conservation plans and provide clues for understanding mechanisms affecting genetic variation, adaptation and evolution. Developing genomic tools and resources including genomic libraries and a genetic map of the California condor is a prerequisite for identification of candidate loci for a heritable embryonic lethal condition. The white-throated sparrow exhibits a stable genetic polymorphism (i.e. chromosomal rearrangements) associated with variation in morphology, physiology, and behavior (e.g., aggression, social behavior, sexual behavior, parental care). In this paper we outline the utility of these species as well as report on recent advances in the study of their genomes. Results: Genotyping of the condor resource population at 17 microsatellite loci provided a better assessment of the current population's genetic variation. Specific New World vulture repeats were found in the condor genome. Using condor BAC library and clones, chicken-condor comparative maps were generated. A condor fibroblast cell line transcriptome was characterized using the 454 sequencing technology. Our karyotypic analyses of the sparrow in combination with other studies indicate that the rearrangements in both chromosomes 2(m) and 3(a) are complex and likely involve multiple inversions, interchromosomal linkage, and pleiotropy. At least a portion of the rearrangement in chromosome 2(m) existed in the common ancestor of the four North American species of Zonotrichia, but not in the one South American species, and that the 2(m) form, originally thought to be the derived condition, might actually be the ancestral one. Conclusion: Mining and characterization of candidate loci in the California condor using molecular genetic and genomic techniques as well as linkage and comparative genomic mapping will eventually enable the identification of carriers of the chondrodystrophy allele, resulting in improved genetic management of this disease. In the white-throated sparrow, genomic studies, combined with ecological data, will help elucidate the basis of genic selection in a natural population. Morphs of the sparrow provide us with a unique opportunity to study intraspecific genomic differences, which have resulted from two separate yet linked evolutionary trajectories. Such results can transform our understanding of evolutionary and conservation biology. C1 [Romanov, Michael N.; Houck, Marlys L.; Modi, William S.; Chemnick, Leona G.; Mork, Emily M. Stremel; Otten, Christie A.; Renner, Tanya; Ryder, Oliver A.] Arnold & Mabel Beckman Ctr Conservat Res, Zool Soc San Diego, San Diego Zoos Inst Conservat Res, Div Genet, Escondido, CA 92027 USA. [Tuttle, Elaina M.; Korody, Marisa L.] Indiana State Univ, Dept Biol, Terre Haute, IN 47809 USA. [Jones, Kenneth C.] Genet Identificat Serv, Chatsworth, CA 91311 USA. [Dandekar, Sugandha; Papp, Jeanette C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, UCLA Sequencing & Genotyping Core, Los Angeles, CA 90095 USA. [Da, Yang] Univ Minnesota, Dept Anim Sci, St Paul, MN 55108 USA. [Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA. [Magrini, Vincent; Hickenbotham, Matthew T.; Glasscock, Jarret; McGrath, Sean; Mardis, Elaine R.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. [Romanov, Michael N.] Childrens Hosp, Oakland Res Inst, BACPAC Resources, Oakland, CA 94609 USA. RP Romanov, MN (reprint author), Arnold & Mabel Beckman Ctr Conservat Res, Zool Soc San Diego, San Diego Zoos Inst Conservat Res, Div Genet, 15600 San Pasqual Valley Rd, Escondido, CA 92027 USA. EM MRomanov@chori.org; etuttle2@indstate.edu; MHouck@sandiegozoo.org; WModi@sandiegozoo.org; lchemnick@sandiegozoo.org; mkorody@indstate.edu; not@valid.com; not@valid.com; trenner@berkeley.edu; kcjones@genetic-id-services.com; uma@ucla.edu; jcpapp@mednet.ucla.edu; yda@umn.edu; egreen@nhgri.nih.gov; vmagrini@watson.wustl.edu; mhickenb@watson.wustl.edu; jglassco@watson.wustl.edu; smcgrath@watson.wustl.edu; emardis@watson.wustl.edu; oryder@ucsd.edu RI Romanov, Michael/O-9419-2014; Tuttle, Elaina/A-1485-2016 OI Romanov, Michael/0000-0003-3584-4644; Tuttle, Elaina/0000-0002-2465-918X FU Intramural NIH HHS NR 84 TC 45 Z9 45 U1 2 U2 47 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR S10 DI 10.1186/1471-2164-10-S2-S10 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BW UT WOS:000268635000011 PM 19607652 ER PT J AU Wang, LJ Yang, MQ Yang, JY AF Wang, Liangjiang Yang, Mary Qu Yang, Jack Y. TI Prediction of DNA-binding residues from protein sequence information using random forests SO BMC GENOMICS LA English DT Article ID STRUCTURAL INFORMATION; SITES AB Background: Protein-DNA interactions are involved in many biological processes essential for cellular function. To understand the molecular mechanism of protein-DNA recognition, it is necessary to identify the DNA-binding residues in DNA-binding proteins. However, structural data are available for only a few hundreds of protein-DNA complexes. With the rapid accumulation of sequence data, it becomes an important but challenging task to accurately predict DNA-binding residues directly from amino acid sequence data. Results: A new machine learning approach has been developed in this study for predicting DNA-binding residues from amino acid sequence data. The approach used both the labelled data instances collected from the available structures of protein-DNA complexes and the abundant unlabeled data found in protein sequence databases. The evolutionary information contained in the unlabeled sequence data was represented as position-specific scoring matrices (PSSMs) and several new descriptors. The sequence-derived features were then used to train random forests (RFs), which could handle a large number of input variables and avoid model overfitting. The use of evolutionary information was found to significantly improve classifier performance. The RF classifier was further evaluated using a separate test dataset, and the predicted DNA-binding residues were examined in the context of three-dimensional structures. Conclusion: The results suggest that the RF-based approach gives rise to more accurate prediction of DNA-binding residues than previous studies. A new web server called BindN-RF http://bioinfo.ggc.org/bindn-rf/ has thus been developed to make the RF classifier accessible to the biological research community. C1 [Wang, Liangjiang] Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. [Wang, Liangjiang] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept HHS, Bethesda, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wang, LJ (reprint author), Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. EM liangjw@clemson.edu; yangma@mail.nih.gov; Dr.Yang@JHU.edu NR 17 TC 43 Z9 46 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR S1 DI 10.1186/1471-2164-10-S1-S1 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BV UT WOS:000268634900002 PM 19594868 ER PT J AU Yang, MQ Athey, BD Arabnia, HR Sung, AH Liu, QZ Yang, JY Mao, JH Deng, YP AF Yang, Mary Qu Athey, Brian D. Arabnia, Hamid R. Sung, Andrew H. Liu, Qingzhong Yang, Jack Y. Mao, Jinghe Deng, Youping TI High-throughput next-generation sequencing technologies foster new cutting-edge computing techniques in bioinformatics SO BMC GENOMICS LA English DT Article AB The advent of high-throughput next generation sequencing technologies have fostered enormous potential applications of supercomputing techniques in genome sequencing, epi-genetics, metagenomics, personalized medicine, discovery of non-coding RNAs and protein-binding sites. To this end, the 2008 International Conference on Bioinformatics and Computational Biology (Biocomp) - 2008 World Congress on Computer Science, Computer Engineering and Applied Computing (Worldcomp) was designed to promote synergistic inter/multidisciplinary research and education in response to the current research trends and advances. The conference attracted more than two thousand scientists, medical doctors, engineers, professors and students gathered at Las Vegas, Nevada, USA during July 14-17 and received great success. Supported by International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design (IJCBDD), International Journal of Functional Informatics and Personalized Medicine (IJFIPM) and the leading research laboratories from Harvard, M. I. T., Purdue, UIUC, UCLA, Georgia Tech, UT Austin, U. of Minnesota, U. of Iowa etc, the conference received thousands of research papers. Each submitted paper was reviewed by at least three reviewers and accepted papers were required to satisfy reviewers' comments. Finally, the review board and the committee decided to select only 19 high-quality research papers for inclusion in this supplement to BMC Genomics based on the peer reviews only. The conference committee was very grateful for the Plenary Keynote Lectures given by: Dr. Brian D. Athey (University of Michigan Medical School), Dr. Vladimir N. Uversky (Indiana University School of Medicine), Dr. David A. Patterson (Member of United States National Academy of Sciences and National Academy of Engineering, University of California at Berkeley) and Anousheh Ansari (Prodea Systems, Space Ambassador). The theme of the conference to promote synergistic research and education has been achieved successfully. C1 [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Athey, Brian D.] Univ Michigan, NCIBI, Ann Arbor, MI 48109 USA. [Athey, Brian D.] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Sung, Andrew H.; Liu, Qingzhong] New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. [Yang, Jack Y.] Harvard Univ, Cambridge, MA 02140 USA. [Mao, Jinghe] Tougaloo Coll, Dept Biol, Tougaloo, MS 39174 USA. RP Deng, YP (reprint author), Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. EM yangma@mail.NIH.gov; bleu@umich.edu; hra@cs.uga.edu; sung@cs.nmt.edu; sung@cs.nmt.edu; Dr.Yang@JHU.edu; jmao@tougaloo.edu; Youping.deng@usm.edu OI Athey, Brian/0000-0002-9793-535X NR 19 TC 3 Z9 4 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2009 VL 10 AR I1 DI 10.1186/1471-2164-10-S1-I1 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 479BV UT WOS:000268634900001 PM 19594867 ER PT J AU Stojadinovic, A Peoples, GE Libutti, SK Henry, LR Eberhardt, J Howard, RS Gur, D Elster, EA Nissan, A AF Stojadinovic, Alexander Peoples, George E. Libutti, Steven K. Henry, Leonard R. Eberhardt, John Howard, Robin S. Gur, David Elster, Eric A. Nissan, Aviram TI Development of a clinical decision model for thyroid nodules SO BMC SURGERY LA English DT Article ID FINE-NEEDLE-ASPIRATION; CORONARY-ARTERY SURGERY; CANCER; RISK; MORTALITY; SURVIVAL AB Background: Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10-18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20-30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70-80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery. Methods: Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules. Results: Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82-0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%-91%) and 79% (95%CI: 72%-86%), respectively. Conclusion: An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials. C1 [Stojadinovic, Alexander] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. [Peoples, George E.] Brooke Army Med Ctr, Dept Surg, Ft Sam Houston, TX 78234 USA. [Stojadinovic, Alexander; Peoples, George E.; Henry, Leonard R.; Nissan, Aviram] US Mil Canc Inst, Washington, DC USA. [Libutti, Steven K.] NCI, Angiogenesis Sect, Surg Branch, Bethesda, MD 20892 USA. [Henry, Leonard R.; Elster, Eric A.] Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA. [Eberhardt, John] DecisionQ, BioInformat Div, Washington, DC USA. [Howard, Robin S.] Walter Reed Army Med Ctr, Dept Clin Invest, Div Biostat, Washington, DC 20307 USA. [Gur, David] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. [Gur, David] Magee Womens Hosp, Pittsburgh, PA USA. [Nissan, Aviram] Hadassah Hebrew Univ, Med Ctr, Dept Surg, Jerusalem, Israel. RP Stojadinovic, A (reprint author), Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. EM alexander.stojadinovic@amedd.army.mil; georgepeoples@hotmail.com; slibutti@nih.gov; leonard.henry@med.navy.mil; john.eberhardt@decisionq.com; robin.howard@amedd.army.mil; gurd@upmc.edu; eric.elster@med.navy.mil; anissan@hadassah.org.il FU Department of Surgery and Department of Clinical Investigation, Walter Reed Army Medical Center FX This study was support by the Department of Surgery and Department of Clinical Investigation, Walter Reed Army Medical Center. NR 38 TC 24 Z9 26 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2482 J9 BMC SURG JI BMC Surg. PY 2009 VL 9 AR 12 DI 10.1186/1471-2482-9-12 PG 11 WC Surgery SC Surgery GA V19YD UT WOS:000208106800012 PM 19664278 ER PT J AU Wilson, SM Brambati, SM Henry, RG Handwerker, DA Agosta, F Miller, BL Wilkins, DP Ogar, JM Gorno-Tempini, ML AF Wilson, Stephen M. Brambati, Simona M. Henry, Roland G. Handwerker, Daniel A. Agosta, Federica Miller, Bruce L. Wilkins, David P. Ogar, Jennifer M. Gorno-Tempini, Maria Luisa TI The neural basis of surface dyslexia in semantic dementia SO BRAIN LA English DT Article ID VISUAL WORD RECOGNITION; TEMPORAL-LOBE ATROPHY; PRIMARY-PROGRESSIVE-APHASIA; VOXEL-BASED MORPHOMETRY; FORM AREA; ALZHEIMERS-DISEASE; FLUENT APHASIA; SPIRAL-IN/OUT; READING ALOUD; DUAL-ROUTE AB Semantic dementia (SD) is a neurodegenerative disease characterized by atrophy of anterior temporal regions and progressive loss of semantic memory. SD patients often present with surface dyslexia, a relatively selective impairment in reading low-frequency words with exceptional or atypical spelling-to-sound correspondences. Exception words are typically over-regularized in SD and pronounced as they are spelled (e.g. sew is pronounced as sue). This suggests that in the absence of sufficient item-specific knowledge, exception words are read by relying mainly on subword processes for regular mapping of orthography to phonology. In this study, we investigated the functional anatomy of surface dyslexia in SD using functional magnetic resonance imaging (fMRI) and studied its relationship to structural damage with voxel-based morphometry (VBM). Five SD patients and nine healthy age-matched controls were scanned while they read regular words, exception words and pseudowords in an event-related design. Vocal responses were recorded and revealed that all patients were impaired in reading low-frequency exception words, and made frequent over-regularization errors. Consistent with prior studies, fMRI data revealed that both groups activated a similar basic network of bilateral occipital, motor and premotor regions for reading single words. VBM showed that these regions were not significantly atrophied in SD. In control subjects, a region in the left intraparietal sulcus was activated for reading pseudowords and low-frequency regular words but not exception words, suggesting a role for this area in subword mapping from orthographic to phonological representations. In SD patients only, this inferior parietal region, which was not atrophied, was also activated by reading low-frequency exception words, especially on trials where over-regularization errors occurred. These results suggest that the left intraparietal sulcus is involved in subword reading processes that are differentially recruited in SD when word-specific information is lost. This loss is likely related to degeneration of the anterior temporal lobe, which was severely atrophied in SD. Consistent with this, left mid-fusiform and superior temporal regions that showed reading-related activations in controls were not activated in SD. Taken together, these results suggest that the left inferior parietal region subserves subword orthographic-to-phonological processes that are recruited for exception word reading when retrieval of exceptional, item-specific word forms is impaired by degeneration of the anterior temporal lobe. C1 [Wilson, Stephen M.; Brambati, Simona M.; Agosta, Federica; Miller, Bruce L.; Ogar, Jennifer M.; Gorno-Tempini, Maria Luisa] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Brambati, Simona M.] Inst Univ Geriatrie Montreal, Ctr Rech, Montreal, PQ, Canada. [Henry, Roland G.; Handwerker, Daniel A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Handwerker, Daniel A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Natl Inst Mental Hlth, Bethesda, MD 20892 USA. [Wilkins, David P.; Ogar, Jennifer M.] Vet Adm No Calif Hlth Care Serv, Ctr Aphasia & Related Disorders, Martinez, CA USA. RP Gorno-Tempini, ML (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, 350 Parnassus Ave,Suite 905, San Francisco, CA 94143 USA. EM marilu@memory.ucsf.edu RI Gorno-Tempini, Maria Luisa/E-7203-2012; Agosta, Federica/J-9908-2016 OI Agosta, Federica/0000-0003-3121-4979 FU National Institutes of Health [NINDS R01 NS050915, NIA P50 AG03006, NIA P01 AG019724, DHS 04-35516]; Alzheimer's Disease Research Center of California [03-75271 DHS/ADP/ARCC]; Larry L. Hillblom Foundation; John Douglas French Alzheimer's Foundation; Koret Family Foundation; McBean Family Foundation FX National Institutes of Health (NINDS R01 NS050915, NIA P50 AG03006, NIA P01 AG019724); State of California (DHS 04-35516); Alzheimer's Disease Research Center of California ( 03-75271 DHS/ADP/ARCC); Larry L. Hillblom Foundation; John Douglas French Alzheimer's Foundation; Koret Family Foundation; McBean Family Foundation. NR 72 TC 60 Z9 62 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JAN PY 2009 VL 132 BP 71 EP 86 DI 10.1093/brain/awn300 PN 1 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 398FN UT WOS:000262718100010 PM 19022856 ER PT J AU Wortmann, SB Rodenburg, RJT Jonckheere, A de Vries, MC Huizing, M Heldt, K van den Heuvel, LP Wendel, U Kluijtmans, LA Engelke, UF Wevers, RA Smeitink, JAM Morava, E AF Wortmann, Saskia B. Rodenburg, Richard J. T. Jonckheere, An de Vries, Maaike C. Huizing, Marjan Heldt, Katrin van den Heuvel, Lambert P. Wendel, Udo Kluijtmans, Leo A. Engelke, Udo F. Wevers, Ron A. Smeitink, Jan A. M. Morava, Eva TI Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy SO BRAIN LA English DT Article ID MITOCHONDRIAL-DNA DEPLETION; POLYMERASE-GAMMA POLG1; BARTH-SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; OXIDATIVE-PHOSPHORYLATION; CONGENITAL CATARACT; PEARSON SYNDROME; LACTIC-ACIDOSIS; DEFICIENCIES; MUTATIONS AB The heterogeneous group of 3-methylglutaconic aciduria type IV consists of patients with various organ involvement and mostly progressive neurological impairment in combination with 3-methylglutaconic aciduria and biochemical features of dysfunctional oxidative phosphorylation. Here we describe the clinical and biochemical phenotype in 18 children and define 4 clinical subgroups (encephalomyopathic, hepatocerebral, cardiomyopathic, myopathic). In the encephalomyopathic group with neurodegenerative symptoms and respiratory chain complex I deficiency, two of the children, presenting with mild Methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness, harboured SUCLA2 mutations. In children with a hepatocerebral phenotype most patients presented with complex I deficiency and mtDNA-depletion, three of which carried POLG1-mutations. In the cardiomyopathic subgroup most patients had complex V deficiency and an overlapping phenotype with that previously described in isolated complex V deficiency, in three patients a TMEM70 mutation was confirmed. In one male with a pure myopathic form and severe combined respiratory chain disorder, based on the pathogenomic histology of central core disease, RYR1 mutations were detected. In our patient group the presence of the biochemical marker 3-methylglutaconic acid was indicative for nuclear coded respiratory chain disorders. By delineating patient-groups we elucidated the genetic defect in 10 out of 18 children. Depending on the clinical and biochemical phenotype we suggest POLG1, SUCLA2, TMEM70 and RYR1 sequence analysis and mtDNA-depletion studies in children with 3-methylglutaconic aciduria type IV. C1 [Wortmann, Saskia B.; Rodenburg, Richard J. T.; de Vries, Maaike C.; Smeitink, Jan A. M.; Morava, Eva] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Paediat, NL-6500 HB Nijmegen, Netherlands. [Jonckheere, An; van den Heuvel, Lambert P.; Kluijtmans, Leo A.; Engelke, Udo F.; Wevers, Ron A.] Radboud Univ Nijmegen, Med Ctr, Lab Paediat & Neurol, NL-6500 HB Nijmegen, Netherlands. [Huizing, Marjan] NHGRI, NIH, Bethesda, MD 20892 USA. [Heldt, Katrin; Wendel, Udo] Univ Childrens Hosp, Dept Gen Paediat, Dusseldorf, Germany. RP Morava, E (reprint author), Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Paediat, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM e.morava@cukz.umcn.nl RI Rodenburg, Richard/N-3579-2014; Wortmann, Saskia/E-6125-2010; Smeitink, Jan/D-6064-2011; Smeitink, Jan/C-1351-2013; Wevers, Ron/H-8116-2014; Heuvel, L.P.W.J./H-8044-2014; Engelke, U.F.H./L-4293-2015; Morava, E./L-4529-2015; Vries, M.C./L-4735-2015 OI Rodenburg, Richard/0000-0001-5227-3527; Wevers, Ron/0000-0003-2278-9746; NR 38 TC 47 Z9 48 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2009 VL 132 BP 136 EP 146 DI 10.1093/brain/awn296 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 398FN UT WOS:000262718100015 PM 19015156 ER PT J AU Wills, S Cabanlit, M Bennett, J Ashwood, P Amaral, DG Van de Water, J AF Wills, Sharifia Cabanlit, Maricel Bennett, Jeff Ashwood, Paul Amaral, David G. Van de Water, Judy TI Detection of autoantibodies to neural cells of the cerebellum in the plasma of subjects with autism spectrum disorders SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Autism spectrum disorders (ASD); Brain; Immune; Autoantibody; Cerebellum; Golgi cell; Immunohistochemistry ID ANTIBRAIN ANTIBODIES; INFANTILE-AUTISM; CHILDREN; BRAIN; SCHIZOPHRENIA; MAINTENANCE; SUBCLASSES; PROTEINS; BEHAVIOR; IMMUNITY AB Autism spectrum disorders (ASD) are a group of heterogeneous, behaviorally defined disorders characterized by disturbances in social interaction and communication, often with repetitive and stereotyped behavior. Previous studies have described the presence of antibodies to various neural proteins in autistic individuals as well as post-mortem evidence of neuropathology in the cerebellum. We examined plasma from children with ASD, as well as age-matched typically developing controls, for antibodies directed against human cerebellar protein extracts using Western blot analysis. In addition, the presence of cerebellar specific antibodies was assessed by immunohistochemical staining of sections from Macaca fascicularis monkey cerebellum. Western blot analysis revealed that 13/63 (21%) of subjects with ASD possessed antibodies that demonstrated specific reactivity to a cerebellar protein with an apparent molecular weight of approximately 52 kDa compared with only 1/63 (2%) of the typically developing controls (p = 0.0010). Intense immunoreactivity, to what was determined morphologically to be the Golgi cell of the cerebellum, was noted for 7/34 (21%) of subjects with ASD, compared with 0/23 of the typically developing controls. Furthermore, there was a strong association between the presence of antibodies reactive to the 52 kDa protein by Western blot with positive immunohistochemical staining of cerebellar Golgi cells in the ASD group (r = 0.76; p = 0.001) but not controls. These studies suggest that when compared with age-matched typically developing controls, children with ASID exhibit a differential antibody response to specific cells located in the cerebellum and this response may be associated with a protein of approximately 52 kDa. (c) 2008 Elsevier Inc. All rights reserved. C1 [Wills, Sharifia; Cabanlit, Maricel; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Bennett, Jeff; Amaral, David G.] Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Neurosci, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Bennett, Jeff; Ashwood, Paul; Amaral, David G.; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Wills, Sharifia; Cabanlit, Maricel; Ashwood, Paul; Van de Water, Judy] Univ Calif Davis, NIEHS, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU NIEHS [1 P01 ES11269-01]; US Environmental Protection Agency (US EPA) [R829388]; UC Davis MIND Institute FX The authors thank the families for-their continued support of this work. This work was supported by NIEHS 1 P01 ES11269-01, the US Environmental Protection Agency (US EPA) through the Science to Achieve Results (STAR) program (Grant R829388), and the UC Davis MIND Institute. NR 55 TC 80 Z9 82 U1 4 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2009 VL 23 IS 1 BP 64 EP 74 DI 10.1016/j.bbi.2008.07.007 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 384YK UT WOS:000261779900010 PM 18706993 ER PT J AU Reilly, KM AF Reilly, Karlyne M. TI Brain Tumor Susceptibility: the Role of Genetic Factors and Uses of Mouse Models to Unravel Risk SO BRAIN PATHOLOGY LA English DT Article DE astrocytoma; genetic risk factors; glioblastoma multiforme; mouse models; neurofibromatosis; peripheral nerve sheath tumors ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LI-FRAUMENI-SYNDROME; NERVE SHEATH TUMORS; NEUROFIBROMATOSIS TYPE-1; COLLABORATIVE CROSS; SYSTEMS GENETICS; FAMILIAL GLIOMA; HUMAN GENOME; GLIOBLASTOMA-MULTIFORME; INTESTINAL NEOPLASIA AB Brain tumors are relatively rare but deadly cancers, and present challenges in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain, with surgery, radiation and chemotherapy options carrying potentially lasting morbidity for patients and incomplete cure of the tumor. The development of methods to prevent or detect brain tumors at an early stage is extremely important to reduce damage to the brain from the tumor and the therapy. Developing effective prevention or early detection methods requires a deep understanding of the risk factors for brain tumors. This review explores the difficulties in assessing risk factors in rare diseases such as brain tumors, and discusses how mouse models of cancer can aid in a better understanding of genetic risk factors for brain tumors. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, W 7th St Ft Detrick,POB B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC010539-05] NR 85 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2009 VL 19 IS 1 BP 121 EP 131 DI 10.1111/j.1750-3639.2008.00236.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 379KN UT WOS:000261395200013 PM 19076777 ER PT B AU Mack, DL Smith, GH Booth, BW AF Mack, David L. Smith, Gilbert H. Booth, Brian W. BE Giordano, A Normanno, N TI Mammary Glands, Stem Cells, and Breast Cancer SO BREAST CANCER IN THE POST-GENOMIC ERA SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE Breast cancer; Mammary gland; Stem cells; Progenitors; Tumorigenesis ID TEMPLATE DNA STRANDS; ADULT BONE-MARROW; EPITHELIAL-CELLS; SELF-RENEWAL; TRANSGENIC MICE; IN-VIVO; PROGESTERONE-RECEPTOR; MYOGENIC PROGENITORS; MUSCLE REGENERATION; FATE DETERMINATION AB The mammary gland is unique in that most of its development Occurs after birth with dramatic changes in proliferation and differentiation taking place during puberty and pregnancy. Different subsets of mammary-specific stem/progenitor cells have been shown to drive the individual stages of mammary gland development, and their regulation requires coordination between localized signals and systemic hormones. That sophisticated integration and control is achieved through the function of the stern cell niche. The goal of this chapter is to review why somatic stem cells are thought to exist in the mouse mammary gland, how they are being isolated and assayed, how their fate is influenced by the surrounding microenvironment, and how aberrant regulation of this process might contribute to breast cancer. If the components of the niche could be defined, each might then be targeted as a method to modify the fate of stem or progenitor cells during normal organ regeneration or repaired after tumorigenesis has been initiated. C1 [Mack, David L.; Smith, Gilbert H.; Booth, Brian W.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mack, DL (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 85 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-944-4 J9 CURR CLIN ONCOL PY 2009 BP 19 EP 38 DI 10.1007/978-1-60327-945-1_2 D2 10.1007/978-1-60327-945-1 PG 20 WC Oncology; Pathology SC Oncology; Pathology GA BKY32 UT WOS:000269609900002 ER PT B AU Strizzi, L Watanabe, K Mancino, M Salomon, DS Bianco, C AF Strizzi, Luigi Watanabe, Kazuhide Mancino, Mario Salomon, David S. Bianco, Caterina BE Giordano, A Normanno, N TI Role of the EGF-CFC Family in Mammary Gland Development and Neoplasia SO BREAST CANCER IN THE POST-GENOMIC ERA SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE Cripto-1, TGF beta signaling; Human breast cancer; Serological markers for cancer; Epithelial to mesenchymal transition; Transgenic mouse models ID EPITHELIAL-MESENCHYMAL TRANSITION; NODAL SIGNALING PATHWAY; HUMAN BREAST CARCINOMAS; EARLY MOUSE DEVELOPMENT; GROWTH-FACTOR FAMILY; ONE-EYED-PINHEAD; LEFT-RIGHT AXIS; HUMAN CRIPTO-1; VERTEBRATE DEVELOPMENT; BETA-CATENIN AB Members of the Epidermal Growth Factor-Cripto-1/FRL-1/Cryptic (EGF-CFC) family, such as human Cripto-1, are important mediators of crucial events that take place during embryonic pattern formation. New evidences from gene expression and transgenic mouse studies have also shown that perturbation of Cripto-1 signaling may lead to cell transformation and tumor formation in vivo. In addition, Cripto-1 is expressed at high levels in a wide variety of human carcinomas including early and late breast cancers. Despite the clear correlation between Cripto-1 overexpression and human and mouse tumors, the exact molecular mechanism of Cripto-1 contribution to the cell transformation process is not clear. Cripto-1 has been shown to activate multiple signaling pathways to promote either differentiation during embryogenesis or cancer growth. In this review we will discuss the multifunction properties of the EGF-CFC family of proteins and the complex network of signaling molecules activated by Cripto-1 focusing in particular on the mammary gland. A better understanding of the intracellular signaling pathways that mediate Cripto-1 activity in human tumors might identify novel points of intervention to target Cripto-1 in human malignancies. C1 [Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Childrens Mem Res Ctr, Chicago, IL 60614 USA. [Watanabe, Kazuhide; Mancino, Mario; Salomon, David S.; Bianco, Caterina] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Strizzi, L (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Childrens Mem Res Ctr, 2300 Childrens Plaza,Box 222, Chicago, IL 60614 USA. NR 113 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-944-4 J9 CURR CLIN ONCOL PY 2009 BP 87 EP 102 DI 10.1007/978-1-60327-945-1_6 D2 10.1007/978-1-60327-945-1 PG 16 WC Oncology; Pathology SC Oncology; Pathology GA BKY32 UT WOS:000269609900006 ER PT J AU Dimitrakakis, C Bondy, C AF Dimitrakakis, Constantine Bondy, Carolyn TI Androgens and the breast SO BREAST CANCER RESEARCH LA English DT Review ID STEROID-HORMONE CONCENTRATIONS; RANDOMIZED CONTROLLED-TRIAL; CAG REPEAT POLYMORPHISM; POSTMENOPAUSAL WOMEN; CANCER RISK; PREMENOPAUSAL WOMEN; PROSTATE-CANCER; MAMMOGRAPHIC DENSITY; RECEPTOR EXPRESSION; MAMMARY-GLAND AB Androgens have important physiological effects in women while at the same time they may be implicated in breast cancer pathologies. However, data on the effects of androgens on mammary epithelial proliferation and/or breast cancer incidence are not in full agreement. We performed a literature review evaluating current clinical, genetic and epidemiological data regarding the role of androgens in mammary growth and neoplasia. Epidemiological studies appear to have significant methodological limitations and thus provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is still in its infancy. Clinical and nonhuman primate studies suggest that androgens inhibit mammary epithelial proliferation and breast growth while conventional estrogen treatment suppresses endogenous androgens. Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens using conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Addition of testosterone to the usual hormone therapy regimen may diminish the estrogen/progestin increase in breast cancer risk but the impact of this combined use on mammary gland homeostasis still needs evaluation. C1 [Dimitrakakis, Constantine; Bondy, Carolyn] NICHHD, Dev Endocrinol Branch, NIH, CRC, Bethesda, MD 20892 USA. [Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece. RP Dimitrakakis, C (reprint author), NICHHD, Dev Endocrinol Branch, NIH, CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM dimitrac@mail.nih.gov NR 54 TC 56 Z9 56 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 5 AR 212 DI 10.1186/bcr2413 PG 9 WC Oncology SC Oncology GA 540OD UT WOS:000273342300008 PM 19889198 ER PT J AU Heckman-Stoddard, BM Vargo-Gogola, T McHenry, PR Jiang, V Herrick, MP Hilsenbeck, SG Settleman, J Rosen, JM AF Heckman-Stoddard, Brandy M. Vargo-Gogola, Tracy McHenry, Peter R. Jiang, Vivian Herrick, Matthew P. Hilsenbeck, Susan G. Settleman, Jeffrey Rosen, Jeffrey M. TI Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression SO BREAST CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; GTPASE-ACTIVATING PROTEIN; TRANSGENIC MICE; DUCTAL MORPHOGENESIS; ANGIOGENIC SWITCH; MAMMARY-GLAND; GROWTH-FACTOR; CELL; EXPRESSION; OVEREXPRESSION AB Introduction Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis. Methods To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis. Results P190B deficiency reduced tumor penetrance (53% of p190B(+/-)Neu mice vs. 100% of p190B(+/+)Neu mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in p190B(+/-)Neu mammary glands. Transplantation of p190B(+/-)Neu tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, p190B(+/+)Neu tumor fragments were unable to grow when transplanted into p190B(+/-)Neu recipients. Conclusions These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression. C1 [Heckman-Stoddard, Brandy M.; Jiang, Vivian; Herrick, Matthew P.; Rosen, Jeffrey M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Heckman-Stoddard, Brandy M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD 20852 USA. [Vargo-Gogola, Tracy; McHenry, Peter R.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, South Bend, IN 46617 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Hilsenbeck, Susan G.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM jrosen@bcm.edu FU DOD [W81XWH-06-1-0704]; [CA030195-22]; [K99CA127361] FX These studies were supported through grant CA030195-22. TV-G is funded by K99CA127361. BMH-S was funded by DOD predoctoral fellowship W81XWH-06-1-0704 and is currently a NCI Cancer Prevention Fellow. The authors thank Shirley Small for her help with animal husbandry and colony management, and Maria Gonzalez-Rimbau for technical support. NR 37 TC 11 Z9 11 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 4 AR R61 DI 10.1186/bcr2352 PG 12 WC Oncology SC Oncology GA 514RT UT WOS:000271414000024 PM 19703301 ER PT J AU Hsieh, SM Look, MP Sieuwerts, AM Foekens, JA Hunter, KW AF Hsieh, Szu-Min Look, Maxime P. Sieuwerts, Anieta M. Foekens, John A. Hunter, Kent W. TI Distinct inherited metastasis susceptibility exists for different breast cancer subtypes: a prognosis study SO BREAST CANCER RESEARCH LA English DT Article ID SURVIVAL; PROGRESSION; POLYMORPHISMS; CONCORDANCE; POPULATION; ORIGINS; TUMORS; TRIAL; SIPA1 AB Introduction Previous studies in mouse models and pilot epidemiology studies have demonstrated that inherited polymorphisms are associated with inherited risk of tumor progression and poor outcome in human breast cancer. To extend these studies and gain better understanding of the function of inherited polymorphism in breast cancer progression, a validation prognosis study was performed in a large independent breast cancer patient population. Methods The study population consisted of 1863 Dutch patients with operable primary breast cancer from Rotterdam, The Netherlands. Genomic DNA was genotyped for the missense Pro436Leu RRP1B single nucleotide polymorphism (SNP) rs9306160 and the intronic SIPA1 SNP rs2448490 by SNP-specific PCR. Results A significant association of variants in RRP1B with metastasis-free survival was observed (P = 0.012), validating the role of RRP1B with inherited metastatic susceptibility. Stratification of patients revealed that association with patients' survival was found to be specifically restricted to estrogen receptor positive, lymph node-negative (ER+/LN-) patients (P = 0.011). The specific association with metastasis-free survival only in ER+/LN- patients was replicated for SIPA1, a second metastasis susceptibility gene known to physically interact with RRP1B (P = 0.006). Combining the genotypes of these two genes resulted in the significant ability to discriminate patients with poor metastasis-free survival (HR: 0.40, 95% CI: 0.24 to 0.68, P = 0.001). Conclusions These results validate SIPA1 and RRP1B as metastasis susceptibility genes and suggest that genotyping assays may be a useful supplement to other clinical and molecular indicators of prognosis. The results also suggest that lymphatic and hematogeneous metastases are genetically distinct that may involve different mechanisms. If true, these results suggest that metastatic disease, like primary breast cancer, may be multiple diseases and that stratification of late stage patients may therefore be required to fully understand breast cancer progression and metastasis. C1 [Hsieh, Szu-Min; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Look, Maxime P.; Sieuwerts, Anieta M.; Foekens, John A.] Erasmus MC, Dept Med Oncol, Josephine Nefkens Inst, NL-3015 GE Rotterdam, Netherlands. [Look, Maxime P.; Sieuwerts, Anieta M.; Foekens, John A.] Canc Genom Ctr, NL-3015 GE Rotterdam, Netherlands. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, Room 5046,37 Convent Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) FX We thank Drs Nigel Crawford and Stefan Ambs for critical comments on this manuscript. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research to KWH and in part by The Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) to JAF. NR 32 TC 33 Z9 34 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 5 AR R75 DI 10.1186/bcr2412 PG 9 WC Oncology SC Oncology GA 540OD UT WOS:000273342300020 PM 19825179 ER PT J AU Meyer, MJ Fleming, JM Ali, MA Pesesky, MW Ginsburg, E Vonderhaar, BK AF Meyer, Matthew J. Fleming, Jodie M. Ali, Mustapha A. Pesesky, Mitchell W. Ginsburg, Erika Vonderhaar, Barbara K. TI Dynamic regulation of CD24 and the invasive, CD44(pos)CD24(neg) phenotype in breast cancer cell lines SO BREAST CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; PROGNOSTIC-SIGNIFICANCE; INITIATING CELLS; MAMMARY-GLAND; TUMOR-CELLS; IN-VIVO; EXPRESSION; GROWTH; CD44 AB Introduction The invasive, mesenchymal phenotype of CD44(pos)CD24(neg) breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44(neg/low)CD24(pos) breast cancer cells lack the ability to give rise to their invasive CD44(pos)CD24(neg) counterpart. Here we demonstrate that noninvasive, epithelial-like CD44(pos)CD24(pos) cells readily give rise to invasive, mesenchymal CD44(pos)CD24(neg) progeny in vivo and in vitro. This interconversion was found to be dependent upon Activin/Nodal signaling. Methods Breast cancer cell lines were sorted into CD44(pos)CD24(pos) and CD44(pos)CD24(neg) populations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts. Results CD24 expression was dynamically regulated in vitro in all evaluated breast cancer cell lines. Furthermore, a single noninvasive, epithelial-like CD44(pos)CD24(pos) cell had the ability to give rise to invasive, mesenchymal CD44(pos)CD24(neg) progeny. Importantly, this interconversion occurred in vivo as CD44(pos)CD24(pos) cells gave rise to xenografts with locally invasive borders as seen in xenografts initiated with CD44(pos)CD24(neg) cells. Lastly, the ability of CD44(pos)CD24(pos) cells to give rise to mesenchymal progeny, and vice versa, was blocked upon ablation of Activin/Nodal signaling. Conclusions Our data demonstrate that the invasive, mesenchymal CD44(pos)CD24(neg) phenotype is under dynamic control in breast cancer cell lines both in vitro and in vivo. Furthermore, our observations suggest that therapies targeting CD44(pos)CD24(neg) tumor cells may have limited success in preventing primary tumor metastasis unless Activin/Nodal signaling is arrested. C1 [Meyer, Matthew J.; Fleming, Jodie M.; Ali, Mustapha A.; Pesesky, Mitchell W.; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Meyer, MJ (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 1106, Bethesda, MD 20892 USA. EM meyerm@mail.nih.gov; bv10w@nih.gov FU Center for Cancer Research; National Cancer Institute; Breast Cancer Research FX The authors thank Barbara Taylor and Subhadra Banerjee of the CCR Flow Cytometry Core for their expert advice and patience. We would also like to acknowledge Max Bush for his assistance with the xenograft experiments. This research was supported by the Center for Cancer Research, an Intramural Research Program of the National Cancer Institute, and by Breast Cancer Research Stamp proceeds awarded through competitive peer review. NR 55 TC 70 Z9 72 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2009 VL 11 IS 6 AR R82 DI 10.1186/bcr2449 PG 14 WC Oncology SC Oncology GA 556DG UT WOS:000274568000010 PM 19906290 ER PT J AU Anderson, WF Luo, S Chatterjee, N Rosenberg, PS Matsuno, RK Goodman, MT Hernandez, BY Reichman, M Dolled-Filhart, MP O'Regan, RM Garcia-Closas, M Perou, CM Jatoi, I Cartun, RW Sherman, ME AF Anderson, W. F. Luo, S. Chatterjee, N. Rosenberg, P. S. Matsuno, R. K. Goodman, M. T. Hernandez, B. Y. Reichman, M. Dolled-Filhart, M. P. O'Regan, R. M. Garcia-Closas, M. Perou, C. M. Jatoi, I. Cartun, R. W. Sherman, M. E. TI Human epidermal growth factor receptor-2 and estrogen receptor expression, a demonstration project using the residual tissue respository of the Surveillance, Epidemiology, and End Results (SEER) program SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Immunohistochemical stains; Tissue microarrays; Human epidermal growth factor receptor-2 (HER2); Estrogen receptor (ER); Breast cancer incidence and survival; SEER ID HER2-POSITIVE BREAST-CANCER; STEROID-RECEPTORS; ADJUVANT CHEMOTHERAPY; HER-2/NEU; AMPLIFICATION; TRASTUZUMAB; ONCOGENE; PATTERNS; SURVIVAL; HER2/NEU AB Background In 2001, the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program established Residual Tissue Repositories (RTR) in the Hawaii, Iowa, and Los Angeles Tumor Registries to collect discarded tissue blocks from pathologic laboratories within their catchment areas. To validate the utility of the RTR for supplementing SEER's central database, we assessed human epidermal growth factor receptor-2 (HER2) and estrogen receptor expression (ER) in a demonstration project. Materials Using a prepared set of tissue microarrays (TMAs) residing in the Hawaii Tumor Registry (HTR), we performed standard immunohistochemistry. Breast cancers in the TMA were diagnosed in 1995, followed through 2006, and linked to SEER's main database. Results The TMA included 354 cases, representing 51% of 687 breast cancers in the HTR (1995). The HTR and TMA cases were similar with respect to patient demographics and tumor characteristics. Seventy-six percent (76%, 268 of 354) of TMA cases were HER2+ and/or ER+, i.e., 28 HER2+ER-, 12 HER2+ER+, and 228 HER2-ER+. There were 67 HER2-ER- cases and 19 were unclassified. Age distributions at diagnosis were bimodal with dominant early-onset modes for HER2+ER- tumors and dominant late-onset modes for HER2-ER+ breast cancers. Epidemiologic patterns for concordant HER2+ER+ (double-positive) and HER2-ER- (double-negative) were intermediate to discordant HER2+ER- and HER2-ER+. Conclusion Results showed contrasting incidence patterns for HER2+ (HER2+ER-) and ER+ (HER2-ER+) breast cancers, diagnosed in 1995. Though sample sizes were small, this demonstration project validates the potential utility of the RTR for supplementing the SEER program. C1 [Anderson, W. F.; Luo, S.; Chatterjee, N.; Rosenberg, P. S.; Matsuno, R. K.; Garcia-Closas, M.; Sherman, M. E.] NIH NCI DCEG, Bethesda, MD 20852 USA. [Goodman, M. T.; Hernandez, B. Y.] Univ Hawaii, Honolulu, HI 96822 USA. [Reichman, M.] NIH NCI DCCPS, Bethesda, MD USA. [Dolled-Filhart, M. P.] HistoRx, Branford, CT USA. [O'Regan, R. M.] Emory Univ, Atlanta, GA 30322 USA. [Perou, C. M.] Univ N Carolina, Chapel Hill, NC USA. [Jatoi, I.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Jatoi, I.] Natl Naval Med Ctr, Bethesda, MD USA. [Cartun, R. W.] Hartford Hosp, Hartford, CT 06115 USA. RP Anderson, WF (reprint author), NIH NCI DCEG, EPS Room 8036,6120 Executive Blvd, Bethesda, MD 20852 USA. EM wanderso@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NIH/National Cancer Institute; DHHS/NIH [N01-PC-67001] FX This research was supported in part by the Intramural Research Program of the NIH/National Cancer Institute, and the Public Health Service contract N01-PC-67001 from DHHS/NIH. NR 30 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2009 VL 113 IS 1 BP 189 EP 196 DI 10.1007/s10549-008-9918-3 PG 8 WC Oncology SC Oncology GA 387KM UT WOS:000261951100022 PM 18256926 ER PT J AU Rahman, M Davis, SR Pumphrey, JG Bao, J Nau, MM Meltzer, PS Lipkowitz, S AF Rahman, Monzur Davis, Sean R. Pumphrey, Janet G. Bao, Jing Nau, Marion M. Meltzer, Paul S. Lipkowitz, Stanley TI TRAIL induces apoptosis in triple-negative breast cancer cells with a mesenchymal phenotype SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE TRAIL; Apoptosis; Basal breast cancer; Triple-negative breast cancer ID RECEPTOR-SELECTIVE MUTANTS; EXPRESSION PATTERNS; LIGAND; GROWTH; LINES; GENE; CARCINOMA; AMPLIFICATION; INHIBITOR; KINASES AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in some but not all breast cancer cell lines. Breast cancers can be divided into those which express the estrogen (ER) and progesterone (PR) receptors, those with HER-2 amplification, and those without expression of ER, PR, or HER-2 amplification (referred to as basal or triple-negative breast cancer). We tested a panel of 20 breast cancer cell lines representing the different types of breast cancer to evaluate if the molecular phenotype of the breast cancer cells determined their response to TRAIL. The most striking finding was that eight of eleven triple-negative cell lines are sensitive to TRAIL-mediated apoptosis. The eight TRAIL-sensitive triple-negative cell lines have a mesenchymal phenotype while the three TRAIL-resistant triple-negative cell lines have an epithelial phenotype. Two of five cell lines with HER-2 amplification were sensitive to TRAIL and none of the five ER positive cell lines were sensitive. RNAi-mediated knockdown of TRAIL receptor expression demonstrated that TRAIL Receptor 2 (TRAIL-R2) mediates the effects of TRAIL, even when both TRAIL-R1 and TRAIL-R2 are expressed. Finally, inhibition of EGFR, expressed in both TRAIL-sensitive and TRAIL-resistant triple-negative breast cancer cell lines, using a small molecule tyrosine kinase inhibitor (AG1478), enhanced TRAIL-induced apoptosis in TRAIL-sensitive cell lines but did not convert resistant cells into TRAIL-sensitive cells. Together, these findings suggest that a subset of triple-negative breast cancer, those with mesenchymal features, may be the most likely to benefit from TRAIL targeted therapy. These findings could form the basis to select breast cancer patients for clinical trials of TRAIL-R2 ligands. C1 [Rahman, Monzur; Pumphrey, Janet G.; Bao, Jing; Nau, Marion M.; Lipkowitz, Stanley] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Davis, Sean R.; Meltzer, Paul S.] NCI, Dept Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lipkowitz, S (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Blg 37,Room 2066,37 Convent Dr, Bethesda, MD 20892 USA. EM lipkowis@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX We thank Steven Shaw for helpful discussion about moesin and for providing the anti-moesin antibody. We thank Jeffrey Rubin for his careful review of this manuscript and thoughtful comments. Funding This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 36 TC 79 Z9 80 U1 0 U2 10 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 JAN PY 2009 VL 113 IS 2 BP 217 EP 230 DI 10.1007/s10549-008-9924-5 PG 14 WC Oncology SC Oncology GA 391KV UT WOS:000262233100004 PM 18266105 ER PT J AU Swain, SM Land, SR Ritter, MW Costantino, JP Cecchini, RS Mamounas, EP Wolmark, N Ganz, PA AF Swain, Sandra M. Land, Stephanie R. Ritter, Marcie W. Costantino, Joseph P. Cecchini, Reena S. Mamounas, Eleftherios P. Wolmark, Norman Ganz, Patricia A. TI Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE Amenorrhea; Breast cancer; Docetaxel ID QUALITY-OF-LIFE; POSITIVE BREAST-CANCER; SURGICAL ADJUVANT BREAST; RANDOMIZED-TRIALS; PREVENTION TRIAL; CHEMOTHERAPY; TAMOXIFEN; THERAPY AB The NSABP B-30 trial addresses whether amenorrhea after adjuvant chemotherapy increases survival. Preliminary to the trial outcome analysis, we examined the incidence of amenorrhea and its relationship to symptoms and quality of life (QOL) in the standard-care arm of this adjuvant breast cancer trial. Premenopausal women treated on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm were included. Questionnaires assessing menstrual history, QOL, and symptoms were administered at baseline, day 1 of cycle 4 (or 9 weeks from start of chemotherapy for those who stopped chemotherapy early), and at 6, 12, and 24 months. Seven hundred and eight patients were evaluable for the analysis, with median potential follow-up of 57.5 months. Of these, 321 patients also participated in the QOL substudy. Of the 708 patients, 83% reported a parts per thousand yen1 episode of amenorrhea for a parts per thousand yen6 months. The estimated rate of resumption of menses at 24 months was 45.3% for women < 40 years, 10.9% for women 40-50, and 3.2% for women > 50 years. Those treated with tamoxifen were more likely to become amenorrheic (p = 0.003). Menstrual status was not significantly associated with QOL or symptoms. Prolonged amenorrhea is associated with a regimen that contains doxorubicin, cyclophosphamide, and docetaxel, and is age dependent and impacted by tamoxifen use. Vasomotor symptoms are common in this patient population but are not associated with menstrual status. These results can be used to inform premenopausal women about the risk and time course of amenorrhea associated with this common adjuvant therapy regimen, along with the effects on symptoms and QOL. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Swain, Sandra M.; Land, Stephanie R.; Ritter, Marcie W.; Costantino, Joseph P.; Cecchini, Reena S.; Mamounas, Eleftherios P.; Wolmark, Norman; Ganz, Patricia A.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Land, Stephanie R.; Ritter, Marcie W.; Costantino, Joseph P.; Cecchini, Reena S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Mamounas, Eleftherios P.] Altman Hlth Fdn, Canton, OH USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Sandra.M.Swain@Medstar.net OI Cecchini, Reena/0000-0002-9075-9357; Swain, Sandra/0000-0002-1320-3830 FU NCI NIH HHS [U10 CA069651, U10 CA012027, U10 CA037377, U10 CA069974, U10CA-12027, U10CA-37377, U10CA-69651, U10CA-69974] NR 20 TC 51 Z9 51 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2009 VL 113 IS 2 BP 315 EP 320 DI 10.1007/s10549-008-9937-0 PG 6 WC Oncology SC Oncology GA 391KV UT WOS:000262233100014 PM 18302020 ER PT J AU Meeske, KA Sullivan-Halley, J Smith, AW McTiernan, A Baumgartner, KB Harlan, LC Bernstein, L AF Meeske, Kathleen A. Sullivan-Halley, Jane Smith, Ashley W. McTiernan, Anne Baumgartner, Kathy B. Harlan, Linda C. Bernstein, Leslie TI Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer survivors; Black breast cancer survivors; Arm lymphedema; Risk factors for arm lymphedema; Hypertension; Body mass index; Race ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; NODE DISSECTION; CONSERVATION THERAPY; SURVIVORS; MORBIDITY; CARCINOMA; EDEMA; SYMPTOMS; SURGERY AB Purpose Lymphedema of the arm is a potential complication of breast cancer therapy. This study examines pre-disposing factors that may operate in conjunction with treatment-related factors in the development of arm lymphedema in a large cohort of White and Black breast cancer survivors. Methods 494 women (271 White and 223 Black) with in situ to Stage III-A primary breast cancer completed a baseline interview within 18 months of diagnosis. Information on lymphedema was collected during a follow-up interview, conducted on average 50 months after diagnosis. Self-reported data were used to classify women with or without lymphedema. Multivariable logistic regression models were developed to identify risk factors for arm lymphedema. Results Arm lymphedema was associated with younger age at diagnosis (odds ratio, OR per year of age = 0.96; 95% confidence interval, CI = 0.93-0.99), positive history of hypertension (OR = 2.31; 95% CI = 1.38-3.88), obesity (OR for body mass index, BMIa parts per thousand yen30 = 2.48; 95% CI = 1.05-5.84) and having had surgery where 10 or more lymph nodes were excised (OR = 2.16; 95% CI = 1.12-4.17). While Black women had higher prevalence of arm lymphedema than White women (28% vs. 21%), race was not associated with lymphedema risk in models adjusted for multiple factors (adjusted OR = 1.01; 95% CI = 0.63-1.63). Conclusion Risk of arm lymphedema did not differ significantly for Black and White women. Risk factors identified in this study offer opportunities for interventions (weight loss, control of blood pressure, use of sentinel node biopsy where possible) for reducing incidence of lymphedema or controlling the symptoms associated with this condition. C1 [Sullivan-Halley, Jane; Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Div Populat Sci, Duarte, CA 91010 USA. [Sullivan-Halley, Jane; Bernstein, Leslie] Ctr Comprehens Canc, Duarte, CA 91010 USA. [Meeske, Kathleen A.; Sullivan-Halley, Jane; Bernstein, Leslie] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Smith, Ashley W.; Harlan, Linda C.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. RP Bernstein, L (reprint author), City Hope Natl Med Ctr, Dept Canc Etiol, Div Populat Sci, 1500 Duarte Rd,Bldg 173, Duarte, CA 91010 USA. EM lbernstein@coh.org FU National Cancer Institute [N01-PC-35139, CA 116848]; USC Center for Transdisciplinary Research on Energetics and Cancer; National Institute of Child Health and Human Development [N01 HD 3-3175] FX This project has been supported with funds from the National Institutes of Health: National Cancer Institute Contract No. N01-PC-35139 for the Los Angeles HEAL Study, National Cancer Institute grant CA 116848 for the USC Center for Transdisciplinary Research on Energetics and Cancer and National Institute of Child Health and Human Development Contract N01 HD 3-3175 for the Women's CARE Study. A STOP CANCER Career Development Award also supports Dr. Meeske. The collection of California cancer incidence data providing the patient base for this publication was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The ideas and opinions expressed herein are those of the authors, and no endorsement by the State of California, Department of Health Services is intended or should be inferred. NR 45 TC 70 Z9 82 U1 0 U2 7 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 JAN PY 2009 VL 113 IS 2 BP 383 EP 391 DI 10.1007/s10549-008-9940-5 PG 9 WC Oncology SC Oncology GA 391KV UT WOS:000262233100021 PM 18297429 ER PT J AU Aniba, MR Siguenza, S Friedrich, A Plewniak, F Poch, O Marchler-Bauer, A Thompson, JD AF Aniba, Mohamed Radhouene Siguenza, Sophie Friedrich, Anne Plewniak, Frederic Poch, Olivier Marchler-Bauer, Aron Thompson, Julie Dawn TI Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis SO BRIEFINGS IN BIOINFORMATICS LA English DT Article ID PROTEIN SEQUENCES; RETRIEVAL-SYSTEM; BIOLOGY; BIOINFORMATICS; INFORMATION; ALGORITHMS; AUTOMATION; TRANSFORM; PROGRAMS; DATABASE AB The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented. C1 [Aniba, Mohamed Radhouene; Siguenza, Sophie; Plewniak, Frederic; Poch, Olivier; Thompson, Julie Dawn] IGBMC, CNRS, INSERM, ULP, F-67400 Illkirch Graffenstaden, France. [Aniba, Mohamed Radhouene] Univ Strasbourg, F-67070 Strasbourg, France. [Marchler-Bauer, Aron] NIH, Natl Ctr Biotechnol Informat NLM, Bethesda, MD 20892 USA. RP Thompson, JD (reprint author), IGBMC, CNRS, INSERM, ULP, F-67400 Illkirch Graffenstaden, France. EM julie@igbmc.fr RI Marchler-Bauer, Aron/A-9681-2009; Thompson, Julie/F-3208-2010; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU Institut National de la Sante et de la Recherche Medicale; Centre National de la Recherche Scientifique; Universite Louis Pasteur de Strasbourg FX Institut National de la Sante et de la Recherche Medicale; the Centre National de la Recherche Scientifique; the Universite Louis Pasteur de Strasbourg. NR 55 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 EI 1477-4054 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JAN PY 2009 VL 10 IS 1 BP 11 EP 23 DI 10.1093/bib/bbn045 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 401QW UT WOS:000262957900002 PM 18971242 ER PT J AU Hill, A Rother, RP Wang, X Sapsford, RJ Collinson, PO Gaze, DC Morris, SM Scally, A Quinn-Senger, K Richards, SJ Bessler, M Kelly, R Hillmen, P Gladwin, MT AF Hill, A. Rother, R. P. Wang, X. Sapsford, R. J. Collinson, P. O. Gaze, D. C. Morris, S. M. Scally, A. Quinn-Senger, K. Richards, S. J. Bessler, M. Kelly, R. Hillmen, P. Gladwin, M. T. TI Eculizumab reduces pulmonary hypertension through inhibition of haemolysis-associated nitric oxide consumption in patients with paroxysmal nocturnal haemoglobinuria SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 49th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 27-29, 2009 CL Brighton, ENGLAND C1 [Hill, A.] Bradford Teaching Hosp Fdn Trust, Dept Haematol, Bradford, W Yorkshire, England. [Rother, R. P.; Quinn-Senger, K.] Alex Pharmaceut Inc, Cheshire, CT USA. [Wang, X.; Gladwin, M. T.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Sapsford, R. J.] Leeds Gen Infirm, Dept Echocardiog, Leeds, W Yorkshire, England. [Collinson, P. O.; Gaze, D. C.] Univ London St Georges Hosp, Dept Chem Pathol, London, England. [Morris, S. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Scally, A.] Univ Bradford, Bradford BD7 1DP, W Yorkshire, England. [Richards, S. J.; Kelly, R.; Hillmen, P.] St James Inst Oncol, Dept Haematol, Leeds, W Yorkshire, England. [Bessler, M.] Washington Univ, Sch Med, Div Haematol, St Louis, MO USA. [Gladwin, M. T.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. 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 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PY 2009 VL 145 MA 119 BP 49 EP 49 PG 1 WC Hematology SC Hematology GA 431NU UT WOS:000265069200119 ER PT J AU Dores, GM Landgren, O McGlynn, KA Curtis, RE Linet, MS Devesa, SS AF Dores, Graca M. Landgren, Ola McGlynn, Katherine A. Curtis, Rochelle E. Linet, Martha S. Devesa, Susan S. TI Plasmacytoma of bone, extramedullary plasmacytoma, and multiple myeloma: incidence and survival in the United States, 1992-2004 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE epidemiology; myeloma; lymphoid malignancies; lymphoproliferative disease; plasmacytoma ID RARE-CANCER-NETWORK; SOLITARY PLASMACYTOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PROGNOSTIC-FACTORS; WORKING GROUP; PATTERNS; RADIOTHERAPY; MANAGEMENT; FEATURES AB Population-based plasmacytoma incidence and survival data are sparse. We analyzed incidence rates (IRs), IR ratios (IRRs), and 5-year relative survival for plasmacytoma overall and by site - bone (P-bone) and extramedullary (P-extramedullary) - in the Surveillance, Epidemiology and End Results(SEER) Program (1992-2004). For comparison, we included cases of multiple myeloma (MM) diagnosed over the same time period in SEER. Incidence of MM (n = 23 544; IR 5.35/100 000 person-years) was 16-times higher than plasmacytoma overall (n = 1543; IR = 0.34), and incidence of P-bone was 40% higher than P-extramedullary (P < 0.0001). The male-to-female IRRs for P-bone, P-extramedullary, and MM were 2.0, 2.6, and 1.5, respectively. For plasmacytoma and MM, IRs were highest in Blacks, intermediate in Whites, and lowest in Asian/Pacific Islanders. Compared with Whites, the Black IR was approximate to 30% higher for P-extramedullary and P-bone and 120% higher for MM. IRs for all neoplasms increased exponentially with advancing age, less prominently at older ages for plasmacytoma than MM. Distinct age, gender, and race incidence patterns of plasma cell disorders suggest underlying differences in clinical detection, susceptibility, disease biology and/or aetiological heterogeneity. Five-year relative survival for P-bone, P-extramedullary, and MM varied significantly by age (<60/60+ years), supporting age-related differences in disease burden at presentation, disease biology, and/or treatment approaches. C1 [Dores, Graca M.] Med Serv, Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. [Dores, Graca M.; Landgren, Ola; McGlynn, Katherine A.; Curtis, Rochelle E.; Linet, Martha S.; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Dores, GM (reprint author), Med Serv 111, Dept Vet Affairs Med Ctr, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM doresg@mail.nih.gov FU Department of Veterans Affairs; National Cancer Institute/National Institutes of Health FX This research was supported by the Department of Veterans Affairs and the Intramural Research Program of the National Cancer Institute/National Institutes of Health. NR 42 TC 47 Z9 55 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2009 VL 144 IS 1 BP 86 EP 94 DI 10.1111/j.1365-2141.2008.07421.x PG 9 WC Hematology SC Hematology GA 382WG UT WOS:000261635500010 PM 19016727 ER PT J AU Scheinberg, P Wu, CO Nunez, O Young, NS AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Young, Neal S. TI Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE aplastic anaemia; antibody therapy; bone marrow failure ID BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; ANTITHYMOCYTE GLOBULIN; ANTILYMPHOCYTE GLOBULIN; HEMATOPOIETIC SUPPRESSION; PROGNOSTIC-FACTORS; INTERFERON-GAMMA; UNRELATED DONORS; FAS ANTIGEN; CYCLOSPORINE AB Horse anti-thymocyte globulin (h-ATG) and ciclosporin are the initial therapy for most patients with severe aplastic anaemia (SAA), but there is no practical and reliable method to predict response to this treatment. To determine whether pretreatment blood counts discriminate patients with SAA who have a higher likelihood of haematological response at 6 months to immunosuppressive therapy (IST), we conducted a single institution retrospective analysis on 316 SAA patients treated with h-ATG-based IST from 1989 to 2005. In multivariate analysis, younger age, higher baseline absolute reticulocyte count (ARC), and absolute lymphocyte count (ALC) were highly predictive of response at 6 months. Patients with baseline ARC 25 >= 10(9)/l and ALC >= 1 x 10(9)/l had a much greater probability of response at 6 months following IST compared to those with lower ARC and ALC (83% vs. 41%, respectively; P < 0.001). This higher likelihood of response translated to greater rate of 5-year survival in patients in the high ARC/ALC group (92%) compared to those with a low ARC/ALC (53%). In the era of IST, the baseline ARC and ALC together serve as a simple predictor of response following IST, which should guide in risk stratification among patients with SAA. C1 [Scheinberg, Phillip; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Rm 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@mail.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU NIH, National Heart, Lung and Blood Institute FX This research was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. NR 44 TC 74 Z9 98 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2009 VL 144 IS 2 BP 206 EP 216 DI 10.1111/j.1365-2141.2008.07450.x PG 11 WC Hematology SC Hematology GA 385SW UT WOS:000261834900007 PM 19036108 ER PT J AU Bodnar, LM Catov, JM Wisner, KL Klebanoff, MA AF Bodnar, Lisa M. Catov, Janet M. Wisner, Katherine L. Klebanoff, Mark A. TI Racial and seasonal differences in 25-hydroxyvitamin D detected in maternal sera frozen for over 40 years SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Vitamin D; Pregnancy; Racial groups; Seasons ID VITAMIN-D DEFICIENCY; UNITED-STATES; PROSTATE-CANCER; D INSUFFICIENCY; HYPOVITAMINOSIS-D; NATIONAL-HEALTH; HIGH PREVALENCE; D METABOLITES; HUMAN PLASMA; WHITE WOMEN AB Serum banks from large, decades-old epidemiological studies provide a valuable opportunity to explore the contributions of in utero vitamin D exposure to fetal origins of adult diseases. We compared 25-hydroxyvitamin D (25(OH)D) by race and season (two powerful predictors of vitamin D status) in sera frozen for >= 40 years with sera frozen for <= 2 years to determine whether 25(OH)D is stable enough to test vitamin D-related hypotheses. Data and sera came from seventy-nine pregnant women at 29-32 weeks' gestation in the Boston Collaborative Perinatal Project (CPP; 1959-66) and 124 women at 20-36 weeks' gestation in a 2003-2006 Pittsburgh cohort study. Multivariable linear regression models were used to test main and joint effects of race and season after confounder adjustment. In both cohorts, serum 25(OH)D levels were lower among black than white women (CPP 33.3 v. 46.7 nmol/l, P<0.01; Pittsburgh 47.1 v. 89.6 nmol/l; P<0.0001) and in winter than summer (CPP 32.7 v. 47.6 nmol/l, P<0.0001; Pittsburgh 66.7 v. 89.8 nmol/l, P<0.001), with no evidence of a race X season interaction in either cohort. Differences remained significant after confounder adjustment. When CPP and Pittsburgh results were compared, there was no 4 significant difference in the race or season effects. The similarity in the relative change in 25(OH)D in these cohorts by two powerful predictors A of vitamin D status suggests that, even if 25(OH)D deteriorated somewhat, it did so similarly across samples. Therefore, trends could be obtained from the decades-old serum data that would be relevant in exploring vitamin D-related hypotheses in future studies. C1 [Bodnar, Lisa M.; Catov, Janet M.; Wisner, Katherine L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Bodnar, Lisa M.; Catov, Janet M.; Wisner, Katherine L.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15261 USA. [Bodnar, Lisa M.; Wisner, Katherine L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Bodnar, Lisa M.; Catov, Janet M.; Wisner, Katherine L.] Magee Womens Res Inst, Pittsburgh, PA USA. [Klebanoff, Mark A.] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Bodnar, LM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, A742 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM bodnar@edc.pitt.edu FU National Institutes of Health [K01 MH074092, P30 DK046204, R01 MH060335]; National Institutes of Child Health and Human Development; National Institute of Mental Health; Stanley Medical Research Foundation; American Society for Bariatric Surgery and Pfizer FX The present study was partially supported by National Institutes of Health grants K01 MH074092, P30 DK046204 and R01 MH060335. M. A. K. was supported by intramural funds from the National Institutes of Child Health and Human Development. L. M. B., J. M. C. and M. A. K declare no conflicts of interest. K. L W. is on the Speaker's Bureau of GlaxoSmithKline and receives funding from the National Institute of Mental Health, the Stanley Medical Research Foundation, the American Society for Bariatric Surgery and Pfizer. We gratefully acknowledge Dr Robert Powers and Marcia Gallaher at the Magee-Women's Research Institute for their technical assistance with the 25(OH)D assays. NR 40 TC 30 Z9 30 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD JAN PY 2009 VL 101 IS 2 BP 278 EP 284 DI 10.1017/S0007114508981460 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 398DH UT WOS:000262712300017 PM 18430263 ER PT J AU McNeil, SE AF McNeil, Scott E. TI In Review: Nanomaterial safety SO BULLETIN OF THE ATOMIC SCIENTISTS LA English DT Article ID WALLED-CARBON-NANOTUBES; PULMONARY TOXICITY; MICE C1 Natl Canc Inst, NCL, Bethesda, MD 20892 USA. RP McNeil, SE (reprint author), Natl Canc Inst, NCL, Bethesda, MD 20892 USA. RI Nanotechnology Characterization Lab, NCL/K-8454-2012 NR 12 TC 0 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0096-3402 J9 B ATOM SCI JI Bull. Atom. Scient. PD JAN-FEB PY 2009 VL 65 IS 1 BP 56 EP 61 DI 10.2968/065001007 PG 6 WC International Relations; Social Issues SC International Relations; Social Issues GA 624IA UT WOS:000279809700007 ER PT J AU McCrae, RR AF McCrae, Robert R. BE Corr, PJ Matthews, G TI The Five-Factor Model of personality traits: consensus and controversy SO CAMBRIDGE HANDBOOK OF PERSONALITY PSYCHOLOGY LA English DT Article; Book Chapter ID HIGHER-ORDER FACTORS; MULTITRAIT-MULTIMETHOD ANALYSES; SELF-OTHER AGREEMENT; BIG 5; ASSESSMENT INVENTORY; Q-SET; RATINGS; UNIVERSAL; OPENNESS; CULTURES C1 NIA, Bethesda, MD 20892 USA. RP McCrae, RR (reprint author), NIA, Bethesda, MD 20892 USA. NR 76 TC 33 Z9 33 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-86218-9 PY 2009 BP 148 EP 161 D2 10.1017/CBO9780511596544 PG 14 WC Psychology, Social SC Psychology GA BFB77 UT WOS:000319121200012 ER PT J AU Warner, HR Sierra, F AF Warner, Huber R. Sierra, Felipe TI Canadian Institutes of Health Research Institute of Aging : Profiles The Longevity Dividend: Why Invest in Basic Aging Research? SO CANADIAN JOURNAL ON AGING-REVUE CANADIENNE DU VIEILLISSEMENT LA English DT Article ID MICE; CENTENARIANS; RESTRICTION; BIOMARKERS; DECLINE; LIFE C1 [Warner, Huber R.] Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. [Sierra, Felipe] NIA, Div Aging Biol, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), Univ Minnesota, Coll Biol Sci, St Paul, MN 55108 USA. EM warne033@umn.edu NR 22 TC 5 Z9 5 U1 0 U2 0 PU CANADIAN ASSOC GERONTOLOGY-ASSOC CANADIENNE DE GERONTOLOGIE PI OTTAWA PA 100-824 MEATH ST, OTTAWA, ON K1Z 6E8, CANADA SN 0714-9808 J9 CAN J AGING JI Can. J. Aging-Rev. Can. Vieil. PY 2009 VL 28 IS 4 BP 391 EP 394 DI 10.1017/S0714980809990286 PG 4 WC Gerontology SC Geriatrics & Gerontology GA 634TF UT WOS:000280607500009 ER PT J AU Tandle, A Hanna, E Lorang, D Hajitou, A Moya, CA Pasqualini, R Arap, W Adem, A Starker, E Hewitt, S Libutti, SK AF Tandle, Anita Hanna, Engy Lorang, Dominique Hajitou, Amin Moya, Catherine A. Pasqualini, Renata Arap, Wadih Adem, Asha Starker, Elizabeth Hewitt, Stephen Libutti, Steven K. TI Tumor Vasculature-targeted Delivery of Tumor Necrosis Factor-alpha SO CANCER LA English DT Article DE targeted gene therapy; tumor necrosis factor alpha; adeno-associated virus phage vector; antivascular; human melanoma ID ENDOTHELIAL-CELL MONOLAYERS; ISOLATED LIMB PERFUSION; GENE DELIVERY; FILAMENTOUS BACTERIOPHAGE; SPECIES SPECIFICITY; CANCER-TREATMENT; MAMMALIAN-CELLS; PHAGE DISPLAY; TISSUE FACTOR; THERAPY AB BACKGROUND: Recently, considerable efforts have been directed toward antivascular therapy as a new modality to treat human cancers. However, targeting a therapeutic gene of interest to the tumor vasculature with minimal toxicity to other tissues remains the objective of antivascular gene therapy. Tumor necrosis factor-alpha (TNF-alpha) is a potent antivascular agent but has limited clinical utility because of significant systemic toxicity. At the maximum tolerated doses of systemic TNF-alpha, there is no meaningful antitumor activity. Hence, the objective of this study was to deliver TNF-alpha targeted to tumor vasculature by systemic delivery to examine its antitumor activity. METHODS: A hybrid adeno-associated virus phage vector (AAVP) was used that targets tumor endothelium to express TNF-alpha (AAVP-TNF-alpha). The activity of AAVP-TNF-alpha was analyzed in various in vitro and in vivo settings using a human melanoma tumor model. RESULTS: In vitro, AAVP-TNF-alpha infection of human melanoma cells resulted in high levels of TNF-alpha expression. Systemic administration of targeted AAVP-TNF-alpha to melanoma xenografts in mice produced the specific delivery of virus to tumor vasculature. In contrast, the nontargeted vector did not target to tumor vasculature. Targeted AAVP delivery resulted in expression of TNF-alpha, induction of apoptosis in tumor vessels, and significant inhibition of tumor growth. No systemic toxicity to normal organs was observed. CONCLUSIONS: Targeted AAVP vectors can be used to deliver TNF-alpha specifically to tumor vasculature, potentially reducing its systemic toxicity. Because TNF-alpha, is a promising antivascular agent that currently is limited by its toxicity, the current results suggest the potential for clinical translation of this strategy. Cancer 2009;115:128-39. Published 2008 by the American Cancer Society. C1 [Tandle, Anita; Hanna, Engy; Lorang, Dominique; Adem, Asha; Starker, Elizabeth; Libutti, Steven K.] NCI, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Hajitou, Amin] Univ London Imperial Coll Sci Technol & Med, Wright Flemming Inst, Div Med, Dept Gene Therapy, London, England. [Moya, Catherine A.; Pasqualini, Renata; Arap, Wadih] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Hewitt, Stephen] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res,NIH, Bldg 10,Room 4W-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 39 TC 40 Z9 46 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2009 VL 115 IS 1 BP 128 EP 139 DI 10.1002/cncr.24001 PG 12 WC Oncology SC Oncology GA 401MC UT WOS:000262943800017 PM 19090007 ER PT J AU Pressler, H Figg, WD AF Pressler, Heather Figg, W. Douglas TI Phenotypic approach to drug discovery SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE drug discovery; drug prioritization; target prediction; network; side effects; compound; molecular target; drug-drug; binding sites; statistical prediction C1 [Pressler, Heather; Figg, W. Douglas] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Pressler, Heather] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z99 CA999999] NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2009 VL 8 IS 1 BP 11 EP 12 DI 10.4161/cbt.8.1.7330 PG 2 WC Oncology SC Oncology GA 419GN UT WOS:000264207500006 PM 19164944 ER PT J AU Truman, JP Rotenberg, SA Kang, JH Lerman, G Fuks, Z Kolesnick, R Marquez, VE Haimovitz-Friedman, A AF Truman, Jean-Philip Rotenberg, Susan A. Kang, Ji-Hye Lerman, Gabriel Fuks, Zvi Kolesnick, Richard Marquez, Victor E. Haimovitz-Friedman, Adriana TI PKC alpha activation downregulates ATM and radio-sensitizes androgen-sensitive human prostate cancer cells in vitro and in vivo SO CANCER BIOLOGY & THERAPY LA English DT Article DE ionizing radiation; ATM; apoptosis; prostate; PKC alpha ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; RADIATION-INDUCED APOPTOSIS; SKIN TUMOR PROMOTION; CERAMIDE SYNTHASE; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED APOPTOSIS; DNA FRAGMENTATION; PHORBOL ESTERS; MELANOMA-CELLS; LNCAP CELLS AB We previously demonstrated that treatment of human androgen-responsive prostate cancer cell lines LNCaP and CWR22-Rvl with 12-O-tetradecanoylphorbol 13-acetate (TPA), a known protein kinase C (PKC) activator, decreases ATM protein levels, thus de-repressing the enzyme ceramide synthase (CS) and promoting apoptosis as well as radio-sensitizing these cefls.(1) Here we show that PKC(x mediates the TPA effect on ATM expression, since ATM suppression and apoptosis induced by either TPA or diacylglycerol-lactone (DAG-lactone), both inducing PKC alpha activation,(2) are abrogated in LNCaP cells following transfection of a kinase-dead PKC alpha mutant (KD-PKC alpha). Similarly, KD-PKC alpha blocks the apoptotic response elicited by combination of TPA and radiation, whereas expression of constitutively active PKC alpha is sufficient to sensitize cells to radiation alone, without a need to pre-treat the cells with TPA. These findings identify CS activation as a downstream event of PKC alpha activity in LNCaP cells. Similar results were obtained in CWR22-Rvl cells with DAG-lactone treatment. Using the LNCaP orthotopic prostate model it is shown that treatment with TPA or DAG-lactone induces significant reduction in tumor ATM levels coupled with tumor growth delay. Furthermore, while fractionated radiation alone produces significant tumor growth delay, pretreatment with TPA or DAG-lactone significantly potentiates tumor cure. These findings support a model in which activation of PKC alpha downregulates ATM, thus relieving CS repression by ATM and enhancing apoptosis via ceramide generation. This model may provide a basis for the design of new therapies in prostate cancer. C1 [Truman, Jean-Philip; Lerman, Gabriel; Fuks, Zvi; Haimovitz-Friedman, Adriana] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Kolesnick, Richard] Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. [Rotenberg, Susan A.] CUNY, Dept Chem & Biochem, Queens Coll, New York, NY USA. [Kang, Ji-Hye; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Haimovitz-Friedman, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave,Box 280, New York, NY 10021 USA. EM haimovia@mskcc.org FU NIH [RO1 CA105125, ROI CA85704]; The Virginia and D.K. Ludwig Fund for Cancer Research; National Cancer Institute; Center for Cancer Research FX We thank John Fuller for assistance with the ChIP assay. This work was supported by NIH RO1 #CA105125 to A.H-F., NIH ROI #CA85704 to R.K. and a gift from the The Virginia and D.K. Ludwig Fund for Cancer Research to Z.F. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research to V.E.M. NR 35 TC 15 Z9 16 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2009 VL 8 IS 1 BP 54 EP 63 DI 10.4161/cbt.8.1.7119 PG 10 WC Oncology SC Oncology GA 419GN UT WOS:000264207500014 PM 19029835 ER PT J AU Foley, R Marignol, L Thomas, AZ Cullen, IM Perry, AS Tewari, P O'Grady, A Kay, E Dunne, B Loftus, B Watson, RW Fitzpatrick, JM Woodson, K Lehman, T Hollywood, D Lynch, TH Lawler, M AF Foley, R. Marignol, L. Thomas, A. Z. Cullen, I. M. Perry, A. S. Tewari, P. O'Grady, A. Kay, E. Dunne, B. Loftus, B. Watson, R. W. Fitzpatrick, J. M. Woodson, K. Lehman, T. Hollywood, D. Lynch, T. H. Lawler, M. TI The HIF-1 alpha C1772T polymorphism may be associated with susceptibility to clinically localised prostate cancer but not with elevated expression of hypoxic biomarkers SO CANCER BIOLOGY & THERAPY LA English DT Article DE prostate cancer; hypoxia; polymorphism ID INDUCIBLE FACTOR 1-ALPHA; DEGRADATION DOMAIN; FACTOR-I; FACTOR-1-ALPHA HIF-1-ALPHA; CELLS; GENE; MUTATION; RATIO AB We investigated the role of the C1772T polymorphisms in exon 12 of the Hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene C1772T genotype in prostate cancer (PCa) and amplification of the hypoxic response. We identified the heterozygous germline CT genotype as an increased risk factor for clinically localised prostate cancer (Odds ratio = 6.2; p < 0.0001). While immunostaining intensity for HIF-1 alpha and VEGF was significantly enhanced in 75% of PCa specimens when compared to matched benign specimens (p < 0.0001), the CT genotype did not modulate the kinetics of HIF-1 alpha protein expression in hypoxia in vitro, and was not associated with enhanced expression of hypoxic biomarkers. This study provides the first evidence of an increased risk for clinically localised prostate cancer in men carrying the C1772T HIF-1 alpha gene polymorphism. Although our results did not suggest an association between expression of hypoxic biomarkers and genotype status, the correlation may merit further investigation. C1 [Foley, R.; Marignol, L.; Thomas, A. Z.; Cullen, I. M.; Perry, A. S.; Tewari, P.; Hollywood, D.; Lawler, M.] St James Hosp, Dept Haematol, Dublin 8, Ireland. [Foley, R.; Marignol, L.; Thomas, A. Z.; Cullen, I. M.; Perry, A. S.; Tewari, P.; Hollywood, D.; Lawler, M.] Inst Mol Med, Acad Unit Clin & Mol Oncol, Dublin, Ireland. [Dunne, B.] St James Hosp, Dept Histopathol, Dublin, Ireland. [Dunne, B.; Loftus, B.] Univ Dublin Trinity Coll, Dublin 2, Ireland. [Thomas, A. Z.; Cullen, I. M.; Lynch, T. H.] St James Hosp, Dept Urol, Dublin, Ireland. [O'Grady, A.; Kay, E.] Beaumont Hosp, Dept Histopathol, Dublin 9, Ireland. [O'Grady, A.; Kay, E.] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Loftus, B.] Dublin Incorporating Natl Childrens Hosp, Dept Histopathol, Adelaide & Meath Hosp, Dublin, Ireland. [Watson, R. W.; Fitzpatrick, J. M.] Univ Calif Davis, Conway Inst Biomol & Biomed Res, Sch Med & Med Sci, Davis, CA 95616 USA. Univ Coll Dublin, Mater Misericordiae Univ Hosp, Dublin 2, Ireland. [Woodson, K.] NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. [Lehman, T.] BioServe Biotechnol, Laurel, MD USA. RP Marignol, L (reprint author), St James Hosp, Dept Haematol, Jamess St, Dublin 8, Ireland. EM marignol@tcd.ie OI Perry, Antoinette/0000-0002-6108-512X FU Cancer Research Ireland; Research arm of the Irish Cancer Society FX The sponsor provided financial support and played no other role. NR 23 TC 36 Z9 39 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2009 VL 8 IS 2 BP 118 EP 124 PG 7 WC Oncology SC Oncology GA 395BK UT WOS:000262496900003 PM 19106642 ER PT J AU Hardee, M Eapen, R Rabbani, Z Dreher, M Marks, J Blackwell, K Dewhirst, M AF Hardee, Matthew E. Eapen, Rose J. Rabbani, Zahid N. Dreher, Matthew R. Marks, Jeffrey Blackwell, Kimberly L. Dewhirst, Mark W. TI Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu(+) tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Her2/neu; Angiogenesis; Tumor hypoxia; Breast cancer ID EPIDERMAL-GROWTH-FACTOR; BREAST-CANCER; SOLID TUMORS; GLUCOSE CONSUMPTION; HYPOXIA; CELLS; EXPRESSION; SPHEROIDS; FRACTION; RECEPTOR AB Purpose Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her2(+) may have an altered state of oxygenation, relative to Her2(-) tumors, due to differences in tumor growth rate and angiogenesis. Methods Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2(+) and Her2(-) MCF7 xenograft tumors. Results Treatment with trastuzumab in Her2(+) tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her(2+) tumors. The Her(2+) xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture). Conclusions These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response. C1 [Rabbani, Zahid N.; Blackwell, Kimberly L.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Hardee, Matthew E.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Eapen, Rose J.] Univ N Carolina, Med Ctr, Dept Otolaryngol, Chapel Hill, NC USA. [Dreher, Matthew R.] NIH, Ctr Clin, Dept Radiat Oncol, Bethesda, MD 20892 USA. [Marks, Jeffrey] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Blackwell, Kimberly L.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Dewhirst, M (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. EM dewhi001@mc.duke.edu FU NCI NIH HHS [P01 CA042745, R01 CA040355] NR 32 TC 14 Z9 16 U1 0 U2 5 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 JAN PY 2009 VL 63 IS 2 BP 219 EP 228 DI 10.1007/s00280-008-0729-3 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 377XX UT WOS:000261286800004 PM 18365198 ER PT J AU Tsou, JA Kazarian, M Patel, A Galler, JS Laird-Offringa, IA Carpenter, CL London, SJ AF Tsou, Jeffrey A. Kazarian, Meleeneh Patel, Ankur Galler, Janice S. Laird-Offringa, Ite A. Carpenter, Catherine L. London, Stephanie J. TI Low level anti-Hu reactivity: A risk marker for small cell lung cancer? SO CANCER DETECTION AND PREVENTION LA English DT Article DE Carcinoma; Small cell; Paraneoplastic encephalomyelitis; PEM/SN; HuD antigen; Autoantibodies; Case-control studies; Survival ID ENCEPHALOMYELITIS SENSORY NEURONOPATHY; RNA-BINDING PROTEINS; PARANEOPLASTIC ENCEPHALOMYELITIS; LIMBIC ENCEPHALITIS; CIGARETTE-SMOKING; CALCIUM-CHANNELS; ANTIBODIES; CARCINOMA; EXPRESSION; ELAV AB Background: Previous experimental and laboratory studies have implicated antibodies against Hu proteins (anti-Hu) as a potential marker for small cell lung cancer (SCLC); there are no estimates of the association between anti-Hu and SCLC using a population-based design. Methods: We used stored plasma specimens to evaluate anti-Hu reactivity in relationship to small cell lung cancer in a population-based case-control study. Using Western Blot analysis, we measured anti-Hu reactivity against recombinant Hu family member, HuD, in plasma samples from 41 SCLC cases and 79 controls individually matched for age, race, sex, and smoking status (never, past, current). We analyzed the association between anti-Hu reactivity and SCLC using conditional logistic regression. Results: Anti-Hu reactivity was associated with SCLC, both before and after adjustment for amount of smoking. We observed a smoking-adjusted odds ratio of 3.2 (95% confidence interval from 0.98 to 13.4) comparing subjects above 1800 units (the lower limit of the second tertile of the distribution among antibody positive controls) to subjects with lower reactivity. We also found suggestive evidence in follow-up of our cases that anti-Hu above 1800 units was related to longer-term survival from SCLC. The present research is the first report of anti-Hu reactivity and SCLC in a population-based study. Conclusions: Given the suggestive evidence in this study, prospective analyses to examine whether anti-Hu reactivity might predict risk of developing SCLC, or whether anti-Hu reactivity could serve as an early marker for SCLC, may be warranted. Published by Elsevier Ltd. C1 [Carpenter, Catherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. [Tsou, Jeffrey A.; Kazarian, Meleeneh; Patel, Ankur; Galler, Janice S.; Laird-Offringa, Ite A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Tsou, Jeffrey A.; Kazarian, Meleeneh; Patel, Ankur; Galler, Janice S.; Laird-Offringa, Ite A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90089 USA. [London, Stephanie J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Carpenter, CL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, 900 Vet Ave,Box 95-1742, Los Angeles, CA 90095 USA. EM ccarpenter@mednet.ucla.edu OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES101574-05]; NCI NIH HHS [N01PC35136, N01PC35139, N02 PC015105] NR 42 TC 7 Z9 9 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2009 VL 32 IS 4 BP 292 EP 299 DI 10.1016/j.cdp.2008.06.006 PG 8 WC Oncology SC Oncology GA 425EC UT WOS:000264618800003 PM 19070439 ER PT J AU Wang, SS Zuna, RE Wentzensen, N Dunn, ST Sherman, ME Gold, MA Schiffman, M Wacholder, S Allen, RA Block, I Downing, K Jeronimo, J Carreon, JD Safaeian, M Brown, D Walker, JL AF Wang, Sophia S. Zuna, Rosemary E. Wentzensen, Nicolas Dunn, S. Terence Sherman, Mark E. Gold, Michael A. Schiffman, Mark Wacholder, Sholom Allen, Richard A. Block, Ingrid Downing, Kim Jeronimo, Jose Carreon, J. Daniel Safaeian, Mahboobeh Brown, David Walker, Joan L. TI Human Papillomavirus Cofactors by Disease Progression and Human Papillomavirus Types in the Study to Understand Cervical Cancer Early Endpoints and Determinants SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ASCUS-LSIL TRIAGE; COLLABORATIVE REANALYSIS; BETHESDA SYSTEM; INDIVIDUAL DATA; HORMONAL CONTRACEPTIVES; WOMEN; NEOPLASIA; DIAGNOSES; CARCINOMA; SMOKING AB Human papillomavirus (HPV) cofactors for cervical cancer include smoking, multiparity, and oral contraceptive use, but their mechanisms of action are not fully understood. It is also unknown whether cofactors vary by HPV genotypes. The Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED) is a cross-sectional study comprising women referred to the University of Oklahoma from November 2003 to September 2007 for abnormal cervical screening results. Detailed questionnaire data and liquid cytology specimens were collected and the latter was genotyped for HPV using the LINEAR ARRAY HPV Genotyping Test. The present analysis includes women with both questionnaire and HPV data and diagnosed with < CIN1 (n = 535), CIN1 (n = 497), CIN2 (n = 336), CIN3 (n = 292), and cancer (n = 80). We evaluated HPV types and cofactors among HPV-infected women by calculating odds ratios (OR) and 95% confidence intervals (950% CI) for CIN3 and CIN2 separately compared with < CIN2 using a polytomous logistic regression model; cancers were excluded from further analysis due to the substantially higher ages of these women. We found that HPV-infected women with minor histologic or cytologic abnormalities (e.g., CIN1., ASCUS, and LSIL) were indistinguishable from those with normal histology/cytology and were thus combined to form the referent group (< CTN2). Among women positive for oncogenic HPV, current smokers had a 2.5-fold increased risk for CIN3 (95% CI, 1.8-3.6) compared with nonsmokers. Among HPV16-infected women, current smokers had elevated risk for both CIN2 (OR, 1.9; 95%, Cl, 1.1-3.2) and CIN3 (OR, 2.7; 951% CI, 1.6-4.6). Our data suggest that non-HPV16-related CIN2 likely reflects a combination of CIN1. and CIN3 diagnosis, whereas HPV16-related CIN2 may indicate a precancerous state. Investigations oil the molecular distinctions along the disease continuum of cervical pathogenesis by HPV type are needed. (Cancer Epidemiol Biomarkers Prev 2009;1,8(1):113-20) C1 [Wang, Sophia S.; Wentzensen, Nicolas; Sherman, Mark E.; Schiffman, Mark; Wacholder, Sholom; Jeronimo, Jose; Carreon, J. Daniel; Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20854 USA. [Zuna, Rosemary E.; Dunn, S. Terence; Gold, Michael A.; Allen, Richard A.; Block, Ingrid; Downing, Kim; Brown, David; Walker, Joan L.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5104, Rockville, MD 20854 USA. EM wangso@mail.nih.gov FU National Cancer Institute Intramural program FX This work was supported by the National Cancer Institute Intramural program. NR 26 TC 50 Z9 53 U1 1 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 JAN PY 2009 VL 18 IS 1 BP 113 EP 120 DI 10.1158/1055-9965.EPI-08-0591 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200015 PM 19124488 ER PT J AU Harper, S Lynch, J Meersman, SC Breen, N Davis, WW Reichman, MC AF Harper, Sam Lynch, John Meersman, Stephen C. Breen, Nancy Davis, William W. Reichman, Marsha C. TI Trends in Area-Socioeconomic and Race-Ethnic Disparities in Breast Cancer incidence, Stage at Diagnosis, Screening, Mortality, and Survival among Women Ages 50 Years and Over (1987-2005) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; ESTROGEN-RECEPTOR STATUS; UNITED-STATES; RACIAL DISPARITIES; AFRICAN-AMERICAN; SOCIAL DISPARITIES; NATIONAL-HEALTH; WHITE WOMEN; MAMMOGRAPHY; US AB Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States and varies systematically by race-ethnicity and socioeconomic status. Previous research has often focused on disparities between particular groups, but few studies have summarized disparities across multiple subgroups defined by race-ethnic and socioeconomic position. Methods: Data on breast cancer incidence, stage, mortality, and 5-year cause-specific probability of death (100 - survival) were obtained from the Surveillance, Epidemiology, and End Results program and data on mammography screening from the National Health Interview Survey from 1987 to 2005. We used four area-socioeconomic groups based on the percentage of poverty in the county of residence (< 10, 10-15, 15-20, +20%) and five race-ethnic groups (White, Black, Asian, American Indian, and Hispanic). We used summary measures of disparity based on both rate differences and rate ratios. Results: From 1987 to 2004, area-socioeconomic disparities declined by 20% to 30% for incidence, stage at diagnosis, and 5-year cause-specific probability of death, and by roughly 100% for mortality, whether measured on the absolute or relative scale. In contrast, relative area-socioeconomic disparities in mammography use increased by 1.61%. Absolute race-ethnic disparities declined across all outcomes, with the largest reduction for mammography (56% decline). Relative race-ethnic disparities for mortality and 5-year cause-specific probability of death increased by 24% and 1.7%, respectively. Conclusions: Our analysis suggests progress towards race-ethnic and area-socioeconomic disparity goals for breast cancer, especially when measured on the absolute scale. However, greater progress is needed to address increasing relative socioeconomic disparities in mammography and race-ethnic disparities in mortality and 5-year cause-specific probability of death. (Cancer Epidemiol Biomarkers Prev 2009;18(1):121-31) C1 [Harper, Sam; Lynch, John] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Lynch, John] Univ S Australia, Div Hlth Sci, Adelaide, SA 5001, Australia. [Lynch, John] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Meersman, Stephen C.; Breen, Nancy; Davis, William W.; Reichman, Marsha C.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Harper, S (reprint author), McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 1020 Pine Ave W,Room 34, Montreal, PQ H3A 1A2, Canada. EM sam.harper@mcgill.ca RI Harper, Sam/A-3406-2008; Lynch, John/A-4797-2008 OI Harper, Sam/0000-0002-2767-1053; Lynch, John/0000-0003-2781-7902 FU National Cancer Institute [263-MQ-611198] FX This project was carried out under contract with the National Cancer Institute (263-MQ-611198). The contents of this publication does not necessarily reflect the views or policies of the National Cancer Institute. NR 84 TC 85 Z9 90 U1 3 U2 15 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 JAN PY 2009 VL 18 IS 1 BP 121 EP 131 DI 10.1158/1055-9965.EPI-08-0679 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200016 PM 19124489 ER PT J AU Lam, TK Gallicchio, L Lindsley, K Shiels, M Hammond, E Tao, XG Chen, LW Robinson, KA Caulfield, LE Herman, JG Guallar, E Alberg, AJ AF Lam, Tram Kim Gallicchio, Lisa Lindsley, Kristina Shiels, Meredith Hammond, Edward Tao, Xuguang (Grant) Chen, Liwei Robinson, Karen A. Caulfield, Laura E. Herman, James G. Guallar, Eliseo Alberg, Anthony J. TI Cruciferous Vegetable Consumption and Lung Cancer Risk: A Systematic Review SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID S-TRANSFERASE POLYMORPHISMS; DIETARY-INTAKE; GENETIC POLYMORPHISMS; NORTHEAST CHINA; BETA-CAROTENE; FRUIT; ISOTHIOCYANATES; WOMEN; SULFORAPHANE; SMOKING AB Background: Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants. Methods: A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included. Results: The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01). Conclusions: Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a genediet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1. (Cancer Epidemiol Biomarkers Prev 2009;18(1):184-95) C1 [Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Alberg, Anthony J.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Lam, Tram Kim] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Lam, Tram Kim; Lindsley, Kristina; Shiels, Meredith; Hammond, Edward; Robinson, Karen A.; Guallar, Eliseo; Alberg, Anthony J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Chen, Liwei; Caulfield, Laura E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Gallicchio, Lisa] Mercy Hosp, Baltimore, MD USA. [Tao, Xuguang (Grant)] Johns Hopkins Univ, Sch Med, Dept Occupat & Environm Med, Baltimore, MD USA. [Robinson, Karen A.] Johns Hopkins Univ, Sch Med, Dept Gen Internal Med, Baltimore, MD USA. [Herman, James G.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, 86 Jonathan Lucas St,POB 250955, Charleston, SC 29425 USA. EM alberg@musc.edu RI Guallar, Eliseo/D-3807-2014 OI Guallar, Eliseo/0000-0002-4471-9565 FU World Cancer Research Fund FX World Cancer Research Fund, NR 65 TC 83 Z9 85 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2009 VL 18 IS 1 BP 184 EP 195 DI 10.1158/1055-9965.EPI-08-0710 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200024 PM 19124497 ER PT J AU Johnson, JR Lacey, JV Lazovich, D Geller, MA Schairer, C Schatzkin, A Flood, A AF Johnson, Jill R. Lacey, James V., Jr. Lazovich, DeAnn Geller, Melissa A. Schairer, Catherine Schatzkin, Arthur Flood, Andrew TI Menopausal Hormone Therapy and Risk of Colorectal Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LARGE-BOWEL-CANCER; ESTROGEN REPLACEMENT THERAPY; EXOGENOUS FEMALE HORMONES; POSTMENOPAUSAL WOMEN; COLON-CANCER; UNITED-STATES; REPRODUCTIVE FACTORS; PLUS PROGESTIN; ER-BETA; COHORT AB We evaluated colorectal cancer risk associated with the duration and recency of specific menopausal hormone therapy formulations (i.e., unopposed estrogen versus estrogen plus progestin) and regimens (i.e., sequential versus continuous estrogen plus progestin use) among 56,733 postmenopausal women participating in the Breast Cancer Detection Demonstration Project follow-up study. Hormone therapy use and other risk factors were ascertained through telephone interviews and mailed questionnaires from 1979 to 1998. The final cancer group included 960 women who were identified from self-report, medical records, state registry data, and the National Death Index. Poisson regression was used to generate multivariable rate ratios (RR) and 95% confidence intervals (95% CI). We observed a decreased risk of colorectal cancer among ever users of unopposed estrogen therapy (RR, 0.83; 95% Cl, 0.70-0.99). Among estrogen users, the largest reduced risk was observed for current users (RR, 0.75; 95% Cl, 0.54-1.05) and users of 2 ten years duration (RR, 0.74; 95% Cl, 0.56-0.96). We found a reduced risk among users of estrogen plus progestin therapy (RR, 0.78; 95% CI, 0.60-1.02), with sequential regimen users (progestin < 15 days per cycle) having the largest risk reduction (RR, 0.64; 95% Cl, 0.43-0.95). Past users of >= 5 years ago (RR, 0.55; 95% CI, 0.32-0.98) had the largest risk reduction. In this study, estrogen plus progestin use, especially sequential regimen use, was associated with the largest overall reduction of colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(1):196-203) C1 [Johnson, Jill R.; Lazovich, DeAnn; Flood, Andrew] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Geller, Melissa A.] Univ Minnesota, Dept Obstet Gynecol & Womens Hlth, Div Gynecol Oncol, Minneapolis, MN USA. [Lacey, James V., Jr.; Schairer, Catherine; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Johnson, JR (reprint author), 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM joh02544@umn.edu FU Intramural NIH HHS [Z01 CP010182-06]; NCI NIH HHS [K07 CA108910-01A1] NR 53 TC 50 Z9 51 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 JAN PY 2009 VL 18 IS 1 BP 196 EP 203 DI 10.1158/1055-9965.EPI-08-0596 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200025 PM 19124498 ER PT J AU Enewold, L Mechanic, LE Bowman, ED Zheng, YL Yu, ZP Trivers, G Alberg, AJ Harris, CC AF Enewold, Lindsey Mechanic, Leah E. Bowman, Elise D. Zheng, Yun-Ling Yu, Zhipeng Trivers, Glenwood Alberg, Anthony J. Harris, Curtis C. TI Serum Concentrations of Cytokines and Lung Cancer Survival in African Americans and Caucasians SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NECROSIS-FACTOR-ALPHA; CELL-LINES; IN-VITRO; PROINFLAMMATORY CYTOKINES; PROGNOSTIC-FACTOR; TNF-ALPHA; TUMOR; INTERLEUKIN-6; CARCINOMA; POLYMORPHISMS AB Accumulating evidence suggests a role for inflammation in the development and progression of cancer. Our group recently identified a cytokine gene signature in lung tissue associated with lung cancer prognosis. Therefore, we hypothesized that concentrations of circulating cytokines in serum may be associated with lung cancer survival. Ten serum cytokines, namely, interleukin (M-1 beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, interferon (IFN)-gamma, and tumor necrosis factor-alpha, were assessed in 353 non-small cell lung cancer cases from a case-control study of lung cancer in the greater Baltimore, Maryland area. Cytokines were measured using an ultrasensitive electrochemiluminescence immunoassay. IL-6 serum concentrations (>= 4.0 pg/mL) were associated with significantly poorer survival in both African Americans [hazard ratio (HR), 2.71; 95% confidence interval (CI) 1.26-5.80] and Caucasians (HR, 1.71; 95% CI, 1.22-2.40). IL-10 (HR, 2.62; 95% CI, 1.33-5.15) and IL-12 (HR, 1.98; 95% CI, 1.14-3.44) were associated with lung cancer survival only in African Americans. Some evidence for an association of tumor necrosis factor-alpha levels with survival in Caucasians was observed, although these results were not significant. These hypothesis-generating findings indicate that selected serum cytokine concentrations are associated with lung cancer survival, and indicate that further research is warranted to better understand the mechanistic underpinnings of these associations. (Cancer Epidemiol Biomarkers Prev 2009;18(1):215-22) C1 [Mechanic, Leah E.; Bowman, Elise D.; Yu, Zhipeng; Trivers, Glenwood; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Enewold, Lindsey; Zheng, Yun-Ling] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Alberg, Anthony J.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU NIH; NCI; CCR FX Intramural Research Program of the NIH, NCI and CCR. NR 52 TC 48 Z9 48 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 JAN PY 2009 VL 18 IS 1 BP 215 EP 222 DI 10.1158/1055-9965.EPI-08-0705 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200027 PM 19124500 ER PT J AU Setiawan, VW Doherty, JA Shu, XO Akbari, MR Chen, C De Vivo, I DeMichele, A Garcia-Closas, M Goodman, MT Haiman, CA Hankinson, SE Henderson, BE Horn-Ross, PL Lacey, JV Le Marchand, L Levine, DA Liang, X Lissowska, J Lurie, G McGrath, M Narod, SA Rebbeck, TR Ursin, G Weiss, NS Xiang, YB Yang, HP Zheng, W Olson, SH AF Setiawan, Veronica Wendy Doherty, Jennifer A. Shu, Xiao-ou Akbari, Mohammad R. Chen, Chu De Vivo, Immaculata DeMichele, Angela Garcia-Closas, Montserrat Goodman, Marc T. Haiman, Christopher A. Hankinson, Susan E. Henderson, Brian E. Horn-Ross, Pamela L. Lacey, James V., Jr. Le Marchand, Loic Levine, Douglas A. Liang, Xiaolin Lissowska, Jolanta Lurie, Galina McGrath, Monica Narod, Steven A. Rebbeck, Timothy R. Ursin, Giske Weiss, Noel S. Xiang, Yong-Bing Yang, Hannah P. Zheng, Wei Olson, Sara H. TI Two Estrogen-Related Variants in CYP19A1 and Endometrial Cancer Risk: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN ADIPOSE-CELLS; BREAST-CANCER; POSTMENOPAUSAL WOMEN; AROMATASE-ACTIVITY; GENETIC POLYMORPHISMS; BIOSYNTHESIS GENES; STEROID-HORMONES; ASSOCIATION; OBESITY AB Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 X 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age :55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >= 55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women. (Cancer Epidemiol Biomarkers Prev 2009;18(1):242-7) C1 [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. [Setiawan, Veronica Wendy; Haiman, Christopher A.; Henderson, Brian E.; Ursin, Giske] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Doherty, Jennifer A.; Chen, Chu; Weiss, Noel S.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Shu, Xiao-ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Akbari, Mohammad R.; Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [De Vivo, Immaculata; Hankinson, Susan E.; McGrath, Monica] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [De Vivo, Immaculata; Hankinson, Susan E.; McGrath, Monica] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [DeMichele, Angela; Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Garcia-Closas, Montserrat; Lacey, James V., Jr.; Yang, Hannah P.] Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. [Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA. [Goodman, Marc T.; Le Marchand, Loic; Lurie, Galina] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. [Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Olson, SH (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63 St, New York, NY 10065 USA. EM olsons@mskcc.org RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS; NCI NIH HHS [CA077398, CA105212, CA112523, CA116543, CA33619, CA39779, CA54281, CA58598, CA63464, CA75977, CA77596, CA80636, CA82838, CA83918, CA91019, CA92002, CA92585, CN67001, K05 CA092002, K07 CA116543, N01 PC035137, N01-PC-35137, N01PC35137, P01 CA033619, P01 CA077596, R01 CA054281, R01 CA058598, R01 CA058598-10, R01 CA063464, R01 CA077398, R01 CA077398-11, R01 CA082838, R01 CA083918, R01 CA091019, R01 CA092585, R01 CA105212, R01 CA112523, R03 CA080636, R37 CA054281, U01 CA063464]; NICHD NIH HHS [K12 HD051959, K12 HD051959-01, N01 HD023166] NR 25 TC 40 Z9 42 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2009 VL 18 IS 1 BP 242 EP 247 DI 10.1158/1055-9965.EPI-08-0689 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200031 PM 19124504 ER PT J AU Church, TR Anderson, KE Caporaso, NE Geisser, MS Le, CT Zhang, Y Benoit, AR Carmella, SG Hecht, SS AF Church, Timothy R. Anderson, Kristin E. Caporaso, Neil E. Geisser, Mindy S. Le, Chap T. Zhang, Yan Benoit, Adam R. Carmella, Steven G. Hecht, Stephen S. TI A Prospectively Measured Serum Biomarker for a Tobacco-Specific Carcinogen and Lung Cancer in Smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HYDROCARBON METABOLIC-ACTIVATION; DNA-ADDUCTS; PHENETHYL ISOTHIOCYANATE; TRANSDERMAL NICOTINE; PULMONARY NEOPLASIA; CIGARETTE SMOKERS; A/J MICE; RISK; PHENANTHRENE; EXPOSURE AB Background: No prior studies have related a tobacco-specific carcinogen to the risk of lung cancer in smokers. Of the over 60 known carcinogens in cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is specific to tobacco and causes lung cancer in laboratory animals. Its metabolites, 4(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), have been studied as biomarkers of exposure to NNK. We studied the relation of prospectively measured NNK biomarkers to lung cancer risk. Methods: In a case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we randomly selected 100 lung cancer cases and 100 controls who smoked at baseline and analyzed their baseline serum for total NNAL, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbon exposure and metabolic activation. To examine the association of the biomarkers with all lung cancers and for histologic subtypes, we computed odds ratios for total NNAL, PheT, and cotinine using logistic regression to adjust for potential confounders. Findings: Individual associations of age, smoking duration, and total NNAL with lung cancer risk were statistically significant. After adjustment, total NNAL was the only biomarker significantly associated with risk (odds ratio, 1.57 per unit SD increase; 95% confidence interval, 1.08-2.28). A similar statistically significant result was obtained for adenocarcinoma risk, but not for nonadenocarcinoma. Conclusions: This first reporting of the effect of the prospectively measured tobacco-specific biomarker total NNAL, on risk of lung cancer in smokers provides insight into the etiology of smoking-related lung cancer and reinforces targeting NNK for cancer prevention. (Cancer Epidemiol Biomarkers Prev 2009;18(1):260-6) C1 [Church, Timothy R.; Geisser, Mindy S.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN 55455 USA. [Anderson, Kristin E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Le, Chap T.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Church, Timothy R.; Anderson, Kristin E.; Le, Chap T.; Zhang, Yan; Benoit, Adam R.; Carmella, Steven G.; Hecht, Stephen S.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Church, TR (reprint author), 420 Delaware St SE,Room 1260,MMC 807, Minneapolis, MN 55455 USA. EM trc@cccs.umn.edu OI Hecht, Stephen/0000-0001-7228-1356; Church, Timothy R./0000-0003-3292-5035 FU U.S. National Cancer Institute; NIH [DA-13333]; Department of Health and Human Services [N01-CN-25513] FX U.S. National Cancer Institute, NIH, Department of Health and Human Services (contract number N01-CN-25513); NIH (grant DA-13333). NR 36 TC 71 Z9 73 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2009 VL 18 IS 1 BP 260 EP 266 DI 10.1158/1055-9965.EPI-08-0718 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200034 PM 19124507 ER PT J AU Peters, TM Schatzkin, A Gierach, GL Moore, SC Lacey, JV Wareham, NJ Ekelund, U Hollenbeck, AR Leitzmanni, MF AF Peters, Tricia M. Schatzkin, Arthur Gierach, Gretchen L. Moore, Steven C. Lacey, James V., Jr. Wareham, Nicholas J. Ekelund, Ulf Hollenbeck, Albert R. Leitzmanni, Michael F. TI Physical Activity and Postmenopausal Breast Cancer Risk in the NIH-AARP Diet and Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE-RECEPTOR STATUS; ESTROGEN-RECEPTOR; WOMENS HEALTH; RECREATIONAL EXERCISE; TUMOR CHARACTERISTICS; UNITED-STATES; LARGE COHORT; IN-SITU; AGE; PROGESTERONE AB Background: Although physical activity has been associated with reduced breast cancer risk, whether this association varies across breast cancer subtypes or is modified by reproductive and lifestyle factors is unclear. Methods: We examined physical activity in relation to postmenopausal breast cancer risk in 1.82,862 U.S. women in the NIH-AARP Diet and Health Study. Physical activity was assessed by self-report at baseline (1995-1996), and 6,609 incident breast cancers were identified through December 31, 2003. Cox regression was used to estimate the relative risk (RR) and 95%, confidence interval (95% CI) of postmenopausal breast cancer overall and by tumor characteristics. Effect modification by select reproductive and lifestyle factors was also explored. Results: In multivariate models, the most active women experienced a 13% lower breast cancer risk versus inactive women (RR, 0.87; 95% CI, 0.81-0.95). This inverse relation was not modified by tumor stage or histology but was suggestively stronger for estrogen receptor (ER)-negative (RR, 0.75; 95% CI, 0.54-1.04) than ER-positive (RR, 0.97; 95% CI, 0.841.12) breast tumors and was suggestively stronger for overweight/obese (RR, 0.86; 95% CI, 0.77-0.96) than lean (RR, 0.95; 95% CI, 0.87-1.05) women. The inverse relation with physical activity was also more pronounced among women who had never used menopausal hormone therapy and those with a positive family history of breast cancer than their respective counterparts. Conclusions: Physical activity was associated with reduced postmenopausal breast cancer risk, particular to ER-negative tumors. These results, along with heterogeneity in the physical activity-breast cancer relation for subgroups of menopausal hormone therapy use and adiposity, indicate that physical activity likely influences breast cancer risk via both estrogenic and estrogen-independent mechanisms. (Cancer Epidemiol Biomarkers Prev 2009;18(1):289-96) C1 [Peters, Tricia M.; Schatzkin, Arthur; Moore, Steven C.; Leitzmanni, Michael F.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gierach, Gretchen L.; Lacey, James V., Jr.] NCI, Hormonal & Reprod Epicemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gierach, Gretchen L.; Hollenbeck, Albert R.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Peters, Tricia M.; Wareham, Nicholas J.; Ekelund, Ulf] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Hollenbeck, Albert R.] Amer Assoc Retired Persons, Washington, DC USA. RP Peters, TM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7232, Bethesda, MD 20892 USA. EM peterst@mail.nih.gov RI Gierach, Gretchen/E-1817-2016; Moore, Steven/D-8760-2016 OI Gierach, Gretchen/0000-0002-0165-5522; Moore, Steven/0000-0002-8169-1661 FU NIH; National Cancer Institute FX Intramural Research Program of the NIH, National Cancer Institute. NR 47 TC 48 Z9 48 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2009 VL 18 IS 1 BP 289 EP 296 DI 10.1158/1055-9965.EPI-08-0768 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200038 PM 19124511 ER PT J AU Mckay, JD McCullough, ML Ziegler, RG Kraft, P Saltzman, BS Riboli, E Barricarte, A Berg, CD Bergland, G Bingham, S Brustad, M Bueno-De-Mesquita, HB Burdette, L Buring, J Calle, EE Chanock, SJ Clavel-Chapelon, F Cox, DG Dossus, L Feigelson, HS Haiman, CA Hankinson, SE Hoover, RN Hunter, DJ Husing, A Kaaks, R Kolonel, LN Le Marchand, L Linseisen, J McCarty, CA Overvad, K Panico, S Purdue, MP Stram, DO Stevens, VL Trichopoulos, D Willett, WC Yuenger, J Thun, MJ AF McKay, James D. McCullough, Marjorie L. Ziegler, Regina G. Kraft, Peter Saltzman, Barbara S. Riboli, Elio Barricarte, Aurelio Berg, Christine D. Bergland, Goran Bingham, Sheila Brustad, Magritt Bueno-de-Mesquita, H. Bas Burdette, Laurie Buring, Julie Calle, Eugenia E. Chanock, Stephen J. Clavel-Chapelon, Francoise Cox, David G. Dossus, Laure Feigelson, Heather Spencer Haiman, Christopher A. Hankinson, Susan E. Hoover, Robert N. Hunter, David J. Husing, Anika Kaaks, Rudolph Kolonel, Laurence N. Le Marchand, Loic Linseisen, Jakob McCarty, Catherine A. Overvad, Kim Panico, Salvatore Purdue, Mark P. Stram, Daniel O. Stevens, Victoria L. Trichopoulos, Dimitrios Willett, Walter C. Yuenger, Jeffrey Thun, Michael J. TI Vitamin D Receptor Polymorphisms and Breast Cancer Risk: Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UK CAUCASIAN POPULATION; GENE POLYMORPHISMS; UNITED-STATES; SUN EXPOSURE; AFRICAN-AMERICAN; ASSOCIATION; 25-HYDROXYVITAMIN-D; GENOTYPE; SURVIVAL; WOMEN AB Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs154441.0 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokIff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability. Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. Results: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1-1.6; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.1.0; 95% CI, 0.981.24). No association was noted between rs1544410 (Bsm I) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297-305) C1 [McCullough, Marjorie L.; Calle, Eugenia E.; Feigelson, Heather Spencer; Stevens, Victoria L.; Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30303 USA. [McKay, James D.] IARC, Lyon, France. [Ziegler, Regina G.; Hoover, Robert N.; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Kraft, Peter; Cox, David G.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Cambridge, MA 02138 USA. [Hankinson, Susan E.; Trichopoulos, Dimitrios; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Buring, Julie] Harvard Univ, Sch Publ Hlth, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA. [Saltzman, Barbara S.; Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Barricarte, Aurelio] CIBERESP, Publ Hlth Inst Navarra, Pamplona, Spain. [Bergland, Goran] Lund Univ, Univ Hosp UMAS, Dept Lab Med, Malmo, Sweden. [Bergland, Goran] Lund Univ, Univ Hosp UMAS, Dept Clin Sci Malmo, Malmo, Sweden. [Bingham, Sheila] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Brustad, Magritt] Univ Tromso, Inst Community Med, Tromso, Norway. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, Bilhoven, Netherlands. [Clavel-Chapelon, Francoise] Natl Canc Inst Frederick, Sci Applicat Int Corp Frederick Inc, Core Genotyping Facil, Gaithersburg, MD USA. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. [Dossus, Laure; Husing, Anika; Kaaks, Rudolph; Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Los Angeles, CA USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Overvad, Kim] Arhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy. RP McCullough, ML (reprint author), Amer Canc Soc, 6D,250 Williams St, Atlanta, GA 30303 USA. EM marji.mccullough@cancer.org RI Cox, David/A-2023-2009; Dossus, Laure/B-2875-2013; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Purdue, Mark/C-9228-2016; Panico, Salvatore/K-6506-2016 OI Cox, David/0000-0002-2152-9259; Dossus, Laure/0000-0003-2716-5748; Linseisen, Jakob/0000-0002-9386-382X; Purdue, Mark/0000-0003-1177-3108; Panico, Salvatore/0000-0002-5498-8312 FU National Cancer Institute; NIH [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758, N01-CO-12400] FX National Cancer Institute, NIH cooperative agreements U01-CA98233, U01-CA98710, U01-CA98216, and U01-CA98758 and contract N01-CO-12400. NR 38 TC 48 Z9 49 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 JAN PY 2009 VL 18 IS 1 BP 297 EP 305 DI 10.1158/1055-9965.EPI-08-0539 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200039 PM 19124512 ER PT J AU Freedman, DM Fuhrman, B Graubard, BI Chang, SC AF Freedman, D. Michal Fuhrman, Barbara Graubard, Barry I. Chang, Shih-Chen TI Vitamin D and Cancer Mortality SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 [Freedman, D. Michal; Fuhrman, Barbara; Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chang, Shih-Chen] AstraZeneca, Wilmington, DE USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. OI Fuhrman, Barbara/0000-0002-1777-9888; Grant, William/0000-0002-1439-3285 FU Intramural NIH HHS [Z99 CA999999] NR 2 TC 10 Z9 10 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 JAN PY 2009 VL 18 IS 1 BP 359 EP 359 DI 10.1158/1055-9965.EPI-08-1023 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 394CW UT WOS:000262424200049 PM 19124522 ER PT J AU Aragon-Ching, JB Ning, YM Chen, CC Latham, L Guadagnini, JP Gulley, JL Arlen, PM Wright, JJ Parnes, H Figg, WD Dahut, WL AF Aragon-Ching, Jeanny B. Ning, Yang-Min Chen, Clara C. Latham, Lea Guadagnini, Jean-Pierre Gulley, James L. Arlen, Philip M. Wright, John J. Parnes, Howard Figg, William D. Dahut, William L. TI Higher Incidence of Osteonecrosis of the Jaw (ONJ) in Patients with Metastatic Castration Resistant Prostate Cancer Treated with Anti-Angiogenic Agents SO CANCER INVESTIGATION LA English DT Article DE Osteonecrosis of the jaw; Bisphosphonates; Anti-angiogenesis; Chemotherapy; Prostate pancer ID ZOLEDRONIC ACID; MULTIPLE-MYELOMA; RISK-FACTORS; BISPHOSPHONATES; CHEMOTHERAPY; BONE; RECOMMENDATIONS; PREVENTION; BREAST AB ONJ is an important toxicity in cancer patients receiving bisphosphonate therapy. Here we report a higher than usual incidence of ONJ, 11 of 60 (18.3%, 95% Confidence Interval, CI: 9%-28%) patients enrolled in a phase II clinical trial combining bevacizumab, docetaxel, thalidomide, and prednisone (ATTP) in chemotherapy-naive men with metastatic castration resistant prostate cancer (mCRPC). The use of bisphosphonates was allowed at study entry. Our study suggests that anti-angiogenic and chemotherapy agents can predispose to the development of ONJ in men with mCRPC on zoledronic acid. Imaging modalities, such as bone scans, may be useful in following the clinical course of patients who develop ONJ. C1 [Aragon-Ching, Jeanny B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Clara C.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. [Guadagnini, Jean-Pierre] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Parnes, Howard] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Aragon-Ching, JB (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chingj@mail.nih.gov; dahutw@mail.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016; OI Gulley, James/0000-0002-6569-2912; Aragon-Ching, Jeanny/0000-0002-6714-141X FU National Cancer Institute; Center for Cancer Research; National Institutes of Health FX This project has been supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health. The content of this publication does not 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 34 TC 61 Z9 63 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 EI 1532-4192 J9 CANCER INVEST JI Cancer Invest. PY 2009 VL 27 IS 2 BP 221 EP 226 AR PII 908975688 DI 10.1080/07357900802208608 PG 6 WC Oncology SC Oncology GA 411KU UT WOS:000263649300014 PM 19235596 ER PT S AU Greenwald, P Dunn, BK AF Greenwald, Peter Dunn, Barbara K. BE Senn, HJ Kapp, U Otto, F TI Do We Make Optimal Use of the Potential of Cancer Prevention? SO CANCER PREVENTION II SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT 5th International Cancer Prevention Conference CY 2008 CL St Gallen, SWITZERLAND SP Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, Canc Res UK, Union Int Contre Canc, European Assoc Canc Res, Amer Canc Soc, Swiss Canc League ID PROSTATE-CANCER; BREAST-CANCER; SCREENING TRIAL; RISK; DISEASE; TAMOXIFEN; MEDICINE; EXPOSURE; SCIENCE; BIOLOGY AB Three decades of intensive experimental and clinical research on cancer prevention have yielded ail impressive body of scientific knowledge about cancer epidemiology, causation, and preventative measures. Despite our increased understanding in these critical areas, this knowledge is not being translated adequately into initiatives that will impact public health. The recent release of the World Cancer Research Fund/American Institute for Cancer Research report on diet and lifestyle strategies for cancer prevention-grounded in an evidence-based, systematic review of the published literature-is a strong acknowledgment of the benefits of a lifestyle approach to reduce cancer risk. The report also emphasizes the need to increase basic nutritional science research to make optimal use of the knowledge gained in the past three decades. Medical approaches-represented by chemoprevention clinical trials-also have become more focused based on results from basic science leads. The expansion of preclinical chemoprevention studies and greater attention to "first-in-human" prevention trials that safely shorten the timeline for new drug development are needed. The development of a prevention focus fir what the U.S. Food and Drug Administration calls "exploratory investigational new drug studies" and what investigators at the National Cancer Institute are calling "phase 0" clinical trials will contribute to the decision-making involved in designing larger cancer prevention clinical trials. Past achievements in phase III prevention clinical trials-such as the Prostate Cancer Prevention Trial, the Breast Cancer Prevention Trial, and the Study of Tamoxifen and Raloxifene-have provided early successes as evidence of the potential for public benefit to be derived from this research. Nevertheless, the application of these findings to clinical practice and the design of future prevention trials remains a challenge. Current strategies include the refinement of risk assessment models for several major cancers. Additional initiatives, based on emerging basic and clinical research, involve the development of potential biomarkers for cancer risk and early detection by the National Cancer Institute's Early Detection Research Network. Although a recent progress report indicates that biomarkers of cancer susceptibility and exposure have been identified, continued work is needed to validate such markers for clinical use. Using this information optimally for prevention through lifestyle changes or medical interventions will. C1 [Greenwald, Peter; Dunn, Barbara K.] NCI, NIH, Canc Prevent Div, EPN 2056, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, NIH, Canc Prevent Div, EPN 2056, Room 2040,6130 Execut Blvd, Bethesda, MD 20892 USA. EM hursens@mail.nih.gov NR 33 TC 5 Z9 5 U1 3 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-540-69296-6 J9 RECENT RES CANCER PY 2009 VL 181 BP 3 EP 17 PG 15 WC Oncology SC Oncology GA BIR96 UT WOS:000262395600001 PM 19213552 ER PT S AU Wickerham, DL Costantino, JP Vogel, VG Cronin, WM Cecchini, RS Ford, LG Wolmark, N AF Wickerham, D. Lawrence Costantino, Joseph P. Vogel, Victor G. Cronin, Walter M. Cecchini, Reena S. Ford, Leslie G. Wolmark, Norman BE Senn, HJ Kapp, U Otto, F TI The Use of Tamoxifen and Raloxifene for the Prevention of Breast Cancer SO Cancer Prevention II SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT 5th International Cancer Prevention Conference CY 2008 CL St Gallen, SWITZERLAND SP Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, Canc Res UK, Union Int Contre Canc, European Assoc Canc Res, Amer Canc Soc, Swiss Canc League ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; TRIAL; RISK; NSABP AB The NSABP Study of Tamoxifen and Raloxifene (STAR). launched in 1999, compared tamoxifen with raloxifene in a population of healthy postmenopausal women at increased risk for breast cancer to determine the relative effects on the risk of invasive breast cancer. To be eligible for participation, a woman had to be healthy with at least a 5-year predicted breast cancer risk of 1.66'% based on the Gail model or a history of lobular carcinoma in situ (LCIS) treated by local excision alone. All participants were at least 35 years of age and postmenopausal. Between July 1999 and November 2004, 19,747 participants were randomized to receive either tamoxifen (20 mg, plus placebo) or raloxifene (60 mg, plus placebo) daily for a 5-year period. The mean age of the participants was 58.5 years; 93% were white and 51.6% had a hysterectomy prior to entering the study. Of the women, 71% had one or more first degree female relatives (mother, sister, daughter) with a history of breast cancer and 9.2% of the women had a personal history of LCIS. A history of atypical hyperplasia of the breast was noted in 22.7% of the participants. The mean predicted 5-year risk of developing breast cancer among the study population was 4.03% (SD, 2.17%) with a lifetime predicted risk of 16%. The mean tune of follow-up is 3.9 years (SD, 1.6 years). There was no difference between the effect of tamoxifen and the effect of raloxifene on the incidence of invasive breast cancer; there were 163 cases of invasive breast cancer in the tamoxifen-treated group and 168 cases in those women assigned to raloxifene (incidence 4.30 per 1,000 vs 4.41 per 1,000; RR 1.02; 95% Cl, 082-1.28). There were fewer cases of noninvasive breast cancer (LCIS and ductal carcinoma in situ [DCIS]) in the tamoxifen group (57 cases) than in the raloxifene group (80 cases), although the difference is not yet statistically significant (incidence 1.51 vs 2.11 per 1,000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 cases with raloxifene (RR, 0.63; 95%) CI, 0.35-1.08). C1 [Wickerham, D. Lawrence; Costantino, Joseph P.; Vogel, Victor G.; Cronin, Walter M.; Cecchini, Reena S.] Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Operat Ctr, Pittsburgh, PA 15212 USA. [Costantino, Joseph P.; Cecchini, Reena S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Ford, Leslie G.] NCI, Canc Prevent Div, NIH, EPN 2046, Bethesda, MD 20892 USA. [Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Wickerham, DL (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Operat Ctr, 5th Floor, Pittsburgh, PA 15212 USA. EM larry.wickerham@nsabp.org OI Cecchini, Reena/0000-0002-9075-9357 FU NCI NIH HHS [UG1 CA189867, U10 CA037377, U10 CA069974] NR 10 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-540-69296-6 J9 RECENT RES CANCER PY 2009 VL 181 BP 113 EP 119 PG 7 WC Oncology SC Oncology GA BIR96 UT WOS:000262395600012 PM 19213563 ER PT S AU Dunn, BK Ryan, A Ford, LG AF Dunn, Barbara K. Ryan, Anne Ford, Leslie G. BE Senn, HJ Kapp, U Otto, F TI Selenium and Vitamin E Cancer Prevention Trial: A Nutrient Approach to Prostate Cancer Prevention SO Cancer Prevention II SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT 5th International Cancer Prevention Conference CY 2008 CL St Gallen, SWITZERLAND SP Int Soc Canc Prevent, European Sch Oncol, European Soc Med Oncol, Canc Res UK, Union Int Contre Canc, European Assoc Canc Res, Amer Canc Soc, Swiss Canc League ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; ALPHA-TOCOPHEROL; BETA-CAROTENE; SUPPLEMENTATION; SELECT; RISK; CELLS; CARCINOMA; LINXIAN AB Prostate cancer continues to be both a major health threat, especially among African-American men, and a public health burden. However, growing evidence suggests that selenium and vitamin E may decrease the risk of this disease. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), a phase III randomized, placebo-controlled study, is designed to determine whether selenium and vitamin E, alone or in combination, decrease the risk of prostate cancer in healthy men. SELECT opened to accrual on 25 July 2001 in more than 400 clinical sites across the United States, Puerto Rico, and Canada; the goal was to randomize 32,400 men. Accrual was completed in June 2004, 2 years ahead of schedule, with a total of 35,534 men randomized. Eligibility requirements include age of at least 55 years (African-American then at least 50 years), and no evidence of prostate cancer as determined by a serum PSA level of no more than 4 ng/ml and a digital rectal exam (DRE) not suspicious for prostate cancer. Participants were randomized to receive selenium (200 mu g/day of l-selenomethionine) and/or vitamin E (400 IU/day of all-rue-alpha-tocopheryl acetate) supplementation for a minimum of 7 years (maximum of 12 years). The rationale for choosing these agents was based on preclinical data as well as analyses of secondary endpoints in cancer prevention clinical trials. The primary endpoint of SELECT is occurrence of prostate cancer based on community standards of diagnosis. Several other non-cancer endpoints are also being explored. C1 [Dunn, Barbara K.; Ryan, Anne; Ford, Leslie G.] NCI, Canc Prevent Div, NIH, EPN 2046, Bethesda, MD 20892 USA. RP Ford, LG (reprint author), NCI, Canc Prevent Div, NIH, EPN 2046, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM fordl@mail.nih.gov NR 34 TC 10 Z9 11 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 978-3-540-69296-6 J9 RECENT RES CANCER PY 2009 VL 181 BP 183 EP 193 PG 11 WC Oncology SC Oncology GA BIR96 UT WOS:000262395600017 PM 19213568 ER PT J AU Dennis, PA AF Dennis, Phillip A. TI Rapamycin for Chemoprevention of Upper Aerodigestive Tract Cancers SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID ADVANCED SOLID TUMORS; PHASE-I; MAMMALIAN TARGET; ANTITUMOR-ACTIVITY; MTOR INHIBITION; AKT ACTIVATION; LUNG-CANCER; MODEL; EVEROLIMUS; SCHEDULE C1 NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 26 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2009 VL 2 IS 1 BP 7 EP 9 DI 10.1158/1940-6207.CAPR-08-0215 PG 3 WC Oncology SC Oncology GA 420MQ UT WOS:000264294300002 PM 19139011 ER PT J AU Czeminski, R Amornphimoltham, P Patel, V Molinolo, AA Gutkind, JS AF Czeminski, Rakefet Amornphimoltham, Panomwat Patel, Vyomesh Molinolo, Alfredo A. Gutkind, J. Silvio TI Targeting Mammalian Target of Rapamycin by Rapamycin Prevents Tumor Progression in an Oral-Specific Chemical Carcinogenesis Model SO CANCER PREVENTION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; NECK-CANCER; HEAD; CHEMOPREVENTION; MTOR; INHIBITORS; DISEASE; COMPLEX; TONGUE AB The increased molecular understanding of cancerous growth may now afford the opportunity to develop novel therapies targeting specific dysregulated molecular mechanisms contributing to the progression of each cancer type. In this regard, the aberrant activation of Akt/mammalian target of rapamycin ( mTOR) pathway is a frequent event in head and neck squamous cell carcinomas (HNSCC), thus representing a potential molecular target for the treatment of HNSCC patients. The ability to translate this emerging body of information into effective therapeutic strategies, however, has been hampered by the limited availability of animal models for oral malignancies. Here, we show that the administration in the drinking water to mice of 4-nitroquinoline-1 oxide, a DNA adduct-forming agent that serves as a surrogate of tobacco exposure, leads to the progressive appearance of preneoplastic and tumoral lesions in the tongue and oral mucosa, with 100% incidence after only 16 weeks of carcinogen exposure. Remarkably, many of these lesions evolve spontaneously into highly malignant SCCs few weeks after 4-nitroquinoline-1 oxide withdrawal. In this model, we have observed that the activation of the Akt-mTOR biochemical route represents an early event, which is already detectable in dysplastic lesions. Furthermore, we show that the inhibition of mTOR by the chronic administration of rapamycin halts the malignant conversion of precancerous lesions and promotes the regression of advanced carcinogen-induced SCCs. Together, these findings support the contribution of the mTOR signaling pathway to HNSCC progression and provide a strong rationale for the early evaluation of mTOR inhibitors as a molecular-targeted strategy for HNSCC chemoprevention and treatment. C1 [Czeminski, Rakefet; Amornphimoltham, Panomwat; Patel, Vyomesh; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU NIH; National Institute of Dental and Craniofacial Research FX Intramural Research Program of NIH, National Institute of Dental and Craniofacial Research. NR 43 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2009 VL 2 IS 1 BP 27 EP 36 DI 10.1158/1940-6207.CAPR-08-0147 PG 10 WC Oncology SC Oncology GA 420MQ UT WOS:000264294300006 ER PT J AU Mentor-Marcel, RA Bobe, G Barrett, KG Young, MR Albert, PS Bennink, MR Lanza, E Colburn, NH AF Mentor-Marcel, Roycelynn A. Bobe, Gerd Barrett, Kathleen G. Young, Matthew R. Albert, Paul S. Bennink, Maurice R. Lanza, Elaine Colburn, Nancy H. TI Inflammation-Associated Serum and Colon Markers as Indicators of Dietary Attenuation of Colon Carcinogenesis in ob/ob Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; COLORECTAL-CANCER; ADIPOSE-TISSUE; OBESE SUBJECTS; INSULIN-RESISTANCE; CIRCULATING LEVELS; NAVY BEANS; INTERLEUKIN-6; EXPRESSION; MOUSE AB Although inflammatory cytokines and obesity-associated serum proteins have been reported as biomarkers of colorectal adenoma risk in humans, little is known of biomarkers of response to interventions that attenuate tumorigenesis. Dietary navy beans and their fractions attenuate colon carcinogenesis in carcinogen-induced genetically obese mice. We hypothesized that this attenuation would be associated with changes in inflammatory cytokines and obesity-related serum proteins that may serve as measures of efficacy. ob/ob mice (n = 160) were injected with the carcinogen azoxymethane (AOM) to induce colon cancer and randomly placed on one of four diets (control, whole navy bean, bean residue fraction, or bean extract fraction) for 26 to 28 wk. Serum was analyzed for 14 inflammation-or obesity-related proteins, and colon RNA was analyzed for expression of 84 inflammation-associated genes. Six of 14 serum proteins were increased [i.e., interleukin (IL)-4, IL-5, IL-6, IL-10, IFN gamma, granulocyte macrophage colony-stimulating factor] in hyperplastic/dysplastic stages of colon carcinogenesis. Bean-fed mice had significantly higher monocyte chemoattractant protein-1 and lower IL-6 levels in serum. In colon mucosa, 55 of 84 inflammation-associated genes differed between AOM-induced and noninduced mice. Of the 55 AOM-induced genes, 5 were counteracted by bean diets, including IL-6 whose increase in expression levels was attenuated by bean diets in AOM-induced mice. In summary, IL-6 emerged as a serum protein that was increased in hyperplastic/dysplastic stages of colon carcinogenesis, but attenuated with bean-based diet in serum and colon mucosa. Changes in a subset of inflammation-associated serum proteins and colon gene expression may serve as response indicators of dietary attenuation of colon carcinogenesis. C1 [Mentor-Marcel, Roycelynn A.; Bobe, Gerd; Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. [Mentor-Marcel, Roycelynn A.; Bobe, Gerd; Young, Matthew R.; Colburn, Nancy H.] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Mentor-Marcel, Roycelynn A.; Bobe, Gerd] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Frederick, MD 21702 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Frederick, MD 21702 USA. [Barrett, Kathleen G.; Bennink, Maurice R.] Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. RP Mentor-Marcel, RA (reprint author), NCI, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 576,Room 110, Frederick, MD 21702 USA. EM marcelr@mail.nih.gov FU NIH; National Cancer Institute; United States Agency for International Development; Michigan Agricultural Experiment Station FX NIH Intramural Research Program, National Cancer Institute; the United States Agency for International Development through Bean/Cowpea Collaborative Research Support Program; and Michigan Agricultural Experiment Station. NR 50 TC 15 Z9 16 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2009 VL 2 IS 1 BP 60 EP 69 DI 10.1158/1940-6207.CAPR-08-0086 PG 10 WC Oncology SC Oncology GA 420MQ UT WOS:000264294300010 PM 19139019 ER PT J AU Huang, F Greer, A Hurlburt, W Han, X Hafezi, R Wittenberg, GM Reeves, K Chen, JW Robinson, D Li, AX Lee, FY Gottardis, MM Clark, E Helman, L Attar, RM Dongre, A Carboni, JM AF Huang, Fei Greer, Ann Hurlburt, Warren Han, Xia Hafezi, Rameh Wittenberg, Gayle M. Reeves, Karen Chen, Jiwen Robinson, Douglas Li, Aixin Lee, Francis Y. Gottardis, Marco M. Clark, Edwin Helman, Lee Attar, Ricardo M. Dongre, Ashok Carboni, Joan M. TI The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; BINDING-PROTEINS; EWINGS-SARCOMA; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; RESISTANCE; TUMORS; CHEMOTHERAPY; DOXORUBICIN; EXPRESSION AB Overexpression and enhanced activity of insulin-like growth factor-I receptor (IGF-IR) in diverse tumor types make it an attractive target for cancer therapy. BMS-536924 is a potent small molecule inhibitor of IGF-IR, which shows antitumor activity in multiple tumor models, including sarcoma. To facilitate the development of IGF-IR inhibitors as cancer therapy, identification of biomarkers for selecting patients most likely to derive clinical benefit is needed. To do so, 28 sarcoma and neuroblastoma cell lines were screened for in vitro response to BMS-536924 to identify sensitive and resistant cell lines. Notably, Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma are more responsive to BMS-536924, suggesting these specific subtypes may represent potential targeted patient subpopulations for the IGF-IR inhibitor. Gene expression and protein profiling were performed on these cell lines, and candidate biomarkers correlating with intrinsic and/or acquired resistance to BMS-536924 were identified. TGF-I, IGF-II, and IGF-IR were highly expressed in sensitive cell lines, whereas IGFBP-3 and IGFBP-6 were highly expressed in resistant lines. Overexpression of epidermal growth factor receptor (EGFR) and its ligands in resistant cell lines may represent one possible resistance mechanism by the adaptation of IGF-IR-independent growth using alternative signaling pathways. Based on cross-talk between IGF-IR and EGFR pathways, combination studies to target both pathways were performed, and enhanced inhibitory activities were observed. These results provide a strategy for testing combinations of IGF-IR inhibitors with other targeted therapies in clinical studies to achieve improved patient outcomes. Further exploration of mechanisms for intrinsic and acquired drug resistance by these preclinical studies may lead to more rationally designed drugs that target multiple pathways for enhanced antitumor efficacy. [Cancer Res 2009;69(1):161-70] C1 [Huang, Fei; Greer, Ann; Hurlburt, Warren; Han, Xia; Hafezi, Rameh; Wittenberg, Gayle M.; Reeves, Karen; Chen, Jiwen; Robinson, Douglas; Li, Aixin; Lee, Francis Y.; Gottardis, Marco M.; Clark, Edwin; Attar, Ricardo M.; Dongre, Ashok; Carboni, Joan M.] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. [Helman, Lee] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Huang, F (reprint author), Bristol Myers Squibb Co, POB 5400,HW3B-2-02, Princeton, NJ 08543 USA. EM fei.huang@bms.com; joan.carboni@bms.com NR 50 TC 118 Z9 124 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2009 VL 69 IS 1 BP 161 EP 170 DI 10.1158/0008-5472.CAN-08-0835 PG 10 WC Oncology SC Oncology GA 391ZQ UT WOS:000262273100022 PM 19117999 ER PT J AU Lukes, L Crawford, NPS Walker, R Hunter, KW AF Lukes, Luanne Crawford, Nigel P. S. Walker, Renard Hunter, Kent W. TI The Origins of Breast Cancer Prognostic Gene Expression Profiles SO CANCER RESEARCH LA English DT Article ID METASTATIC PROGRESSION; SIGNATURE; TUMORS; SURVIVAL; CELLS; BONE; POPULATION; PATTERNS; TISSUES; SIPA1 AB Recent high profile clinical trials show that microarray-based gene expression profiling has the potential to become an important tool for predicting prognosis in breast cancer. Earlier work in our laboratory using mouse models and human breast cancer populations has enabled us to show that metastasis susceptibility is an inherited trait. This same combined approach facilitated the identification of a number of candidate genes that, when dysregulated, have the potential to induce prognostic gene expression profiles in human data sets. To investigate if these gene expression signatures were of somatic or germline origin and to assess the contribution of different cell types to the induction of these signatures, we have performed a series of expression profiling experiments in a mouse model of metastatic breast cancer. These results show that both the tumor epithelium and invading stromal tissues contribute to the development of prognostic gene signatures. Furthermore, analysis of normal tissues and tumor transplants suggests that prognostic signatures result from both somatic and inherited components, with the inherited components being more consistently predictive. [Cancer Res 2009;69(1):310-8] C1 [Lukes, Luanne; Crawford, Nigel P. S.; Walker, Renard; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 5046C,37 Convent Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU NIH National Cancer Institute Center for Cancer Research FX Grant support: Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research. NR 43 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2009 VL 69 IS 1 BP 310 EP 318 DI 10.1158/0008-5472.CAN-08-3520 PG 9 WC Oncology SC Oncology GA 391ZQ UT WOS:000262273100039 PM 19118016 ER PT J AU Cataisson, C Ohman, R Patel, G Pearson, A Tsien, M Jay, S Wright, L Hennings, H Yuspa, SH AF Cataisson, Christophe Ohman, Rebecca Patel, Gopal Pearson, Andrea Tsien, Margaret Jay, Steve Wright, Lisa Hennings, Henry Yuspa, Stuart H. TI Inducible Cutaneous Inflammation Reveals a Protumorigenic Role for Keratinocyte CXCR2 in Skin Carcinogenesis SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; KINASE-C-ALPHA; PROTEIN-KINASE; TUMOR-GROWTH; INTRAEPIDERMAL INFLAMMATION; CHEMOKINE EXPRESSION; TARGETED DISRUPTION; EPIDERMAL NEOPLASIA; CARCINOMA-CELLS; TRANSGENIC MICE AB Transgenic mice that overexpress PKC alpha, in the epidermis (K5-PKC alpha mice) exhibit acute CXCR2-mediated intraepidermal neutrophilic inflammation and a strong epidermal hyperplasia in response to application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We now show that hyperplasia is independent of infiltrating neutrophils. Furthermore, when K5-PKC alpha mice were initiated with 7,12-dimethylbenz(a)annthracene (DMBA) and promoted with a low dose of TPA, 58% of K5-PKC alpha mice developed skin papillomas that progressed to carcinoma, whereas wild-type mice did not develop tumors. We confirmed that CXCR2 is expressed by keratinocytes and showed that transformation by oncogenic ras (a hallmark of DMBA initiation) or TPA exposure induced all CXCR2 ligands. Ras induction of CXCR2 ligands was mediated by autocrine activation of epidermal growth factor receptor and nuclear factor-kappa B, and potentiated by PKC alpha. Oncogenic ras also induced CXCR2 ligands in keratinocytes genetically ablated for CXCR2. However, ras transformed CXCR2 null keratinocytes formed only small skin tumors in ortbotopic skin grafts to CXCR2 intact hosts, whereas transformed wild-type keratinocytes produced large tumors. In vitro, CXCR2 was essential for CXCR2 ligand-stimulated migration of ras-transformed keratinocytes and for ligand activation of the extracellular signal-regulated kinase (ERK) and Akt pathways. Both migration and activation of ERK and Akt were restored by CXCR2 reconstitution of CXCR2 null keratinocytes. Thus, activation of CXCR2 on ras-transformed keratinocytes has both promigratory and protumorigenic functions. The up-regulation of CXCR2 ligands after initiation by oncogenic ras and promotion with TPA fit the mouse skin model provides a mechanism to stimulate migration by both autocrine and paracrine pathways and contribute to tumor development. [Cancer Res 2009;69(1):319-28] C1 [Cataisson, Christophe; Ohman, Rebecca; Patel, Gopal; Pearson, Andrea; Tsien, Margaret; Jay, Steve; Wright, Lisa; Hennings, Henry; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov RI Patel, Girish/N-7075-2013 FU NIH; NCI; Center for Cancer Research FX Grant support: Intramural Research program of the NIH, NCI, Center for Cancer Research. NR 50 TC 41 Z9 43 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2009 VL 69 IS 1 BP 319 EP 328 DI 10.1158/0008-5472.CAN-08-2490 PG 10 WC Oncology SC Oncology GA 391ZQ UT WOS:000262273100040 PM 19118017 ER PT J AU Anderberg, C Li, H Fredriksson, L Andrae, J Betsholtz, C Li, XR Eriksson, U Pietras, K AF Anderberg, Charlotte Li, Hong Fredriksson, Linda Andrae, Johanna Betsholtz, Christer Li, Xuri Eriksson, Ulf Pietras, Kristian TI Paracrine Signaling by Platelet-Derived Growth Factor-CC Promotes Tumor Growth by Recruitment of Cancer-Associated Fibroblasts SO CANCER RESEARCH LA English DT Article ID MESENCHYMAL STEM-CELLS; FACTOR-RECEPTOR-ALPHA; STROMAL FIBROBLASTS; BREAST-CANCER; INTERSTITIAL FIBROSIS; PROSTATE-CANCER; KEY DETERMINANT; LUNG-CARCINOMA; PHASE-I; PDGF AB Cancer results from the concerted performance of malignant cells and stromal cells. Cell types populating the microenvironment are enlisted by the tumor to secrete a host of growth-promoting cues, thus upholding tumor initiation and progression. Platelet-derived growth factors (PDGF) support the formation of a prominent tumor stromal compartment. by as of yet unidentified molecular effectors. Whereas PDGF-CC induces fibroblast reactivity and fibrosis in a range of tissues, little is known about the function of PDGF-CC in shaping the tumor-stroma interplay. Herein, we present evidence for a paracrine signaling network involving PDGF-CC and PDGF receptor-alpha in malignant melanoma. Expression of PDGFC in a mouse model accelerated tumor growth through recruitment and activation of different subsets of cancer-associated fibroblasts. In seeking the molecular identify of the supporting factors provided by cancer-associated fibroblasts, we made use of antibody arrays and an in vivo coinjection model to identify osteopontin as the effector of the augmented tumor growth induced by PDGF-CC. In conclusion, we establish paracrine signaling by PDGF-CC as a potential drug target to reduce stromal support in malignant melanoma. [Cancer Res 2009;69(1):369-78] C1 [Anderberg, Charlotte; Li, Hong; Fredriksson, Linda; Andrae, Johanna; Betsholtz, Christer; Eriksson, Ulf; Pietras, Kristian] Ludwig Inst Canc Res Ltd, Stockholm Branch, SE-17177 Stockholm, Sweden. [Andrae, Johanna; Betsholtz, Christer] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden. [Li, Xuri] NEI, NIH, Bethesda, MD 20892 USA. RP Pietras, K (reprint author), Ludwig Inst Canc Res Ltd, Stockholm Branch, Nobels Vag 3,Box 240, SE-17177 Stockholm, Sweden. EM Kristian.Pietras@LICR.KI.SE OI Fredriksson, Linda/0000-0003-4952-2742 FU Swedish Research Council Linnaeus; Swedish Cancer Society; Karolinska Institutet Cancer Strategic grant; Karolinska Institutet FX Grant support: Swedish Research Council Linnaeus grant. to the STARGEt consortium (K. Pietras, C. Betsholtz, and U. Eriksson), the Swedish Cancer Society (K. Pietras and U. Erksson), Karolinska Institutet Cancer Strategic grant. (K. Pietras), and Karolinska Institutet (C. Anderberg and U. Eriksson). NR 49 TC 105 Z9 107 U1 1 U2 11 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 JAN 1 PY 2009 VL 69 IS 1 BP 369 EP 378 DI 10.1158/0008-5472.CAN-08-2724 PG 10 WC Oncology SC Oncology GA 391ZQ UT WOS:000262273100045 PM 19118022 ER PT J AU Yang, YL Kitagaki, J Wang, H Hou, DX Perantoni, AO AF Yang, Yili Kitagaki, Jirouta Wang, Honghe Hou, De-Xing Perantoni, Alan O. TI Targeting the ubiquitin-proteasome system for cancer therapy SO CANCER SCIENCE LA English DT Review ID NF-KAPPA-B; SMALL-MOLECULE ANTAGONISTS; TUMOR-SUPPRESSOR PROTEIN; DNA-DAMAGE RESPONSE; LIGASE ACTIVITY; FANCONI-ANEMIA; P53 PATHWAY; IN-VIVO; RING DOMAIN; INHIBITORS AB The ubiquitin-proteasome system plays a critical role in controlling the level, activity and location of various cellular proteins. Significant progress has been made in investigating the molecular mechanisms of ubiquitination, particularly in understanding the structure of the ubiquitination machinery and identifying ubiquitin protein ligases, the primary specificity-determining enzymes. Therefore, it is now possible to target specific molecules involved in ubiquitination and proteasomal degradation to regulate many cellular processes such as signal transduction, proliferation and apoptosis. In particular, alterations in ubiquitination are observed in most, if not all, cancer cells. This is manifested by destabilization of tumor suppressors, such as p53, and overexpression of oncogenes such as c-Myc and c-Jun. In addition to the development and clinical validation of proteasome inhibitor, bortezomib, in myeloma therapy, recent studies have demonstrated that it is possible to develop inhibitors for specific ubiquitination and deubiquitination enzymes. With the help of structural studies, rational design and chemical synthesis, it is conceivable that we will be able to use 'druggable' inhibitors of the ubiquitin system to evaluate their effects in animal tumor models in the not-so-distant future. (Cancer Sci 2009; 100: 24-28). C1 [Yang, Yili; Kitagaki, Jirouta; Wang, Honghe; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. [Hou, De-Xing] Kagoshima Univ, Dept Biochem Sci & Technol, Fac Agr, Kagoshima 8900065, Japan. RP Yang, YL (reprint author), NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. EM yangyili@ncifcrf.gov RI Hou, De-Xing/C-9296-2011 FU Intramural NIH HHS [Z99 CA999999] NR 71 TC 74 Z9 80 U1 2 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JAN PY 2009 VL 100 IS 1 BP 24 EP 28 DI 10.1111/j.1349-7006.2008.01013.x PG 5 WC Oncology SC Oncology GA 390FN UT WOS:000262149800004 PM 19037995 ER PT J AU Maynard, S Schurman, SH Harboe, C de Souza-Pinto, NC Bohr, VA AF Maynard, Scott Schurman, Shepherd H. Harboe, Charlotte de Souza-Pinto, Nadja C. Bohr, Vilhelm A. TI Base excision repair of oxidative DNA damage and association with cancer and aging SO CARCINOGENESIS LA English DT Review ID STRAND BREAK REPAIR; AMYOTROPHIC-LATERAL-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; RADICAL-INDUCED DAMAGE; HAMSTER OVARY CELLS; LIGASE-I GENE; MITOCHONDRIAL-DNA; NITRIC-OXIDE; ALZHEIMERS-DISEASE; POLYMERASE-BETA AB Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA readily, generating a variety of DNA lesions, such as oxidized bases and strand breaks. If not properly removed, DNA damage can be potentially devastating to normal cell physiology, leading to mutagenesis and/or cell death, especially in the case of cytotoxic lesions that block the progression of DNA/RNA polymerases. Damage-induced mutagenesis has been linked to various malignancies. The major mechanism that cells use to repair oxidative damage lesions, such as 8-hydroxyguanine, formamidopyrimidines, and 5-hydroxyuracil, is base excision repair (BER). The BER pathway in the nucleus is well elucidated. More recently, BER was shown to also exist in the mitochondria. Here, we review the association of BER of oxidative DNA damage with aging, cancer and other diseases. C1 [Maynard, Scott; Schurman, Shepherd H.; Harboe, Charlotte; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [de Souza-Pinto, Nadja C.] Univ Sao Paulo, Dept Biochem, Inst Chem, BR-05508000 Sao Paulo, Brazil. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov RI Souza-Pinto, Nadja/C-3462-2013; OI Souza-Pinto, Nadja/0000-0003-4206-964X; Maynard, Scott/0000-0001-5625-936X; Schurman, Shepherd/0000-0002-9133-7906 FU National Institute on Aging/National Institutes of Health Intramural Research Program. FX National Institute on Aging/National Institutes of Health Intramural Research Program. NR 185 TC 259 Z9 266 U1 7 U2 45 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2009 VL 30 IS 1 BP 2 EP 10 DI 10.1093/carcin/bgn250 PG 9 WC Oncology SC Oncology GA 398FP UT WOS:000262718300001 PM 18978338 ER PT J AU Lan, Q Zhang, LP Shen, M Jo, WJ Vermeulen, R Li, GL Vulpe, C Lim, S Ren, XF Rappaport, SM Berndt, SI Yeager, M Yuenger, J Hayes, RB Linet, M Yin, SN Chanock, S Smith, MT Rothman, N AF Lan, Qing Zhang, Luoping Shen, Min Jo, William J. Vermeulen, Roel Li, Guilan Vulpe, Christopher Lim, Sophia Ren, Xuefeng Rappaport, Stephen M. Berndt, Sonja I. Yeager, Meredith Yuenger, Jeff Hayes, Richard B. Linet, Martha Yin, Songnian Chanock, Stephen Smith, Martyn T. Rothman, Nathaniel TI Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity SO CARCINOGENESIS LA English DT Article ID MODIFIES BREAST-CANCER; ACUTE MYELOID-LEUKEMIA; DOUBLE-STRAND BREAK; HOMOLOGOUS RECOMBINATION; DIFFERENT MECHANISMS; MUTATION CARRIERS; MAMMALIAN-CELLS; CHINESE WORKERS; RISK; POLYMORPHISMS AB Benzene is an established human hematotoxicant and leukemogen but its mechanism of action is unclear. To investigate the role of single-nucleotide polymorphisms (SNPs) on benzene-induced hematotoxicity, we analyzed 1395 SNPs in 411 genes using an Illumina GoldenGate assay in 250 benzene-exposed workers and 140 unexposed controls. Highly significant findings clustered in five genes (BLM, TP53, RAD51, WDR79 and WRN) that play a critical role in DNA repair and genomic maintenance, and these regions were then further investigated with tagSNPs. One or more SNPs in each gene were associated with highly significant 10-20% reductions (P values ranged from 0.0011 to 0.0002) in the white blood cell (WBC) count among benzene-exposed workers but not controls, with evidence for gene-environment interactions for SNPs in BLM, WRN and RAD51. Further, among workers exposed to benzene, the genotype-associated risk of having a WBC count < 4000 cells/mu l increased when using individuals with progressively higher WBC counts as the comparison group, with some odds ratios > 8-fold. In vitro functional studies revealed that deletion of SGS1 in yeast, equivalent to lacking BLM and WRN function in humans, caused reduced cellular growth in the presence of the toxic benzene metabolite hydroquinone, and knockdown of WRN using specific short hairpin RNA increased susceptibility of human TK6 cells to hydroquinone toxicity. Our findings suggest that SNPs involved in DNA repair and genomic maintenance, with particular clustering in the homologous DNA recombination pathway, play an important role in benzene-induced hematotoxicity. C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Zhang, Luoping; Jo, William J.; Vulpe, Christopher; Lim, Sophia; Ren, Xuefeng; Rappaport, Stephen M.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Vermeulen, Roel] Univ Utrecht, Environm & Occupat Hlth Div, Utrecht, Netherlands. [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X FU National Institutes of Health [RO1ES06721, P42ES04705, P30ES01896, P42ES05948, P30ES10126] FX National Institutes of Health intramural research program; National Institutes of Health (RO1ES06721, P42ES04705, P30ES01896 to M. T. S.; P42ES05948, P30ES10126 to S. M. R.). NR 50 TC 37 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2009 VL 30 IS 1 BP 50 EP 58 DI 10.1093/carcin/bgn249 PG 9 WC Oncology SC Oncology GA 398FP UT WOS:000262718300007 PM 18978339 ER PT J AU Freedman, ND Ahn, J Hou, LF Lissowska, J Zatonski, W Yeager, M Chanock, SJ Chow, WH Abnet, CC AF Freedman, Neal D. Ahn, Jiyoung Hou, Lifang Lissowska, Jolanta Zatonski, Witold Yeager, Meredith Chanock, Stephen J. Chow, Wong Ho Abnet, Christian C. TI Polymorphisms in estrogen- and androgen-metabolizing genes and the risk of gastric cancer SO CARCINOGENESIS LA English DT Article ID HORMONE-BINDING GLOBULIN; CATECHOL-O-METHYLTRANSFERASE; ADDITIONAL CARBOHYDRATE CHAIN; ADJUVANT TAMOXIFEN THERAPY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; REPRODUCTIVE FACTORS; PROSTATE-CANCER; STOMACH-CANCER; LINKAGE PHASE AB Androgens and estrogens may play a role in gastric cancer etiology. To investigate the association of gastric cancer with single-nucleotide polymorphisms (SNPs) in six genes (COMT, CYP1B1, CYP17A1, CYP19A1, HSD17B1 and SHBG) involved in estrogen and androgen synthesis and metabolism, 58 haplotype-tagging SNPs were genotyped in 295 gastric cancer cases and 415 controls from a population-based study in Poland. We assessed differences in haplotype frequency between cases and controls using a global score test and calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for individual haplotypes using logistic regression. We found associations in one linkage disequilibrium (LD) block containing the 3' untranslated region of COMT (rs9332377, rs165728, rs165849 and rs1110478), global score test (df = 4, P = 0.033). Relative to the most frequent GATA haplotype, the GATG haplotype was associated with statistically significant increased gastric cancer risk (OR = 1.50, 95% CI: 1.06-2.12; false discovery rate (FDR) value = 0.459) and the AACA haplotype with borderline increased risk (OR = 1.36, 95% CI = 1.00-1.85; FDR = 0.50). We also found associations for the LD block containing part of the SHBG coding region (rs6258, rs6259, rs2955617, rs1641544 and rs1641537). The CACCC haplotype was associated with statistically significant lower gastric cancer risk relative to the referent CGACC haplotype (OR = 0.55, 95% CI = 0.34-0.90; FDR = 0.459), but the overall score test was statistically non-significant. No other statistically significant associations were observed. In summary, we found possible associations between gastric cancer and polymorphisms in COMT, involved in estrogen inactivation, and SHBG, a modulator of hormone bioavailability. These findings should be interpreted cautiously until replicated in other studies. C1 [Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Lissowska, Jolanta; Zatonski, Witold] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Lissowska, Jolanta/0000-0003-2695-5799 FU USA National Cancer Institute [N02-CP-40501, N01-CP-05626, N02CP-71103]; National Cancer Institute Office of Women's Health; National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics. FX USA National Cancer Institute (N02-CP-40501, N01-CP-05626, N02CP- 71103); National Cancer Institute Office of Women's Health; Intramural Research Program of National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 58 TC 13 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2009 VL 30 IS 1 BP 71 EP 77 DI 10.1093/carcin/bgn258 PG 7 WC Oncology SC Oncology GA 398FP UT WOS:000262718300010 PM 19015200 ER PT J AU Wang, HX Patel, V Miyazaki, H Gutkind, JS Yeudall, WA AF Wang, Huixin Patel, Vyomesh Miyazaki, Hiroshi Gutkind, J. Silvio Yeudall, W. Andrew TI Role for EPS8 in squamous carcinogenesis SO CARCINOGENESIS LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; FOCAL ADHESION KINASE; GENE-EXPRESSION ANALYSIS; FACTOR RECEPTOR; CELL CARCINOMAS; TUMOR PROGRESSION; BINDING-PROTEIN; CANCER-CELLS; C-SRC; FUNCTIONAL-CHARACTERIZATION AB We have investigated the role of the signaling intermediate, EPS8, in tumor progression using a model system and in vivo. HN4 primary tumor cells express low levels of EPS8, similar to normal keratinocytes, and show minimal invasion in vitro in response to epidermal growth factor, whereas HN12 cells express high levels of EPS8 and are highly motile in vitro and tumorigenic in vivo. Additional independent tumor cell lines also showed elevated EPS8 expression compared with normal keratinocytes. Using retroviral transduction, we generated HN4 cell lines expressing EPS8 (HN4/EPS8) at levels equivalent to those present in HN12 cells. HN4/EPS8 cells showed increased proliferation and migration compared with controls, together with elevated expression and activity of matrix metalloprotease (MMP)-9, which was dependent on protein kinase B (AKT) activity. Introduction of plasmids that direct synthesis of EPS8 short hairpin RNA (shRNA) into HN12 cells resulted in decreased EPS8 expression in these cells, which correlated with a decrease in their capacity to migrate and invade in vitro. In addition, shRNA-mediated knockdown of EPS8 reduced expression and activity of MMP-9 produced by these cells and reduced MMP-9 promoter activity. EPS8 knockdown cells showed decreased tumorigenicity in vivo compared with controls and lower MMP-9 expression. Conversely, overexpression of EPS8 in HN4 cells was sufficient to induce growth of these non-tumorigenic cells in orthotopic transplantation assays. Furthermore, EPS8 expression in clinical samples of squamous cell carcinoma showed variable expression levels and broadly paralleled expression of MMP-9. The data support a role for EPS8 in squamous carcinogenesis. C1 [Wang, Huixin; Miyazaki, Hiroshi; Yeudall, W. Andrew] Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. RP Yeudall, WA (reprint author), Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, POB 980566,521 N 11th St, Richmond, VA 23298 USA. EM wayeudall@vcu.edu RI Gutkind, J. Silvio/A-1053-2009 FU Commonwealth Health Research Board of the State Council of Higher Education for Virginia; Philip Morris USA FX Commonwealth Health Research Board of the State Council of Higher Education for Virginia; Philip Morris USA to W. A. Y. NR 71 TC 29 Z9 35 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2009 VL 30 IS 1 BP 165 EP 174 DI 10.1093/carcin/bgn252 PG 10 WC Oncology SC Oncology GA 398FP UT WOS:000262718300022 PM 19008210 ER PT J AU Zhou, YF Wang, SN Yu, ZX Sachdev, V Arai, AE Horvath, KA AF Zhou, Y. F. Wang, S. N. Yu, Z. X. Sachdev, V Arai, A. E. Horvath, K. A. TI Transplantation of Autologous Mesenchymal Stromal Cells Improves Left Ventricular Function in the Porcine Chronic Ischemic Model through Enhanced Angiogenesis and Neovascularization SO CARDIOLOGY LA English DT Meeting Abstract C1 [Zhou, Y. F.; Wang, S. N.; Yu, Z. X.; Sachdev, V; Arai, A. E.; Horvath, K. A.] NIH, Cellular Biol Sect, Cardiothorac Surg Res Program, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 114 BP 87 EP 88 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 527QR UT WOS:000272382100164 ER PT J AU Karlsdottir, G Aspelund, T Sigurdsson, S Eiriksdottir, G Aspelund, T Arai, AE Harris, TB Launer, L Detrano, R Gudnason, V AF Karlsdottir, Gyda Aspelund, Thor Sigurdsson, Sigurdur Eiriksdottir, Gudny Aspelund, Thor Arai, Andrew E. Harris, Tamara B. Launer, Lenor Detrano, Robert Gudnason, Vilmundur TI Potential association of the localisation of myocardial infarction detected by magnetic resonance imaging, and the quantification of calcium in the coronary arteries detected with computed tomography and calcium scoring software SO CARDIOLOGY LA English DT Meeting Abstract C1 [Karlsdottir, Gyda] Hjartavernd, Kopavogur, Iceland. [Aspelund, Thor; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Arai, Andrew E.] NHLBI, IRP, Bethesda, MD 20892 USA. [Harris, Tamara B.; Launer, Lenor] NIA, Bethesda, MD 20892 USA. [Detrano, Robert] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 113 BP 98 EP 98 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 452WV UT WOS:000266572800133 ER PT J AU Karlsdottir, G Sigurdsson, S Aspelund, T Eiriksdottir, G Launer, L Harris, TB Gudnason, V Detrano, R AF Karlsdottir, Gyda Sigurdsson, Sigurdur Aspelund, Thor Eiriksdottir, Gudny Launer, Lenor Harris, Tamara B. Gudnason, Vilmundur Detrano, Robert TI Thoracic aortic calcification in the elderly SO CARDIOLOGY LA English DT Meeting Abstract C1 [Karlsdottir, Gyda] Hjartavernd, Kopavogur, Iceland. [Sigurdsson, Sigurdur; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland. [Launer, Lenor; Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Detrano, Robert] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 113 BP 99 EP 99 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 452WV UT WOS:000266572800134 ER PT J AU Schelbert, E Cao, J Sigurdsson, S Kellman, P Aletras, A Aspelund, T Eiriksdottir, G Launer, L Harris, T Gudnason, V Arai, A AF Schelbert, Erik Cao, Jie Sigurdsson, Sigurdur Kellman, Peter Aletras, Anthony Aspelund, Thor Eiriksdottir, Gudny Launer, Lenore Harris, Tamara Gudnason, Vilmundur Arai, Andrew TI Prevalence of unrecognized and recognized myocardial infarction in older individuals with elevated NT proBNP SO CARDIOLOGY LA English DT Meeting Abstract C1 [Cao, Jie; Kellman, Peter; Aletras, Anthony; Arai, Andrew] NHLBI, Bethesda, MD 20892 USA. [Sigurdsson, Sigurdur; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, Lenore; Harris, Tamara] NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2009 VL 113 BP 104 EP 104 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 452WV UT WOS:000266572800148 ER PT B AU Tang, GW Russell, RM AF Tang, Guangwen Russell, Robert M. BE Britton, G LiaaenJensen, S Pfander, H TI Carotenoids as Provitamin A SO CAROTENOIDS, VOL 5: NUTRITION AND HEALTH SE Carotenoids Series LA English DT Article; Book Chapter ID ISOTOPE REFERENCE METHOD; RICH LIPOPROTEIN FRACTION; VITAMIN-A EQUIVALENCE; IONIZATION MASS-SPECTROMETRY; GREEN LEAFY VEGETABLES; TRANS BETA-CAROTENE; RETINOIC ACID; INTESTINAL-ABSORPTION; EXCENTRIC CLEAVAGE; CARDIOVASCULAR-DISEASE C1 [Tang, Guangwen] Tufts Univ, Carotenoids & Hlth Lab, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Russell, Robert M.] NIH, Off Director, Washington, DC USA. RP Tang, GW (reprint author), Tufts Univ, Carotenoids & Hlth Lab, Jean Mayer USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM guangwen.tang@tufts.edu; russellr2@od.nih.gov NR 100 TC 9 Z9 9 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 978-3-7643-7500-3 J9 CAROTENOIDS SER PY 2009 VL 5 BP 149 EP 172 DI 10.1007/978-3-7643-7501-0_8 D2 10.1007/978-3-7643-7501-0 PG 24 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BLX14 UT WOS:000271255500008 ER PT B AU Yeum, KJ Aldini, G Russell, RM Krinsky, NI AF Yeum, Kyung-Jin Aldini, Giancarlo Russell, Robert M. Krinsky, Norman I. BE Britton, G LiaaenJensen, S Pfander, H TI Antioxidant/Pro-oxidant Actions of Carotenoids SO CAROTENOIDS, VOL 5: NUTRITION AND HEALTH SE Carotenoids Series LA English DT Article; Book Chapter ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE DNA-DAMAGE; RADICAL ABSORBENCY CAPACITY; HUMAN SKIN FIBROBLASTS; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; PIGMENT OPTICAL-DENSITY; PRIMARY RAT HEPATOCYTES; SMOKE-EXPOSED FERRETS; BETA-CAROTENE C1 [Yeum, Kyung-Jin; Krinsky, Norman I.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Dept Biochem,Sch Med, Boston, MA 02111 USA. [Russell, Robert M.] NIH, Off Director, Washington, DC USA. [Aldini, Giancarlo] Univ Milan, Dept Pharmaceut Sci, Fac Pharm, I-20133 Milan, Italy. RP Yeum, KJ (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Dept Biochem,Sch Med, 711 Washington St, Boston, MA 02111 USA. EM kyungjin.yeum@tufts.edu; giancarlo.aldini@unimi.it; russellr2@od.nih.gov NR 213 TC 16 Z9 16 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 978-3-7643-7500-3 J9 CAROTENOIDS SER PY 2009 VL 5 BP 235 EP 268 DI 10.1007/978-3-7643-7501-0_12 D2 10.1007/978-3-7643-7501-0 PG 34 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BLX14 UT WOS:000271255500012 ER PT S AU Kaplan, BB Gioio, AE Hillefors, M Aschrafi, A AF Kaplan, Barry B. Gioio, Anthony E. Hillefors, Mi Aschrafi, Armaz BE Koenig, E TI Axonal Protein Synthesis and the Regulation of Local Mitochondrial Function SO CELL BIOLOGY OF THE AXON SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID LONG-TERM FACILITATION; RETINAL GROWTH CONES; SQUID GIANT-AXON; MESSENGER-RNAS; SYMPATHETIC NEURONS; SYNAPSE FORMATION; TRANSLATION; NERVE; EXPRESSION; TRANSPORT AB Axons and presynaptic nerve terminals of both invertebrate and mammalian SCG neurons contain a heterogeneous population of nuclear-encoded mitochondrial mRNAs and a local cytosolic protein synthetic system. Nearly one quarter of the total protein synthesized in these structural/functional domains of the neuron is destined for mitochondria. Acute inhibition of axonal protein synthesis markedly reduces the functional activity of mitochondria. The blockade of axonal protein into mitochondria had similar effects on the organelle's functional activity. In addition to mitochondrial mRNAs, SCG axons contain approximately 200 different microRNAs (miRs), short, noncoding RNA molecules involved in the posttranscriptional regulation of gene expression. One of these miRs (miR-338) targets cytochrome c oxidase IV (COXIV) mRNA. This nuclear-encoded mRNA codes for a protein that plays a key role in the assembly of the mitochondrial enzyme complex IV and oxidative phosphorylation. Over-expression of miR-338 in the axon markedly decreases COXIV expression, mitochondrial functional activity, and the uptake of neurotransmitter into the axon. Conversely, the inhibition of endogeneous miR-338 levels in the axon significantly increased mitochondrial activity and norepinephrine uptake into the axon. The silencing of COXIV expression in the axon using short, inhibitory RNAs (siRNAs) yielded similar results, a finding that indicated that the effects of miR-338 on mitochondrial activity and axon function were mediated, at least in part, through local COXIV mRNA translation. Taken together, recent findings establish that proteins requisite for mitochondrial activity are synthesized locally in the axon and nerve terminal, and call attention to the intimacy of the relationship that has evolved between the distant cellular domains of the neuron and its energy generating systems. C1 [Kaplan, Barry B.; Gioio, Anthony E.; Hillefors, Mi; Aschrafi, Armaz] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM kaplanb@mail.nih.gov RI Aschrafi, Armaz/E-2202-2012 FU Intramural NIH HHS [Z01 MH002768-10, Z01 MH002768-11, ZIA MH002768-12] NR 43 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-03018-5 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2009 VL 48 BP 225 EP 242 DI 10.1007/400_2009_1 D2 10.1007/978-3-642-03019-2 PG 18 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BLT06 UT WOS:000270967100011 PM 19343315 ER PT S AU Crispino, M Cefaliello, C Kaplan, B Giuditta, A AF Crispino, Marianna Cefaliello, Carolina Kaplan, Barry Giuditta, Antonio BE Koenig, E TI Protein Synthesis in Nerve Terminals and the Glia-Neuron Unit SO CELL BIOLOGY OF THE AXON SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID SQUID GIANT-AXON; TERM SYNAPTIC PLASTICITY; RAT CEREBRAL-CORTEX; MESSENGER-RNA; RIBONUCLEIC ACID; SYNAPTOSOMAL FRACTION; LEARNING EXPERIMENT; FIBRE COMPONENTS; BASE COMPOSITION; LOCAL SYNTHESIS AB The progressive philogenetic lengthening of axonal processes and the increase in complexity of terminal axonal arborizations markedly augmented the demands of the neuronal cytoplasmic mass on somatic gene expression. It is proposed that in an adaptive response to this challenge, novel gene expression functions developed in the axon compartment, consisting of axonal and presynaptic translation systems that rely on the delivery of transcripts synthesized in adjacent glial cells. Such intercellular mode of gene expression would allow more rapid plastic changes to occur in spatially restricted neuronal domains, down to the size of individual synapses. The cell body contribution to local gene expression in well-differentiated neurons remains to be defined. The history of this concept and the experimental evidence supporting its validity are critically discussed in this article. The merit of this perspective lies with the recognition that plasticity events represent a major occurrence in the brain, and that they largely occur at synaptic sites, including presynaptic endings. C1 [Crispino, Marianna; Cefaliello, Carolina; Giuditta, Antonio] Univ Naples Federico 2, Dept Biol Sci, Naples, Italy. [Kaplan, Barry] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Giuditta, A (reprint author), Univ Naples Federico 2, Dept Biol Sci, Naples, Italy. EM kaplanb@mail.nih.gov; giuditta@unina.it NR 156 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-03018-5 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2009 VL 48 BP 243 EP 267 DI 10.1007/400_2009_9 D2 10.1007/978-3-642-03019-2 PG 25 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BLT06 UT WOS:000270967100012 PM 19554280 ER PT J AU Donaldson, M Antignani, A Milner, J Zhu, N Wood, A Cardwell-Miller, L Changpriroa, CM Jackson, SH AF Donaldson, M. Antignani, A. Milner, J. Zhu, N. Wood, A. Cardwell-Miller, L. Changpriroa, C. M. Jackson, S. H. TI p47(phox)-deficient immune microenvironment signals dysregulate naive T-cell apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE p47(phox); T cells; apoptosis; cytokines; apoptosis ID NADPH OXIDASE; HOMEOSTASIS; IL-7; DEATH; CYTOKINES; INTERLEUKIN-4; ACTIVATION; PATHWAYS; SURVIVAL; DISEASE AB The phagocyte NADPH oxidase is a multicomponent enzyme complex mediating microbial killing. We find that NADPH oxidase p47(phox)-deficient (p47(phox-/-)) chronic granulomatous disease (CGD) mice develop lymph node hyperplasia even without obvious infection, where increased number of T and B lymphocytes is associated with increased percent of naive cells and a lower T : B cell ratio than wild type. Paradoxically, despite lymphoid hyperplasia in vivo, when lymphocytes are placed in culture, p47(phox-/-) CD8(+) lymphocytes progress more rapidly to apoptosis than wild type. This is associated in cultured p47(phox-/-) CD8(+) lymphocytes with the induction of proapoptotic Bim and Puma expression, increased mitochondrial outer membrane permeabilization and depressed Bcl-2 expression. Addition of IL-7 to the culture partially corrects Bcl-2 levels in cultured p47(phox-/-) CD8(+) lymphocytes and improves the survival. Adding glucose oxidase to the culture to generate hydrogen peroxide along with IL-7 further improves p47(phox-/-) CD8(+) lymphocyte survival, but only to 30% of wild type. We conclude that p47(phox-/-) CD8(+) lymphocytes have an intrinsic survival defect likely in part related to the oxidase deficiency, but in vivo in lymph nodes of CGD mice, there are microenvironmental factors yet to be delineated that suppress the progression of apoptosis and allow the accumulation of lymphocytes leading to lymphoid hyperplasia. C1 [Donaldson, M.; Zhu, N.; Wood, A.; Cardwell-Miller, L.; Changpriroa, C. M.; Jackson, S. H.] NIAID, NIH, Lab Host Def, Monocyte Trafficking Unit, Bethesda, MD 20892 USA. [Antignani, A.] NINDS, NIH, Biochem Sect, Surg Neurol Branch, Bethesda, MD 20892 USA. [Milner, J.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Jackson, SH (reprint author), NIAID, NIH, Lab Host Def, Monocyte Trafficking Unit, CRC Bldg 5 West Labs,Room 5-3942,10 Ctr Dr MSC 14, Bethesda, MD 20892 USA. EM sjackson@niaid.nih.gov FU Division of Intramural Research of the National Institutes of Health/ National Institute of Allergy and Infectious Diseases FX We thank Kevin Gardner and Richard Youle for helpful discussions and critique of an earlier draft of this manuscript. We also thank Harry Malech and Michael Davis for careful review of this manuscript. This research was supported by the Division of Intramural Research of the National Institutes of Health/ National Institute of Allergy and Infectious Diseases. NR 33 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2009 VL 16 IS 1 BP 125 EP 138 DI 10.1038/cdd.2008.129 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 383SL UT WOS:000261693600015 PM 18806761 ER PT J AU Zhang, YE AF Zhang, Ying E. TI Non-Smad pathways in TGF-beta signaling SO CELL RESEARCH LA English DT Review DE TGF-beta; Erk; JNK; p38; RhoA; Akt; Smad ID GROWTH-FACTOR-BETA; ACTIVATED PROTEIN-KINASE; EPITHELIAL-CELL PLASTICITY; BREAST-CANCER CELLS; MESENCHYMAL TRANSITION; TRANSFORMING GROWTH-FACTOR-BETA-1; PHOSPHATIDYLINOSITOL 3-KINASE; INDUCED APOPTOSIS; REGULATED KINASE; GENE-EXPRESSION AB Transforming growth factor-beta utilizes a multitude of intracellular signaling pathways in addition to Smads to regulate a wide array of cellular functions. These non-canonical, non-Smad pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. These non-Smad pathways include various branches of MAP kinase pathways, Rho-like GTPase signaling pathways, and phosphati-dylinositol-3- kinase/AKT pathways. This review focuses on recent advances in the understanding of the molecular and biochemical mechanisms of non-Smad pathways. In addition, functions of these non-Smad pathways are also discussed. C1 [Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM yingz@helix.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU Intramural Research Program of the NIH, USA; National Cancer Institute, Center for Cancer Research FX The research in Ying E Zhang's group is supported by the Intramural Research Program of the NIH, USA, National Cancer Institute, Center for Cancer Research. NR 94 TC 590 Z9 608 U1 6 U2 63 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2009 VL 19 IS 1 BP 128 EP 139 DI 10.1038/cr.2008.328 PG 12 WC Cell Biology SC Cell Biology GA 406ID UT WOS:000263287300013 PM 19114990 ER PT B AU Atkins, JW AF Atkins, J. W. BE Gee, A TI Quality SO CELL THERAPY: CGMP FACILITIES AND MANUFACTURING LA English DT Article; Book Chapter AB Functional quality systems are essential to a successful cellular therapy program. A major driver to implementation of a quality management system in the United States is the federal law outlined in the Code of Federal Regulations (CFR) Title 21 parts 211 and 1271. Almost every accrediting agency now requires the implementation of a quality program including the AABB, Centers for Medicare and Medicaid Services (CMS), The Joint Commission (TJC), the College of American Pathologists (CAP), the Foundation for the Accreditation of Cellular Therapy (FACT), the International Standards Organization (ISO), the American Association of Tissue Banks (AATB), and the Clinical Laboratory Standards Institute (CLSI). C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Atkins, JW (reprint author), NIH, Dept Transfus Med, Ctr Clin, Ctr Dr, Bethesda, MD 20892 USA. EM jatkins@mail.cc.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89583-3 PY 2009 BP 187 EP 197 DI 10.1007/b102110_16 D2 10.1007/b102110 PG 11 WC Cell Biology SC Cell Biology GA BMH95 UT WOS:000272402600016 ER PT B AU Read, EJ Khuu, HM AF Read, E. J. Khuu, H. M. BE Gee, A TI Use of a Facility Master File to Facilitate Regulatory Submissions for Cell Therapy Products SO CELL THERAPY: CGMP FACILITIES AND MANUFACTURING LA English DT Article; Book Chapter AB Investigational new drug applications (INDs) for novel cell therapy products require written documentation not only of the proposed clinical protocol and specific product manufacturing process, but also of information on items that may be generic for all products manufactured within a given facility. For facilities supporting multiple IND-related protocols, this generic information can be organized into a Drug Master File (DMF). This chapter will discuss the rationale, design, maintenance, and use of a DMF, either as an official submission to the U.S. Food and Drug Administration, or as an internal reference document that compiles information for subsequent extraction and incorporation into IND submissions. C1 [Read, E. J.] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA. [Khuu, H. M.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Read, EJ (reprint author), Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94118 USA. EM eread@bloodsystems.org; hkhuu@mail.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-89583-3 PY 2009 BP 229 EP 236 DI 10.1007/b102110_19 D2 10.1007/b102110 PG 8 WC Cell Biology SC Cell Biology GA BMH95 UT WOS:000272402600019 ER PT J AU Santiago, LY Clavijo-Alvarez, J Brayfield, C Rubin, JP Marra, KG AF Santiago, Lizzie Y. Clavijo-Alvarez, Julio Brayfield, Candace Rubin, J. Peter Marra, Kacey G. TI Delivery of Adipose-Derived Precursor Cells for Peripheral Nerve Repair SO CELL TRANSPLANTATION LA English DT Article DE Adipose; Progenitor cells; Peripheral nerve repair; Nerve guide; Polycaprolactone ID PROCESSED LIPOASPIRATE CELLS; AUTOLOGOUS SCHWANN-CELLS; MESENCHYMAL STEM-CELLS; SCIATIC-NERVE; GUIDANCE CHANNELS; IN-VITRO; NEURITE OUTGROWTH; GUIDE CONDUITS; GROWTH-FACTOR; LONG-GAP AB To test the hypothesis that the transplantation of adipose precursor cells (APCs) improves nerve regeneration and functional recovery, human APCs were transplanted into the lumen of a nerve guide in a 6-mm unilateral sciatic nerve defect in athymic rats. The three control groups for the study were biodegradable, polycaprolactone-based nerve conduit without APCs, autograft, and empty defect. Behavioral tests were performed every 3 weeks, and the sciatic functional index (SFI) was calculated based on measurements from the hindlimb prints. After 12 weeks, the nerve as well as right and left gastrocnemius muscles were removed and preserved for histological evaluation. Full regeneration of the sciatic nerve occurred on the rats that received the autograft, the guide, and the guide with APCs; no regeneration was observed on any of the rats in which the defect was left untreated (empty defect). APCs survived transplantation for up to 12 weeks in the injured peripheral nerve. No significant colocalization was observed between the immunostaining for glial fibrillary protein and anti-human lamin A/C, implying that the APCs did not differentiate into Schwann cells at the site of injury. In comparison with the rats with untreated defects, a decrease in muscle atrophy was observed on those rats that received the autograft and the guide with cells as indicated by the gastrocnemius Muscle weight ratio and the muscle fiber ratio. Significant differences in SFI were observed 3 weeks postinjury between the rats in which the guide was left empty and those that received the guide with APCs; however, these differences were not observed at 12 weeks. The transplantation of APCs promoted the formation of it more robust nerve as evidenced by the results from the cross-sectional area of regenerated nerve, and the transplantation of APCs produced a decrease in muscle atrophy. C1 [Marra, Kacey G.] Univ Pittsburgh, Dept Surg, Div Plast Surg, Pittsburgh, PA 15261 USA. [Santiago, Lizzie Y.] NHLBI, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Rubin, J. Peter; Marra, Kacey G.] McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Brayfield, Candace; Marra, Kacey G.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. RP Marra, KG (reprint author), Univ Pittsburgh, Dept Surg, Div Plast Surg, 1655E BST,200 Lothrop St, Pittsburgh, PA 15261 USA. EM marrak@upmc.edu OI Marra, Kacey/0000-0002-8437-4864 NR 35 TC 66 Z9 67 U1 2 U2 9 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 145 EP 158 PG 14 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800004 PM 19499703 ER PT J AU Airavaara, M Harvey, B Chiocco, M Howard, D Peranen, J Saarma, M Wang, Y Hoffer, B AF Airavaara, M. Harvey, B. Chiocco, M. Howard, D. Peranen, J. Saarma, M. Wang, Y. Hoffer, B. TI Adeno-Associated Viral (AAV) Vector Expressing Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Protects Cortical Neurons Against Ischemia-Induced Toxicity in Rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Airavaara, M.; Harvey, B.; Chiocco, M.; Howard, D.; Wang, Y.; Hoffer, B.] IRP, Natl Inst Drug Abuse, Baltimore, MD USA. [Peranen, J.; Saarma, M.] Univ Helsinki, Viikki Bioctr, Inst Biotechnol, FIN-00014 Helsinki, Finland. NR 0 TC 2 Z9 2 U1 1 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 207 EP 208 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800013 ER PT J AU Harvey, BK Chou, J Shen, H Chiang, YH Hoffer, BJ Wang, Y AF Harvey, B. K. Chou, J. Shen, H. Chiang, Y. H. Hoffer, B. J. Wang, Y. TI Diadenosine Tetraphosphate Reduces Toxicity Caused by High-Dose Methamphetamin Adminstration SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Harvey, B. K.; Chou, J.; Shen, H.; Hoffer, B. J.; Wang, Y.] Natl Inst Drug Abuse, Baltimore, MD USA. [Chiang, Y. H.] Taipei Med Univ, Taipei, Taiwan. NR 0 TC 2 Z9 2 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 217 EP 217 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800040 ER PT J AU Lee, CT Chen, J Errico, S Worden, LT Amable, R Freed, WJ AF Lee, C. -T. Chen, J. Errico, S. Worden, L. T. Amable, R. Freed, W. J. TI Cocaine and Brain Development SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Lee, C. -T.; Chen, J.; Errico, S.; Worden, L. T.; Amable, R.; Freed, W. J.] Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 221 EP 221 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800051 ER PT J AU Luo, Y Kuo, CC Shen, H Chou, J Greig, NH Hoffer, BJ Wang, Y AF Luo, Y. Kuo, C. -C. Shen, H. Chou, J. Greig, N. H. Hoffer, B. J. Wang, Y. TI Delayed Treatment With a p53 Inhibitor Enhances Endogenous Neurogenesis and Functional Recovery of the Brain After Ischemic Injury in Rodents SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 Natl Inst Drug Abuse, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RI luo, Yu (Agnes)/E-4446-2010 NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 223 EP 223 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800055 ER PT J AU Ross, JM Brene, S Oberg, J Sitnikov, R Pernold, K Terzioglu, M Trifunovic, A Kehr, J Larsson, NG Hoffer, BJ Olson, L AF Ross, J. M. Brene, S. Oberg, J. Sitnikov, R. Pernold, K. Terzioglu, M. Trifunovic, A. Kehr, J. Larsson, N. -G. Hoffer, B. J. Olson, L. TI Elevated Lactate in Brain and Other Tissues Is an Early Endophenotype in the Prematurely Aging mtDNA Mutator Mouse SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Ross, J. M.; Hoffer, B. J.] NIDA, NIH, Baltimore, MD USA. [Ross, J. M.; Pernold, K.; Olson, L.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Brene, S.] Karolinska Inst, Dept Neurobiol Hlth Sci & Soc, Stockholm, Sweden. [Oberg, J.; Sitnikov, R.] Karolinska Inst, Dept Clintec, Stockholm, Sweden. [Terzioglu, M.; Trifunovic, A.; Larsson, N. -G.] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Kehr, J.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Larsson, N. -G.] Max Planck Inst Biol Ageing, Cologne, Germany. RI Ross, Jaime/A-6893-2012 NR 0 TC 2 Z9 2 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 232 EP 233 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800082 ER PT J AU Vazin, T Becker, KG Chen, J Zhang, Y Worden, L Freed, WJ AF Vazin, T. Becker, K. G. Chen, J. Zhang, Y. Worden, L. Freed, W. J. TI A Combination of Factors, Termed SPIE, Which Mimics the Effect of Stromal-Derived Inducing Activity in Promoting Dopaminergic Differentiation of Human Embryonic Stem Cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Vazin, T.; Chen, J.; Worden, L.; Freed, W. J.] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. [Becker, K. G.; Zhang, Y.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 U1 0 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 238 EP 239 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800099 ER PT J AU Worden, LT Lee, CT Freed, WJ AF Worden, L. T. Lee, C. -T. Freed, W. J. TI Comparison of Dopaminergic Differentiation Between Human Embryonic Stem Cell Lines SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Worden, L. T.; Lee, C. -T.; Freed, W. J.] NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, DHHS,NIH, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 241 EP 241 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800106 ER PT J AU Yu, S Hayashi, T Kaneko, Y Bae, E Stahl, CE Wang, Y Borlongan, CV AF Yu, S. Hayashi, T. Kaneko, Y. Bae, E. Stahl, C. E. Wang, Y. Borlongan, C. V. TI Severity of Controlled Cortical Impact Traumatic Brain Injury in Rats and Mice Dictates Degree of Behavioral Deficits SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-for-Neural-Therapy-and-Repair CY APR 30-MAY 02, 2009 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 [Yu, S.; Hayashi, T.; Kaneko, Y.; Bae, E.; Borlongan, C. V.] Univ S Florida, Dept Neurosurg, Ctr Aging & Brain Repair, Tampa, FL USA. [Stahl, C. E.] Dwight D Eisenhower Army Med Ctr, Dept Internal Med, Augusta, GA USA. [Wang, Y.] NIDA, Neural Protect & Regenerat Sect, NIH, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2009 VL 18 IS 2 BP 241 EP 242 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 449OV UT WOS:000266340800107 ER PT J AU Inkson, CA Ono, M Bi, YM Kuznetsov, SA Fisher, LW Young, MF AF Inkson, Colette A. Ono, Mitsuaki Bi, Yanming Kuznetsov, Sergei A. Fisher, Larry W. Young, Marian F. TI The Potential Functional Interaction of Biglycan and WISP-1 in Controlling Differentiation and Proliferation of Osteogenic Cells SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Biglycan; WISP-1/CCN4; WISP-1va; Osteogenesis; Proliferation ID OSTEOBLAST DIFFERENTIATION; BONE; PROTEOGLYCANS; OSTEOPOROSIS; DECORIN; FAMILY; MICE AB Biglycan ( BGN) and WISP-1 are 2 extracellular matrix proteins that bind to each other and colocalize in mineralizing tissue. Here we show that WISP-1 abrogates the repression of proliferation in bone marrow stromal cells induced by BGN. We also demonstrate that WISP-1 and its variant WISP-1va can alleviate the repressed osteogenic differentiation caused by the absence of BGN. These preliminary data suggest that WISP-1 and BGN may functionally interact and control each other's activity, thus regulating the differentiation and proliferation of osteogenic cells. Copyright (C) 2008 S. Karger AG, Basel C1 [Young, Marian F.] Natl Inst Dent & Craniofacial Res, Mol Biol Bones & Teeth Unit, CSDB,DIR,NIH, Craniofacial & Skeletal Dis Branch,DHHS Bethesda, Bethesda, MD 20892 USA. RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, Mol Biol Bones & Teeth Unit, CSDB,DIR,NIH, Craniofacial & Skeletal Dis Branch,DHHS Bethesda, Bldg 30,Room 225,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM myoung@dir.nidcr.nih.gov OI Inkson, Colette/0000-0003-1215-312X FU Intramural NIH HHS [Z01 DE000379-24] NR 12 TC 21 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 153 EP 157 DI 10.1159/000151377 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000027 PM 18701807 ER PT J AU Gibson, CW Li, Y Daly, B Suggs, C Yuan, ZA Fong, H Simmons, D Aragon, M Kulkarni, AB Wright, JT AF Gibson, Carolyn W. Li, Yong Daly, Bill Suggs, Cynthia Yuan, Zhi-an Fong, Hanson Simmons, Darrin Aragon, Melissa Kulkarni, Ashok B. Wright, J. Timothy TI The Leucine-Rich Amelogenin Peptide Alters the Amelogenin Null Enamel Phenotype SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Enamel; Amelogenin; Leucine-rich amelogenin peptide; Mineral; Null mice; Transgenic mice ID EXPRESSION; MATRIX; PROTEINS; GENE; IDENTIFICATION; ODONTOBLASTS; RESCUE; CELLS; MICE; LRAP AB Introduction: The amelogenin proteins secreted by ameloblasts during dental enamel development are required for normal enamel structure. Amelx null (KO) mice have hypoplastic, disorganized enamel similar to that of human patients with mutations in the AMELX gene, and provide a model system for studies of the enamel defect amelogenesis imperfecta. Because many amelogenin proteins are present in developing enamel due to RNA alternative splicing and proteolytic processing, understanding the function of individual amelogenins has been challenging. Purpose: Our objective was to better understand the role of LRAP, a 59 amino acid leucine-rich amelogenin peptide, in the development of enamel. Approach: Teeth from transgenic mice that express LRAP under control of the Amelx regulatory regions were analyzed for mechanical properties, and transgenic males were mated with female KO mice. Male offspring with a null background that were transgene positive or transgene negative were compared to determine phenotypic differences using microcomputed tomography (microCT) and scanning electron microscopy (SEM). Results: Nanoindentation revealed no differences between LRAP transgenic and wild-type murine enamel. Using microCT, LRAPKO enamel volume and density measurements were similar to those from KO mice. However, in etched samples examined by SEM, the organization of the enamel rod pattern was altered by the presence of the LRAP transgene. Conclusions: The presence of LRAP leads to changes in enamel appearance compared to enamel from KO mice. Expression of a combination of amelogenin transgenes in KO mice may lead to rescue of the individual characteristics of normal enamel. Copyright (C) 2008 S. Karger AG, Basel C1 [Gibson, Carolyn W.; Li, Yong; Aragon, Melissa] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Daly, Bill; Suggs, Cynthia; Yuan, Zhi-an; Simmons, Darrin; Wright, J. Timothy] Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC USA. [Fong, Hanson] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA. [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM gibson@biochem.dental.upenn.edu FU NIDCR NIH HHS [R01 DE011089, DE011089] NR 22 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 EI 1422-6421 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 169 EP 174 DI 10.1159/000151384 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000030 PM 18701811 ER PT J AU Goldberg, M Ono, M Septier, D Bonnefoix, M Kilts, TM Bi, YM Embree, M Ameye, L Young, MF AF Goldberg, Michel Ono, Mitsuaki Septier, Dominique Bonnefoix, Mireille Kilts, Tina M. Bi, Yanming Embree, Mildred Ameye, Laurent Young, Marian F. TI Fibromodulin-Deficient Mice Reveal Dual Functions for Fibromodulin in Regulating Dental Tissue and Alveolar Bone Formation SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Fibromodulin; Dentinogenesis; Amelogenesis; Osteogenesis; Collagen fibrillation; Enamel; Alveolar bone; Mineralization ID LEUCINE-RICH PROTEOGLYCANS; PROTEINS; COLLAGEN; EXPRESSION; DECORIN; ENAMEL; FAMILY; GENES AB The extracellular matrix of newborn, 7- and 21-day-old fibromodulin-deficient (Fmod KO) mice was compared with age-matched wild-type (WT) mice. Western blotting of proteins from 21-day-old WT mice revealed that the molecular weight of Fmod is smaller in dental tissues (approx. 40 kDa) compared to alveolar bone extracts (approx. 52 kDa). Dentin matrix protein1 (DMP1) was slightly increased in Fmod KO versus WT tooth extracts. After chondroitinase ABC digestion, dentin sialophosphoprotein (DSPP) appeared as 2 strong bands (approx. 150 and 70 kDa) in incisors from 21-day-old Fmod KO mice, whereas the smaller-sized species of DSPP was nearly absent in WT molars and no difference was detected between WT and KO mice in molars. Dentin mineralization was altered in newborn and 7-day-old KO mice, but seemed normal in 21-day-old KO mice. DMP1 and DSPP may be involved in compensatory mechanisms. The enamel had a twisted appearance and looked porous at day 21 in KO incisor, and the outer aprismatic layer was missing in the molar. Alveolar bone formation was enhanced in Fmod KO mice at days 0 and 7, whereas no difference was detected at day 21. We conclude that Fmod may control dental tissue formation and early maturation, where it acts mostly as an inhibitor in alveolar bone accumulation, excerpting its effects only at early developing stages. These dual functions may be related to the different forms of Fmod found in bone versus teeth. Copyright (C) 2008 S. Karger AG, Basel C1 [Goldberg, Michel; Septier, Dominique; Bonnefoix, Mireille] Univ Paris 05, Fac Chirurg Dent, EA 2496, Lab Reparat & Remodelage Tissues Orofaciaux, FR-92120 Montrouge, France. [Ono, Mitsuaki; Kilts, Tina M.; Bi, Yanming; Embree, Mildred; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Ameye, Laurent] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. RP Goldberg, M (reprint author), Univ Paris 05, Fac Chirurg Dent, EA 2496, Lab Reparat & Remodelage Tissues Orofaciaux, 1 Rue Maurice Arnoux, FR-92120 Montrouge, France. EM mgoldod@aol.com FU Intramural NIH HHS [Z01 DE000379-24] NR 13 TC 8 Z9 8 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 198 EP 202 DI 10.1159/000151370 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000034 PM 18698127 ER PT J AU Wright, JT Hart, TC Hart, PS Simmons, D Suggs, C Daley, B Simmer, J Hu, J Bartlett, JD Li, Y Yuan, ZA Seow, WK Gibson, CW AF Wright, J. Timothy Hart, Thomas C. Hart, P. Suzanne Simmons, Darrin Suggs, Cynthia Daley, Bill Simmer, Jim Hu, Jan Bartlett, John D. Li, Yong Yuan, Zhi-An Seow, W. Kim Gibson, Carolyn W. TI Human and Mouse Enamel Phenotypes Resulting from Mutation or Altered Expression of AMEL, ENAM, MMP20 and KLK4 SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 9th International Conference on the Chemistry and Biology of Mineralized Tissues CY NOV 04-08, 2007 CL Lakeland, TX DE Enamel; Amelogenesis imperfecta; Mouse; Human; Gene; Mutation ID DOMINANT AMELOGENESIS IMPERFECTA; MICE DISPLAY; GENE; NOMENCLATURE; DEFECTS; PROTEIN AB Amelogenesis imperfecta (AI) is caused by AMEL, ENAM, MMP20 and KLK4 gene mutations. Mice lacking expression of the AmelX, Enam and Mmp20 genes have been generated. These mouse models provide tools for understanding enamel formation and AI pathogenesis. This study describes the AI phenotypes and relates them to their mouse model counterparts. Human AI phenotypes were determined in a clinical population of AI families and published cases. Human and murine teeth were evaluated using light and electron microscopy. A total of 463 individuals from 54 families were evaluated and mutations in the AMEL, ENAM and KLK4 genes were identified. The majority of human mutations for genes coding enamel nonproteinase proteins (AMEL and ENAM) resulted in variable hypoplasia ranging from local pitting to a marked, generalized enamel thinning. Specific AMEL mutations were associated with abnormal mineralization and maturation defects. Amel and Enam null murine models displayed marked enamel hypoplasia and a complete loss of prism structure. Human mutations in genes coding for the enamel proteinases (MMP20 and KLK4) cause variable degrees of hypomineralization. The murine Mmp20 null mouse exhibits both hypoplastic and hypomineralized defects. The currently available Amel and Enam mouse models for AI exhibit enamel phenotypes (hypoplastic) that are generally similar to those seen in humans. Mmp20 null mice have a greater degree of hypoplasia than humans with MMP20 mutations. Mice lacking expression of the currently known genes associated with the human AI conditions provide useful models for understanding the pathogenesis of these conditions. Copyright (C) 2008 S. Karger AG, Basel C1 [Wright, J. Timothy] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. [Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Hart, P. Suzanne] NHGRI, NIH, Human Genome Project, Bethesda, MD 20892 USA. [Simmer, Jim; Hu, Jan] Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Bartlett, John D.] Forsyth Inst, Boston, MA USA. [Li, Yong; Yuan, Zhi-An; Gibson, Carolyn W.] Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Seow, W. Kim] Univ Queensland, Dept Dent, Brisbane, Qld, Australia. RP Wright, JT (reprint author), Univ N Carolina, Sch Dent, Dept Pediat Dent, Brauer Hall 7450, Chapel Hill, NC 27599 USA. EM tim_wright@dentistry.unc.edu RI Seow, W. Kim/F-2765-2010; Seow, W. K./F-7314-2010; OI Seow, Wan Kim/0000-0002-7876-4524 FU NIDCR NIH HHS [R01 DE011301, DE011089, DE01627, DE11301, DE12879, R01 DE011089, R01 DE011089-11, R01 DE011301-09, R01 DE012879, R01 DE012879-05, R01 DE016276, R01 DE016276-04, R29 DE011301, R56 DE011301] NR 24 TC 46 Z9 50 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2009 VL 189 IS 1-4 BP 224 EP 229 DI 10.1159/000151378 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 384VJ UT WOS:000261772000039 PM 18714142 ER PT J AU Rumble, JM Oetjen, KA Stein, PL Schwartzberg, PL Moore, BB Duckett, CS AF Rumble, Julie M. Oetjen, Karolyn A. Stein, Paul L. Schwartzberg, Pamela L. Moore, Bethany B. Duckett, Colin S. TI Phenotypic differences between mice deficient in XIAP and SAP, two factors targeted in X-linked lymphoproliferative syndrome (XLP) SO CELLULAR IMMUNOLOGY LA English DT Article DE Immunodeficiency; Viral; Apoptosis; Signal transduction ID MOLECULE-ASSOCIATED PROTEIN; SYNDROME GENE-PRODUCT; NKT CELL-DEVELOPMENT; HUMORAL IMMUNITY; ENCODING GENE; CUTTING EDGE; DISEASE; ACTIVATION; MUTATIONS; INFECTION AB Mutations in the X-linked inhibitor of apoptosis (XIAP) have recently been identified in patients with the rare genetic disease, X-linked lymphoproliferative syndrome (XLP), which was previously thought to be solely attributable to mutations in a distinct gene, SAP. To further understand the roles of these two factors in the pathogenesis of XLP, we have compared mice deficient in Xiap with known phenotypes of Sap-null mice. We show here that in contrast to Sap-deficient mice, animals lacking Xiap have apparently normal NKT cell development and no apparent defect in humoral responses to T cell-dependent antigens. However, Xiap-deficient cells were more susceptible to death upon infection with the murine herpesvirus MHV-68 and gave rise to more infectious virus. These differences could be rescued by restoration of XIAP. These data provide insight into the differing roles of XIAP and SAP in the pathogenesis of XLP. (C) 2009 Elsevier Inc. All rights reserved. C1 [Rumble, Julie M.; Oetjen, Karolyn A.; Duckett, Colin S.] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. [Moore, Bethany B.; Duckett, Colin S.] Univ Michigan, Dept Internal Med, Sch Med, Ann Arbor, MI 48109 USA. [Rumble, Julie M.] Univ Michigan, Grad Program Immunol, Sch Med, Ann Arbor, MI 48109 USA. [Stein, Paul L.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Stein, Paul L.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), Univ Michigan, Dept Pathol, Sch Med, 109 Zina Pitcher Pl,BSRB Room 2057, Ann Arbor, MI 48109 USA. EM colind@umich.edu OI Rumble, Julie/0000-0001-7220-7631; Moore, Bethany/0000-0003-3051-745X FU Department of Defense [W81XWH-06-1-0429]; American Heart Association; National Institutes of Health [CA86867, A1065543, HLO87846]; American Asthma Foundation [GM067827] FX We thank Dr. J. Silke for providing murine XIAP plasmids, and to Maria Soengas for providing El A and Ras plasmids. We are grateful to Josh Stoolman for help in the construction of plasmids for reconstitution of Xiap-null MEFs, to Carol Wilke for assistance with MHV-68 studies and to members of the Duckett lab for critical reading of the paper. This work was supported in part by award W81XWH-06-1-0429 from the Department of Defense to K.A.C., an American Heart Association and National Institutes of Health Grants CA86867 to P.LS., A1065543 and HLO87846 to B.B.M., and GM067827 and an award from the American Asthma Foundation Program for Asthma Research to C.S.D. NR 30 TC 21 Z9 22 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2009 VL 259 IS 1 BP 82 EP 89 DI 10.1016/j.cellimm.2009.05.017 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 488NJ UT WOS:000269356200013 PM 19595300 ER PT J AU Glushakova, S Mazar, J Hohmann-Marriott, MF Hama, E Zimmerberg, J AF Glushakova, Svetlana Mazar, Julia Hohmann-Marriott, Martin F. Hama, Erinn Zimmerberg, Joshua TI Irreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes SO CELLULAR MICROBIOLOGY LA English DT Article ID RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM MEROZOITES; ELECTRON MICROSCOPY; HOST ERYTHROCYTE; EGRESS; PROTEINS; INVASION; CULTURE; SURFACE; MATURE AB By studying the inactivation of malaria parasite culture by cysteine protease inhibition using confocal microscopy of living cells and electron microscopy of high-pressure frozen and freeze-substituted cells, we report the precise step in the release of malaria parasites from erythrocytes that is likely regulated by cysteine proteases: the opening of the erythrocyte membrane, liberating parasites for the next round of infection. Inhibition of cysteine proteases within the last few minutes of cycle does not affect rupture of the parasitophorus vacuole but irreversibly blocks the subsequent rupture of the host cell membrane, locking in resident parasites, which die within a few hours of captivity. This irreversible inactivation of mature parasites inside host cells makes plasmodial cysteine proteases attractive targets for antimalarials, as parasite-specific cysteine protease inhibitors may significantly augment multi-target drug cocktails. C1 [Glushakova, Svetlana; Mazar, Julia; Hama, Erinn; Zimmerberg, Joshua] NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. [Hohmann-Marriott, Martin F.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. EM joshz@mail.nih.gov FU Intramural Research Program of the NIH; NICHD FX This research was supported by the Intramural Research Program of the NIH, NICHD. We thank Dr. Kamran Melikov and Dr. Glen Humphrey for a fruitful discussion and Dr. Richard Leapman for the use of his facilities and important discussions. NR 31 TC 24 Z9 24 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JAN PY 2009 VL 11 IS 1 BP 95 EP 105 DI 10.1111/j.1462-5822.2008.01242.x PG 11 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 390FQ UT WOS:000262150100008 PM 19016793 ER PT J AU Meaburn, K Gudla, P Khan, S Nandy, K Lockett, S Misteli, T AF Meaburn, Karen Gudla, Prabhaka Khan, Sameena Nandy, Kaustav Lockett, Stephen Misteli, Tom TI BREAST CANCER DIAGNOSTICS BASED ON INTERPHASE SPATIAL GENOME POSITIONING SO CELLULAR ONCOLOGY LA English DT Meeting Abstract CT 3rd Marie Curie-Genome Architecture in Relation to Disease Meeting (MC-GARD) CY APR 01-05, 2009 CL Edinburgh, SCOTLAND C1 [Meaburn, Karen; Gudla, Prabhaka; Khan, Sameena; Nandy, Kaustav; Lockett, Stephen; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. EM meaburnk@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2009 VL 31 IS 2 BP 89 EP 90 PG 2 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 439OB UT WOS:000265635300005 ER PT J AU Meier, H Bullinger, J Marx, G Deten, A Horn, LC Rassler, B Zimmer, HG Briest, W AF Meier, Henning Bullinger, Joerg Marx, Grit Deten, Alexander Horn, Lars-Christian Rassler, Beate Zimmer, Heinz-Gerd Briest, Wilfried TI Crucial Role of Interleukin-6 in the Development of Norepinephrine-induced Left Ventricular Remodeling in Mice SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Interleukins; Extracellular matrix; Hypertrophy; Remodeling ID INDUCED CARDIAC-HYPERTROPHY; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; GENE-EXPRESSION; RATS; ACTIVATION; GP130; PROGRESSION; CYTOKINES AB Background: Elevated serum concentration of interleukin (IL)-6 is a predictor for poor prognosis in congestive heart failure. It was shown previously in rats, that IL-6 expression in the left ventricle (LV) was followed by LV hypertrophy. Methods: Using IL-6 deficient mice (IL-6(-/-)), we studied the role of IL-6 in a model of norepinephrine (NE)-induced LV hypertrophy. Results: In wild type (WT) mice, IL-6 mRNA expression and its concentration in the serum were elevated after 4 h of NE-treatment (s.c. 0.25 mg/kg . h). Further, NE-induced LV hypertrophy was detected: LV weight/body weight (LVW/BW) ratio (+ 12.3 +/- 3%, p < 0.05) and mRNA expression of atrial natriuretic peptide (ANP) in WT mice (+ 120 +/- 25%, p < 0.05) after 3 days were increased. In contrast, NE did not induce elevation of LVW/BW ratio and ANP expression in IL-6(-/-) mice. Replacement with recombinant IL-6 restored the hypertrophy-inducing effect of NE in IL-6(-/-) mice. As to the extracellular matrix (ECM) proteins, NE increased collagen type I and III expression only in WT mice and not in IL-6(-/-) mice. The addition of recombinant IL-6 elevated the expression of the ECM proteins to the WT level. Conclusion: IL-6 is a major player in the development of NE-induced LV hypertrophy in mice. Copyright (C) 2009 S. Karger AG, Basel C1 [Meier, Henning; Bullinger, Joerg; Marx, Grit; Deten, Alexander; Rassler, Beate; Zimmer, Heinz-Gerd; Briest, Wilfried] Univ Leipzig, Carl Ludwig Inst Physiol, Leipzig, Germany. [Horn, Lars-Christian] Univ Leipzig, Inst Pathol, Leipzig, Germany. RP Briest, W (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM briestw@mail.nih.gov OI Briest, Wilfried/0000-0003-4556-4849 FU Deutsche Forschungsgemeinschaft [ZI 199/10-4]; Medical Faculty of the University of Leipzig [1-10]; BMBF [01ZZ01106]; Ernst von Weber foundation FX We thank M. Kopf for the IL-6-/- mice and B. Mix for excellent technical assistance. This study was supported by grant from the Deutsche Forschungsgemeinschaft (ZI 199/10-4), by grant of the Medical Faculty of the University of Leipzig (formel. 1-10), by a grant of BMBF (NBL-3-support; No 01ZZ01106) and by a grant of Ernst von Weber foundation. NR 37 TC 10 Z9 10 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2009 VL 23 IS 4-6 BP 327 EP 334 DI 10.1159/000218180 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 442TY UT WOS:000265864700011 PM 19471100 ER PT J AU Sherry, B Patton, JT Dermody, TS AF Sherry, Barbara Patton, John T. Dermody, Terence S. BE Brasier, AR Garcia Sastre, A Lemon, SM TI Innate Immune Responses Elicited by Reovirus and Rotavirus SO CELLULAR SIGNALING AND INNATE IMMUNE RESPONSES TO RNA VIRUS INFECTIONS LA English DT Article; Book Chapter ID NF-KAPPA-B; DOUBLE-STRANDED-RNA; INTERFERON REGULATORY FACTOR-3; INDUCED ACUTE MYOCARDITIS; DEPRIVED NEWBORN CALVES; HOST-RANGE RESTRICTION; PROTEIN-KINASE PKR; HEPATITIS-C VIRUS; PATTERN-RECOGNITION RECEPTORS; MEMBRANE-PENETRATION PROTEIN C1 [Sherry, Barbara] N Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. [Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. [Dermody, Terence S.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. [Dermody, Terence S.] Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. RP Sherry, B (reprint author), N Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. RI Patton, John/P-1390-2014 NR 192 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-556-1 PY 2009 BP 403 EP 422 PG 20 WC Biochemistry & Molecular Biology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Immunology; Microbiology GA BOY06 UT WOS:000278003900026 ER PT J AU Donaldson, JG Porat-Shliom, N Cohen, LA AF Donaldson, Julie G. Porat-Shliom, Natalie Cohen, Lee Ann TI Clathrin-independent endocytosis: A unique platform for cell signaling and PM remodeling SO CELLULAR SIGNALLING LA English DT Review DE Arf6; Clathrin-independent; Endocytosis; Macropinocytosis; Phosphoinositides; Signaling; Src; Ras ID PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; CONSTITUTIVE MACROPINOCYTOSIS; DOWNSTREAM ACTIVATION; NEUROENDOCRINE CELLS; RECEPTOR ENDOCYTOSIS; RECYCLING PATHWAY; EXCHANGE FACTORS; ARF6 RECRUITS; RAS PROTEINS AB There is increasing interest in endocytosis that occurs independently of clathrin coats and the fates of membrane proteins internalized by this mechanism. The appearance of clathrin-independent endocytic and membrane recycling pathways seems to vary with different cell types and cargo molecules. In this review we focus on studies that have been performed using HeLa and COS cells as model systems for understanding this membrane trafficking system. These endosomal membranes contain signaling molecules including H-Ras, Rac1, Arf6 and Rab proteins, and a lipid environment rich in cholesterol and PIP(2) providing a unique platform for cell signaling. Furthermore, activation of some of these signaling molecules (H-Ras, Rac and Arf6) can switch the constitutive form of clathrin-independent endocytosis into a stimulated one, associated with PM ruffling and macropinocytosis. Published by Elsevier Inc. C1 [Donaldson, Julie G.; Porat-Shliom, Natalie; Cohen, Lee Ann] NHLBI, LCB, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, LCB, NIH, Bldg 50,Rm 2503, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov FU Intramural Research Program of the National Heart, Lung and Blood Institute, NIH FX We thank Ed Korn and Craig Eyster for comments. This work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute, NIH. NR 73 TC 112 Z9 113 U1 4 U2 17 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 JAN PY 2009 VL 21 IS 1 BP 1 EP 6 DI 10.1016/j.cellsig.2008.06.020 PG 6 WC Cell Biology SC Cell Biology GA 389AB UT WOS:000262060900001 PM 18647649 ER PT J AU Lerner, A Bagic, A Hanakawa, T Boudreau, EA Pagan, F Mari, Z Bara-Jimenez, W Aksu, M Sato, S Murphy, DL Hallett, M AF Lerner, Alicja Bagic, Anto Hanakawa, Takashi Boudreau, Eilis A. Pagan, Fernando Mari, Zoltan Bara-Jimenez, William Aksu, Murat Sato, Susumu Murphy, Dennis L. Hallett, Mark TI Involvement of Insula and Cingulate Cortices in Control and Suppression of Natural Urges SO CEREBRAL CORTEX LA English DT Article ID EVENT-RELATED FMRI; OBSESSIVE-COMPULSIVE DISORDER; OLD-WORLD MONKEY; STOP-SIGNAL TASK; RESPONSE-INHIBITION; FUNCTIONAL MRI; PHYSIOLOGICAL CONDITION; VOLUNTARY SUPPRESSION; TOURETTE-SYNDROME; BRAIN RESPONSES AB The physiology of control and suppression of natural urges is not well understood. We used [(15)O]H(2)O positron-emission tomography imaging to identify neural circuits involved in suppression of spontaneous blinking as a model of normal urges. Suppression of blinking was associated with prominent activation of bilateral insular-claustrum regions, right more than left; activation was also found in bilateral anterior cingulate cortex (ACC), supplementary motor areas, and the face area of the primary motor cortex bilaterally. These results suggest a central role for the insula possibly together with ACC in suppression of blinking. C1 [Lerner, Alicja; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Bagic, Anto] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Hanakawa, Takashi] Natl Ctr Neurol & Psychiat, Dept Cort Funct Disorder, Tokyo 1878502, Japan. [Boudreau, Eilis A.] Portland VA Med Ctr, Hlth Sci Res & Dev Program, Portland, OR 97239 USA. [Pagan, Fernando] Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. [Mari, Zoltan] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Bara-Jimenez, William] Bethesda Neurosci Clin, Bethesda, MD 20885 USA. [Aksu, Murat] Erciyes Univ, Fac Med, Dept Neurol, TR-38039 Kayseri, Turkey. [Sato, Susumu] Natl Inst Neurol Disorders & Stroke, EEG Sect, Bethesda, MD 20892 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Lerner, A (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM lernera@mail.nih.gov FU Intramural Research Programs of the National Institute of Neurological Disorders and Stroke; National Institute of Mental Health with the National Institutes of Health FX Intramural Research Programs of the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health with the National Institutes of Health. NR 69 TC 43 Z9 46 U1 4 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2009 VL 19 IS 1 BP 218 EP 223 DI 10.1093/cercor/bhn074 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 383ND UT WOS:000261679400021 PM 18469316 ER PT J AU Tomasi, D Wang, RL Telang, F Boronikolas, V Jayne, MC Wang, GJ Fowler, JS Volkow, ND AF Tomasi, D. Wang, R. L. Telang, F. Boronikolas, V. Jayne, M. C. Wang, G. -J. Fowler, J. S. Volkow, N. D. TI Impairment of Attentional Networks after 1 Night of Sleep Deprivation SO CEREBRAL CORTEX LA English DT Article ID VISUAL-ATTENTION; WORKING-MEMORY; SPATIAL ATTENTION; SUSTAINED ATTENTION; SELECTIVE ATTENTION; FUNCTIONAL-ANATOMY; BRAIN-FUNCTION; NEURAL BASIS; 4 TESLA; FMRI AB Here, we assessed the effects of sleep deprivation (SD) on brain activation and performance to a parametric visual attention task. Fourteen healthy subjects underwent functional magnetic resonance imaging of ball-tracking tasks with graded levels of difficulty during rested wakefulness (RW) and after 1 night of SD. Self-reports of sleepiness were significantly higher and cognitive performance significantly lower for all levels of difficulty for SD than for RW. For both the RW and the SD sessions, task difficulty was associated with activation in parietal cortex and with deactivation in visual and insular cortices and cingulate gyrus but this pattern of activation/deactivation was significantly lower for SD than for RW. In addition, thalamic activation was higher for SD than for RW, and task difficulty was associated with increases in thalamic activation for the RW but not the SD condition. This suggests that thalamic resources, which under RW conditions are used to process increasingly complex tasks, are being used to maintain alertness with increasing levels of fatigue during SD. Thalamic activation was also inversely correlated with parietal and prefrontal activation. Thus, the thalamic hyperactivation during SD could underlie the reduced activation in parietal and blunted deactivation in cingulate cortices, impairing the attentional networks that are essential for accurate visuospatial attention performance. C1 [Tomasi, D.; Wang, R. L.; Telang, F.; Boronikolas, V.; Jayne, M. C.; Wang, G. -J.; Fowler, J. S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Volkow, N. D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Tomasi, D (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA. EM tomasi@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU Department of Energy (Office of Biological and Environmental Research [FWP CO-15]; National Institutes of Health Intramural Program and National Center for Research Resources [GCRC 5-MO1-RR-10710] FX Department of Energy (Office of Biological and Environmental Research FWP CO-15); the National Institutes of Health Intramural Program and National Center for Research Resources (GCRC 5-MO1-RR-10710). NR 72 TC 89 Z9 91 U1 3 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2009 VL 19 IS 1 BP 233 EP 240 DI 10.1093/cercor/bhn073 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 383ND UT WOS:000261679400023 PM 18483003 ER PT J AU Nyquist, PA Winkler, CA McKenzie, LM Yanek, LR Becker, LC Becker, DM AF Nyquist, Paul A. Winkler, Cherie A. McKenzie, Louise M. Yanek, Lisa R. Becker, Lewis C. Becker, Diane M. TI Single Nucleotide Polymorphisms in Monocyte Chemoattractant Protein-1 and Its Receptor Act Synergistically to Increase the Risk of Carotid Atherosclerosis SO CEREBROVASCULAR DISEASES LA English DT Article DE Carotid atherosclerosis; Monocyte chemoattractant protein; Single nucleotide polymorphisms; Inflammation ID INTIMA-MEDIA THICKNESS; E-DEFICIENT MICE; MYOCARDIAL-INFARCTION; MCP-1 GENE; NORTHERN MANHATTAN; HAPLOTYPE RECONSTRUCTION; ETHNIC-DIFFERENCES; ISCHEMIC-STROKE; POPULATION; ASSOCIATION AB Background: Monocyte chemoattractant protein 1 (MCP-1), acting in concert with its receptor chemokine receptor 2 (CCR2), promotes recruitment of macrophages into atherosclerotic plaque. We examined whether single nucleotide polymorphism (SNP) variants in the MCP-1 or CCR2 genes independently or in combination are associated with carotid artery atherosclerosis in an African American population at increased risk of vascular disease. Methods: Four SNPs in MCP-1 and 1 in CCR2 were genotyped. Carotid artery duplex ultrasonography was used to identify the presence or absence of carotid plaque >1 mm. The study population included 325 apparently healthy 30- to 59-year-old black siblings of 185 probands with premature coronary artery disease (<60 years old). Associations between each independent SNP and the presence of carotid plaque were examined using multivariate logistic regression models adjusted for age, sex, educational level, diabetes, smoking, hypertension, obesity, low-density lipoprotein cholesterol and non-independence within families. Interactions between SNPs in the MCP-1 gene and the SNP in the CCR2 gene were examined by multivariate analysis. Results: Siblings were 32% males, with a mean age of 46 8 7 years, and 77 (24%) demonstrated carotid plaque. In multivariate analyses, the CC genotype of MCP-1 SNP rs2857656 was independently associated with plaque (p = 0.05). Subjects who had both the MCP-1 CC genotype and were heterozygotic or homozygotic for the CCR2 V64I genotype (rs1799864; n = 12) had an even higher risk of carotid atherosclerosis (odds ratio 6.14, 95% confidence interval 1.82-20.73; p = 0.0037). Conclusion: The MCP-1 rs2857656 CC genotype is independently associated with carotid artery plaque in African American from families with premature coronary artery disease. The combination of the MCP-1 CC homozygous genotype and the homozygotic or heterozygote CCR2 V64I genotype is associated with a particularly high prevalence of carotid artery plaque. Copyright (C) 2009 S. Karger AG, Basel C1 [Nyquist, Paul A.] Johns Hopkins Sch Med, Dept Anesthesiol Crit Care Med, Baltimore, MD 21287 USA. [Nyquist, Paul A.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Nyquist, Paul A.] Johns Hopkins Sch Med, Dept Neurol Surg, Baltimore, MD 21287 USA. [Yanek, Lisa R.; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Winkler, Cherie A.; McKenzie, Louise M.] NCI, NIH, Frederick, MD 21701 USA. RP Nyquist, PA (reprint author), Johns Hopkins Sch Med, Dept Anesthesiol Crit Care Med, Meyer 8-140,600 N Wolfe St, Baltimore, MD 21287 USA. EM pnyquis1@jhmi.edu FU NCRR NIH HHS [M01-RR000052, M01 RR000052]; NHLBI NIH HHS [R18 HL58625, U01 HL72518, U01 HL072518] NR 41 TC 13 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2009 VL 28 IS 2 BP 124 EP 130 DI 10.1159/000223437 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 466GS UT WOS:000267650000004 PM 19506371 ER PT J AU Sanossian, N Starkman, S Liebeskind, DS Ali, LK Restrepo, L Hamilton, S Conwit, R Saver, JL AF Sanossian, Nerses Starkman, Sidney Liebeskind, David S. Ali, Latisha K. Restrepo, Lucas Hamilton, Scott Conwit, Robin Saver, Jeffrey L. CA FAST-MAG Trial Investigators TI Simultaneous Ring Voice-over-Internet Phone System Enables Rapid Physician Elicitation of Explicit Informed Consent in Prehospital Stroke Treatment Trials SO CEREBROVASCULAR DISEASES LA English DT Article DE Prehospital trials; Stroke; Magnesium; Informed consent; Clinical trial ID CLINICAL-TRIALS; IMPACT; FIELD AB Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials. Methods: The NIH Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively. Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and unconsentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean 8 SD: 8.4 +/- 2.5 min, range 6-14) was longer than non-enrollment calls (5.5 +/- 3.5, range 2-13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset. Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials. Copyright (C) 2009 S. Karger AG, Basel C1 [Sanossian, Nerses] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA. [Starkman, Sidney; Liebeskind, David S.; Ali, Latisha K.; Restrepo, Lucas; Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Starkman, Sidney; Liebeskind, David S.; Ali, Latisha K.; Restrepo, Lucas; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Conwit, Robin] NINDS, Div Extramural Res, NIH, Bethesda, MD 20892 USA. RP Sanossian, N (reprint author), Univ So Calif, Dept Neurol, 1200 N State St,Room 5640, Los Angeles, CA 90033 USA. EM sanossia@yahoo.com RI Emchi, Karma/Q-1952-2016; OI Saver, Jeffrey/0000-0001-9141-2251 FU NIH-NINDS [U01 NS 44364] FX This work was supported by NIH-NINDS Award U01 NS 44364. NR 14 TC 23 Z9 23 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2009 VL 28 IS 6 BP 539 EP 544 DI 10.1159/000247596 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 524LC UT WOS:000272143800001 PM 19844092 ER PT J AU Ravindran, A Kobrinsky, E Lao, QZ Soldatov, NM AF Ravindran, Arippa Kobrinsky, Evgeny Lao, Qi Zong Soldatov, Nikolai M. TI Functional properties of the Ca(V)1.2 calcium channel activated by calmodulin in the absence of alpha(2)delta subunits SO CHANNELS LA English DT Article DE beta(2d) subunit; alpha(2)delta subunit; prepulse facilitation; recovery from inactivation; inactivation; Ca2+-induced inactivation; COS1 cells ID VOLTAGE-DEPENDENT FACILITATION; MAMMALIAN HEART-CELLS; GATED CA2+ CHANNELS; CA2+-DEPENDENT INACTIVATION; PREPULSE FACILITATION; ALPHA(1) SUBUNIT; BETA-SUBUNITS; EXPRESSION; MODULATION; KINASE AB Voltage-activated Ca(V)1.2 calcium channels require association of the pore-forming alpha(1C) subunit with accessory Ca-V beta and alpha(2)delta subunits. Binding of a single calmodulin (CaM) to alpha(1C) supports Ca2+-dependent inactivation (CDI). The human CaV1.2 channel is silent in the absence of Ca-V beta and/or alpha(2)delta. Recently, we found that coexpression of exogenous CaM (CaMex) supports plasma membrane targeting, gating facilitation and CDI of the channel in the absence of Ca-V beta. Here we discovered that CaMex and its Ca2+-insensitive mutant (CaM1234) rendered active alpha(1C)/Ca-V beta channel in the absence of alpha(2)delta. Coexpression of CaMex with alpha(1C) and beta(2d) in calcium-channel- free COS-1 cells recovered gating of the channel and supported CDI. Voltage-dependence of activation was shifted by approximate to+40 mV to depolarization potentials. The calcium current reached maximum at +40 mV (20 mM Ca2+) and exhibited approximately 3 times slower activation and 5 times slower inactivation kinetics compared to the wild-type channel. Furthermore, both CaMex and CaM1234 accelerated recovery from inactivation and induced facilitation of the calcium current by strong depolarization prepulse, the properties absent from the human vascular/neuronal Ca(V)1.2 channel. The data suggest a previously unknown action of CaM that in the presence of Ca-V beta translates into activation of the alpha(2)delta-deficient calcium channel and alteration of its properties. C1 [Ravindran, Arippa; Kobrinsky, Evgeny; Lao, Qi Zong; Soldatov, Nikolai M.] NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM soldatovN@grc.nia.nih.gov FU NIA Intramural Research Program [Z01 AG000294-08] FX This work was supported by NIA Intramural Research Program (Z01 AG000294-08 to Nikolai M. Soldatov). NR 37 TC 5 Z9 5 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6950 J9 CHANNELS JI Channels PD JAN-FEB PY 2009 VL 3 IS 1 BP 25 EP 31 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432FY UT WOS:000265120100006 PM 19106618 ER PT J AU Avino, A Perez-Rentero, S Garibotti, AV Siddiqui, MA Marquez, VE Eritja, R AF Avino, Anna Perez-Rentero, Sonia Garibotti, Alejandra V. Siddiqui, Maqbool A. Marquez, Victor E. Eritja, Ramon TI Synthesis and Hybridization Properties of Modified Oligodeoxynucleotides Carrying Non-Natural Bases SO CHEMISTRY & BIODIVERSITY LA English DT Article ID DNA METHYLTRANSFERASES; CRYSTAL-STRUCTURE; OLIGONUCLEOTIDES; ZEBULARINE; INHIBITION; HAIRPIN; RECOGNITION; EQUILIBRIA; STABILITY; MECHANISM AB The impact of the presence of nonnatural bases on the properties of oligodeoxynucleotides has been studied. First, oligodeoxynucleotides carrying 2'-deoxyzebularine were prepared, and the stability of duplexes carrying this analogue was determined by DNA melting experiments. Melting temperatures and thermodynamic data indicated the preference of 2'-deoxyzebularine for 2'-deoxyguanosine, which behaves as a 2'-deoxycytidine analogue, forming a less stable base pair due to the absence of the amino group at position 4. Moreover, the duplex-hairpin equilibrium of a self-complementary oligodeoxynucleotide carrying several natural and normatural bases including 2'-deoxyzebularine as a central mispair, was studied. Depending on the base present in the middle of the sequence, it is possible to affect the stability of the bimolecular duplex modulating the duplex-hairpin equilibrium. Magnesium ions were shown to stabilize preferentially the bimolecular duplex form. The results indicate the importance of the modifications and the role of cations in shifting the structural equilibrium. C1 [Avino, Anna; Perez-Rentero, Sonia; Garibotti, Alejandra V.; Eritja, Ramon] CSIC, Inst Biomed Res, CIBER BBN Networking Ctr Bioengn Biomat & Nanomed, IQAC, E-08028 Barcelona, Spain. [Siddiqui, Maqbool A.; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Eritja, R (reprint author), CSIC, Inst Biomed Res, CIBER BBN Networking Ctr Bioengn Biomat & Nanomed, IQAC, Edifici Helix,Baldiri Reixac 15, E-08028 Barcelona, Spain. EM recgma@cid.csic.es RI eritja, ramon/B-5613-2008; Avino, Anna/N-5223-2015 OI eritja, ramon/0000-0001-5383-9334; Avino, Anna/0000-0003-3047-738X FU Intramural NIH HHS NR 21 TC 5 Z9 5 U1 0 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1612-1872 J9 CHEM BIODIVERS JI Chem. Biodivers. PY 2009 VL 6 IS 2 BP 117 EP 126 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 414GF UT WOS:000263851200001 PM 19235163 ER PT B AU Fang, L Hwang, ST AF Fang, Lei Hwang, Sam T. BE Fulton, AM TI Roles for CCR7 in Cancer Biology SO CHEMOKINE RECEPTORS IN CANCER SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter ID CHEMOKINE RECEPTOR CCR7; LYMPH-NODE METASTASIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; CELL-LUNG-CANCER; MATURE DENDRITIC CELLS; B16 TUMOR-CELLS; GROWTH FACTOR-C; BREAST-CANCER; IN-VITRO; T-CELLS AB Since 2001, the association of CCR7 expression by tumor cells with LN metastasis (and associated poor clinical outcome) has been validated in a large number of solid tumors as well as in hematopoietic malignancies. Local factors such as hypoxia, cytokines (endothelins), or epigenetic changes may be involved in the upregulation of CCR7 by tumor cells. Through distinct signaling pathways, activation of CCR7 by its cognate ligands, CCL21 or CCL19, promotes migration, invasion and proliferation of tumor cells in vitro. In addition to responding to exogenous sources of CCR7 ligands, CCR7-expressing tumor cells facilitate their own migration towards CCL21-expressing lymphatics by generating transcellular gradients of CCL19/21. While CCR7 antagonists appear to block LN metastasis in short-term experimental models, the dual roles of CCR7 in protective immunity and tolerance suggests that these agents must be carefully evaluated. Meanwhile, increasing CCR7 expression in DCs may represent a potentially useful means of improving the efficacy of in vivo DC vaccination strategies. C1 [Hwang, Sam T.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Fang, Lei] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. EM sthwang@mcw.edu NR 80 TC 6 Z9 6 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-266-7 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2009 BP 93 EP 108 DI 10.1007/978-1-60327-267-4_6 D2 10.1007/978-1-60327-267-4 PG 16 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BKJ74 UT WOS:000268327700006 ER PT S AU Martin, D Gutkind, JS AF Martin, Daniel Gutkind, J. Silvio BE Handel, TM Hamel, DJ TI KAPOSI'S SARCOMA VIRALLY ENCODED, G-PROTEIN-COUPLED RECEPTOR: A PARADIGM FOR PARACRINE TRANSFORMATION SO CHEMOKINES, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID NF-KAPPA-B; CHEMOKINE RECEPTOR; GENE-EXPRESSION; HERPESVIRUS; KINASE; CELLS; VGPCR; ACTIVATION; SECRETION; IDENTIFICATION AB Kaposi's sarcoma (KS) is an angioproliferative disease caused by infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). This virus encodes 84 open-reading frames (ORFs), many of which represent pirated versions of human genes. One of them, ORF74, encodes a predicted seven-span transmembrane receptor termed vGPCR that is similar to the human IL8 receptor CXCR2, which displays strong oncogenic activity in vitro and in vivo by a complex interplay of direct and autocrine/paracrine mechanisms. vGPCR has been shown to be both necessary and sufficient for the formation and progression of KS-like lesions in experimental model systems. Due to the fundamental role of vGPCR in the pathogenesis of KS, understanding the molecular mechanisms elicited by this unique chemokine receptor can be exploited to devise new strategies for KS management, as welt as to gain novel insights into how KSHV subverts key physiological processes such as cell proliferation, chemotaxis, angiogenesis, and immunomodulation for its replicative advantage. Here we describe multiple techniques and strategies that have been used to study the unique properties and functions of vGPCR and its role in oncogenesis. C1 [Martin, Daniel; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Martin, D (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 FU National Institutes of Health; National Institute of Dental and Craniofacial Research FX This research was supported by the National Institutes of Health Intramural AIDS Targeted Antiviral Program and the National Institute of Dental and Craniofacial Research. NR 47 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374908-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2009 VL 460 BP 125 EP 150 DI 10.1016/S0076-6879(09)05206-9 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJL14 UT WOS:000266737100006 PM 19446723 ER PT S AU Kriebel, PW Parent, CA AF Kriebel, Paul W. Parent, Carole A. BE Jin, T Hereld, D TI Group Migration and Signal Relay in Dictyostelium SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Adenylyl cyclase; G proteins; Chemotaxis; cAMP; Methods ID ADENYLYL-CYCLASE; CHEMOATTRACTANT; CHEMOTAXIS; EDGE AB The ability of cells to migrate directionally in gradients of chemoattractant is a fundamental biological response that is essential for the survival of the social amoebae Dictyostelium discoideum. In Dictyostelium, cAMP is the most potent chemoattractant and the detection, synthesis, and degradation of cAMP is exquisitely regulated. Interestingly, as Dictyostelium cells migrate directionally, they do so in a head-to-tail fashion, forming characteristic streams. This group behavior is acquired through the relay of the cAMP signals to neighboring cells. This chapter describes experimental procedures used to obtain synchronized populations of chemotactically competent cells and to assess their streaming behavior. In addition, we provide a detailed account of the method used to measure the ability of chemoattractants to directly stimulate adenylyl cyclase activity. Together, these techniques provide a way to combine cell biological and biochemical approaches to the study of signal relay. C1 [Kriebel, Paul W.; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kriebel, PW (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 10 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 111 EP 124 DI 10.1007/978-1-60761-198-1_7 D2 10.1007/978-1-60761-198-1 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700007 PM 19763962 ER PT S AU Park, C Hwang, IY Kehrl, JH AF Park, Chung Hwang, Il-Young Kehrl, John H. BE Jin, T Hereld, D TI Intravital Two-Photon Imaging of Adoptively Transferred B Lymphocytes in Inguinal Lymph Nodes SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE B lymphocytes; Inguinal lymph node; Intravital imaging; Two-photon microscopy ID IN-VIVO; DENDRITIC CELLS; MOTILITY; TRAFFICKING; MICROSCOPY AB Intravital two-photon imaging allows the observation of immune cells in intact organs of live animals in real time. Recently, several studies using two-photon microscopy have detailed the motility of mouse B and T lymphocyte within lymph nodes and have shown a dependence upon chemokine receptor signaling for the basal velocity of the cells. For, example, T cells from Gnia2(-/-)mice, deficient in the heterotrimer G-protein Got subunit G(alpha i2) have markedly impaired chemokine-triggered chemotaxis. In vivo these cells have reduced motility and impaired positioning within lymph nodes. Gnia2(-/-) B cells exhibit similar defects. In addition, B cells from Rgs1(-/-) mice, deficient in a major negative regulator of G(alpha i2), have a more robust motility than do wild-type B cells. Here, we describe procedures for visualizing the behavior of fluorescently labeled and adoptively transferred B lymphocytes within the inguinal lymph node of live mice. C1 [Park, Chung; Hwang, Il-Young; Kehrl, John H.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Park, C (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X FU Intramural NIH HHS NR 18 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 199 EP 207 DI 10.1007/978-1-60761-198-1_13 D2 10.1007/978-1-60761-198-1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700013 PM 19763968 ER PT S AU Liao, XH Kimmel, AR AF Liao, Xin-Hua Kimmel, Alan R. BE Jin, T Hereld, D TI Biochemical Responses to Chemoattractants in Dictyostelium: Ligand-Receptor Interactions and Downstream Kinase Activation SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Receptor affinities; cAMP; PIP3; ERK; GSK3; Folate; G proteins ID CAMP RECEPTOR; G-PROTEIN; DISCOIDEUM; SIGNAL; GENE; ERK2; MECHANISMS; EXPRESSION; CELLS; GSK3 AB Dictyostelium discoideum is one of the most facile eukaryotic systems for the study of chemotactic response to secreted chemical ligands. Dictyostelium grow as individual cells, using bacteria and fungi as primary nutrient sources; during growth, Dictyostelium moves directionally toward folate, a bacterial byproduct. Upon nutrient depletion Dictyostelium initiates a multicellular development program characterized by the production and secretion of cAMP. Cell surface receptors specifically recognize extracellular cAMP, which serves as both a morphogen to promote development and a chemoattractant to organize multicellularity. We discuss several approaches for the study of ligand-receptor interaction, with focus on affinity class determination and quantification of ligand binding sites (i.e., receptors) per cell. We further present examples for the application of biochemical assays to characterize the ligand-induced kinase activation of PI3K, GSK3, and ERK2. C1 [Liao, Xin-Hua; Kimmel, Alan R.] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Liao, XH (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 24 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 271 EP 281 DI 10.1007/978-1-60761-198-1_18 D2 10.1007/978-1-60761-198-1 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700018 PM 19763973 ER PT S AU Xu, XH Brzostowski, JA Jin, T AF Xu, Xuehua Brzostowski, Joseph A. Jin, Tian BE Jin, T Hereld, D TI Monitoring Dynamic GPCR Signaling Events Using Fluorescence Microscopy, FRET Imaging, and Single-Molecule Imaging SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Confocal fluorescence microscopy; Forster resonance energy transfer; Total internal reflection fluorescence microscopy; Single-molecule imaging; GPCR; Heterotrimeric G-proteins; Spatiotemporal dynamics ID CHEMOKINE RECEPTORS; CHEMOTAXIS; DICTYOSTELIUM; CELLS AB How a eukaryotic cell translates a small concentration difference of a chemoattractant across the length of its surface into highly polarized intracellular responses is a fundamental question in chemotaxis. Chemoattractants arc detected by G-protein-coupled receptors (GPCRs). Binding of chemoattractants to GPCRs induces the dissociation of heterotrimeric G-proteins into G alpha, and G beta gamma subunits, which in turn, activate downstream signaling networks. To fully understand the molecular mechanisms of chemotaxis, it is essential to quantitatively measure the dynamic changes of chemoattractant concentrations around cells, activation of heterotrimeric G-proteins, and the mobility of GPCR and G-protein subunits in the cell membrane. Here, we outline fluorescence imaging methods including Forster resonance energy transfer (FRET) imaging and a single-molecule analysis that allow us to measure the dynamic properties of GPCR signaling in single live cells. C1 [Xu, Xuehua] Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20057 USA. [Brzostowski, Joseph A.; Jin, Tian] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Xu, XH (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20057 USA. EM tjin@niaid.nih.gov; tjin@niaid.nih.gov OI xu, xuehua/0000-0002-3863-9593 FU Intramural NIH HHS NR 15 TC 12 Z9 13 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 371 EP 383 DI 10.1007/978-1-60761-198-1_25 D2 10.1007/978-1-60761-198-1 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700025 PM 19763980 ER PT S AU Tolar, P Meckel, T AF Tolar, Pavel Meckel, Tobias BE Jin, T Hereld, D TI Imaging B-Cell Receptor Signaling by Single-Molecule Techniques SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Single-molecule imaging; single particle tracking; Receptors; Intracellular signaling; B-cell receptor; Immunological synapse; Planar lipid bilayers ID PROTEINS AB B-cell activation initiates antibody responses against pathogens. Recent imaging of B cells in vivo shows that B cells move rapidly through lymphoid tissues to search for antigens captured on the surfaces of antigen-presenting cells. Recognition of antigens by the B-cell antigen receptor (BCR) leads to microclustering of the BCR and the initiation of intracellular signaling that prompts the B cells to stop and form immunological synapses with the antigen-presenting cells. Although the biochemical signaling pathways downstream of the BCR that mediate these events arc becoming better characterized, the initial molecular steps in BCR microclustering and activation remain elusive. In part, this is because the dynamics of the cell-cell contact makes the observation of the antigen-induced changes in the BCR technically challenging. Here we review single-molecule imaging techniques that help to provide new information on the molecular behavior of small populations of the BCR as the), initiate intracellular signaling in a dynamically moving B cell. The techniques are generally applicable to the study of a broad range of membrane receptors involved in cell-cell contacts. C1 [Tolar, Pavel; Meckel, Tobias] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Tolar, P (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Meckel, Tobias/F-4372-2010 OI Meckel, Tobias/0000-0003-0759-2072 FU Intramural NIH HHS NR 6 TC 2 Z9 2 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 437 EP 453 DI 10.1007/978-1-60761-198-1_29 D2 10.1007/978-1-60761-198-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700029 PM 19763984 ER PT S AU Meier-Schellersheim, M Klauschen, F Angermann, B AF Meier-Schellersheim, Martin Klauschen, Frederick Angermann, Bastian BE Jin, T Hereld, D TI Computational Modeling of Signaling Networks for Eukaryotic Chemosensing SO CHEMOTAXIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Eukaryotic chemosensing; Computational model; Signaling network; Spatially resolved simulation; Reaction-diffusion system; Modeling software ID CELLS; CHEMOTAXIS; MECHANISMS; DICTYOSTELIUM; MOVEMENT; 3-KINASE; PTEN AB The task of developing and simulating computational models of signaling networks for eukaryotic chemosensing confronts the modeler with several challenges: (1) The stimuli that initiate the cellular responses one wishes to study are provided by extracellular concentration gradients. This means that the computational model must have a spatially resolved representation of extracellular molecular concentrations. (2) The intracellular responses consist of the generation of intracellular accumulations and/or translocations of signaling molecules, requiring spatially resolved computational representations of the simulated cells. (3) The signaling networks responsible for eukaryotic chemosensing comprise a multitude of components acting as receptors, adaptors, (lipid- and protein-) kinases (including GTPases), (lipid- and protein-) phosphatases, and molecule types used by others for membrane attachment. Models of such signaling networks may become quite complicated, unless one wishes to rely on abstract functional modules with certain input-output characteristics as modeling "shortcuts" replacing subnetworks of biological signaling molecules. In this chapter, we describe how modelers can use a modeling tool ("simmune") developed to facilitate the design and simulation of detailed computational models of signaling pathways (for eukaryotic chemosensing here), thereby avoiding the technical difficulties typically associated with building and simulating such quantitative models. C1 [Meier-Schellersheim, Martin; Klauschen, Frederick] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. [Angermann, Bastian] CHU Montreal, Ctr Rech, Immunol Lab, Montreal, PQ, Canada. RP Meier-Schellersheim, M (reprint author), NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Klauschen, Frederick/C-5637-2015 FU Intramural NIH HHS NR 17 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 571 BP 507 EP 526 DI 10.1007/978-1-60761-198-1_33 D2 10.1007/978-1-60761-198-1 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMH92 UT WOS:000272401700033 PM 19763988 ER PT J AU Conde-Agudelo, A Romero, R Lindheimer, MD AF Conde-Agudelo, Agustin Romero, Roberto Lindheimer, Marshall D. BE Lindheimer, MD Roberts, JM Cunningham, FG TI Tests to Predict Preeclampsia SO CHESLEY'S HYPERTENSIVE DISORDERS IN PREGNANCY, 3RD EDITION LA English DT Article; Book Chapter ID UTERINE ARTERY DOPPLER; HUMAN CHORIONIC-GONADOTROPIN; PREGNANCY-INDUCED HYPERTENSION; VELOCITY WAVE-FORMS; INTRAUTERINE GROWTH-RETARDATION; SERUM ALPHA-FETOPROTEIN; ANGIOTENSIN SENSITIVITY TEST; UTEROPLACENTAL BLOOD-FLOW; CALCIUM CREATININE RATIO; ROLL-OVER TEST C1 [Conde-Agudelo, Agustin] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD USA. [Conde-Agudelo, Agustin] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Detroit, MI USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] NICHD, Intramural Div, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Detroit, MI 48202 USA. [Romero, Roberto] Michigan State Univ, E Lansing, MI 48824 USA. [Lindheimer, Marshall D.] Univ Chicago, Dept Obstet & Gynecol & Med, Chicago, IL 60637 USA. [Lindheimer, Marshall D.] Univ Chicago, Comm Clin Pharmacol & Pharmacogenet, Chicago, IL 60637 USA. RP Conde-Agudelo, A (reprint author), NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Bethesda, MD USA. NR 245 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092118-1 PY 2009 BP 189 EP 211 DI 10.1016/B978-0-12-374213-1.00011-2 PG 23 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BEQ23 UT WOS:000317673700012 ER PT J AU Masur, H AF Masur, Henry TI Caring for AIDS Patients in the ICU Expanding Horizons SO CHEST LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTENSIVE-CARE; HIV-INFECTION; OUTCOMES C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Room 2C-145, Bethesda, MD 20892 USA. EM hmasur@nih.gov RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 12 TC 2 Z9 3 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2009 VL 135 IS 1 BP 1 EP 2 DI 10.1378/chest.08-2199 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 392LN UT WOS:000262304300001 PM 19136397 ER PT J AU Hirschtritt, ME Hammond, CJ Luckenbaugh, D Buhle, J Thurm, AE Casey, BJ Swedo, SE AF Hirschtritt, Matthew E. Hammond, Christopher J. Luckenbaugh, David Buhle, Jason Thurm, Audrey E. Casey, B. J. Swedo, Susan E. TI Executive and Attention Functioning Among Children in the PANDAS Subgroup SO CHILD NEUROPSYCHOLOGY LA English DT Article DE PANDAS; Executive functioning; Attention; Obsessive-compulsive disorder; Tourette syndrome ID OBSESSIVE-COMPULSIVE DISORDER; EVENT-RELATED POTENTIALS; LA-TOURETTE-SYNDROME; NEUROPSYCHOLOGICAL PERFORMANCE; SYDENHAMS CHOREA; BASAL GANGLIA; SHORT-FORM; HYPERACTIVITY DISORDER; UNMEDICATED PATIENTS; INHIBITORY DEFICITS AB Evidence from past studies indicates that adults and children with Obsessive-Compulsive Disorder (OCD) and Tourette syndrome (TS) experience subtle neuropsychological deficits. Less is known about neuropsychological functioning of children and adolescents with a symptom course consistent with the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection) subgroup of OCD and tics. To provide such information, we administered three tests of attention control and two of executive function to 67 children and adolescents (ages 5-16) diagnosed with OCD and/or tics and a symptom course consistent with the PANDAS subgroup and 98 healthy volunteers (HV) matched by age, sex, and IQ. In a paired comparison of the two groups, the PANDAS subjects were less accurate than HV in a test of response suppression. Further, in a two-step linear regression analysis of the PANDAS group in which clinical variables were added stepwise into the model and in the second step matching variables (age, sex, and IQ) were added, IQ emerged as a predictor of performance on this task. In the same analysis, ADHD diagnosis and age emerged as predictors of response time in a continuous performance task. Subdividing the PANDAS group by primary psychiatric diagnosis revealed that subjects with TS or OCD with tics exhibited a longer response time compared to controls than subjects with OCD only, replicating previous findings within TS and OCD. This study demonstrates that children with PANDAS exhibit neuropsychological profiles similar to those of their primary psychiatric diagnosis. C1 [Hirschtritt, Matthew E.; Hammond, Christopher J.; Thurm, Audrey E.; Swedo, Susan E.] NIMH, NIH, Dept Hlth & Human Serv, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. [Hirschtritt, Matthew E.] Johns Hopkins Univ, Baltimore, MD USA. [Hammond, Christopher J.] Univ Florida, Coll Med, Gainesville, FL USA. [Buhle, Jason; Casey, B. J.] Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10021 USA. [Buhle, Jason] Columbia Univ, Social Cognit Affect Neurosci Unit, Dept Psychol, New York, NY USA. RP Swedo, SE (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. EM swedos@mail.nih.gov RI Buhle, Jason/D-1610-2012; OI Hammond, Christopher/0000-0002-3227-2620 FU National Institute of Mental Health (NIMH); National Institutes of Health (NIH); HHS FX This research was supported by the Intramural Program of the National Institute of Mental Health (NIMH), National Institutes of Health (NIH). The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the United States Government. NR 64 TC 12 Z9 13 U1 6 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PY 2009 VL 15 IS 2 BP 179 EP 194 AR PII 794921751 DI 10.1080/09297040802186899 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 426AC UT WOS:000264678700006 PM 18622810 ER PT J AU Kenworthy, L Black, DO Harrison, B Della Rosa, A Wallace, GL AF Kenworthy, Lauren Black, David O. Harrison, Bryan Della Rosa, Anne Wallace, Gregory L. TI ARE EXECUTIVE CONTROL FUNCTIONS RELATED TO AUTISM SYMPTOMS IN HIGH-FUNCTIONING CHILDREN? SO CHILD NEUROPSYCHOLOGY LA English DT Article DE Autism; Executive control; Asperger Syndrome; Communication; Social; Repetitive behavior; Fluency; Attention ID SPECTRUM DISORDERS; YOUNG-CHILDREN; COMMUNICATION IMPAIRMENTS; DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; MIND; DYSFUNCTION; DEFICIT; SYMPTOMATOLOGY; INDIVIDUALS AB Background: Linking autism symptoms to cognitive abilities can expand phenotypic descriptions and facilitate investigations into the etiology and treatment of this multiplex disorder. Executive dysfunction is one of several potential cognitive phenotypes in autism. Method: Archival clinical data on 89 children diagnosed with Autism Spectrum Disorders and administered a large neuropsychological battery were evaluated for relationships between executive functioning and autism symptoms. Results: Significant relationships between both laboratory tasks and behavior rating scales of executive functions and autism symptoms were identified. Multiple regression analyses revealed that measures of semantic fluency, divided auditory attention, and behavioral regulation were significantly correlated with autism symptoms, even after accounting for the variance from correlated "nuisance variables," such as vocabulary and age. Conclusions: Executive dysfunction is related to all three clusters of behavioral symptoms in Autism Spectrum Disorders. C1 [Kenworthy, Lauren; Harrison, Bryan; Della Rosa, Anne] Childrens Natl Med Ctr, Rockville, MD 20850 USA. [Black, David O.; Wallace, Gregory L.] NIMH, Bethesda, MD 20892 USA. RP Kenworthy, L (reprint author), Childrens Natl Med Ctr, 14801 Phys Lane, Rockville, MD 20850 USA. EM lkenwort@cnmc.org OI Wallace, Gregory/0000-0003-0329-5054 NR 64 TC 39 Z9 40 U1 3 U2 29 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PY 2009 VL 15 IS 5 BP 425 EP 440 DI 10.1080/09297040802646983 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 500LC UT WOS:000270300800002 PM 19173090 ER PT J AU Chu, YW Gress, R Shlomchik, WD AF Chu, Yu-Waye Gress, Ronald Shlomchik, Warren D. BE Vogelsang, GB Pavletic, SZ TI ANIMAL MODELS OF CHRONIC GRAFT VERSUS HOST DISEASE SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID BONE-MARROW-TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; STEM-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CD4(+) T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IDIOPATHIC PNEUMONIA SYNDROME; GENE POLYMORPHISMS ASSOCIATE; CHRONIC ALLOGENEIC DISEASE C1 [Chu, Yu-Waye; Gress, Ronald] NCI, NIH, Bethesda, MD 20892 USA. [Shlomchik, Warren D.] Yale Univ, Sch Med, Dept Immunol, New Haven, CT USA. RP Chu, YW (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 156 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 31 EP 45 DI 10.1017/CBO9780511576751.005 D2 10.1017/CBO9780511576751 PG 15 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800005 ER PT J AU Jagasia, M Shulman, HM Filipovich, AH Pavletic, SZ AF Jagasia, Madan Shulman, Howard M. Filipovich, Alexandra H. Pavletic, Steven Z. BE Vogelsang, GB Pavletic, SZ TI DIAGNOSIS AND STAGING SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; OF-THE-LITERATURE; CHRONIC GRAFT; CLINICAL-TRIALS; CRITERIA; AUTOANTIBODIES C1 [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol,Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Shulman, Howard M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Dept Pathol, Seattle, WA 98195 USA. [Filipovich, Alexandra H.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Hematol Oncol, Immunodeficiency & Histiocytosis Program,Diagnost, Cincinnati, OH USA. [Pavletic, Steven Z.] NCI, Graft Versus Host & Autoimmun Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Jagasia, M (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol,Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 87 EP 100 DI 10.1017/CBO9780511576751.010 D2 10.1017/CBO9780511576751 PG 14 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800010 ER PT J AU Hughes, T McGuire, TR AF Hughes, Thomas McGuire, Timothy R. BE Vogelsang, GB Pavletic, SZ TI CHRONIC GRAFT VERSUS HOST DISEASE PHARMACOLOGY SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID RENAL-TRANSPLANT RECIPIENTS; STEM-CELL TRANSPLANT; NECROSIS-FACTOR-ALPHA; MYCOPHENOLATE-MOFETIL; CLINICAL PHARMACOKINETICS; DRUG-INTERACTIONS; CYCLOSPORINE-A; GLUCOCORTICOID-RECEPTORS; SIROLIMUS RAPAMYCIN; CYTOKINE PRODUCTION C1 [Hughes, Thomas] NCI, NIH, Bethesda, MD 20892 USA. [McGuire, Timothy R.] Univ Nebraska Med Ctr, Dept Pharm Practice, Coll Pharm, Omaha, NE USA. RP Hughes, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 90 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 101 EP 116 DI 10.1017/CBO9780511576751.011 D2 10.1017/CBO9780511576751 PG 16 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800011 ER EF